ID DOCK4_HUMAN Reviewed; 1966 AA. AC Q8N1I0; O14584; O94824; Q8NB45; DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 183. DE RecName: Full=Dedicator of cytokinesis protein 4; GN Name=DOCK4; Synonyms=KIAA0716; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, INTERACTION WITH CRK, RAP1 ACTIVATION, AND VARIANTS RP ILE-87; GLN-606; THR-1059; LEU-1718; ALA-1733; PRO-1755; MET-1884; RP ILE-1914; LEU-1917 AND LEU-1926. RX PubMed=12628187; DOI=10.1016/s0092-8674(03)00155-7; RA Yajnik V., Paulding C., Sordella R., McClatchey A.I., Saito M., RA Wahrer D.C.R., Reynolds P., Bell D.W., Lake R., van den Heuvel S., RA Settleman J., Haber D.A.; RT "DOCK4, a GTPase activator, is disrupted during tumorigenesis."; RL Cell 112:673-684(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 645-1426 (ISOFORM 3). RC TISSUE=Fetal brain, and Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 550-1966 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [5] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R., Ishikawa K., Suyama M.; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NOMENCLATURE. RX PubMed=12432077; DOI=10.1242/jcs.00219; RA Cote J.-F., Vuori K.; RT "Identification of an evolutionarily conserved superfamily of DOCK180- RT related proteins with guanine nucleotide exchange activity."; RL J. Cell Sci. 115:4901-4913(2002). RN [7] RP FUNCTION (ISOFORM 2), INTERACTION WITH RAC1 AND USH1C, DOMAIN, ALTERNATIVE RP SPLICING, AND TISSUE SPECIFICITY (ISOFORM 2). RX PubMed=16464467; DOI=10.1016/j.jmb.2006.01.017; RA Yan D., Li F., Hall M.L., Sage C., Hu W.H., Giallourakis C., Upadhyay G., RA Ouyang X.M., Du L.L., Bethea J.R., Chen Z.Y., Yajnik V., Liu X.Z.; RT "An isoform of GTPase regulator DOCK4 localizes to the stereocilia in the RT inner ear and binds to harmonin (USH1C)."; RL J. Mol. Biol. 357:755-764(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1614 AND SER-1618, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1614; SER-1618 AND SER-1620, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [11] RP FUNCTION, INTERACTION WITH ELMO2 AND EPHA2, AND SUBCELLULAR LOCATION. RX PubMed=20679435; DOI=10.1083/jcb.201005141; RA Hiramoto-Yamaki N., Takeuchi S., Ueda S., Harada K., Fujimoto S., RA Negishi M., Katoh H.; RT "Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent RT mechanism."; RL J. Cell Biol. 190:461-477(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Functions as a guanine nucleotide exchange factor (GEF) that CC promotes the exchange of GDP to GTP, converting inactive GDP-bound CC small GTPases into their active GTP-bound form (PubMed:12628187, CC PubMed:16464467). Involved in regulation of adherens junction between CC cells (PubMed:12628187). Plays a role in cell migration CC (PubMed:20679435). {ECO:0000269|PubMed:12628187, CC ECO:0000269|PubMed:16464467, ECO:0000269|PubMed:20679435}. CC -!- FUNCTION: [Isoform 2]: Has a higher guanine nucleotide exchange factor CC activity compared to other isoforms. {ECO:0000269|PubMed:16464467}. CC -!