Supplementary Tables S1. GO-Slim terms...

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Supplementary Tables

S1. GO-Slim termsDrosophila genes were classified by mapping BDGP 3.1 GO annotations to a reduced setof 116 GO terms from GO-slim version 1.1 (Adams et al. 2000 Science 287: 2185-2195).Columns are GO TERM (the name of the GO-slim category); # GENES (# of BDGP 3.1genes having a GO annotation that is a descendant of this GO-slim category); GOID (theGO ID for this term, with multiple IDs separated by spaces); and CODE (a unique codefor each term).

S2. Multi-gene clustersMulti-gene clusters were generated when a bait or prey sequence mapped equally well tomultiple Drosophila genes using BDGP 3.1 gene structures. Columns are # GENES(number of genes joined into the cluster); CG (CG numbers for each gene); NAME(names for each gene); FBGN (FBgn numbers for each gene); CYTO (cytologicallocation of each gene in standard format division-subdivision-band); # DIVISION(number of unique cytological divisions represented by the genes); # SUBDIVISION(number of unique subdivisions); # BAND (number of unique bands).

S3. Fly-Yeast ortholog pairsPairs of interacting fly proteins whose yeast orthologs are reported to interact have beengrouped by category. Columns are CG1/CG1 (CG numbers for the fly proteins);NAME1/NAME2 (names for the fly proteins); YEAST1/YEAST1 (names for the yeastproteins from Saccharomyces Genome Database); METHOD (method used to identifythe interaction in yeast, y2h = yeast two-hybrid, coip = mass spectrometry of proteincomplexes from co-immunoprecipitation).

S4. Ortholog enrichment / depletionSignificance levels are reported for enrichment or depletion of fly/yeast interactionorthologs classified according to various hierarchies by the annotations of the Drosophilaproteins in each pair. Results are provided for category pairs that are significant at a p-value of 0.05 or better prior to correction for multiple testing. Columns areHIERARCHY (process, function, component from GO-Slim; structure from Pfam);CATEGORY 1/2 (the pair of categories); PVAL MULTI (p-value after correcting formultiple testing); PVAL SINGLE (p-value prior to correcting for multiple testing);DIRECTION (enriched or depleted); # OBS (number of fly interactions with proteinsannotated for this category pair and having a reported orthologous yeast interaction); #EXP (number of expected fly interactions for this category pair); # TOT (number of flyinteractions with proteins annotated for this hierarchy); # CLASS (number of flyinteractions with proteins annotated for this category pair); # ORTH (number of flyinteractions with proteins annotated for this hierarchy and having a reported orthologousyeast interaction); DBID 1/2 (database identifiers for the pair of categories). The singlep-values for # OBS were calculated from a hypergeometric distribution based on # TOT,# CLASS, # ORTH.

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S5. Protein enrichment / depletionSignificance levels are reported for enrichment or depletion of proteins in the high-confidence network classified according to various hierarchies. Results are reported forcategories that are significant at a p-value of 0.05 or better prior to correction for multipletesting. Categories are HIERARCHY (process, function, and component from GO-slim,and structure from Pfam); CATEGORY (name of the category); PVAL MULTI (p-valueafter correcting for multiple testing); PVAL SINGLE (p-value from hypergeometricdistribution prior to correcting for multiple testing); # OBS (number of fly proteinsannotated as this category and in the network); # EXP (number of such proteinsexpected); # TOT (number of fly proteins annotated for this hierarchy); # NET (numberof proteins annotated for this hierarchy and in the network); # CLASS (number ofproteins annotated for this category); DBID (database identifier for this category). Thesingle p-values were calculated from a hypergeometric distribution based on # TOT, #CLASS, and # NET.

S6. Pair enrichment / depletionSignificance levels are reported for enrichment or depletion of fly interactions in thehigh-confidence network classified according to various hierarchies. Results are reportedfor category pairs that are significant at a p-value of 0.05 or better prior to correction formultiple testing. Columns are HIERARCHY (process, function, component from GO-slim, and structure from Pfam); CATEGORY 1/2 (the pair of categories considered);PVAL MULTI (p-value after correction for multiple testing); PVAL SINGLE (p-valueprior to correction for multiple testing); DIRECTION (enriched or depleted); # OBS(number of interactions with proteins annotated for this pair of categories); # EXP(number of interactions expected from re-sampling of randomized networks); VAR(#EXP) (variance estimate for # EXP); DBID 1/2 (database identifiers for the pair ofcategories); RESAMPLING (single p-value calculated from the number of randomconfigurations with the number of interactions for this category pair equal to or moreextreme than the observed number); POISSON (single p-value calculated from a Poissondistribution based on # EXP).

S7. Drosophila protein-protein interactionsProtein-protein interactions identified in this work are listed with confidence scores andunderlying explanatory variables. Columns are cg1/2 (BDGP 3.1 CG numbers); p1/2(gene names); norient (1 = observed as bait/prey or prey/bait; 2 = observed in bothorientations); baitprey (number of clones with first protein as bait and second as prey);preybait (number of clones with first protein as prey and second as bait); cdna (number ofclones from cDNA screen); collection (number of clones from collection screen); baitrgn,bait5utr, baitcds13, bait3utr, baitother (number of bait sequences corresponding to 5UTR, CDS frame 13, and 3 UTR); preyrgn, prey5utr, preycds13, prey3utr, preyother(corresponding numbers for prey sequences); totclone (total number of clonescorresponding to this pair of proteins); baitneigh (number of unique interactions havingthe same bait as this interaction); preyneigh (number of unique interactions having thesame prey as this interaction); aneigh (number of unique interactions involving protein1); bneigh (number of unique interactions involving protein 2); maxneigh (the larger ofaneigh and bneigh); geomneigh (the geometric mean of aneigh and bneigh); nbridge (the

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number of proteins connected to both protein a and protein b); jac (the Jaccard correlationcalculated as nbridge divided by aniegh + bneigh nbridge 2); hexpect, yexpert,cexpert (1/0 indicator variables for training sets generated by human experts,bioinformatics, and the union of the two methods); cconf (predicted interactionconfidence).

Supplemental Table S1. GO-Slim terms

GO TERM # GENES GOID CODEbiological_process 2710 GO:0008150 1 behavior 78 GO:0007610 1.1 biological_process unknown 0 GO:0000004 1.2 cell communication 468 GO:0007154 1.3.1 cell adhesion 58 GO:0007155 1.3.1.1 signal transduction 309 GO:0007165 1.3.1.7 cell death 40 GO:0008219 1.3.2 apoptosis 36 GO:0006915 1.3.2.3.1 cell ion homeostasis 8 GO:0006873 1.3.4.3.3 cytoplasm organization and biogenesis 311 GO:0007028 1.3.4.4.3 organelle organization and biogenesis 294 GO:0006996 1.3.4.4.3.3 cytoskeleton organization and biogenesis 226 GO:0007010 1.3.4.4.3.3.1 mitochondrion organization and biogenesis 9 GO:0007005 1.3.4.4.3.3.7 cell proliferation 210 GO:0008283 1.3.4.5 cell cycle 175 GO:0007049 1.3.4.5.2 DNA replication 47 GO:0006260 1.3.4.5.2.2.4 chemi-mechanical coupling 0 GO:0006943 1.3.4.7 transport 280 GO:0006810 1.3.4.10 intracellular protein transport 63 GO:0006886 1.3.4.10.14.10 protein targeting 57 GO:0006605 1.3.4.10.14.10.3 mitochondrial transport 2 GO:0006839 1.3.4.10.14.14 ion transport 48 GO:0006811 1.3.4.10.15 lipid transport 1 GO:0006869 1.3.4.10.17 endocytosis 37 GO:0006897 GO:0016196 1.3.4.10.32.1 cell motility 78 GO:0006928 1.3.5 plasma membrane fusion 0 GO:0045026 GO:0006947 1.3.6.3 development 613 GO:0007275 1.4 sex determination 21 GO:0007530 1.4.19 small molecule transport 0 GO:0006832 1.5.166 physiological processes 2233 GO:0007582 1.6 amino acid and derivative metabolism 37 GO:0006519 1.6.20.4

protein biosynthesis 276GO:0006412 GO:0006416 GO:0006453 1.6.20.7.21.2

carbohydrate metabolism 37 GO:0005975 1.6.20.8 main pathways of carbohydrate metabolism 22 GO:0006092 1.6.20.8.11 proteolysis and peptidolysis 100 GO:0006508 1.6.20.10.20.2.5 coenzymes and prosthetic group metabolism 28 GO:0006731 1.6.20.11 electron transport 17 GO:0006118 1.6.20.13 energy pathways 23 GO:0006091 1.6.20.14 lipid metabolism 27 GO:0006629 1.6.20.21 nucleobase, nucleoside, nucleotide and nucleic acid metabolism496 GO:0006139 1.6.20.25 DNA metabolism 140 GO:0006259 1.6.20.25.1 DNA packaging 48 GO:0006323 1.6.20.25.1.5 DNA repair 49 GO:0006281 1.6.20.25.1.8 transcription 192 GO:0006350 1.6.20.25.12 transcription, DNA-dependent 168 GO:0006351 1.6.20.25.12.2 one-carbon compound metabolism 1 GO:0006730 1.6.20.26 protein metabolism 763 GO:0019538 GO:0006411 1.6.20.33 protein folding 19 GO:0006457 1.6.20.33.11 protein modification 334 GO:0006464 1.6.20.33.13 sensory perception 136 GO:0007600 1.6.34.2.4 defense response 128 GO:0006952 1.6.34.4.2 response to stress 107 GO:0006950 1.6.35molecular_function 5367 GO:0003674 2 apoptosis inhibitor activity 9 GO:0008189 2.4.2 binding activity 1690 GO:0005488 2.5 nucleic acid binding activity 744 GO:0003676 2.5.19 DNA binding activity 422 GO:0003677 2.5.19.1 transcription factor activity 224 GO:0003700 GO:0000130 2.5.19.1.23 RNA binding activity 267 GO:0003723 2.5.19.3 translation factor activity, nucleic acid binding 59 GO:0008135 2.5.19.4 actin binding activity 95 GO:0003779 2.5.27.12.1

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Supplemental Table S1. GO-Slim terms

transcription factor binding activity 39 GO:0008134 2.5.27.48 receptor binding activity 66 GO:0005102 2.5.29 cell adhesion molecule activity 45 GO:0005194 2.6

chaperone activity 87

GO:0003754 GO:0003757 GO:0003758 GO:0003760 GO:0003761 2.7

defense/immunity protein activity 44 GO:0003793 2.1 enzyme activity 2460 GO:0003824 2.11 protein phosphatase activity 89 GO:0004721 2.11.23.11.6.2.25 peptidase activity 375 GO:0008233 2.11.23.14 endopeptidase activity 231 GO:0004175 GO:0016809 2.11.23.14.7 protein kinase activity 227 GO:0004672 2.11.26.43 enzyme activator activity 62 GO:0008047 2.12.1 enzyme inhibitor activity 38 GO:0004857 2.12.2 molecular_function unknown 0 GO:0005554 2.14 motor activity 60 GO:0003774 2.15 cell cycle regulator 0 GO:0003750 2.17.48 cytochrome P450 0 GO:0005490 2.17.82 DNA repair protein 39 GO:0003685 2.17.87 DNA replication factor 18 GO:0003687 2.17.89 storage protein 0 GO:0005187 2.17.271 tumor suppressor 0 GO:0008181 2.17.283 ubiquitin 0 GO:0005551 2.17.284 signal transducer activity 590 GO:0004871 2.21 receptor activity 371 GO:0004872 2.21.6 transmembrane receptor activity 336 GO:0004888 2.21.6.17 G-protein coupled receptor activity 198 GO:0004930 2.21.6.17.7 olfactory receptor activity 55 GO:0004984 2.21.6.17.7.7.12 receptor signaling protein activity 153 GO:0005057 2.21.8 structural molecule activity 311 GO:0005198 2.22 structural constituent of cytoskeleton 37 GO:0005200 2.22.8

structural constituent of ribosome 140

GO:0003735 GO:0003736 GO:0003737 GO:0003738 GO:0003739 GO:0003740 GO:0003741 GO:0003742 2.22.15

transporter activity 631 GO:0005215 2.27 ion channel activity 106 GO:0005216 2.27.6.1.2 electron transporter activity 28 GO:0005489 2.27.8 neurotransmitter transporter activity 12 GO:0005326 2.27.13cellular_component 2910 GO:0005575 3 cell 2696 GO:0005623 3.1 intracellular 2043 GO:0005622 3.1.10 cytoplasm 1151 GO:0005737 3.1.10.8 synaptic vesicle 44 GO:0008021 3.1.10.8.9.3.1.4 cytoskeleton 199 GO:0005856 3.1.10.8.10 centrosome 21 GO:0005813 3.1.10.8.10.4.4.3.1 cytosol 239 GO:0005829 3.1.10.8.11 endoplasmic reticulum 114 GO:0005783 3.1.10.8.16 Golgi apparatus 40 GO:0005794 3.1.10.8.29 peroxisome 22 GO:0005777 3.1.10.8.34.2 mitochondrion 305 GO:0005739 3.1.10.8.36 ribosome 147 GO:0005840 3.1.10.8.52 lysosome 13 GO:0005764 3.1.10.8.60.3.1 nucleus 981 GO:0005634 3.1.10.19 plasma membrane 434 GO:0005886 3.1.11.13 extracellular 167 GO:0005576 3.3 extracellular matrix 43 GO:0005578 3.3.2 fibrinogen beta chain 0 GO:0005973 GO:0008006 3.5.44 fibrinogen gamma chain 0 GO:0005974 GO:0008007 3.5.45 unlocalized 74 GO:0005941 3.6

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Supplemental Table S2. Multi-gene clusters

