DOCK2_HUMAN
ID DOCK2_HUMAN Reviewed; 1830 AA.
AC Q92608; Q2M3I0; Q96AK7;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Dedicator of cytokinesis protein 2;
GN Name=DOCK2; Synonyms=KIAA0209;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon, and Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY, RAC1 ACTIVATION, AND INTERACTION WITH RAC1 AND RAC2.
RX PubMed=10559471; DOI=10.1016/s0167-4889(99)00133-0;
RA Nishihara H., Kobayashi S., Hashimoto Y., Ohba F., Mochizuki N., Kurata T.,
RA Nagashima K., Matsuda M.;
RT "Non-adherent cell-specific expression of DOCK2, a member of the human CDM-
RT family proteins.";
RL Biochim. Biophys. Acta 1452:179-187(1999).
RN [4]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CRKL AND VAV.
RX PubMed=12393632; DOI=10.1182/blood-2001-11-0032;
RA Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S.;
RT "DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell
RT lines.";
RL Blood 100:3968-3974(2002).
RN [5]
RP INTERACTION WITH CD3Z.
RX PubMed=12176041; DOI=10.1016/s0006-291x(02)00931-2;
RA Nishihara H., Maeda M., Tsuda M., Makino Y., Sawa H., Nagashima K.,
RA Tanaka S.;
RT "DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2
RT transcription.";
RL Biochem. Biophys. Res. Commun. 296:716-720(2002).
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 IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588; SER-593; SER-1685 AND
RP SER-1731, 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304 AND LYS-738, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685; SER-1706; SER-1731 AND
RP SER-1784, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1685, AND IDENTIFICATION BY
RP 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).
RN [16]
RP INVOLVEMENT IN IMD40, AND VARIANTS IMD40 SER-751 AND TRP-1104.
RX PubMed=26083206; DOI=10.1056/nejmoa1413462;
RA Dobbs K., Dominguez Conde C., Zhang S.Y., Parolini S., Audry M., Chou J.,
RA Haapaniemi E., Keles S., Bilic I., Okada S., Massaad M.J., Rounioja S.,
RA Alwahadneh A.M., Serwas N.K., Capuder K., Ciftci E., Felgentreff K.,
RA Ohsumi T.K., Pedergnana V., Boisson B., Haskologlu S., Ensari A.,
RA Schuster M., Moretta A., Itan Y., Patrizi O., Rozenberg F., Lebon P.,
RA Saarela J., Knip M., Petrovski S., Goldstein D.B., Parrott R.E., Savas B.,
RA Schambach A., Tabellini G., Bock C., Chatila T.A., Comeau A.M., Geha R.S.,
RA Abel L., Buckley R.H., Ikinciogullari A., Al-Herz W., Helminen M., Dogu F.,
RA Casanova J.L., Boztug K., Notarangelo L.D.;
RT "Inherited DOCK2 deficiency in patients with early-onset invasive
RT infections.";
RL N. Engl. J. Med. 372:2409-2422(2015).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP STRUCTURE BY NMR OF 8-70.
RG RIKEN structural genomics initiative (RSGI);
RT "The solution structure of human DOCK2 SH3 domain - ELMO1 peptide chimera
RT complex.";
RL Submitted (OCT-2010) to the PDB data bank.
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1192-1622 IN COMPLEX WITH RAC1,
RP INTERACTION WITH RAC1, SUBUNIT, AND FUNCTION.
RX PubMed=21613211; DOI=10.1074/jbc.m111.236455;
RA Kulkarni K., Yang J., Zhang Z., Barford D.;
RT "Multiple factors confer specific Cdc42 and Rac protein activation by
RT dedicator of cytokinesis (DOCK) nucleotide exchange factors.";
RL J. Biol. Chem. 286:25341-25351(2011).
CC -!- FUNCTION: Involved in cytoskeletal rearrangements required for
CC lymphocyte migration in response of chemokines. Activates RAC1 and
CC RAC2, but not CDC42, by functioning as a guanine nucleotide exchange
CC factor (GEF), which exchanges bound GDP for free GTP. May also
CC participate in IL2 transcriptional activation via the activation of
CC RAC2. {ECO:0000269|PubMed:21613211}.
CC -!- SUBUNIT: Homodimer (Probable). Interacts with RAC1 and RAC2. Interacts
CC with CRKL and VAV. Interacts with CD3Z. {ECO:0000269|PubMed:10559471,
CC ECO:0000269|PubMed:12176041, ECO:0000269|PubMed:12393632,
CC ECO:0000269|PubMed:21613211, ECO:0000305}.