- SUBUNIT: Interacts with nucleotide-free Rap1; functions as a guanine CC nucleotide exchange factor (GEF) for Rap1 (PubMed:12628187). Interacts CC (via DOCKER domain) with RAC1; functions as a guanine nucleotide CC exchange factor (GEF) for RAC1 (PubMed:16464467). Interacts with the CC SH3 domain of CRK (PubMed:12628187). Interacts with FASLG CC (PubMed:19807924). Interacts with ELMO2 and EPHA2; mediates activation CC of RAC1 by EPHA2 (PubMed:20679435). Interacts with USH1C (via PDZ 1 CC domain) (PubMed:16464467). {ECO:0000269|PubMed:12628187, CC ECO:0000269|PubMed:16464467, ECO:0000269|PubMed:19807924, CC ECO:0000269|PubMed:20679435}. CC -!- INTERACTION: CC Q8N1I0; P62993: GRB2; NbExp=4; IntAct=EBI-1059186, EBI-401755; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12628187}. Cell CC projection {ECO:0000269|PubMed:20679435}. Cytoplasm, cytosol CC {ECO:0000305|PubMed:20679435}. Note=Colocalizes with EPHA2, RHOG and CC CTTN/cortactin at the tip of protrusions in migrating cells. CC {ECO:0000269|PubMed:20679435}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q8N1I0-1; Sequence=Displayed; CC Name=2; Synonyms=DOCK4-Ex49 {ECO:0000303|PubMed:16464467}; CC IsoId=Q8N1I0-2; Sequence=VSP_007703, VSP_007706; CC Name=3; CC IsoId=Q8N1I0-3; Sequence=VSP_007703; CC Name=4; CC IsoId=Q8N1I0-4; Sequence=VSP_007701, VSP_007705; CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Highly expressed in CC skeletal muscle, prostate and ovary. {ECO:0000269|PubMed:12628187}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: May be specifically expressed in the CC brain and eye. {ECO:0000269|PubMed:16464467}. CC -!- DOMAIN: The DOCKER domain mediates interaction with small GTPases like CC RAC1 and is required for their activation. CC {ECO:0000269|PubMed:16464467}. CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE- CC ProRule:PRU00983}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC03696.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY233380; AAO73565.1; -; mRNA. DR EMBL; AK091557; BAC03696.1; ALT_INIT; mRNA. DR EMBL; AK098050; BAC05221.1; -; mRNA. DR EMBL; AC003077; AAB83946.1; -; Genomic_DNA. DR EMBL; AC003080; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004111; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005047; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB018259; BAA34436.3; -; mRNA. DR CCDS; CCDS47688.1; -. [Q8N1I0-1] DR CCDS; CCDS87541.1; -. [Q8N1I0-3] DR PIR; T01438; T01438. DR RefSeq; NP_055520.3; NM_014705.3. [Q8N1I0-1] DR RefSeq; XP_006716251.1; XM_006716188.2. DR RefSeq; XP_006716252.1; XM_006716189.2. [Q8N1I0-2] DR AlphaFoldDB; Q8N1I0; -. DR SMR; Q8N1I0; -. DR BioGRID; 115081; 70. DR IntAct; Q8N1I0; 19. DR MINT; Q8N1I0; -. DR STRING; 9606.ENSP00000410746; -. DR GlyCosmos; Q8N1I0; 2 sites, 1 glycan. DR GlyGen; Q8N1I0; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q8N1I0; -. DR PhosphoSitePlus; Q8N1I0; -. DR BioMuta; DOCK4; -. DR DMDM; 296439369; -. DR EPD; Q8N1I0; -. DR jPOST; Q8N1I0; -. DR MassIVE; Q8N1I0; -. DR MaxQB; Q8N1I0; -. DR PaxDb; 9606-ENSP00000404179; -. DR PeptideAtlas; Q8N1I0; -. DR ProteomicsDB; 71603; -. [Q8N1I0-1] DR ProteomicsDB; 71604; -. [Q8N1I0-2] DR ProteomicsDB; 71605; -. [Q8N1I0-3] DR ProteomicsDB; 71606; -. [Q8N1I0-4] DR Pumba; Q8N1I0; -. DR Antibodypedia; 31488; 160 antibodies from 22 providers. DR DNASU; 9732; -. DR Ensembl; ENST00000428084.6; ENSP00000410746.1; ENSG00000128512.24. [Q8N1I0-3] DR