COLOR CODESAME BANDSAME SUBDIVSAME DIVISIONDIFFERENT DIV

# GENES CG NAME FBGN CYTO # DIVISIONS # SUB-DIVISIONS

# BANDS

3 CG10530 CG10534 CG18779

Lcp65Ag1 Lcp65Ag2 CG18779

FBgn0020638 FBgn0020637 FBgn0042120

65A6-65A6 65A6-65A6 65A6-65A6

1 1 1

3 CG12519 CG14096 CG18294

CG12519 CG14096 CG18294

FBgn0036872 FBgn0036871 FBgn0036873

76B3-76B3 76B3-76B3 76B3-76B3

1 1 1

3 CG17450 CG32819 CG32820

CG17450 CG32819 CG32820

FBgn0040028 FBgn0052819 FBgn0052820

20A4-20A4 20A4-20A4 20A4-20A4

1 1 1

2 CG11659 CG6300

CG11659 CG6300

FBgn0038731 FBgn0038730

92B2-92B2 92B2-92B2

1 1 1

2 CG11719 CG18396

Mst98Ca Mst98Cb

FBgn0002865 FBgn0004171

98C3-98C3 98C3-98C3

1 1 1

2 CG1179 CG1180

LysB LysE FBgn0004425 FBgn0004428

61F3-61F3 61F3-61F3

1 1 1

2 CG12405 CG12896

Prx2540-1 CG12896

FBgn0033520 FBgn0033521

47A7-47A7 47A7-47A7

1 1 1

2 CG12546 CG14452

CG12546 CG14452

FBgn0037178 FBgn0037180

79F6-79F6 79F6-79F6

1 1 1

2 CG12728 CG32756

CG12728 CG32756

FBgn0029825 FBgn0052756

5C10-5C10 5C10-5C10

1 1 1

2 CG13323 CG13324

CG13323 CG13324

FBgn0033788 FBgn0033789

49F1-49F1 49F1-49F1

1 1 1

2 CG13796 CG31904

CG13796 CG31904

FBgn0031939 FBgn0051904

28C2-28C2 28C2-28C2

1 1 1

2 CG14746 CG8577

PGRP-SC1a PGRP-SC1b

FBgn0043576 FBgn0033327

44E2-44E2 44E2-44E2

1 1 1

2 CG18000 CG32823

Cdic CG32823 FBgn0013761 FBgn0052823

19C1-19C1 19C1-19C1

1 1 1

2 CG18030 CG2229

CG18030 CG2229

FBgn0039778 FBgn0039777

99F6-99F6 99F6-99F6

1 1 1

2 CG18064 CG32197

Met75Cb Met75Ca

FBgn0028415 FBgn0028416

75C7-75C7 75C7-75C7

1 1 1

2 CG18278 CG30059

CG18278 CG30059

FBgn0033836 FBgn0050059

50A5-50A5 50A5-50A5

1 1 1

2 CG18284 CG31872

CG18284 CG31872

FBgn0032274 FBgn0051872

32A2-32A2 32A2-32A2

1 1 1

2 CG18495 CG30382

Prosalpha6 CG30382

FBgn0026781 FBgn0050382

43E18-43E18 43E18-43E18

1 1 1

2 CG18542 CG32939

CG18542 CG32939

FBgn0037731 FBgn0052939

85E4-85E4 85E4-85E4

1 1 1

2 CG31034 CG31362

Ser99Da Ser99Db

FBgn0003356 FBgn0003357

99C7-99C7 99C7-99C7

1 1 1

2 CG31054 CG4849

CG31054 CG4849

FBgn0051054 FBgn0039566

98B6-98B6 98B6-98B6

1 1 1

2 CG3176 CG32817

CG3176 CG32817

FBgn0029524 FBgn0052817

1B4-1B4 1B4-1B4

1 1 1

2 CG32207 CR32205

CG32207 CR32205

FBgn0052207 FBgn0052205

76B3-76B3 76B3-76B3

1 1 1

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Supplemental Table S2. Multi-gene clusters

2 CG32850 TE20416

CG32850 Stalker2{}1505

FBgn0052850 FBti0020416

102B5-102B5 102B5-102B5

1 1 1

2 CG33057 CG7163

CG33057 CG7163

FBgn0053057 FBgn0035889

66C11-66C11 66C11-66C11

1 1 1

2 CG33104 CG33105

CG33104 CG33105

FBgn0053104 FBgn0053105

85E4-85E4 85E4-85E4

1 1 1

2 CG6447 CG6478

CG6447 CG6478

FBgn0039437 FBgn0039436

97C2-97C2 97C2-97C2

1 1 1

2 CG9191 CR32318

Klp61F CR32318

FBgn0004378 FBgn0052318

61F4-61F4 61F4-61F4

1 1 1

2 CG1252 CG2360

Ccp84Ab Ccp84Aa

FBgn0004782 FBgn0004783

84A4-84A4 84A4-84A5

1 1 2

2 CG18816 CG30160

Tsp42Eb CG30160

FBgn0042086 FBgn0050160

42E4-42E4 42E5-42E5

1 1 2

2 CG2947 CG32789

CG2947 CG32789

FBgn0029676 FBgn0052789

3F1-3F1 3F2-3F2

1 1 2

2 CG32598 CG32601

CG32598 CG32601

FBgn0052598 FBgn0052601

12E8-12E8 12E9-12E9

1 1 2

2 CG32745 CG3458

CG32745 Top3beta

FBgn0052745 FBgn0026015

5E4-5E4 5E5-5E5

1 1 2

2 CG32801 CG32803

CG32801 CG32803

FBgn0052801 FBgn0052803

2B15-2B15 2B14-2B15

1 1 2

3 CG2941 CG32783 CG32786

CG2941 CG32783 CG32786

FBgn0029686 FBgn0052783 FBgn0052786

3F7-3F7 3F9-3F9 3F8-3F9

1 1 3

2 CG14477 CG33197

mm CG33197 FBgn0015514 FBgn0053197

54B4-54B5 54B1-54B5

1 1 3

2 CG1524 CG1527

RpS14a RpS14b

FBgn0004403 FBgn0004404

7C6-7C7 7C7-7C8

1 1 3

2 CG17210 CG5106

CG17210 CG5106

FBgn0037888 FBgn0037879

86E1-86E1 86D10-86D10

1 2 2

2 CG32164 CG32165

CG32164 CG32165

FBgn0042177 FBgn0042178

73B1-73B1 73A11-73B1

1 2 2

2 CG32581 CG8974

CG32581 CG8974

FBgn0052581 FBgn0030693

13F1-13F1 13E18-13F1

1 2 2

2 CG1683 CG16944

Ant2 sesB FBgn0025111 FBgn0003360

9E9-9F1 9E10-9F1

1 2 3

6 CG18743 CG31359 CG31366 CG31449 CG5834 CG6489

Hsp70Ab Hsp70Bb Hsp70Aa Hsp70Ba Hsp70Bbb Hsp70Bc

FBgn0013276 FBgn0013278 FBgn0013275 FBgn0013277 FBgn0051354 FBgn0013279

87A3-87A3 87B14-87B14 87A2-87A2 87B12-87B12 87B14-87B14 87B14-87B15

1 2 5

2 CG11377 CG32276

CG11377 BcDNA:RE27904

FBgn0031217 FBgn0047135

21A5-21A5 63B11-63B11

2 2 2

2 CG1341 CG2789

Rpt1 CG2789 FBgn0028687 FBgn0031263

43E7-43E7 21D1-21D1

2 2 2

2 CG7977 CG9165

RpL23a l(3)02640

FBgn0026372 FBgn0010786

62A10-62A10 61F6-61F7

2 2 3

2 CG8085 CG8581

RN-tre fra FBgn0020620 FBgn0011592

50C23-50C23 49B2-49B3

2 2 3

2 CG7744 CG8457

CG7744 Cyp6t3

FBgn0034447 FBgn0033697

56D8-56D9 48E7-48E8

2 2 4

3 CG15365 CG4897 CG6287

CG15365 RpL7 CG6287

FBgn0030077 FBgn0005593 FBgn0032350

8C4-8C4 31B1-31B1 32D5-32D5

3 3 3

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Supplemental Table S3. Fly-Yeast ortholog pairs

CATEGORY CG1 CG2 NAME1 NAME2 YEAST1 YEAST2 METHODcytoskeleton, actin binding CG4027 CG5061 Act5C capt ACT1 SRV2 coip+y2hcytoskeleton, actin binding CG10540 CG17158 CG10540 cpb CAP1 CAP2 coip+y2hDNA binding, DNA helicase CG4003 CG9750 pont rept RVB1 RVB2 coip+y2hDNA chromatin modification, SAGA complex CG4107 CG9638 Pcaf CG9638 GCN5 ADA2 coip+y2hDNA repair CG10215 CG3697 Ercc1 mei-9 RAD10 RAD1 coipDNA replication factor C CG14999 CG5313 RfC40 RfC3 RFC4 RFC3 coip+y2hDNA replication factor C CG5313 CG8142 RfC3 CG8142 RFC3 RFC2 coipDNA replication, alpha DNA polymerase CG5923 CG6349 DNApol-alpha73 DNApol-alpha180 POL12 POL1 coipGTPase CG11968 CG8707 CG11968 CG8707 GTR1 GTR2 y2hmRNA export nuclear pore, proteolysis CG4673 CG6233 CG4673 Ufd1-like NPL4 UFD1 coip+y2hmRNA polyadenylation CG1078 CG3642 CG1078 Clp FIP1 YTH1 coip+y2hmRNA polyadenylation CG17170 CG7697 su(f) CstF-64 RNA14 RNA15 coip+y2hmRNA processing, poly(A) ribonuclease CG11486 CG8232 CG11486 CG8232 PAN3 PAN2 coip+y2hmRNA splicing CG10418 CG4279 CG10418 CG4279 LSM2 LSM1 coip+y2hmRNA splicing CG1249 CG16792 CG1249 DebB SMD2 SMX3 coip+y2hmRNA splicing CG13277 CG31990 CG13277 CG31990 LSM7 LSM4 coip+y2hmRNA splicing CG13277 CG6610 CG13277 CG6610 LSM7 LSM5 y2hmRNA splicing CG16792 CG18591 DebB CG18591 SMX3 YOR159C y2hmRNA splicing CG2925 CG3193 noi crn PRP9 CLF1 coipmRNA splicing CG3193 CG6905 crn CG6905 CLF1 CEF1 coipmRNA splicing CG3605 CG3780 CG3605 Spx CUS1 HSH49 y2hmRNA transcription factor CG3075 CG3891 CG3075 CG3891 HAP5 YGL237C coip+y2hmRNA transcription factor CG5933 CG7818 CG5933 CG7818 IME4 KAR4 y2hnucleotide binding activity CG10222 CG3704 CG10222 EG:BACR7A4.17 YOR262W YJR072C y2hprotein degradation, 19S proteasome CG10230 CG1100 Rpn9 Rpn5 RPN9 RPN5 coipprotein degradation, 19S proteasome CG18174 CG3416 Rpn11 Mov34 RPN11 RPN8 coip+y2hprotein degradation, 20S proteasome CG4157 CG5648 Rpn12 Prosalpha6T RPN12 PRE5 coipprotein degradation, ubiquitin-ligase CG15010 CG16983 ago skpA MET30 SKP1 coip+y2hprotein degradation, ubiquitin-ligase CG16982 CG9060 Roc1a Zpr1 HRT1 ZPR1 y2hprotein folding, chaperone CG6302 CG6719 l(3)01239 CG6719 GIM4 PAC10 y2hprotein folding, chaperone CG7048 CG7770 CG7048 CG7770 GIM5 YKE2 coip+y2hprotein kinase CG13852 CG8637 CG13852 trc MOB1 CBK1 y2hprotein modification CG11652 CG7265 CG11652 CG7265 YIL103W DPH2 y2hprotein modification, geranylgeranyltransferase CG12007 CG18627 CG12007 betaggt-II BET4 BET2 coipprotein phosphatase CG6593 CG9238 Pp1alpha-96A CG9238 GLC7 GIP2 coipprotein phosphatase CG7109 CG9578 mts CG9578 PPH22 SDF1 y2hprotein synthesis elongation factor CG11901 CG6341 Ef1gamma Ef1beta TEF4 EFB1 coipprotein synthesis initiation factor CG10315 CG2677 eIF2B-delta eIF2B-beta GCD2 GCD7 coip+y2hprotein synthesis initiation factor CG14544 CG9596 CG14544 CG9596 GCD14 GCD10 y2hprotein synthesis initiation factor CG17737 CG4954 CG17737 eIF3-S8 SUI1 NIP1 coip+y2hprotein synthesis initiation factor CG3806 CG8190 eIF2B-epsilon eIF2B-gamma GCD6 GCD1 coip+y2hprotein synthesis initiation factor CG6476 CG9946 Su(var)3-9 eIF-2alpha GCD11 SUI2 coipprotein synthesis initiation, SAGA complex CG2677 CG9638 eIF2B-beta CG9638 GCD7 ADA2 y2hprotein synthesis, ribosome CG4087 CG7490 RpP2 RpP0 RPP1A RPP0 y2hRNA binding activity CG11738 CG2972 CG11738 CG2972 YOR145C NOB1 coipRNA polymerase III CG10685 CG3756 CG10685 CG3756 RPC19 RPC40 coip+y2hsignal transduction, casein kinase II CG15224 CG17520 CkIIbeta CkIIalpha CKB2 CKA1 coip+y2hsignal transduction, casein kinase II CG15224 CG6724 CkIIbeta CG6724 CKB2 YTM1 coipsignal transduction, endocytosis CG2903 CG6521 Hrs Stam VPS27 YHL002W coip+y2hsnRNP, rRNA modification CG11920 CG13097 CG11920 CG13097 IMP4 MPP10 coip+y2hsnRNP, rRNA modification, ribosome CG13097 CG4866 CG13097 CG4866 MPP10 IMP3 coip+y2htranscription CG10318 CG4185 NC2alpha NC2beta BUR6 NCB2 y2htranscription, RNA polymerase II CG6840 CG7885 Rpb11 RpII33 RPB11 RPB3 coiptransport, endocytosis CG5864 CG9113 AP-1sigma AP-1gamma APS1 APL4 coip+y2htransport, endocytosis (VPS25) CG14750 CG6637 CG14750 CG6637 VPS25 SNF8 y2htransport, endocytosis, ER to Golgi CG6773 CG8266 sec13 sec31 SEC13 SEC31 coip+y2htransport, Golgi apparatus CG12404 CG5484 CG12404 CG5484 YIP1 YIF1 y2htransport, hydrogen-transporting ATPase CG1088 CG17332 Vha26 VhaSFD VMA4 VMA13 coiptransport, hydrogen-transporting ATPase CG1088 CG4800 Vha26 CG4800 VMA4 YKL056C coiptransport, mitochondrial electron transport CG14724 CG3460 CoVa Nmd3 COX6 NMD3 coiptransport, vesicle-mediated CG4764 CG5625 CG4764 CG5625 VPS29 VPS35 coiptransport, v-SNARE CG1467 CG6625 Syx16 Snap TLG2 SEC17 coiptransport, v-SNARE CG1467 CG8228 Syx16 CG8228 TLG2 VPS45 coipUNKNOWN CG12797 CG7949 CG12797 CG7949 YDR267C YHR122W y2hUNKNOWN CG5941 CG9099 CG5941 CG9099 YER007C-A YJR014W coip