CC -!- INTERACTION:
CC Q92608; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-448771, EBI-739580;
CC Q92608; Q9BWT7: CARD10; NbExp=3; IntAct=EBI-448771, EBI-3866279;
CC Q92608; O95273: CCNDBP1; NbExp=3; IntAct=EBI-448771, EBI-748961;
CC Q92608; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-448771, EBI-3867333;
CC Q92608; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-448771, EBI-5916454;
CC Q92608; P61978: HNRNPK; NbExp=6; IntAct=EBI-448771, EBI-304185;
CC Q92608; P61978-2: HNRNPK; NbExp=3; IntAct=EBI-448771, EBI-7060731;
CC Q92608; P49639: HOXA1; NbExp=3; IntAct=EBI-448771, EBI-740785;
CC Q92608; Q5VWX1: KHDRBS2; NbExp=6; IntAct=EBI-448771, EBI-742808;
CC Q92608; O75525: KHDRBS3; NbExp=3; IntAct=EBI-448771, EBI-722504;
CC Q92608; Q15323: KRT31; NbExp=3; IntAct=EBI-448771, EBI-948001;
CC Q92608; O76011: KRT34; NbExp=3; IntAct=EBI-448771, EBI-1047093;
CC Q92608; Q6A162: KRT40; NbExp=6; IntAct=EBI-448771, EBI-10171697;
CC Q92608; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-448771, EBI-11959885;
CC Q92608; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-448771, EBI-11749135;
CC Q92608; P60409: KRTAP10-7; NbExp=5; IntAct=EBI-448771, EBI-10172290;
CC Q92608; P60410: KRTAP10-8; NbExp=6; IntAct=EBI-448771, EBI-10171774;
CC Q92608; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-448771, EBI-10172052;
CC Q92608; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-448771, EBI-11953334;
CC Q92608; Q9BYP8: KRTAP17-1; NbExp=3; IntAct=EBI-448771, EBI-11988175;
CC Q92608; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-448771, EBI-9996449;
CC Q92608; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-448771, EBI-3957694;
CC Q92608; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-448771, EBI-10172511;
CC Q92608; Q6L8G8: KRTAP5-7; NbExp=3; IntAct=EBI-448771, EBI-11987425;
CC Q92608; P26371: KRTAP5-9; NbExp=6; IntAct=EBI-448771, EBI-3958099;
CC Q92608; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-448771, EBI-1044640;
CC Q92608; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-448771, EBI-1043191;
CC Q92608; Q9BYQ2: KRTAP9-4; NbExp=3; IntAct=EBI-448771, EBI-10185730;
CC Q92608; Q99750: MDFI; NbExp=8; IntAct=EBI-448771, EBI-724076;
CC Q92608; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-448771, EBI-742948;
CC Q92608; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-448771, EBI-11522433;
CC Q92608; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-448771, EBI-945833;
CC Q92608; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-448771, EBI-22310682;
CC Q92608; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-448771, EBI-11956269;
CC Q92608; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-448771, EBI-742388;
CC Q92608; O15162: PLSCR1; NbExp=3; IntAct=EBI-448771, EBI-740019;
CC Q92608; P63000: RAC1; NbExp=3; IntAct=EBI-448771, EBI-413628;
CC Q92608; Q6N022: TENM4; NbExp=3; IntAct=EBI-448771, EBI-12827077;
CC Q92608; P22735: TGM1; NbExp=3; IntAct=EBI-448771, EBI-2562368;
CC Q92608; P36406: TRIM23; NbExp=3; IntAct=EBI-448771, EBI-740098;
CC Q92608-2; Q99732: LITAF; NbExp=3; IntAct=EBI-25875570, EBI-725647;
CC Q92608-2; P10636: MAPT; NbExp=3; IntAct=EBI-25875570, EBI-366182;
CC Q92608-2; P10636-6: MAPT; NbExp=3; IntAct=EBI-25875570, EBI-7796455;
CC Q92608-2; Q9P1N4; NbExp=3; IntAct=EBI-25875570, EBI-25878161;
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000269|PubMed:12393632}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12393632}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12393632}. Note=Colocalizes with F-actin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92608-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92608-2; Sequence=VSP_007696, VSP_007697, VSP_007698,
CC VSP_007699, VSP_007700;
CC -!- TISSUE SPECIFICITY: Specifically expressed in hematopoietic cells.
CC Highly expressed in peripheral blood leukocytes, and expressed at
CC intermediate level in thymus and spleen. Expressed at very low level in
CC the small intestine and colon. {ECO:0000269|PubMed:10559471}.
CC -!- DOMAIN: The DOCKER domain may mediate the GEF activity. {ECO:0000250}.