Ensembl; ENST00000437633.6; ENSP00000404179.1; ENSG00000128512.24. [Q8N1I0-1] DR GeneID; 9732; -. DR KEGG; hsa:9732; -. DR MANE-Select; ENST00000428084.6; ENSP00000410746.1; NM_001363540.2; NP_001350469.1. [Q8N1I0-3] DR UCSC; uc003vfx.4; human. [Q8N1I0-1] DR AGR; HGNC:19192; -. DR CTD; 9732; -. DR DisGeNET; 9732; -. DR GeneCards; DOCK4; -. DR HGNC; HGNC:19192; DOCK4. DR HPA; ENSG00000128512; Tissue enhanced (brain). DR MIM; 607679; gene. DR neXtProt; NX_Q8N1I0; -. DR OpenTargets; ENSG00000128512; -. DR PharmGKB; PA134939318; -. DR VEuPathDB; HostDB:ENSG00000128512; -. DR eggNOG; KOG1998; Eukaryota. DR eggNOG; KOG3166; Eukaryota. DR GeneTree; ENSGT00940000155659; -. DR InParanoid; Q8N1I0; -. DR OMA; MRDFGHS; -. DR OrthoDB; 8258at2759; -. DR PhylomeDB; Q8N1I0; -. DR TreeFam; TF300423; -. DR PathwayCommons; Q8N1I0; -. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013404; RAC2 GTPase cycle. DR Reactome; R-HSA-9013408; RHOG GTPase cycle. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; Q8N1I0; -. DR SIGNOR; Q8N1I0; -. DR BioGRID-ORCS; 9732; 13 hits in 1155 CRISPR screens. DR ChiTaRS; DOCK4; human. DR GeneWiki; Dock4; -. DR GenomeRNAi; 9732; -. DR Pharos; Q8N1I0; Tbio. DR PRO; PR:Q8N1I0; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q8N1I0; Protein. DR Bgee; ENSG00000128512; Expressed in endothelial cell and 199 other cell types or tissues. DR ExpressionAtlas; Q8N1I0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032420; C:stereocilium; ISS:HGNC-UCL. DR GO; GO:0032421; C:stereocilium bundle; ISS:HGNC-UCL. DR GO; GO:0005096; F:GTPase activator activity; IEA:InterPro. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0030165; F:PDZ domain binding; IPI:HGNC-UCL. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0031267; F:small GTPase binding; IDA:HGNC-UCL. DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB. DR GO; GO:1904694; P:negative regulation of vascular associated smooth muscle contraction; IMP:BHF-UCL. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IMP:BHF-UCL. DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro. DR CDD; cd08695; C2_Dock-B; 1. DR CDD; cd11705; DHR2_DOCK4; 1. DR CDD; cd12049; SH3_DOCK4_B; 1. DR Gene3D; 1.20.58.740; -; 1. DR Gene3D; 1.25.40.410; -; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.20.1270.350; Dedicator of cytokinesis N-terminal subdomain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR037811; C2_Dock-B. DR InterPro; IPR027007; C2_DOCK-type_domain. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR037014; DHR2_DOCK4. DR InterPro; IPR026791; DOCK. DR InterPro; IPR035769; DOCK4_SH3. DR InterPro; IPR043161; DOCK_C_lobe_A. DR InterPro; IPR043162; DOCK_C_lobe_C. DR InterPro; IPR032376; DOCK_N. DR InterPro; IPR042455; DOCK_N_sub1. DR InterPro; IPR027357; DOCKER_dom. DR InterPro; IPR046769; DOCKER_Lobe_A. DR InterPro; IPR046770; DOCKER_Lobe_B. DR InterPro; IPR046773; DOCKER_Lobe_C. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR45653; DEDICATOR OF CYTOKINESIS; 1. DR PANTHER; PTHR45653:SF7; DEDICATOR OF CYTOKINESIS PROTEIN 4; 1. DR Pfam; PF06920; DHR-2_Lobe_A; 1. DR Pfam; PF20422; DHR-2_Lobe_B; 1. DR Pfam; PF20421; DHR-2_Lobe_C; 1. DR Pfam; PF14429; DOCK-C2; 1. DR Pfam; PF16172; DOCK_N; 1. DR Pfam; PF07653; SH3_2; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS51650; C2_DOCK; 1. DR PROSITE; PS51651; DOCKER; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q8N1I0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm; KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein; KW Proto-oncogene; Reference proteome; SH3 domain; SH3-binding. FT CHAIN 1..1966 FT /note="Dedicator of cytokinesis protein 4" FT /id="PRO_0000189990" FT DOMAIN 6..67 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 401..574 FT /note="C2 DOCK-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983" FT DOMAIN 1190..1596 FT /note="DOCKER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984" FT REGION 1648..1729 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1742..1966 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1788..1794 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 1648..1699 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1702..1716 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1757..1776 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1797..1874 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 167 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT MOD_RES 193 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT MOD_RES 1599 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT MOD_RES 1607 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT MOD_RES 1614 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1618 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 1620 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1631 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT MOD_RES 1769 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59764" FT VAR_SEQ 1..1687 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007701" FT VAR_SEQ 1134 FT /note="I -> IIPLFGPYPS (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9872452" FT /id="VSP_007703" FT VAR_SEQ 1688..1698 FT /note="NVTSSAPSSAR -> MLMILSLLLFP (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_007705" FT VAR_SEQ 1760..1797 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9872452" FT /id="VSP_007706" FT VARIANT 87 FT /note="T -> I (found in a CNS cancer cell line; FT dbSNP:rs1396518456)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015823" FT VARIANT 535 FT /note="N -> D (in dbSNP:rs12705801)" FT /id="VAR_057517" FT VARIANT 606 FT /note="E -> Q" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015824" FT VARIANT 853 FT /note="R -> H (in dbSNP:rs2074130)" FT /id="VAR_057518" FT VARIANT 1059 FT /note="K -> T (found in a CNS cancer cell line)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015825" FT VARIANT 1570 FT /note="R -> K (in dbSNP:rs3757650)" FT /id="VAR_057519" FT VARIANT 1580 FT /note="F -> L (in dbSNP:rs3757651)" FT /id="VAR_057520" FT VARIANT 1718 FT /note="P -> L (found in prostate and ovarian cancer cell FT lines; abolishes ability to interact with CRK and to FT activate Rap1)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015826" FT VARIANT 1733 FT /note="P -> A (in dbSNP:rs150569245)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015827" FT VARIANT 1755 FT /note="S -> P (found in colorectal cancer cell