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Supplemental Table S4. Ortholog enrichment

COLOR CODESIGNIF ENRICHEDENRICHEDDEPLETEDSIGNIF DEPLETED

HIERARCHY CATEGORY 1 CATEGORY 2 PVAL MULTI PVAL SINGLE DIRECTION # OBS # EXP # TOT # CLASS # ORTH DBID 1 DBID 2

PROCESS nucleobase, nucleoside, nucleotide and nucleic acid metabolism

nucleobase, nucleoside, nucleotide and nucleic acid metabolism

0.000357341 2.50E-06 enriched 14 4.428571 182 26 31 GO:0006139 GO:0006139


DNA replication 0.096769984 0.000711481 enriched 4 0.681319 182 4 31 GO:0006139 GO:0006260

PROCESS DNA metabolism DNA replication 0.096769984 0.000711481 enriched 4 0.681319 182 4 31 GO:0006259 GO:0006260PROCESS DNA replication physiological processes 0.096769984 0.000711481 enriched 4 0.681319 182 4 31 GO:0006260 GO:0007582PROCESS DNA metabolism DNA metabolism 0.360889649 0.003125721 enriched 4 0.851648 182 5 31 GO:0006259 GO:0006259PROCESS protein biosynthesis physiological processes 0.384226406 0.003384999 depleted 5 11.92308 182 70 31 GO:0006412;GO:000641

6;GO:0006453GO:0007582

PROCESS protein biosynthesis protein biosynthesis 0.442978323 0.004083605 enriched 5 1.362637 182 8 31 GO:0006412;GO:0006416;GO:0006453

GO:0006412;GO:0006416;GO:0006453

PROCESS DNA replication DNA replication 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0006260 GO:0006260PROCESS DNA replication cell cycle 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0006260 GO:0007049PROCESS DNA replication cell proliferation 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0006260 GO:0008283PROCESS cell cycle cell cycle 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0007049 GO:0007049PROCESS cell cycle cell proliferation 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0007049 GO:0008283PROCESS cell proliferation cell proliferation 0.478947581 0.004548398 enriched 3 0.510989 182 3 31 GO:0008283 GO:0008283PROCESS physiological processes protein metabolism 0.561821353 0.005753515 depleted 13 19.75824 182 116 31 GO:0007582 GO:0019538;GO:000641

1PROCESS protein modification physiological processes 0.697972006 0.008337327 depleted 1 5.791209 182 34 31 GO:0006464 GO:0007582PROCESS DNA metabolism cell cycle 0.912622428 0.016901117 enriched 4 1.192308 182 7 31 GO:0006259 GO:0007049PROCESS DNA metabolism cell proliferation 0.912622428 0.016901117 enriched 4 1.192308 182 7 31 GO:0006259 GO:0008283PROCESS DNA replication DNA repair 0.983347215 0.028231437 enriched 2 0.340659 182 2 31 GO:0006260 GO:0006281PROCESS protein folding protein folding 0.983347215 0.028231437 enriched 2 0.340659 182 2 31 GO:0006457 GO:0006457PROCESS endocytosis cell communication 0.983347215 0.028231437 enriched 2 0.340659 182 2 31 GO:0006897;GO:001619

6GO:0007154


DNA metabolism 0.986622649 0.029718629 enriched 4 1.362637 182 8 31 GO:0006139 GO:0006259

PROCESS transport protein metabolism 0.990305634 0.031901124 depleted 1 4.598901 182 27 31 GO:0006810 GO:0019538;GO:0006411


protein metabolism 0.996870772 0.039526084 depleted 2 5.791209 182 34 31 GO:0006139 GO:0019538;GO:0006411


cell cycle 0.998982831 0.047044369 enriched 4 1.532967 182 9 31 GO:0006139 GO:0007049


cell proliferation 0.998982831 0.047044369 enriched 4 1.532967 182 9 31 GO:0006139 GO:0008283

FUNCTION nucleic acid binding activity nucleic acid binding activity 0.001929847 2.20E-05 enriched 7 1.132132 333 13 29 GO:0003676 GO:0003676FUNCTION RNA binding activity RNA binding activity 0.051371321 0.000599114 enriched 3 0.261261 333 3 29 GO:0003723 GO:0003723FUNCTION translation factor activity,

nucleic acid bindingtranslation factor activity, nucleic acid binding

0.051371321 0.000599114 enriched 3 0.261261 333 3 29 GO:0008135 GO:0008135

FUNCTION binding activity binding activity 0.080397332 0.000951974 enriched 10 3.570571 333 41 29 GO:0005488 GO:0005488

Giot et al. 1

Supplemental Table S4. Ortholog enrichment

FUNCTION DNA binding activity DNA binding activity 0.477284702 0.007344694 enriched 2 0.174174 333 2 29 GO:0003677 GO:0003677FUNCTION DNA replication factor DNA replication factor 0.477284702 0.007344694 enriched 2 0.174174 333 2 29 GO:0003687 GO:0003687FUNCTION nucleic acid binding activity binding activity 0.478736826 0.007376074 enriched 7 2.525526 333 29 29 GO:0003676 GO:0005488FUNCTION nucleic acid binding activity translation factor activity,

nucleic acid binding0.586486534 0.009984651 enriched 3 0.522523 333 6 29 GO:0003676 GO:0008135

FUNCTION nucleic acid binding activity DNA binding activity 0.767607708 0.016446532 enriched 3 0.60961 333 7 29 GO:0003676 GO:0003677FUNCTION enzyme activity structural molecule activity 0.871827167 0.023074788 depleted 1 5.051051 333 58 29 GO:0003824 GO:0005198FUNCTION nucleic acid binding activity RNA binding activity 0.890009347 0.024771655 enriched 3 0.696697 333 8 29 GO:0003676 GO:0003723FUNCTION binding activity translation factor activity,

nucleic acid binding0.890009347 0.024771655 enriched 3 0.696697 333 8 29 GO:0005488 GO:0008135

FUNCTION chaperone activity chaperone activity 0.970954664 0.039416861 enriched 2 0.348348 333 4 29 GO:0003754;GO:0003757;GO:0003758;GO:0003760;GO:0003761

GO:0003754;GO:0003757;GO:0003758;GO:0003760;GO:0003761

FUNCTION structural constituent of ribosome

enzyme activity 0.979969507 0.043464613 depleted 1 4.441441 333 51 29 GO:0003735;GO:0003736;GO:0003737;GO:0003738;GO:0003739;GO:0003740;GO:0003741;GO:0003742

GO:0003824

COMPONENT nucleus nucleus 1.54E-06 2.85E-08 enriched 18 5.588235 204 38 30 GO:0005634 GO:0005634COMPONENT cell cytoplasm 0.001086209 2.01E-05 depleted 14 23.67647 204 161 30 GO:0005623 GO:0005737COMPONENT cytosol cytosol 0.010445636 0.000194436 enriched 9 2.647059 204 18 30 GO:0005829 GO:0005829COMPONENT intracellular cytoplasm 0.025498064 0.000478196 depleted 14 22.20588 204 151 30 GO:0005622 GO:0005737COMPONENT nucleus cytoplasm 0.044293821 0.000838625 depleted 5 13.08824 204 89 30 GO:0005634 GO:0005737COMPONENT cell ribosome 0.067444018 0.00129224 depleted 1 7.352941 204 50 30 GO:0005623 GO:0005840COMPONENT intracellular ribosome 0.136965385 0.00272407 depleted 1 6.764706 204 46 30 GO:0005622 GO:0005840COMPONENT intracellular mitochondrion 0.222188546 0.00464236 depleted 0 4.558824 204 31 30 GO:0005622 GO:0005739COMPONENT cell mitochondrion 0.222188546 0.00464236 depleted 0 4.558824 204 31 30 GO:0005623 GO:0005739COMPONENT cytoplasm ribosome 0.8025845 0.029598398 depleted 1 4.705882 204 32 30 GO:0005737 GO:0005840COMPONENT cytoplasm mitochondrion 0.936364398 0.049731575 depleted 0 2.647059 204 18 30 GO:0005737 GO:0005739

STRUCTURE Sm protein domain Sm protein domain 0.119419033 0.001531036 enriched 5 1.01476 542 10 55 PF01423 PF01423STRUCTURE RNA polymerase Rpb3/RpoA

insert domainRNA polymerases L / 13 to 16 kDa subunit family

0.570434343 0.010128844 enriched 2 0.202952 542 2 55 PF01000 PF01193

STRUCTURE KE2 protein family Prefoldin subunit family 0.570434343 0.010128844 enriched 2 0.202952 542 2 55 PF01920 PF02996

Giot et al. 2

Supplemental Table S5. Protein enrichment


HIERARCHY CATEGORY PVAL MULTI PVAL SINGLE DIRECTION # OBS # EXP # TOT # NET # CLASS DBID

PROCESS sensory perception 2.03E-05 2.11E-07 depleted 29 56.83 2702 1129 136 GO:0007600

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism 0.00069686 7.26E-06 enriched 251 207.2 2702 1129 496 GO:0006139

PROCESS transcription 0.000984253 1.03E-05 enriched 109 80.23 2702 1129 192 GO:0006350

PROCESS transcription, DNA-dependent 0.147220677 0.001657526 enriched 89 70.2 2702 1129 168 GO:0006351PROCESS signal transduction 0.155504672 0.001759035 depleted 105 129.1 2702 1129 309 GO:0007165PROCESS development 0.158161277 0.001791797 enriched 288 256.1 2702 1129 613 GO:0007275PROCESS transport 0.256690575 0.003085261 enriched 139 117 2702 1129 280 GO:0006810PROCESS protein modification 0.335423417 0.004247259 depleted 117 139.6 2702 1129 334 GO:0006464PROCESS defense response 0.671539252 0.011530281 depleted 40 52.65 2702 1129 126 GO:0006952PROCESS intracellular protein transport 0.82317853 0.017886179 enriched 35 26.32 2702 1129 63 GO:0006886PROCESS sex determination 0.833257611 0.01848642 enriched 14 8.775 2702 1129 21 GO:0007530PROCESS protein targeting 0.969287958 0.035631983 enriched 31 23.82 2702 1129 57 GO:0006605PROCESS carbohydrate metabolism 0.988718033 0.04563975 depleted 10 15.46 2702 1129 37 GO:0005975

FUNCTION nucleic acid binding activity 1.64E-13 2.23E-15 enriched 373 275.3 5351 1980 744 GO:0003676FUNCTION endopeptidase activity 7.25E-09 9.80E-11 depleted 41 84.74 5351 1980 229 GO:0004175;GO:0016809FUNCTION binding activity 1.48E-08 2.01E-10 enriched 729 625.3 5351 1980 1690 GO:0005488

FUNCTIONtransmembrane receptor activity 1.60E-08 2.16E-10 depleted 72 124 5351 1980 335 GO:0004888

FUNCTION ion channel activity 1.38E-07 1.86E-09 depleted 12 39.22 5351 1980 106 GO:0005216FUNCTION peptidase activity 2.55E-07 3.44E-09 depleted 87 138 5351 1980 373 GO:0008233

FUNCTIONG-protein coupled receptor activity 1.78E-06 2.41E-08 depleted 38 73.26 5351 1980 198 GO:0004930

FUNCTION receptor activity 7.12E-06 9.62E-08 depleted 91 136.9 5351 1980 370 GO:0004872FUNCTION RNA binding activity 1.44E-05 1.95E-07 enriched 139 98.8 5351 1980 267 GO:0003723

FUNCTIONtranslation factor activity, nucleic acid binding 0.000361238 4.88E-06 enriched 39 21.83 5351 1980 59 GO:0008135

FUNCTION DNA binding activity 0.000660037 8.92E-06 enriched 198 156.2 5351 1980 422 GO:0003677FUNCTION signal transducer activity 0.001690064 2.29E-05 depleted 173 217.9 5351 1980 589 GO:0004871FUNCTION transporter activity 0.003026941 4.10E-05 depleted 188 232.7 5351 1980 629 GO:0005215

Giot et al. 1


FUNCTION enzyme activity 0.005543949 7.51E-05 depleted 842 909.1 5351 1980 2457 GO:0003824FUNCTION DNA replication factor 0.036377954 0.000500633 enriched 14 6.66 5351 1980 18 GO:0003687FUNCTION transcription factor activity 0.202016169 0.003044908 enriched 103 82.89 5351 1980 224 GO:0003700;GO:0000130FUNCTION structural molecule activity 0.2960641 0.004732926 enriched 136 114 5351 1980 308 GO:0005198

FUNCTIONdefense/immunity protein activity 0.41639644 0.007251061 depleted 8 15.91 5351 1980 43 GO:0003793

FUNCTION olfactory receptor activity 0.578719824 0.011613886 depleted 12 20.35 5351 1980 55 GO:0004984FUNCTION actin binding activity 0.830131547 0.023671161 enriched 45 35.15 5351 1980 95 GO:0003779

COMPONENT intracellular 1.16E-16 3.05E-18 enriched 963 858.7 2907 1223 2041 GO:0005622COMPONENT nucleus 5.06E-14 1.31E-15 enriched 513 412.7 2907 1223 981 GO:0005634COMPONENT plasma membrane 0.002773428 7.31E-05 depleted 146 182.2 2907 1223 433 GO:0005886COMPONENT mitochondrion 0.069289559 0.001887875 depleted 104 127.9 2907 1223 304 GO:0005739COMPONENT cytoplasm 0.824439429 0.044751203 enriched 506 483.4 2907 1223 1149 GO:0005737

