DOCK4_HUMAN
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 03-AUG-2022, entry version 174.
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};
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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; 62.
DR IntAct; Q8N1I0; 19.
DR MINT; Q8N1I0; -.
DR STRING; 9606.ENSP00000404179; -.
DR GlyGen; Q8N1I0; 2 sites, 1 O-linked glycan (2 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; Q8N1I0; -.
DR PeptideAtlas; Q8N1I0; -.
DR PRIDE; Q8N1I0; -.
DR ProteomicsDB; 71603; -. [Q8N1I0-1]
DR ProteomicsDB; 71604; -. [Q8N1I0-2]
DR ProteomicsDB; 71605; -. [Q8N1I0-3]
DR ProteomicsDB; 71606; -. [Q8N1I0-4]
DR Antibodypedia; 31488; 141 antibodies from 21 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 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; 102580at2759; -.
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 1078 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 197 other tissues.
DR ExpressionAtlas; Q8N1I0; baseline and differential.
DR Genevisible; Q8N1I0; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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; cd12049; SH3_DOCK4_B; 1.
DR Gene3D; 1.20.1270.350; -; 1.
DR Gene3D; 1.20.58.740; -; 1.
DR Gene3D; 1.25.40.410; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR037811; C2_Dock-B.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR037014; DOCK4.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR45653; PTHR45653; 1.
DR PANTHER; PTHR45653:SF7; PTHR45653:SF7; 1.
DR Pfam; PF06920; DHR-2; 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; SSF50044; 1.
DR PROSITE; PS51650; C2_DOCK; 1.
DR PROSITE; PS51651; DOCKER; 1.
DR PROSITE; PS50002; SH3; 1.
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