CC -!- DISEASE: Immunodeficiency 40 (IMD40) [MIM:616433]: A form of combined
CC immunodeficiency characterized by lymphopenia, and defective T-cell, B-
CC cell, and NK-cell responses. Patients suffer from severe invasive
CC bacterial and viral infections in early childhood and may die without
CC bone marrow transplantation. {ECO:0000269|PubMed:26083206}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Splicing donor and acceptor sites between
CC exon 6 and exon 7 are not canonical. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13200.1; Type=Erroneous initiation; Note=Extended 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; D86964; BAA13200.1; ALT_INIT; mRNA.
DR EMBL; BC016996; AAH16996.1; -; mRNA.
DR EMBL; BC104900; AAI04901.1; -; mRNA.
DR EMBL; BC113457; AAI13458.1; -; mRNA.
DR CCDS; CCDS4371.1; -. [Q92608-1]
DR RefSeq; NP_004937.1; NM_004946.2. [Q92608-1]
DR PDB; 2RQR; NMR; -; A=8-70.
DR PDB; 2YIN; X-ray; 2.70 A; A/B=1192-1622.
DR PDB; 3A98; X-ray; 2.10 A; A/C=1-177.
DR PDB; 3B13; X-ray; 3.01 A; A/C=1196-1622.
DR PDB; 6TGB; EM; 5.50 A; A/D=1-1830.
DR PDB; 6TGC; EM; 4.10 A; A/D=1-1830.
DR PDBsum; 2RQR; -.
DR PDBsum; 2YIN; -.
DR PDBsum; 3A98; -.
DR PDBsum; 3B13; -.
DR PDBsum; 6TGB; -.
DR PDBsum; 6TGC; -.
DR AlphaFoldDB; Q92608; -.
DR SMR; Q92608; -.
DR BioGRID; 108129; 63.
DR CORUM; Q92608; -.
DR DIP; DIP-31791N; -.
DR IntAct; Q92608; 49.
DR MINT; Q92608; -.
DR STRING; 9606.ENSP00000256935; -.
DR BindingDB; Q92608; -.
DR ChEMBL; CHEMBL4105810; -.
DR iPTMnet; Q92608; -.
DR MetOSite; Q92608; -.
DR PhosphoSitePlus; Q92608; -.
DR BioMuta; DOCK2; -.
DR DMDM; 32469765; -.
DR CPTAC; CPTAC-1604; -.
DR CPTAC; CPTAC-964; -.
DR EPD; Q92608; -.
DR jPOST; Q92608; -.
DR MassIVE; Q92608; -.
DR MaxQB; Q92608; -.
DR PaxDb; Q92608; -.
DR PeptideAtlas; Q92608; -.
DR PRIDE; Q92608; -.
DR ProteomicsDB; 75352; -. [Q92608-1]
DR ProteomicsDB; 75353; -. [Q92608-2]
DR Antibodypedia; 28772; 247 antibodies from 32 providers.
DR DNASU; 1794; -.
DR Ensembl; ENST00000520908.7; ENSP00000429283.3; ENSG00000134516.19. [Q92608-1]
DR GeneID; 1794; -.
DR KEGG; hsa:1794; -.
DR MANE-Select; ENST00000520908.7; ENSP00000429283.3; NM_004946.3; NP_004937.1.
DR UCSC; uc003maf.3; human. [Q92608-1]
DR CTD; 1794; -.
DR DisGeNET; 1794; -.
DR GeneCards; DOCK2; -.
DR HGNC; HGNC:2988; DOCK2.
DR HPA; ENSG00000134516; Group enriched (bone marrow, lung, lymphoid tissue).
DR MalaCards; DOCK2; -.
DR MIM; 603122; gene.
DR MIM; 616433; phenotype.
DR neXtProt; NX_Q92608; -.
DR OpenTargets; ENSG00000134516; -.
DR Orphanet; 447737; DOCK2 deficiency.
DR PharmGKB; PA27454; -.
DR VEuPathDB; HostDB:ENSG00000134516; -.
DR eggNOG; KOG1998; Eukaryota.
DR GeneTree; ENSGT00940000154903; -.
DR HOGENOM; CLU_000595_2_1_1; -.
DR InParanoid; Q92608; -.
DR OMA; MEECFKS; -.
DR PhylomeDB; Q92608; -.
DR TreeFam; TF300423; -.
DR PathwayCommons; Q92608; -.
DR Reactome; R-HSA-164944; Nef and signal transduction.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
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; Q92608; -.
DR BioGRID-ORCS; 1794; 25 hits in 1077 CRISPR screens.