STRUCTURE Trypsin 5.39E-11 1.38E-14 depleted 30 80.1 7757 2890 215 PF00089

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) 2.02E-06 5.19E-10 enriched 80 46.2 7757 2890 124 PF00076

STRUCTURE Zinc finger, C2H2 type 0.000583069 1.50E-07 enriched 159 115.1 7757 2890 309 PF00096STRUCTURE Ligand-gated ion channel 0.125671965 3.46E-05 depleted 0 8.196 7757 2890 22 PF00060STRUCTURE SH3 domain 0.21235751 6.15E-05 enriched 35 20.49 7757 2890 55 PF00018STRUCTURE Carboxylesterase 0.392060186 0.000128128 depleted 3 13.04 7757 2890 35 PF00135STRUCTURE Sm protein 0.513036211 0.000185247 enriched 14 6.334 7757 2890 17 PF01423

STRUCTUREUDP-glucoronosyl and UDP-glucosyl transferase 0.518230821 0.000188008 depleted 3 12.67 7757 2890 34 PF00201

STRUCTURE7 transmembrane receptor (rhodopsin family) 0.769598539 0.000377872 depleted 11 23.84 7757 2890 64 PF00001

STRUCTURE Ion transport protein 0.847904749 0.000484756 depleted 7 17.88 7757 2890 48 PF00520STRUCTURE Immunoglobulin domain 0.953638845 0.000790443 depleted 29 45.83 7757 2890 123 PF00047STRUCTURE PCI domain 0.971328628 0.000914066 enriched 12 5.589 7757 2890 15 PF01399STRUCTURE Leucine Rich Repeat 0.973818603 0.000937435 depleted 22 36.88 7757 2890 99 PF00560STRUCTURE BESS motif 0.997396945 0.001531028 enriched 15 7.824 7757 2890 21 PF02944STRUCTURE alpha/beta hydrolase fold 0.999933025 0.002471499 depleted 6 14.53 7757 2890 39 PF00561

STRUCTURELeucine rich repeat C-terminal domain 0.999963875 0.002630039 depleted 4 11.55 7757 2890 31 PF01463

STRUCTURE Proteasome A-type and B-type 0.999996928 0.003262748 enriched 16 8.942 7757 2890 24 PF00227STRUCTURE Hsp20/alpha crystallin family 0.999997809 0.003349496 enriched 9 4.098 7757 2890 11 PF00011STRUCTURE Alkaline phosphatase 0.999999449 0.003703511 depleted 0 4.471 7757 2890 12 PF00245STRUCTURE Mitochondrial carrier protein 0.999999606 0.003789794 depleted 8 16.77 7757 2890 45 PF00153

Giot et al. 2


STRUCTURE 7tm Odorant receptor 0.999999977 0.004517731 depleted 11 20.49 7757 2890 55 PF02949STRUCTURE ThiF family 0.999999999 0.005352026 enriched 7 2.981 7757 2890 8 PF00899

STRUCTUREProtein of unknown function (DUF229) 1 0.006018894 depleted 1 5.961 7757 2890 16 PF02995

STRUCTUREHelix-loop-helix DNA-binding domain 1 0.00703887 enriched 29 19.75 7757 2890 53 PF00010

STRUCTURE Peptidase family M13 1 0.007084312 depleted 2 7.451 7757 2890 20 PF01431STRUCTURE Peptidase family M1 1 0.007084312 depleted 2 7.451 7757 2890 20 PF01433

STRUCTUREab-hydrolase associated lipase region 1 0.007084312 depleted 2 7.451 7757 2890 20 PF04083

STRUCTUREBacterial transferase hexapeptide (three repeats) 1 0.007162699 enriched 5 1.863 7757 2890 5 PF00132

STRUCTURE

Histone-like transcription factor (CBF/NF-Y) and archaeal histone 1 0.007162699 enriched 5 1.863 7757 2890 5 PF00808

STRUCTURE Mov34/MPN/PAD-1 family 1 0.007462406 enriched 8 3.726 7757 2890 10 PF01398STRUCTURE Cytochrome P450 1 0.007717181 depleted 21 32.04 7757 2890 86 PF00067

STRUCTUREChitin binding Peritrophin-A domain 1 0.008165535 depleted 18 28.32 7757 2890 76 PF01607

STRUCTURETransmembrane amino acid transporter protein 1 0.00905901 depleted 1 5.589 7757 2890 15 PF01490

STRUCTUREAmiloride-sensitive sodium channel 1 0.009422756 depleted 0 3.726 7757 2890 10 PF00858

STRUCTURE SH2 domain 1 0.009794971 enriched 17 10.43 7757 2890 28 PF00017STRUCTURE Lectin C-type domain 1 0.009944566 depleted 4 10.06 7757 2890 27 PF00059STRUCTURE Sugar (and other) transporter 1 0.009962747 depleted 7 14.16 7757 2890 38 PF00083STRUCTURE Ubiquitin family 1 0.010171653 enriched 16 9.687 7757 2890 26 PF00240STRUCTURE BTB/POZ domain 1 0.012562225 enriched 30 21.24 7757 2890 57 PF00651

STRUCTURESodium:neurotransmitter symporter family 1 0.013584653 depleted 1 5.216 7757 2890 14 PF00209

STRUCTUREDiacylglycerol kinase catalytic domain (presumed) 1 0.015028306 depleted 0 3.353 7757 2890 9 PF00781

STRUCTURE Sulfate transporter family 1 0.015028306 depleted 0 3.353 7757 2890 9 PF00916STRUCTURE Dynein heavy chain 1 0.015028306 depleted 0 3.353 7757 2890 9 PF03028STRUCTURE Roadblock/LC7 domain 1 0.01630395 enriched 7 3.353 7757 2890 9 PF03259STRUCTURE MATH domain 1 0.019241998 enriched 4 1.49 7757 2890 4 PF00917STRUCTURE GRIP domain 1 0.019241998 enriched 4 1.49 7757 2890 4 PF01465STRUCTURE Surp module 1 0.019241998 enriched 4 1.49 7757 2890 4 PF01805STRUCTURE KE2 family protein 1 0.019241998 enriched 4 1.49 7757 2890 4 PF01920STRUCTURE CIDE-N domain 1 0.019241998 enriched 4 1.49 7757 2890 4 PF02017STRUCTURE Cyclin, N-terminal domain 1 0.019531807 enriched 9 4.843 7757 2890 13 PF00134

Giot et al. 3


STRUCTURE G-patch domain 1 0.019932801 enriched 10 5.589 7757 2890 15 PF01585

STRUCTUREKunitz/Bovine pancreatic trypsin inhibitor domain 1 0.020400527 depleted 3 7.824 7757 2890 21 PF00014

STRUCTURENeurotransmitter-gated ion-channel ligand binding domain 1 0.020400527 depleted 3 7.824 7757 2890 21 PF02931

STRUCTURE Ras family 1 0.023815087 depleted 14 21.61 7757 2890 58 PF00071STRUCTURE Sulfatase 1 0.023966731 depleted 0 2.981 7757 2890 8 PF00884STRUCTURE RUN domain 1 0.023966731 depleted 0 2.981 7757 2890 8 PF02759

STRUCTURENeurotransmitter-gated ion-channel transmembrane region 1 0.028327107 depleted 3 7.451 7757 2890 20 PF02932

STRUCTURE PAS domain 1 0.030152805 depleted 1 4.471 7757 2890 12 PF00989

STRUCTURE Glycosyl hydrolases family 18 1 0.03033982 depleted 2 5.961 7757 2890 16 PF00704STRUCTURE short chain dehydrogenase 1 0.033193098 depleted 12 18.63 7757 2890 50 PF00106STRUCTURE Spectrin repeat 1 0.034778675 enriched 6 2.981 7757 2890 8 PF00435STRUCTURE PWWP domain 1 0.034778675 enriched 6 2.981 7757 2890 8 PF00855

STRUCTUREViral A-type inclusion protein repeat 1 0.034778675 enriched 6 2.981 7757 2890 8 PF04508

STRUCTURE

ATPase family associated with various cellular activities (AAA) 1 0.034938448 enriched 21 14.9 7757 2890 40 PF00004

STRUCTUREProtein kinase C terminal domain 1 0.036934218 enriched 7 3.726 7757 2890 10 PF00433

STRUCTUREGlutathione S-transferase, N-terminal domain 1 0.037929344 enriched 20 14.16 7757 2890 38 PF02798

STRUCTURE Tetraspanin family 1 0.038052004 depleted 7 12.29 7757 2890 33 PF00335STRUCTURE PAC motif 1 0.038218552 depleted 0 2.608 7757 2890 7 PF00785STRUCTURE Rhomboid family 1 0.038218552 depleted 0 2.608 7757 2890 7 PF01694

STRUCTUREReceptor family ligand binding region 1 0.039073089 depleted 3 7.079 7757 2890 19 PF01094

STRUCTURE GMC oxidoreductase 1 0.043001332 depleted 2 5.589 7757 2890 15 PF00732STRUCTURE GMC oxidoreductase 1 0.043001332 depleted 2 5.589 7757 2890 15 PF05199

STRUCTUREC-type lysozyme/alpha-lactalbumin family 1 0.044574123 depleted 1 4.098 7757 2890 11 PF00062

Giot et al. 4

Supplemental Table S6. Pair enrichment


HIERARCHY CATEGORY 1 CATEGORY 2 PVAL MULTI PVAL SINGLE DIRECTION # OBS # EXP VAR(# EXP) DBID1 DBID2 RESAMPLING POISSON

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism

nucleobase, nucleoside, nucleotide and nucleic acid metabolism 1.11E-11 2.66E-14 enriched 55 16.1 13.96 GO:0006139 GO:0006139 0 2.66E-14

PROCESS transcription transcription 7.32E-06 1.76E-08 enriched 17 2.956 2.862 GO:0006350 GO:0006350 0 1.76E-08

PROCESS transcription transcription, DNA-dependent 2.24E-05 5.37E-08 enriched 16 2.817 2.73 GO:0006350 GO:0006351 0 5.37E-08

PROCESS transcription, DNA-dependent transcription, DNA-dependent 2.65E-05 6.34E-08 enriched 13 1.8 1.773 GO:0006351 GO:0006351 0 6.34E-08

PROCESScytoskeleton organization and biogenesis

cytoskeleton organization and biogenesis 2.75E-05 6.60E-08 enriched 15 2.491 2.38 GO:0007010 GO:0007010 0 6.60E-08

PROCESSorganelle organization and biogenesis

organelle organization and biogenesis 0.001011 2.43E-06 enriched 17 4.238 3.983 GO:0006996 GO:0006996 0 2.43E-06

PROCESS transport transport 0.001041 2.50E-06 enriched 18 4.721 4.464 GO:0006810 GO:0006810 0 2.50E-06

PROCESS mitochondrial transportmitochondrion organization and biogenesis 0.001101 2.64E-06 enriched 2 0.0023 0.002295 GO:0006839 GO:0007005 0 2.64E-06


cytoplasm organization and biogenesis 0.002907 6.98E-06 enriched 17 4.6 4.325 GO:0006996 GO:0007028 0 6.98E-06

PROCESScytoplasm organization and biogenesis

cytoplasm organization and biogenesis 0.002966 7.12E-06 enriched 17 4.607 4.327 GO:0007028 GO:0007028 0 7.12E-06

PROCESSmitochondrion organization and biogenesis

mitochondrion organization and biogenesis 0.00539 1.30E-05 enriched 2 0.0051 0.005074 GO:0007005 GO:0007005 0 1.30E-05


cytoskeleton organization and biogenesis 0.008864 2.14E-05 enriched 15 4.024 3.8 GO:0006996 GO:0007010 0 2.14E-05

PROCESScytoskeleton organization and biogenesis

cytoplasm organization and biogenesis 0.0188 4.55E-05 enriched 15 4.307 4.043 GO:0007010 GO:0007028 0.0001 4.55E-05

PROCESS DNA replication DNA replication 0.02237 5.43E-05 enriched 3 0.07 0.07011 GO:0006260 GO:0006260 0 5.43E-05PROCESS DNA metabolism DNA metabolism 0.0322 7.85E-05 enriched 6 0.6825 0.6602 GO:0006259 GO:0006259 0 7.85E-05PROCESS protein folding protein folding 0.03485 8.51E-05 enriched 2 0.0131 0.01293 GO:0006457 GO:0006457 0 8.51E-05PROCESS development development 0.03903 9.55E-05 enriched 44 23.43 20.26 GO:0007275 GO:0007275 0 9.55E-05PROCESS physiological processes physiological processes 0.04383 0.0001075 enriched 251 196.6 123.3 GO:0007582 GO:0007582 0 0.0001075PROCESS protein targeting mitochondrial transport 0.06116 0.0001514 enriched 2 0.0175 0.0172 GO:0006605 GO:0006839 0 0.0001514PROCESS mitochondrial transport intracellular protein transport 0.09959 0.0002516 enriched 2 0.0226 0.02209 GO:0006839 GO:0006886 0 0.0002516PROCESS DNA metabolism DNA replication 0.228 0.0006207 enriched 4 0.3765 0.372 GO:0006259 GO:0006260 0.0001 0.0006207PROCESS cell communication cell communication 0.3428 0.001007 enriched 21 9.625 8.62 GO:0007154 GO:0007154 0.0002 0.001007PROCESS DNA repair DNA repair 0.4721 0.001532 enriched 2 0.0564 0.05542 GO:0006281 GO:0006281 0.0011 0.001532

PROCESS mitochondrial transportorganelle organization and biogenesis 0.4733 0.001537 enriched 2 0.0565 0.05591 GO:0006839 GO:0006996 0.0013 0.001537

PROCESS mitochondrial transportcytoplasm organization and biogenesis 0.4977 0.001651 enriched 2 0.0586 0.05817 GO:0006839 GO:0007028 0.0015 0.001651