line)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015828" FT VARIANT 1822 FT /note="Q -> K (in dbSNP:rs10281942)" FT /id="VAR_057521" FT VARIANT 1884 FT /note="V -> M (found in a prostate cancer cell line; FT dbSNP:rs369715294)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015829" FT VARIANT 1914 FT /note="V -> I (in dbSNP:rs12705795)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015830" FT VARIANT 1917 FT /note="P -> L (in dbSNP:rs199706346)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015831" FT VARIANT 1926 FT /note="S -> L (in dbSNP:rs34597439)" FT /evidence="ECO:0000269|PubMed:12628187" FT /id="VAR_015832" FT CONFLICT 945 FT /note="R -> K (in Ref. 3; AAB83946)" FT /evidence="ECO:0000305" FT CONFLICT 1080 FT /note="D -> G (in Ref. 1; AAO73565)" FT /evidence="ECO:0000305" FT CONFLICT 1122 FT /note="K -> E (in Ref. 2; BAC03696)" FT /evidence="ECO:0000305" FT CONFLICT 1379..1381 FT /note="YLQ -> CIRTYKGWTQFGTAVITDVGRLGTQIITQIN (in Ref. 3; FT BAC05221)" FT /evidence="ECO:0000305" SQ SEQUENCE 1966 AA; 225206 MW; 9CFB6299F7730AA9 CRC64; MWIPTEHEKY GVVIASFRGT VPYGLSLEIG DTVQILEKCD GWYRGFALKN PNIKGIFPSS YVHLKNACVK NKGQFEMVIP TEDSVITEMT STLRDWGTMW KQLYVRNEGD LFHRLWHIMN EILDLRRQVL VGHLTHDRMK DVKRHITARL DWGNEQLGLD LVPRKEYAMV DPEDISITEL YRLMEHRHRK KDTPVQASSH HLFVQMKSLM CSNLGEELEV IFSLFDSKEN RPISERFFLR LNRNGLPKAP DKPERHCSLF VDLGSSELRK DIYITVHIIR IGRMGAGEKK NACSVQYRRP FGCAVLSIAD LLTGETKDDL ILKVYMCNTE SEWYQIHENI IKKLNARYNL TGSNAGLAVS LQLLHGDIEQ IRREYSSVFS HGVSITRKLG FSNIIMPGEM RNDLYITIER GEFEKGGKSV ARNVEVTMFI VDSSGQTLKD FISFGSGEPP ASEYHSFVLY HNNSPRWSEL LKLPIPVDKF RGAHIRFEFR HCSTKEKGEK KLFGFSFVPL MQEDGRTLPD GTHELIVHKC EENTNLQDTT RYLKLPFSKG IFLGNNNQAM KATKESFCIT SFLCSTKLTQ NGDMLDLLKW RTHPDKITGC LSKLKEIDGS EIVKFLQDTL DTLFGILDEN SQKYGSKVFD SLVHIINLLQ DSKFHHFKPV MDTYIESHFA GALAYRDLIK VLKWYVDRIT EAERQEHIQE VLKAQEYIFK YIVQSRRLFS LATGGQNEEE FRCCIQELLM SVRFFLSQES KGSGALSQSQ AVFLSSFPAV YSELLKLFDV REVANLVQDT LGSLPTILHV DDSLQAIKLQ CIGKTVESQL YTNPDSRYIL LPVVLHHLHI HLQEQKDLIM CARILSNVFC LIKKNSSEKS VLEEIDVIVA SLLDILLRTI LEITSRPQPS SSAMRFQFQD VTGEFVACLL SLLRQMTDRH YQQLLDSFNT KEELRDFLLQ IFTVFRILIR PEMFPKDWTV MRLVANNVII TTVLYLSDAL RKNFLNENFD YKIWDSYFYL AVIFINQLCL QLEMFTPSKK KKVLEKYGDM RVTMGCEIFS MWQNLGEHKL HFIPALIGPF LEVTLIPQPD LRNVMIPIFH DMMDWEQRRS GNFKQVEAKL IDKLDSLMSE GKGDETYREL FNSILLKKIE RETWRESGVS LIATVTRLME RLLDYRDCMK MGEVDGKKIG CTVSLLNFYK TELNKEEMYI RYIHKLYDLH LKAQNFTEAA YTLLLYDELL EWSDRPLREF LTYPMQTEWQ RKEHLHLTII QNFDRGKCWE NGIILCRKIA EQYESYYDYR NLSKMRMMEA SLYDKIMDQQ RLEPEFFRVG FYGKKFPFFL RNKEFVCRGH DYERLEAFQQ RMLNEFPHAI AMQHANQPDE TIFQAEAQYL QIYAVTPIPE SQEVLQREGV PDNIKSFYKV NHIWKFRYDR PFHKGTKDKE NEFKSLWVER TSLYLVQSLP GISRWFEVEK REVVEMSPLE NAIEVLENKN QQLKTLISQC QTRQMQNINP LTMCLNGVID AAVNGGVSRY QEAFFVKEYI LSHPEDGEKI ARLRELMLEQ AQILEFGLAV HEKFVPQDMR PLHKKLVDQF FVMKSSLGIQ EFSACMQASP VHFPNGSPRV CRNSAPASVS PDGTRVIPRR SPLSYPAVNR YSSSSLSSQA SAEVSNITGQ SESSDEVFNM QPSPSTSSLS STHSASPNVT SSAPSSARAS PLLSDKHKHS RENSCLSPRE RPCSAIYPTP VEPSQRMLFN HIGDGALPRS DPNLSAPEKA VNPTPSSWSL DSGKEAKNMS DSGKLISPPV PPRPTQTASP ARHTTSVSPS PAGRSPLKGS VQSFTPSPVE YHSPGLISNS PVLSGSYSSG ISSLSRCSTS ETSGFENQVN EQSAPLPVPV PVPVPSYGGE EPVRKESKTP PPYSVYERTL RRPVPLPHSL SIPVTSEPPA LPPKPLAARS SHLENGARRT DPGPRPRPLP RKVSQL //