DR ChiTaRS; DOCK2; human.
DR GeneWiki; Dock2; -.
DR GenomeRNAi; 1794; -.
DR Pharos; Q92608; Tchem.
DR PRO; PR:Q92608; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q92608; protein.
DR Bgee; ENSG00000134516; Expressed in bone marrow cell and 141 other tissues.
DR ExpressionAtlas; Q92608; baseline and differential.
DR Genevisible; Q92608; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0005096; F:GTPase activator activity; IEA:Ensembl.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0042608; F:T cell receptor binding; IDA:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0046633; P:alpha-beta T cell proliferation; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; IEA:Ensembl.
DR GO; GO:0001768; P:establishment of T cell polarity; IEA:Ensembl.
DR GO; GO:0001771; P:immunological synapse formation; IEA:Ensembl.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0001766; P:membrane raft polarization; IEA:Ensembl.
DR GO; GO:0002277; P:myeloid dendritic cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0007520; P:myoblast fusion; IBA:GO_Central.
DR GO; GO:0045060; P:negative thymic T cell selection; IEA:Ensembl.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0045059; P:positive thymic T cell selection; IEA:Ensembl.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
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; IPR016024; ARM-type_fold.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR026799; DOCK_2.
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:SF6; PTHR45653:SF6; 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; SSF48371; SSF48371; 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 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Disease variant; Guanine-nucleotide releasing factor; Membrane;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..1830
FT /note="Dedicator of cytokinesis protein 2"
FT /id="PRO_0000189986"
FT DOMAIN 8..69
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 423..607
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1211..1622
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT REGION 939..1476
FT /note="Interaction with CRKL"
FT /evidence="ECO:0000269|PubMed:12393632"
FT REGION 1651..1704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1651..1669
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 304
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 593
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 738
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1685
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19367720,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1706
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1731
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1784
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..449
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007696"
FT VAR_SEQ 462..494
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007697"
FT VAR_SEQ 630..766
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007698"
FT VAR_SEQ 934..955
FT /note="SHFVACMTAILNQMGDQHYSFY -> GACCNCGFPSSTPHSLIQWLWG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007699"
FT VAR_SEQ 956..1830
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007700"
FT VARIANT 751
FT /note="R -> S (in IMD40; dbSNP:rs1581090174)"
FT /evidence="ECO:0000269|PubMed:26083206"
FT /id="VAR_073859"
FT VARIANT 1104
FT /note="R -> W (in IMD40; dbSNP:rs780318765)"
FT /evidence="ECO:0000269|PubMed:26083206"
FT /id="VAR_073860"
FT VARIANT 1558
FT /note="D -> A (in dbSNP:rs13179480)"
FT /id="VAR_053064"
FT VARIANT 1746
FT /note="S -> T (in dbSNP:rs2270898)"
FT /id="VAR_015822"
FT VARIANT 1779
FT /note="T -> S (in dbSNP:rs2270898)"
FT /id="VAR_022137"
FT STRAND 12..17
FT /evidence="ECO:0007829|PDB:3A98"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:3A98"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3A98"
FT STRAND 52..60
FT /evidence="ECO:0007829|PDB:3A98"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3A98"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:3A98"