PROCESS transcription sex determination 0.5558 0.001946 enriched 5 0.8617 0.8271 GO:0006350 GO:0007530 0.0013 0.001946PROCESS cell proliferation cell proliferation 0.5657 0.002 enriched 7 1.786 1.724 GO:0008283 GO:0008283 0.002 0.002463PROCESS cell cycle cell proliferation 0.5657 0.002 enriched 7 1.778 1.715 GO:0007049 GO:0008283 0.002 0.002404PROCESS cell motility cell motility 0.6168 0.0023 enriched 4 0.537 0.5407 GO:0006928 GO:0006928 0.0023 0.002264PROCESS development sex determination 0.6168 0.0023 enriched 8 2.404 2.273 GO:0007275 GO:0007530 0.0023 0.003373PROCESS transport mitochondrial transport 0.631 0.002391 enriched 2 0.0708 0.06819 GO:0006810 GO:0006839 0.0012 0.002391

PROCESSorganelle organization and biogenesis physiological processes 0.6618 0.0026 enriched 73 53.78 41.31 GO:0006996 GO:0007582 0.0026 0.007263

PROCESS DNA replication cell cycle 0.7138 0.003 enriched 4 0.587 0.5743 GO:0006260 GO:0007049 0.003 0.003108

Giot et al. 1


PROCESS electron transportcytoplasm organization and biogenesis 0.7255 0.0031 enriched 3 0.3401 0.3223 GO:0006118 GO:0007028 0.0031 0.005092

PROCESS protein targetingmitochondrion organization and biogenesis 0.7255 0.0031 enriched 2 0.0823 0.08173 GO:0006605 GO:0007005 0.0031 0.003206

PROCESS transport cell communication 0.7319 0.003157 enriched 24 12.75 11.46 GO:0006810 GO:0007154 0.0017 0.003157PROCESS cell cycle cell cycle 0.7578 0.0034 enriched 6 1.529 1.477 GO:0007049 GO:0007049 0.0034 0.004873PROCESS DNA replication cell proliferation 0.8033 0.0039 enriched 4 0.6426 0.6321 GO:0006260 GO:0008283 0.0039 0.004273

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism protein modification 0.8033 0.0039 depleted 5 13.45 12.07 GO:0006139 GO:0006464 0.0039 0.007972

PROCESSamino acid and derivative metabolism physiological processes 0.8191 0.0041 depleted 2 8.782 6.979 GO:0006519 GO:0007582 0.0041 0.007417

PROCESScytoplasm organization and biogenesis physiological processes 0.8193 0.004102 enriched 77 55.8 42.9 GO:0007028 GO:0007582 0.001 0.004102

PROCESS DNA metabolism DNA repair 0.8265 0.0042 enriched 3 0.3442 0.3332 GO:0006259 GO:0006281 0.0042 0.005262

PROCESS mitochondrial transport protein metabolism 0.8469 0.0045 enriched 2 0.151 0.1372 GO:0006839GO:0019538;GO:0006411 0.0045 0.01032

PROCESS intracellular protein transportmitochondrion organization and biogenesis 0.8757 0.005 enriched 2 0.1044 0.1035 GO:0006886 GO:0007005 0.005 0.005085

PROCESScytoskeleton organization and biogenesis physiological processes 0.9072 0.0057 enriched 57 41.93 32.39 GO:0007010 GO:0007582 0.0057 0.0154

PROCESS DNA replication DNA repair 0.9699 0.0084 enriched 2 0.132 0.1322 GO:0006260 GO:0006281 0.0084 0.007982

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism transcription, DNA-dependent 0.981 0.0095 enriched 17 9.033 8.309 GO:0006139 GO:0006351 0.0095 0.01147

PROCESS protein metabolism protein metabolism 0.9817 0.0096 enriched 33 21.85 18.56GO:0019538;GO:0006411

GO:0019538;GO:0006411 0.0096 0.01555

PROCESS protein biosynthesis protein biosynthesis 0.9869 0.0104 enriched 7 2.45 2.266

GO:0006412;GO:0006416;GO:0006453

GO:0006412;GO:0006416;GO:0006453 0.0104 0.01285

PROCESS defense response defense response 0.9869 0.0104 enriched 3 0.4636 0.4551 GO:0006952 GO:0006952 0.0104 0.01178PROCESS signal transduction development 0.9894 0.0109 enriched 29 18.41 16.47 GO:0007165 GO:0007275 0.0109 0.01355PROCESS intracellular protein transport intracellular protein transport 0.9902 0.0111 enriched 3 0.466 0.4629 GO:0006886 GO:0006886 0.0111 0.01194

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism transcription 0.9946 0.0125 enriched 19 10.89 9.914 GO:0006139 GO:0006350 0.0125 0.01614

PROCESS transport physiological processes 0.9959 0.0132 enriched 72 56.57 43.36 GO:0006810 GO:0007582 0.0132 0.02701

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism sex determination 0.997 0.0139 enriched 6 2.008 1.87 GO:0006139 GO:0007530 0.0139 0.01687

PROCESS protein modification protein modification 0.9993 0.0173 enriched 7 2.707 2.561 GO:0006464 GO:0006464 0.0173 0.02083

PROCESS ion transportcytoskeleton organization and biogenesis 0.9995 0.0183 enriched 3 0.5636 0.5494 GO:0006811 GO:0007010 0.0183 0.01967

PROCESS signal transduction sex determination 0.9996 0.0188 enriched 4 1.034 1.001 GO:0007165 GO:0007530 0.0188 0.02111

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism physiological processes 0.9997 0.0194 enriched 115 96.76 70.94 GO:0006139 GO:0007582 0.0194 0.03844

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism signal transduction 0.9998 0.0205 depleted 8 15.76 14.31 GO:0006139 GO:0007165 0.0205 0.02508

PROCESS proteolysis and peptidolysis proteolysis and peptidolysis 0.9998 0.0207 enriched 3 0.5916 0.5707 GO:0006508 GO:0006508 0.0207 0.02229

PROCESS electron transportcytoskeleton organization and biogenesis 1 0.025 enriched 2 0.2513 0.2428 GO:0006118 GO:0007010 0.025 0.02675

PROCESS ion transport behavior 1 0.0262 enriched 2 0.2532 0.2511 GO:0006811 GO:0007610 0.0262 0.02713PROCESS intracellular protein transport physiological processes 1 0.029 enriched 27 19.08 14.56 GO:0006886 GO:0007582 0.029 0.05054

Giot et al. 2


PROCESS transcription, DNA-dependent sex determination 1 0.0291 enriched 3 0.6789 0.6495 GO:0006351 GO:0007530 0.0291 0.03162

PROCESSmitochondrion organization and biogenesis protein metabolism 1 0.0292 enriched 3 0.7157 0.6587 GO:0007005

GO:0019538;GO:0006411 0.0292 0.03608

PROCESS response to stress defense response 1 0.0313 enriched 3 0.7068 0.6873 GO:0006950 GO:0006952 0.0313 0.03497

PROCESScytoskeleton organization and biogenesis development 1 0.033 enriched 23 15.35 13.75 GO:0007010 GO:0007275 0.033 0.04038

PROCESS behavior protein metabolism 1 0.0339 depleted 2 6.568 5.969 GO:0007610GO:0019538;GO:0006411 0.0339 0.04092


mitochondrion organization and biogenesis 1 0.0349 enriched 2 0.3033 0.2945 GO:0006996 GO:0007005 0.0349 0.03767

PROCESS cell motility development 1 0.035 enriched 12 6.711 6.123 GO:0006928 GO:0007275 0.035 0.04134PROCESS transport ion transport 1 0.0361 enriched 3 0.7395 0.7197 GO:0006810 GO:0006811 0.0361 0.03912

PROCESS ion transportorganelle organization and biogenesis 1 0.0362 enriched 3 0.7369 0.7111 GO:0006811 GO:0006996 0.0362 0.03878

PROCESS protein targeting protein targeting 1 0.0365 enriched 2 0.3063 0.3047 GO:0006605 GO:0006605 0.0365 0.03835PROCESS transcription development 1 0.0368 enriched 24 16.37 14.65 GO:0006350 GO:0007275 0.0368 0.04528

PROCESSmitochondrion organization and biogenesis

cytoplasm organization and biogenesis 1 0.0371 enriched 2 0.3145 0.3058 GO:0007005 GO:0007028 0.0371 0.04021

PROCESS electron transportorganelle organization and biogenesis 1 0.0391 enriched 2 0.3273 0.3094 GO:0006118 GO:0006996 0.0391 0.04319

PROCESS ion transportcytoplasm organization and biogenesis 1 0.0397 enriched 3 0.766 0.7421 GO:0006811 GO:0007028 0.0397 0.04266

PROCESS

nucleobase, nucleoside, nucleotide and nucleic acid metabolism protein targeting 1 0.0401 enriched 9 4.649 4.285 GO:0006139 GO:0006605 0.0401 0.04754

PROCESS protein modification endocytosis 1 0.042 enriched 4 1.299 1.27 GO:0006464GO:0006897;GO:0016196 0.042 0.04302

PROCESS transport protein metabolism 1 0.043 enriched 28 19.95 17.95 GO:0006810GO:0019538;GO:0006411 0.043 0.05134

PROCESS transportmitochondrion organization and biogenesis 1 0.0439 enriched 2 0.3331 0.3266 GO:0006810 GO:0007005 0.0439 0.04457

PROCESS mitochondrial transport physiological processes 1 0.0444 enriched 2 0.4375 0.3349 GO:0006839 GO:0007582 0.0444 0.07188PROCESS DNA metabolism cell cycle 1 0.0462 enriched 5 1.974 1.908 GO:0006259 GO:0007049 0.0462 0.05036PROCESS response to stress physiological processes 1 0.0482 enriched 23 16.35 12.79 GO:0006950 GO:0007582 0.0482 0.0699PROCESS cell communication development 1 0.0486 enriched 38 28.99 25.64 GO:0007154 GO:0007275 0.0486 0.06173

PROCESS cell cycle protein metabolism 1 0.0492 depleted 6 11.61 10.32 GO:0007049GO:0019538;GO:0006411 0.0492 0.05674

FUNCTION DNA binding activitytranscription factor binding activity 3.99E-11 1.60E-13 enriched 22 2.663 2.498 GO:0003677 GO:0008134 0 1.60E-13

FUNCTION RNA binding activity RNA binding activity 1.65E-07 6.63E-10 enriched 26 5.796 5.416 GO:0003723 GO:0003723 0 6.63E-10

FUNCTION chaperone activity chaperone activity 5.47E-07 2.20E-09 enriched 8 0.3228 0.3172

GO:0003754;GO:0003757;GO:0003758;GO:0003760;GO:0003761

GO:0003754;GO:0003757;GO:0003758;GO:0003760;GO:0003761 0 2.20E-09

FUNCTION nucleic acid binding activitytranscription factor binding activity 1.99E-06 7.99E-09 enriched 23 5.2 4.711 GO:0003676 GO:0008134 0 7.99E-09

FUNCTION transcription factor activitytranscription factor binding activity 7.91E-05 3.18E-07 enriched 11 1.417 1.391

GO:0003700;GO:0000130 GO:0008134 0 3.18E-07

FUNCTION actin binding activitystructural constituent of cytoskeleton 0.0001943 7.81E-07 enriched 6 0.2998 0.2907 GO:0003779 GO:0005200 0 7.81E-07

FUNCTION DNA replication factor DNA replication factor 0.0002084 8.37E-07 enriched 3 0.0172 0.01731 GO:0003687 GO:0003687 0 8.37E-07

FUNCTION binding activitytranscription factor binding activity 0.004169 1.68E-05 enriched 25 9.372 7.699 GO:0005488 GO:0008134 0 1.68E-05

Giot et al. 3


FUNCTION transporter activity transporter activity 0.007862 3.17E-05 enriched 16 4.674 4.335 GO:0005215 GO:0005215 0 3.17E-05FUNCTION nucleic acid binding activity nucleic acid binding activity 0.01149 4.64E-05 enriched 63 36.61 29.92 GO:0003676 GO:0003676 0 4.64E-05FUNCTION binding activity binding activity 0.0116 4.69E-05 enriched 170 123.7 83.7 GO:0005488 GO:0005488 0 4.69E-05FUNCTION DNA binding activity DNA binding activity 0.02021 8.20E-05 enriched 24 9.744 8.794 GO:0003677 GO:0003677 0.0001 8.20E-05

FUNCTION transcription factor activity transcription factor activity 0.04454 0.000183 enriched 11 2.837 2.702GO:0003700;GO:0000130

GO:0003700;GO:0000130 0.0001 0.000183

FUNCTIONtransmembrane receptor activity peptidase activity 0.09652 0.0004076 enriched 8 1.713 1.645 GO:0004888 GO:0008233 0.0002 0.0004076

FUNCTION enzyme activitytransmembrane receptor activity 0.1241 0.0005322 enriched 33 17.36 14.61 GO:0003824 GO:0004888 0 0.0005322

FUNCTION nucleic acid binding activity binding activity 0.256 0.001188 enriched 130 98.08 71.65 GO:0003676 GO:0005488 0.0002 0.001188FUNCTION nucleic acid binding activity enzyme activity 0.2826 0.001334 depleted 100 133.9 103.1 GO:0003676 GO:0003824 0.0001 0.001334FUNCTION nucleic acid binding activity RNA binding activity 0.3829 0.001939 enriched 39 23.39 20.22 GO:0003676 GO:0003723 0.0006 0.001939FUNCTION receptor activity peptidase activity 0.436 0.0023 enriched 8 2.259 2.215 GO:0004872 GO:0008233 0.0023 0.00232

FUNCTIONtranslation factor activity, nucleic acid binding

translation factor activity, nucleic acid binding 0.436 0.0023 enriched 3 0.2721 0.2655 GO:0008135 GO:0008135 0.0023 0.002742

FUNCTION protein phosphatase activity enzyme inhibitor activity 0.4634 0.0025 enriched 3 0.2697 0.2686 GO:0004721 GO:0004857 0.0025 0.002675

FUNCTIONstructural constituent of cytoskeleton binding activity 0.4766 0.0026 enriched 11 4.585 3.852 GO:0005200 GO:0005488 0.0026 0.007605

FUNCTION DNA binding activity transcription factor activity 0.4807 0.002631 enriched 17 7.724 7.146 GO:0003677GO:0003700;GO:0000130 0.0012 0.002631

FUNCTION nucleic acid binding activityreceptor signaling protein activity 0.5126 0.002887 depleted 4 13.36 11.6 GO:0003676 GO:0005057 0.001 0.002887

FUNCTION enzyme activity olfactory receptor activity 0.5262 0.003 enriched 8 2.875 2.384 GO:0003824 GO:0004984 0.003 0.00942FUNCTION actin binding activity structural molecule activity 0.5262 0.003 enriched 9 3.035 2.913 GO:0003779 GO:0005198 0.003 0.004094FUNCTION DNA binding activity enzyme activity 0.5486 0.003194 depleted 47 69.04 56.36 GO:0003677 GO:0003824 0.0012 0.003194FUNCTION DNA binding activity binding activity 0.5952 0.003632 enriched 82 59.76 46.43 GO:0003677 GO:0005488 0.0011 0.003632

FUNCTION endopeptidase activitytransmembrane receptor activity 0.6657 0.0044 enriched 4 0.6304 0.6095

GO:0004175;GO:0016809 GO:0004888 0.0044 0.003996

FUNCTION enzyme activity receptor activity 0.6897 0.0047 enriched 35 22.83 19.22 GO:0003824 GO:0004872 0.0047 0.01069

FUNCTION cell adhesion molecule activitypeptidase activity 0.853 0.0077 enriched 3 0.3988 0.3922 GO:0005194 GO:0008233 0.0077 0.007862

FUNCTION transcription factor activity binding activity 0.8936 0.009 enriched 48 34.73 27.59GO:0003700;GO:0000130 GO:0005488 0.009 0.01888

FUNCTIONtranscription factor binding activity

transcription factor binding activity 0.9013 0.0093 enriched 2 0.1565 0.151 GO:0008134 GO:0008134 0.0093 0.01104

FUNCTION endopeptidase activity cell adhesion molecule activity 0.9061 0.0095 enriched 2 0.1408 0.1416GO:0004175;GO:0016809 GO:0005194 0.0095 0.009029

FUNCTION nucleic acid binding activity signal transducer activity 0.9129 0.0098 depleted 17 28.78 25.41 GO:0003676 GO:0004871 0.0098 0.01268FUNCTION structural molecule activity structural molecule activity 0.9211 0.0102 enriched 10 4.232 4.035 GO:0005198 GO:0005198 0.0102 0.01168

FUNCTION endopeptidase activity receptor activity 0.9337 0.0109 enriched 4 0.8297 0.8142GO:0004175;GO:0016809 GO:0004872 0.0109 0.01027

FUNCTION receptor activitytranscription factor binding activity 0.947 0.0118 enriched 4 0.8873 0.8821 GO:0004872 GO:0008134 0.0118 0.01284

FUNCTION enzyme activity signal transducer activity 0.9544 0.0124 enriched 68 52.33 43.51 GO:0003824 GO:0004871 0.0124 0.02128FUNCTION actin binding activity actin binding activity 0.9694 0.014 enriched 3 0.5233 0.5109 GO:0003779 GO:0003779 0.014 0.01622FUNCTION nucleic acid binding activity structural molecule activity 0.9848 0.0168 depleted 15 25.06 22.33 GO:0003676 GO:0005198 0.0168 0.02168FUNCTION nucleic acid binding activity protein kinase activity 0.9898 0.0184 depleted 6 13.26 11.89 GO:0003676 GO:0004672 0.0184 0.02217FUNCTION enzyme activity enzyme activity 0.9903 0.0186 enriched 143 122.7 86.38 GO:0003824 GO:0003824 0.0186 0.03971FUNCTION RNA binding activity structural molecule activity 0.998 0.025 depleted 4 9.987 9.393 GO:0003723 GO:0005198 0.025 0.0295FUNCTION RNA binding activity signal transducer activity 0.9982 0.0253 depleted 5 11.43 10.53 GO:0003723 GO:0004871 0.0253 0.02898

FUNCTION DNA binding activity chaperone activity 0.9988 0.027 enriched 8 3.643 3.394 GO:0003677

GO:0003754;GO:0003757;GO:0003758;GO:0003760;GO:0003761 0.027 0.03264

Giot et al. 4


FUNCTION protein kinase activity protein kinase activity 0.9992 0.0285 enriched 4 1.176 1.151 GO:0004672 GO:0004672 0.0285 0.03175

FUNCTION transcription factor activity structural molecule activity 0.9992 0.0287 depleted 2 6.998 6.613GO:0003700;GO:0000130 GO:0005198 0.0287 0.02969

FUNCTIONreceptor signaling protein activity

receptor signaling protein activity 0.9995 0.0309 enriched 4 1.192 1.138 GO:0005057 GO:0005057 0.0309 0.03311

FUNCTION olfactory receptor activity peptidase activity 0.9998 0.0338 enriched 2 0.286 0.2846 GO:0004984 GO:0008233 0.0338 0.03388FUNCTION structural molecule activity peptidase activity 0.9999 0.0369 enriched 9 4.53 4.24 GO:0005198 GO:0008233 0.0369 0.04164FUNCTION signal transducer activity peptidase activity 0.9999 0.0384 enriched 10 5.238 5.062 GO:0004871 GO:0008233 0.0384 0.04129

FUNCTION endopeptidase activity signal transducer activity 1 0.0413 enriched 5 1.927 1.822GO:0004175;GO:0016809 GO:0004871 0.0413 0.04632

FUNCTION enzyme activity binding activity 1 0.044 depleted 221 243.5 165.1 GO:0003824 GO:0005488 0.044 0.07772FUNCTION signal transducer activity receptor binding activity 1 0.0447 enriched 3 0.8041 0.7716 GO:0004871 GO:0005102 0.0447 0.04801

COMPONENT nucleus nucleus 2.69E-22 2.34E-24 enriched 178 74.57 55.53 GO:0005634 GO:0005634 0 2.34E-24COMPONENT intracellular intracellular 6.44E-08 5.60E-10 enriched 339 238.6 143.7 GO:0005622 GO:0005622 0 5.60E-10COMPONENT intracellular nucleus 1.42E-06 1.23E-08 enriched 275 192.3 123.4 GO:0005622 GO:0005634 0 1.23E-08COMPONENT cell cell 1.37E-05 1.19E-07 enriched 401 305.9 170.3 GO:0005623 GO:0005623 0 1.19E-07COMPONENT intracellular cell 5.75E-05 5.00E-07 enriched 391 301.8 169.7 GO:0005622 GO:0005623 0 5.00E-07COMPONENT cell nucleus 0.0005589 4.86E-06 enriched 298 227.7 139.8 GO:0005623 GO:0005634 0 4.86E-06COMPONENT cytosol cytosol 0.007789 6.80E-05 enriched 11 2.528 2.395 GO:0005829 GO:0005829 0 6.80E-05COMPONENT endoplasmic reticulum endoplasmic reticulum 0.02553 0.0002249 enriched 5 0.5301 0.5217 GO:0005783 GO:0005783 0 0.0002249COMPONENT cytoskeleton cytoskeleton 0.03191 0.000282 enriched 9 2.048 1.953 GO:0005856 GO:0005856 0.0001 0.000282COMPONENT cytoplasm cytoplasm 0.07905 0.000716 enriched 83 56.97 45.38 GO:0005737 GO:0005737 0.0002 0.000716COMPONENT cell centrosome 0.354 0.0038 enriched 13 6.402 4.786 GO:0005623 GO:0005813 0.0038 0.01434COMPONENT cytoplasm cytosol 0.3971 0.0044 enriched 34 21.58 18.74 GO:0005737 GO:0005829 0.0044 0.008068COMPONENT mitochondrion mitochondrion 0.4564 0.0053 enriched 6 1.609 1.58 GO:0005739 GO:0005739 0.0053 0.006208COMPONENT endoplasmic reticulum cytosol 0.5098 0.0062 enriched 7 2.179 2.108 GO:0005783 GO:0005829 0.0062 0.007096COMPONENT synaptic vesicle synaptic vesicle 0.6646 0.0095 enriched 2 0.1388 0.1397 GO:0008021 GO:0008021 0.0095 0.008786COMPONENT nucleus endoplasmic reticulum 0.7079 0.0107 enriched 21 12.62 10.77 GO:0005634 GO:0005783 0.0107 0.01901COMPONENT nucleus centrosome 0.7366 0.0116 enriched 8 3.233 2.804 GO:0005634 GO:0005813 0.0116 0.01776COMPONENT intracellular centrosome 0.8113 0.0145 enriched 11 5.655 4.436 GO:0005622 GO:0005813 0.0145 0.02998COMPONENT intracellular endoplasmic reticulum 0.8156 0.0147 enriched 32 22.31 17.2 GO:0005622 GO:0005783 0.0147 0.03115COMPONENT cell endoplasmic reticulum 0.8648 0.0174 enriched 35 25.35 18.68 GO:0005623 GO:0005783 0.0174 0.0397COMPONENT nucleus plasma membrane 0.8888 0.0191 depleted 21 32.22 27.36 GO:0005634 GO:0005886 0.0191 0.02384COMPONENT extracellular cell 0.9352 0.0238 depleted 18 27.07 19.49 GO:0005576 GO:0005623 0.0238 0.04323COMPONENT Golgi apparatus ribosome 0.9541 0.0268 enriched 3 0.6612 0.6343 GO:0005794 GO:0005840 0.0268 0.02959COMPONENT extracellular nucleus 0.9739 0.0317 depleted 7 13.46 11.73 GO:0005576 GO:0005634 0.0317 0.04244COMPONENT Golgi apparatus cytosol 0.9778 0.0331 enriched 4 1.247 1.188 GO:0005794 GO:0005829 0.0331 0.038COMPONENT extracellular intracellular 0.9844 0.0362 depleted 16 23.93 17.72 GO:0005576 GO:0005622 0.0362 0.05779COMPONENT nucleus mitochondrion 0.985 0.0365 depleted 14 22.01 19.23 GO:0005634 GO:0005739 0.0365 0.04754COMPONENT cell unlocalized 0.9926 0.0427 depleted 16 23.27 16.32 GO:0005623 GO:0005941 0.0427 0.07426COMPONENT cell lysosome 0.9955 0.0469 enriched 4 1.59 1.169 GO:0005623 GO:0005764 0.0469 0.0774

STRUCTURE Sm protein Sm protein 1.24E-21 5.82E-24 enriched 13 0.0931 0.09284 PF01423 PF01423 0 5.82E-24

STRUCTURE F-box domainSkp1 family, dimerisation domain 9.17E-20 4.29E-22 enriched 11 0.0563 0.05514 PF00646 PF01466 0 4.29E-22

STRUCTURE F-box domainSkp1 family, tetramerisation domain 2.86E-18 1.34E-20 enriched 11 0.0771 0.07496 PF00646 PF03931 0 1.34E-20

STRUCTURE Zinc finger, C2H2 type Zinc finger, C2H2 type 2.75E-14 1.29E-16 enriched 39 7.212 6.794 PF00096 PF00096 0 1.29E-16STRUCTURE EF hand IQ calmodulin-binding motif 1.05E-09 4.91E-12 enriched 9 0.2352 0.2323 PF00036 PF00612 0 4.91E-12

STRUCTUREHelix-loop-helix DNA-binding domain

Helix-loop-helix DNA-binding domain 2.02E-09 9.42E-12 enriched 9 0.2533 0.2466 PF00010 PF00010 0 9.42E-12

STRUCTURE LIM domain LIM-domain binding protein 5.24E-08 2.45E-10 enriched 6 0.0757 0.07598 PF00412 PF01803 0 2.45E-10

STRUCTURE ActinCofilin/tropomyosin-type actin-binding protein 1.77E-07 8.28E-10 enriched 4 0.0119 0.01176 PF00022 PF00241 0 8.28E-10

STRUCTURE KE2 family protein Prefoldin subunit 1.35E-06 6.30E-09 enriched 4 0.0198 0.02001 PF01920 PF02996 0 6.30E-09

Giot et al. 5



Groucho/TLE N-terminal Q-rich domain 2.63E-06 1.23E-08 enriched 5 0.069 0.07005 PF00010 PF03920 0 1.23E-08

STRUCTURE NAC domain NAC domain 1.27E-05 5.93E-08 enriched 3 0.0071 0.00705 PF01849 PF01849 0 5.93E-08

STRUCTURE RhoGAP domainProtein of unknown function (DUF733) 1.38E-05 6.45E-08 enriched 3 0.0073 0.007247 PF00620 PF05306 0 6.45E-08

STRUCTUREMSP (Major sperm protein) domain Oxysterol-binding protein 1.38E-05 6.45E-08 enriched 3 0.0073 0.007247 PF00635 PF01237 0 6.45E-08

STRUCTURE Syntaxin SNAP-25 family 1.38E-05 6.45E-08 enriched 3 0.0073 0.007447 PF00804 PF00835 0 6.45E-08STRUCTURE CIDE-N domain CIDE-N domain 3.04E-05 1.42E-07 enriched 3 0.0095 0.009611 PF02017 PF02017 0 1.42E-07STRUCTURE Homeobox domain LIM-domain binding protein 3.90E-05 1.82E-07 enriched 5 0.1193 0.1217 PF00046 PF01803 0 1.82E-07

STRUCTUREZinc finger, C3HC4 type (RING finger)

Ubiquitin-conjugating enzyme 5.98E-05 2.80E-07 enriched 6 0.2509 0.2452 PF00097 PF00179 0 2.80E-07

STRUCTURE

Transcription initiation factor IIA, gamma subunit, helical domain

Transcription factor IIA, alpha/beta subunit 8.20E-05 3.83E-07 enriched 2 0.0016 0.001598 PF02268 PF03153 0 1.28E-06

STRUCTURE

Transcription initiation factor IIA, gamma subunit, beta-barrel domain

Transcription factor IIA, alpha/beta subunit 8.20E-05 3.83E-07 enriched 2 0.0016 0.001598 PF02751 PF03153 0 1.28E-06

STRUCTUREDomain of unknown function (DUF227)