FT HELIX 84..107
FT /evidence="ECO:0007829|PDB:3A98"
FT HELIX 111..133
FT /evidence="ECO:0007829|PDB:3A98"
FT HELIX 138..158
FT /evidence="ECO:0007829|PDB:3A98"
FT HELIX 1197..1214
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1217..1233
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1237..1248
FT /evidence="ECO:0007829|PDB:2YIN"
FT TURN 1265..1267
FT /evidence="ECO:0007829|PDB:3B13"
FT HELIX 1273..1291
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1294..1310
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1315..1334
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1342..1349
FT /evidence="ECO:0007829|PDB:2YIN"
FT TURN 1354..1358
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1359..1364
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1371..1381
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1385..1387
FT /evidence="ECO:0007829|PDB:3B13"
FT HELIX 1396..1400
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1405..1414
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1419..1421
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1422..1424
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1428..1436
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1437..1449
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1458..1461
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1462..1492
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1494..1518
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1520..1522
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1525..1535
FT /evidence="ECO:0007829|PDB:2YIN"
FT STRAND 1538..1540
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1544..1550
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1553..1558
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1560..1562
FT /evidence="ECO:0007829|PDB:3B13"
FT HELIX 1563..1589
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1593..1595
FT /evidence="ECO:0007829|PDB:2YIN"
FT HELIX 1596..1617
FT /evidence="ECO:0007829|PDB:2YIN"
SQ SEQUENCE 1830 AA; 211948 MW; 18568D3322DAA92A CRC64;
MAPWRKADKE RHGVAIYNFQ GSGAPQLSLQ IGDVVRIQET CGDWYRGYLI KHKMLQGIFP
KSFIHIKEVT VEKRRNTENI IPAEIPLAQE VTTTLWEWGS IWKQLYVASK KERFLQVQSM
MYDLMEWRSQ LLSGTLPKDE LKELKQKVTS KIDYGNKILE LDLIVRDEDG NILDPDNTSV
ISLFHAHEEA TDKITERIKE EMSKDQPDYA MYSRISSSPT HSLYVFVRNF VCRIGEDAEL
FMSLYDPNKQ TVISENYLVR WGSRGFPKEI EMLNNLKVVF TDLGNKDLNR DKIYLICQIV
RVGKMDLKDT GAKKCTQGLR RPFGVAVMDI TDIIKGKAES DEEKQHFIPF HPVTAENDFL
HSLLGKVIAS KGDSGGQGLW VTMKMLVGDI IQIRKDYPHL VDRTTVVARK LGFPEIIMPG
DVRNDIYITL LQGDFDKYNK TTQRNVEVIM CVCAEDGKTL PNAICVGAGD KPMNEYRSVV
YYQVKQPRWM ETVKVAVPIE DMQRIHLRFM FRHRSSLESK DKGEKNFAMS YVKLMKEDGT
TLHDGFHDLV VLKGDSKKME DASAYLTLPS YRHHVENKGA TLSRSSSSVG GLSVSSRDVF
SISTLVCSTK LTQNVGLLGL LKWRMKPQLL QENLEKLKIV DGEEVVKFLQ DTLDALFNIM
MEHSQSDEYD ILVFDALIYI IGLIADRKFQ HFNTVLEAYI QQHFSATLAY KKLMTVLKTY
LDTSSRGEQC EPILRTLKAL EYVFKFIVRS RTLFSQLYEG KEQMEFEESM RRLFESINNL
MKSQYKTTIL LQVAALKYIP SVLHDVEMVF DAKLLSQLLY EFYTCIPPVK LQKQKVQSMN
EIVQSNLFKK QECRDILLPV ITKELKELLE QKDDMQHQVL ERKYCVELLN SILEVLSYQD
AAFTYHHIQE IMVQLLRTVN RTVITMGRDH ILISHFVACM TAILNQMGDQ HYSFYIETFQ
TSSELVDFLM ETFIMFKDLI GKNVYPGDWM AMSMVQNRVF LRAINKFAET MNQKFLEHTN
FEFQLWNNYF HLAVAFITQD SLQLEQFSHA KYNKILNKYG DMRRLIGFSI RDMWYKLGQN
KICFIPGMVG PILEMTLIPE AELRKATIPI FFDMMLCEYQ RSGDFKKFEN EIILKLDHEV
EGGRGDEQYM QLLESILMEC AAEHPTIAKS VENFVNLVKG LLEKLLDYRG VMTDESKDNR
MSCTVNLLNF YKDNNREEMY IRYLYKLRDL HLDCDNYTEA AYTLLLHTWL LKWSDEQCAS
QVMQTGQQHP QTHRQLKETL YETIIGYFDK GKMWEEAISL CKELAEQYEM EIFDYELLSQ
NLIQQAKFYE SIMKILRPKP DYFAVGYYGQ GFPSFLRNKV FIYRGKEYER REDFQMQLMT
QFPNAEKMNT TSAPGDDVKN APGQYIQCFT VQPVLDEHPR FKNKPVPDQI INFYKSNYVQ
RFHYSRPVRR GTVDPENEFA SMWIERTSFV TAYKLPGILR WFEVVHMSQT TISPLENAIE
TMSTANEKIL MMINQYQSDE TLPINPLSML LNGIVDPAVM GGFAKYEKAF FTEEYVRDHP
EDQDKLTHLK DLIAWQIPFL GAGIKIHEKR VSDNLRPFHD RMEECFKNLK MKVEKEYGVR
EMPDFDDRRV GRPRSMLRSY RQMSIISLAS MNSDCSTPSK PTSESFDLEL ASPKTPRVEQ
EEPISPGSTL PEVKLRRSKK RTKRSSVVFA DEKAAAESDL KRLSRKHEFM SDTNLSEHAA
IPLKASVLSQ MSFASQSMPT IPALALSVAG IPGLDEANTS PRLSQTFLQL SDGDKKTLTR
KKVNQFFKTM LASKSAEEGK QIPDSLSTDL