Domain of unknown function (DUF227) 8.75E-05 4.09E-07 enriched 4 0.0566 0.0558 PF02958 PF02958 0 4.09E-07

STRUCTURE

Transcription factor E2F/dimerisation partner (TDP)

Transcription factor E2F/dimerisation partner (TDP) 0.0001845 8.62E-07 enriched 2 0.0006 0.0005997 PF02319 PF02319 0 1.80E-07

STRUCTURE Runt domainCore binding factor beta subunit 0.0003279 1.53E-06 enriched 2 0.0007 0.0006996 PF00853 PF02312 0 2.45E-07

STRUCTURE Cullin familyDomain of unknown function (DUF298) 0.0003279 1.53E-06 enriched 2 0.0006 0.0005997 PF00888 PF03556 0 1.80E-07

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain)

RNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) 0.0003587 1.68E-06 enriched 13 2.419 2.327 PF00076 PF00076 0 1.68E-06

STRUCTURERNA polymerase Rpb3/RpoA insert domain

RNA polymerases L / 13 to 16 kDa subunit 0.0004273 2.00E-06 enriched 2 0.002 0.001996 PF01000 PF01193 0 2.00E-06

STRUCTURE Insect cuticle protein Insect cuticle protein 0.0006262 2.93E-06 enriched 7 0.5892 0.5881 PF00379 PF00379 0 2.93E-06

STRUCTUREHelix-loop-helix DNA-binding domain WD domain, G-beta repeat 0.000726 3.39E-06 enriched 7 0.6028 0.5997 PF00010 PF00400 0 3.39E-06

STRUCTUREElongation factor Tu C-terminal domain ZPR1 zinc-finger domain 0.0007783 3.64E-06 enriched 2 0.0027 0.002693 PF03143 PF03367 0 3.64E-06

STRUCTURE ThiF familyAminolevulinic acid synthase domain 0.001307 6.11E-06 enriched 2 0.0035 0.003488 PF00899 PF02490 0 6.11E-06

STRUCTURE Homeobox domain Homeobox domain 0.001911 8.94E-06 enriched 6 0.4605 0.4425 PF00046 PF00046 0 8.94E-06STRUCTURE Actin CAP protein 0.002063 9.65E-06 enriched 2 0.0044 0.004381 PF00022 PF01213 0 9.65E-06STRUCTURE UBA/TS-N domain NAC domain 0.002416 1.13E-05 enriched 3 0.0412 0.04151 PF00627 PF01849 0 1.13E-05STRUCTURE bZIP transcription factor Jun-like transcription factor 0.002557 1.20E-05 enriched 2 0.0049 0.004876 PF00170 PF03957 0 1.20E-05

STRUCTUREBacterial transferase hexapeptide (three repeats)

Bacterial transferase hexapeptide (three repeats) 0.00277 1.30E-05 enriched 2 0.0051 0.005074 PF00132 PF00132 0 1.30E-05

STRUCTURE BTB/POZ domain BTB/POZ domain 0.003094 1.45E-05 enriched 5 0.2946 0.2896 PF00651 PF00651 0 1.45E-05

STRUCTUREKunitz/Bovine pancreatic trypsin inhibitor domain Heme/Steroid binding domain 0.00322 1.51E-05 enriched 2 0.0055 0.00547 PF00014 PF00173 0 1.51E-05

STRUCTUREElongation factor Tu GTP binding domain ZPR1 zinc-finger domain 0.003337 1.56E-05 enriched 2 0.0056 0.005569 PF00009 PF03367 0 1.56E-05

STRUCTURE Elongation factor Tu domain 2 ZPR1 zinc-finger domain 0.003337 1.56E-05 enriched 2 0.0056 0.005569 PF03144 PF03367 0 1.56E-05

STRUCTURE Glutathione peroxidase

'chromo' (CHRromatin Organisation MOdifier) domain 0.005658 2.65E-05 enriched 2 0.0073 0.007247 PF00255 PF00385 0 2.65E-05

Giot et al. 6


STRUCTURE Eukaryotic initiation factor 4E PAP/25A associated domain 0.005658 2.65E-05 enriched 2 0.0073 0.007247 PF01652 PF03828 0 2.65E-05STRUCTURE SNF7 SNF7 0.005658 2.65E-05 enriched 2 0.0073 0.007447 PF03357 PF03357 0.0001 2.65E-05

STRUCTURE SyntaxinAromatic-di-Alanine (AdAR) repeat 0.005814 2.73E-05 enriched 2 0.0074 0.007346 PF00804 PF02071 0 2.73E-05

STRUCTUREZinc finger, C4 type (two domains)

D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain 0.005832 2.73E-05 enriched 3 0.0555 0.05603 PF00105 PF00389 0 2.73E-05

STRUCTUREZinc finger, C4 type (two domains)

D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain 0.005832 2.73E-05 enriched 3 0.0555 0.05603 PF00105 PF02826 0 2.73E-05

STRUCTURE Mov34/MPN/PAD-1 family Mov34/MPN/PAD-1 family 0.006455 3.03E-05 enriched 2 0.0078 0.00774 PF01398 PF01398 0 3.03E-05

STRUCTURE SPRY domainSkp1 family, tetramerisation domain 0.006675 3.13E-05 enriched 3 0.0581 0.05793 PF00622 PF03931 0.0001 3.13E-05

STRUCTURE Roadblock/LC7 domain Roadblock/LC7 domain 0.006958 3.26E-05 enriched 2 0.0081 0.008035 PF03259 PF03259 0 3.26E-05

STRUCTURE Mitochondrial carrier proteinAcetyltransferase (GNAT) family 0.007304 3.43E-05 enriched 2 0.0083 0.008432 PF00153 PF00583 0.0001 3.43E-05

STRUCTUREThrombospondin type 1 domain Heme/Steroid binding domain 0.007658 3.59E-05 enriched 2 0.0085 0.008429 PF00090 PF00173 0 3.59E-05

STRUCTUREUbiquitin-conjugating enzyme IBR domain 0.008392 3.94E-05 enriched 3 0.0628 0.06226 PF00179 PF01485 0 3.94E-05

STRUCTURE Zinc finger, C2H2 type

D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain 0.00853 4.00E-05 enriched 7 0.8884 0.848 PF00096 PF00389 0 4.00E-05


D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain 0.00853 4.00E-05 enriched 7 0.8884 0.848 PF00096 PF02826 0 4.00E-05

STRUCTURE

Histone-like transcription factor (CBF/NF-Y) and archaeal histone

Histone-like transcription factor (CBF/NF-Y) and archaeal histone 0.008768 4.12E-05 enriched 2 0.0091 0.009018 PF00808 PF00808 0 4.12E-05

STRUCTURE Zinc finger, C2H2 type AT hook motif 0.009275 4.35E-05 enriched 8 1.229 1.154 PF00096 PF02178 0 4.35E-05

STRUCTUREDouble-stranded RNA binding motif

Double-stranded RNA binding motif 0.01187 5.58E-05 enriched 2 0.0106 0.01049 PF00035 PF00035 0 5.58E-05

STRUCTURE Trypsin FG-GAP repeat 0.01277 6.01E-05 enriched 2 0.011 0.01088 PF00089 PF01839 0 6.01E-05

STRUCTURE PH domainMSP (Major sperm protein) domain 0.01572 7.41E-05 enriched 3 0.0778 0.07715 PF00169 PF00635 0 7.41E-05

STRUCTURE Guanylate kinase L27 domain 0.02233 0.0001055 enriched 2 0.0146 0.01459 PF00625 PF02828 0.0001 0.0001055STRUCTURE bZIP transcription factor bZIP transcription factor 0.02264 0.000107 enriched 2 0.0147 0.01449 PF00170 PF00170 0 0.000107STRUCTURE Actin WH2 motif 0.02576 0.000122 enriched 2 0.0157 0.01546 PF00022 PF02205 0 0.000122

STRUCTUREProtein of unknown function (DUF745)

Protein of unknown function (DUF745) 0.02908 0.0001379 enriched 2 0.0167 0.01662 PF05335 PF05335 0.0001 0.0001379

STRUCTUREAminotransferase class I and II ThiF family 0.03046 0.0001445 enriched 2 0.0171 0.01741 PF00155 PF00899 0.0003 0.0001445

STRUCTURE EF handKCNQ voltage-gated potassium channel 0.03441 0.0001636 enriched 2 0.0182 0.01787 PF00036 PF03520 0 0.0001636

STRUCTURE EF hand Ion transport protein 0.03514 0.0001672 enriched 3 0.1027 0.1006 PF00036 PF00520 0.0001 0.0001672STRUCTURE PCI domain PCI domain 0.03742 0.0001782 enriched 2 0.019 0.01924 PF01399 PF01399 0.0003 0.0001782STRUCTURE PHD-finger BTB/POZ domain 0.04229 0.0002019 enriched 4 0.2789 0.2783 PF00628 PF00651 0.0002 0.0002019STRUCTURE Mov34/MPN/PAD-1 family SNF7 0.04339 0.0002073 enriched 2 0.0205 0.02068 PF01398 PF03357 0.0003 0.0002073

STRUCTUREPhorbol esters/diacylglycerol binding domain (C1 domain) Ubiquitin interaction motif 0.05019 0.0002406 enriched 2 0.0221 0.02221 PF00130 PF02809 0.0003 0.0002406

STRUCTURE Ras family TBC domain 0.05698 0.0002741 enriched 2 0.0236 0.02325 PF00071 PF00566 0.0001 0.0002741

STRUCTUREDomain of unknown function (DUF243)

Domain of unknown function (DUF243) 0.06612 0.0003197 enriched 2 0.0255 0.02585 PF03103 PF03103 0.0005 0.0003197

STRUCTURE Fork head domainUbiquitin carboxyl-terminal hydrolase 0.07323 0.0003554 enriched 2 0.0269 0.02678 PF00250 PF00443 0.0003 0.0003554

Giot et al. 7


STRUCTURE C2 domain Ubiquitin interaction motif 0.07532 0.0003659 enriched 2 0.0273 0.02676 PF00168 PF02809 0.0001 0.0003659STRUCTURE Insect cuticle protein Surp module 0.08404 0.0004102 enriched 3 0.1398 0.1371 PF00379 PF01805 0.0004 0.0004102STRUCTURE EF hand Troponin 0.08895 0.0004353 enriched 2 0.0298 0.02971 PF00036 PF00992 0.0004 0.0004353

STRUCTURE LIM domain5'-nucleotidase, C-terminal domain 0.09064 0.000444 enriched 2 0.0301 0.0298 PF00412 PF02872 0.0003 0.000444

STRUCTUREPutative GTPase activating protein for Arf

Domain of unknown function (DUF243) 0.1041 0.0005137 enriched 2 0.0324 0.03215 PF01412 PF03103 0.0004 0.0005137

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) KOW motif 0.1776 0.0009134 enriched 4 0.4181 0.4153 PF00076 PF00467 0.0008 0.0009134

STRUCTURE Homeobox domain5'-nucleotidase, C-terminal domain 0.1889 0.0009783 enriched 2 0.0449 0.04429 PF00046 PF02872 0.0007 0.0009783

STRUCTURE SPRY domainSkp1 family, dimerisation domain 0.1904 0.0009869 enriched 2 0.0451 0.04547 PF00622 PF01466 0.001 0.0009869

STRUCTURE SH3 domain

Ubiquinol-cytochrome C reductase complex 14kD subunit 0.2063 0.001079 enriched 2 0.0472 0.04718 PF00018 PF02271 0.0011 0.001079

STRUCTUREArrestin (or S-antigen), N-terminal domain BED zinc finger 0.214 0.001125 enriched 2 0.0482 0.04788 PF00339 PF02892 0.001 0.001125

STRUCTUREArrestin (or S-antigen), C-terminal domain BED zinc finger 0.214 0.001125 enriched 2 0.0482 0.04788 PF02752 PF02892 0.001 0.001125

STRUCTURE Chromo shadow domain BESS motif 0.2171 0.001143 enriched 2 0.0486 0.04804 PF01393 PF02944 0.0009 0.001143

STRUCTURE EF handActivin types I and II receptor domain 0.2272 0.001204 enriched 2 0.0499 0.04961 PF00036 PF01064 0.0009 0.001204

STRUCTURE Ras familyDomain of unknown function (DUF243) 0.2518 0.001356 enriched 2 0.053 0.0524 PF00071 PF03103 0.0011 0.001356

STRUCTURE EF hand Cytidylyltransferase 0.2935 0.001624 enriched 2 0.0581 0.05813 PF00036 PF01467 0.0015 0.001624STRUCTURE SH2 domain Protein kinase domain 0.3465 0.001988 enriched 4 0.5179 0.5065 PF00017 PF00069 0.0015 0.001988


Zinc finger C-x8-C-x5-C-x3-H type (and similar) 0.3482 0.002 enriched 4 0.6014 0.5832 PF00076 PF00642 0.002 0.003386

STRUCTURE WD domain, G-beta repeat P21-Rho-binding domain 0.3755 0.0022 enriched 2 0.0671 0.067 PF00400 PF00786 0.0022 0.002153

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) DEAD/DEAH box helicase 0.3858 0.002277 enriched 4 0.5379 0.5218 PF00076 PF00270 0.0014 0.002277

STRUCTURE Zinc finger, C2H2 type BTB/POZ domain 0.4017 0.0024 enriched 9 2.959 2.813 PF00096 PF00651 0.0024 0.00348STRUCTURE SH2 domain SH2 domain 0.4389 0.0027 enriched 2 0.0888 0.08632 PF00017 PF00017 0.0027 0.003717STRUCTURE Ankyrin repeat IPT/TIG domain 0.4507 0.0028 enriched 2 0.0777 0.07727 PF00023 PF01833 0.0028 0.002867STRUCTURE BTB/POZ domain helix-turn-helix, Psq domain 0.5065 0.0033 enriched 2 0.0864 0.08634 PF00651 PF05225 0.0033 0.003524

STRUCTURE7 transmembrane receptor (rhodopsin family) Ankyrin repeat 0.5169 0.0034 enriched 2 0.0911 0.09041 PF00001 PF00023 0.0034 0.003906

STRUCTURE SH2 domainLow-density lipoprotein receptor domain class A 0.5272 0.0035 enriched 2 0.0903 0.08955 PF00017 PF00057 0.0035 0.00384

STRUCTUREEnoyl-CoA hydratase/isomerase family TPR Domain 0.5272 0.0035 enriched 2 0.0898 0.08874 PF00378 PF00515 0.0035 0.003799

STRUCTURE Zinc finger, C2H2 type Supt5 repeat 0.547 0.0037 enriched 2 0.114 0.1084 PF00096 PF03439 0.0037 0.006025

STRUCTURECalcineurin-like phosphoesterase PX domain 0.547 0.0037 enriched 2 0.1026 0.1007 PF00149 PF00787 0.0037 0.004917

STRUCTUREPDZ domain (Also known as DHR or GLGF) L27 domain 0.5929 0.0042 enriched 2 0.096 0.09599 PF00595 PF02828 0.0042 0.004323

STRUCTURE BTB/POZ domain LIM-domain binding protein 0.6016 0.0043 enriched 2 0.0993 0.09885 PF00651 PF01803 0.0043 0.004616

STRUCTURE Insect cuticle proteinRas association (RalGDS/AF-6) domain 0.61 0.0044 enriched 2 0.0989 0.09793 PF00379 PF00788 0.0044 0.00458

STRUCTURE Zinc finger, C2H2 type Tub family 0.6342 0.0047 enriched 2 0.1193 0.1149 PF00096 PF01167 0.0047 0.006575STRUCTURE FHA domain BESS motif 0.711 0.0058 enriched 2 0.1073 0.1078 PF00498 PF02944 0.0058 0.005361

Giot et al. 8


STRUCTURE EF handSerpin (serine protease inhibitor) 0.7289 0.0061 enriched 2 0.1142 0.1142 PF00036 PF00079 0.0061 0.006045

STRUCTUREPDZ domain (Also known as DHR or GLGF) Guanylate kinase 0.7347 0.0062 enriched 2 0.1199 0.1195 PF00595 PF00625 0.0062 0.006638

STRUCTURE EF hand ThiF family 0.7616 0.0067 enriched 2 0.1234 0.1228 PF00036 PF00899 0.0067 0.007015

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) PSP 0.7616 0.0067 enriched 2 0.1336 0.1296 PF00076 PF04046 0.0067 0.008168

STRUCTUREZinc finger, C3HC4 type (RING finger)

SAM domain (Sterile alpha motif) 0.7764 0.007 enriched 2 0.1321 0.1303 PF00097 PF00536 0.007 0.007994

STRUCTURE PH domainDomain of unknown function (DUF243) 0.7991 0.0075 enriched 2 0.1437 0.1393 PF00169 PF03103 0.0075 0.009387


Helicase conserved C-terminal domain 0.8034 0.0076 enriched 4 0.789 0.775 PF00076 PF00271 0.0076 0.008664

STRUCTURE Protein kinase domain WH2 motif 0.8075 0.0077 enriched 2 0.1336 0.1324 PF00069 PF02205 0.0077 0.008168


Protein phosphatase 2A regulatory B subunit (B56 family) 0.8075 0.0077 enriched 3 0.4409 0.4149 PF00096 PF01603 0.0077 0.0103

STRUCTURE SH3 domainPutative GTPase activating protein for Arf 0.8271 0.0082 enriched 2 0.1405 0.138 PF00018 PF01412 0.0082 0.008993

STRUCTURE Zinc finger, C2H2 typeAIR synthase related protein, N-terminal domain 0.8378 0.0085 enriched 2 0.1592 0.1513 PF00096 PF00586 0.0085 0.0114

STRUCTURE Zinc finger, C2H2 typeAIR synthase related protein, C-terminal domain 0.8378 0.0085 enriched 2 0.1592 0.1513 PF00096 PF02769 0.0085 0.0114

STRUCTUREPDZ domain (Also known as DHR or GLGF) Major royal jelly protein 0.8848 0.0101 enriched 2 0.1457 0.1463 PF00595 PF03022 0.0101 0.009637


Zinc finger, C4 type (two domains) 0.8943 0.0105 enriched 2 0.1659 0.1618 PF00010 PF00105 0.0105 0.01233

STRUCTURE KH domain LIM domain 0.9128 0.0114 enriched 2 0.1524 0.1532 PF00013 PF00412 0.0114 0.0105STRUCTURE SH2 domain SH3 domain 0.9165 0.0116 enriched 3 0.4624 0.4584 PF00017 PF00018 0.0116 0.0117STRUCTURE Protein kinase domain Protein-tyrosine phosphatase 0.9265 0.0122 enriched 2 0.1811 0.1751 PF00069 PF00102 0.0122 0.01455

STRUCTURE Ankyrin repeatDomain of unknown function (DUF243) 0.9467 0.0137 enriched 2 0.1783 0.1759 PF00023 PF03103 0.0137 0.01413

STRUCTURE Homeobox domainZn-finger in Ran binding protein and others 0.9579 0.0148 enriched 2 0.1989 0.1936 PF00046 PF00641 0.0148 0.01734

STRUCTURE EF hand PX domain 0.9667 0.0159 enriched 2 0.201 0.1968 PF00036 PF00787 0.0159 0.01769STRUCTURE Ankyrin repeat Leucine Rich Repeat 0.9769 0.0176 enriched 2 0.2043 0.2012 PF00023 PF00560 0.0176 0.01823STRUCTURE Zinc finger, C2H2 type BED zinc finger 0.9801 0.0183 enriched 3 0.5965 0.5729 PF00096 PF02892 0.0183 0.02277STRUCTURE Protein kinase domain WD domain, G-beta repeat 0.9805 0.0184 enriched 4 1.001 0.9715 PF00069 PF00400 0.0184 0.01904

STRUCTURE Fibronectin type III domainPDZ domain (Also known as DHR or GLGF) 0.9817 0.0187 enriched 2 0.2031 0.2051 PF00041 PF00595 0.0187 0.01803

STRUCTURE SH3 domain VHS domain 0.9849 0.0196 enriched 2 0.2273 0.2189 PF00018 PF00790 0.0196 0.02223

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) MORN repeat 0.9852 0.0197 enriched 2 0.2289 0.2187 PF00076 PF02493 0.0197 0.02252

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) G-patch domain 0.9873 0.0204 enriched 3 0.5824 0.5799 PF00076 PF01585 0.0204 0.02141

STRUCTURE SH3 domain Ubiquitin interaction motif 0.9878 0.0206 enriched 2 0.2283 0.2234 PF00018 PF02809 0.0206 0.02241

STRUCTURE SH3 domainSAM domain (Sterile alpha motif) 0.9888 0.021 enriched 2 0.2214 0.2192 PF00018 PF00536 0.021 0.02117

STRUCTURE Protein kinase domain Cyclin, N-terminal domain 0.9895 0.0213 enriched 2 0.22 0.2216 PF00069 PF00134 0.0213 0.02093STRUCTURE KH domain Homeobox domain 0.9926 0.0229 enriched 2 0.2336 0.2347 PF00013 PF00046 0.0229 0.02339STRUCTURE SH2 domain PH domain 0.9933 0.0234 enriched 2 0.244 0.2385 PF00017 PF00169 0.0234 0.02534STRUCTURE BTB/POZ domain AT hook motif 0.9955 0.0252 enriched 2 0.2486 0.2452 PF00651 PF02178 0.0252 0.02623

Giot et al. 9


STRUCTURE BTB/POZ domainSeven in absentia protein family 0.9961 0.0259 enriched 2 0.2412 0.2402 PF00651 PF03145 0.0259 0.02481

STRUCTURE EGF-like domain BTB/POZ domain 0.9966 0.0265 enriched 2 0.2562 0.2524 PF00008 PF00651 0.0265 0.02772STRUCTURE SH3 domain PH domain 0.9968 0.0268 enriched 3 0.6424 0.6344 PF00018 PF00169 0.0268 0.02751

STRUCTURECalcineurin-like phosphoesterase LIM domain 0.9968 0.0268 enriched 2 0.2451 0.2523 PF00149 PF00412 0.0268 0.02555

STRUCTURE TPR DomainDomain of unknown function (DUF243) 0.9974 0.0279 enriched 2 0.2537 0.2548 PF00515 PF03103 0.0279 0.02722

STRUCTURE Protein kinase domain PX domain 0.9977 0.0283 enriched 2 0.258 0.2585 PF00069 PF00787 0.0283 0.02808

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) Zinc knuckle 0.9977 0.0284 enriched 3 0.6575 0.6415 PF00076 PF00098 0.0284 0.02918

STRUCTURE Insect cuticle protein TPR Domain 0.998 0.029 enriched 4 1.156 1.123 PF00379 PF00515 0.029 0.03009STRUCTURE SH3 domain LIM domain 0.9984 0.0302 enriched 3 0.6707 0.6639 PF00018 PF00412 0.0302 0.03067


Ubiquitin-conjugating enzyme 0.9992 0.0333 enriched 2 0.2865 0.2832 PF00010 PF00179 0.0333 0.03398

STRUCTURE Protein kinase domain MYND finger 0.9998 0.0388 enriched 2 0.3171 0.3102 PF00069 PF01753 0.0388 0.04081

STRUCTURERNA recognition motif. (a.k.a. RRM, RBD, or RNP domain) Lipase 0.9999 0.0418 enriched 2 0.3237 0.3153 PF00076 PF00151 0.0418 0.04235

STRUCTURE Zinc finger, C2H2 type Dynein light chain type 1 0.9999 0.0437 enriched 3 0.8255 0.7859 PF00096 PF01221 0.0437 0.05116

STRUCTUREHelix-loop-helix DNA-binding domain Immunoglobulin domain 0.9999 0.0439 enriched 2 0.3465 0.3381 PF00010 PF00047 0.0439 0.04781

STRUCTURE Ankyrin repeat Immunoglobulin domain 0.9999 0.0443 enriched 2 0.3426 0.3405 PF00023 PF00047 0.0443 0.04686STRUCTURE SH3 domain Protein kinase domain 0.9999 0.045 enriched 4 1.369 1.3 PF00018 PF00069 0.045 0.05027STRUCTURE Zinc finger, C2H2 type PCI domain 0.9999 0.0457 enriched 3 0.8086 0.7844 PF00096 PF01399 0.0457 0.04867

STRUCTURE

ATPase family associated with various cellular activities (AAA)

PDZ domain (Also known as DHR or GLGF) 1 0.0476 enriched 2 0.3582 0.3513 PF00004 PF00595 0.0476 0.05071

Giot et al. 10

Supplemental Table S7. Drosophila interactions

cg1 cg2 p1 p2 norient baitprey preybait cdna collection baitrgn bait5utr baitcds1 baitcds2 baitcds3 bait3utr baitother preyrgn prey5utr preycds1 preycds2 preycds3 prey3utr preyother totclone baitneigh preyneigh aneigh bneigh maxneigh geomneigh nbridge jac hexpert yexpert cexpert cconfCG10002 CG10032 fkh CG10032 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 37 15 62 62 30.4959 0 0 NA NA NA 0.0624

CG10002 CG11899 fkh ESTS:39C10S 1 1 0 1 0 CDS_F1:1 0 1 0 0 0 0 CDS_F3:1 0 0 0 1 0 0 1 15 5 15 8 15 10.9545 0 0 NA NA NA 0.1697CG10002 CG15224 fkh CkIIbeta 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 16 15 43 43 25.3969 0 0 NA NA NA 0.1116CG10002 CG15529 fkh CG15529 1 4 0 0 4 CDS_F1:4 0 4 0 0 0 0 CDS_F1:4 0 4 0 0 0 0 4 15 13 15 23 23 18.5742 0 0 NA NA NA 0.3413CG10002 CG17419 fkh CG17419 1 1 0 1 0 CDS_F1:1 0 1 0 0 0 0 CDS_F2:1 0 0 1 0 0 0 1 15 11 15 19 19 16.8819 1 0.03225806 NA NA NA 0.4194CG10002 CG17666 fkh CG17666 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 83 15 108 108 40.2492 0 0 NA NA NA 0.0348CG10002 CG17945 fkh Mst84Dc 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 17 15 29 29 20.8567 0 0 NA NA NA 0.1071CG10002 CG17946 fkh Mst84Da 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 20 15 20 20 17.3205 0 0 NA NA NA 0.0959CG10002 CG1925 fkh mus205 1 1 0 1 0 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 7 15 7 15 10.2470 0 0 NA NA NA 0.1368

CG10002CG31054 | CG4849 fkh CG31054 1 2 0 2 0 CDS_F1:2 0 2 0 0 0 0 CDS_F3:2 0 0 0 2 0 0 2 15 4 15 5 15 8.6603 0 0 NA NA NA 0.2574

CG10002 CG4959 fkhBG:DS04095.3 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F3:1 0 0 0 1 0 0 1 15 55 15 55 55 28.7228 0 0 NA NA NA 0.0469

CG10002 CG6238 fkh ssh 1 1 0 1 0 CDS_F1:1 0 1 0 0 0 0 3UTR:1 0 0 0 0 1 0 1 15 4 15 4 15 7.7460 0 0 NA NA NA 0.0519

CG10002 CG6459 fkh CG6459 1 36 0 24 12 CDS_F1:36 0 36 0 0 0 0CDS_F1:12 CDS_F2:24 0 12 24 0 0 0 36 15 46 15 64 64 30.9839 1 0.01315789 NA NA NA 0.9974

CG10002 CG7081 fkh CG7081 1 1 0 1 0 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 2 15 2 15 5.4772 0 0 NA NA NA 0.2905CG10002 CG9572 fkh CG9572 1 1 0 0 1 CDS_F1:1 0 1 0 0 0 0 CDS_F1:1 0 1 0 0 0 0 1 15 40 15 54 54 28.4605 0 0 NA NA NA 0.0590CG10007 CG11205 CG10007 phr 1 0 2 0 2 CDS_F1:2 0 2 0 0 0 0 CDS_F1:2 0 2 0 0 0 0 2 3 2 3 5 5 3.8730 0 0 NA NA NA 0.

Supplementary Tables S1. GO-Slim terms...

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Transcript of Supplementary Tables S1. GO-Slim terms...