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 27-MAR-2024, entry version 204. 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 EMDB; EMD-10497; -. DR EMDB; EMD-10498; -. DR SMR; Q92608; -. DR BioGRID; 108129; 64. DR CORUM; Q92608; -. DR DIP; DIP-31791N; -. DR IntAct; Q92608; 49. DR MINT; Q92608; -. DR STRING; 9606.ENSP00000429283; -. 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; 9606-ENSP00000256935; -. DR PeptideAtlas; Q92608; -. DR ProteomicsDB; 75352; -. [Q92608-1] DR ProteomicsDB; 75353; -. [Q92608-2] DR Pumba; Q92608; -. DR Antibodypedia; 28772; 280 antibodies from 32 providers. DR DNASU; 1794; -. DR Ensembl; ENST00000520908.7; ENSP00000429283.3; ENSG00000134516.20. [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 AGR; HGNC:2988; -. 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; Combined immunodeficiency due to 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; TIVEWAT; -. DR OrthoDB; 8258at2759; -. 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; 28 hits in 1160 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 143 other cell types or tissues. DR ExpressionAtlas; Q92608; baseline and differential. 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 CDD; cd11706; DHR2_DOCK2; 1. DR CDD; cd12050; SH3_DOCK2_A; 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; IPR016024; ARM-type_fold. DR InterPro; IPR027007; C2_DOCK-type_domain. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR026799; DHR2_DOCK2. DR InterPro; IPR026791; DOCK. 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:SF6; DEDICATOR OF CYTOKINESIS PROTEIN 2; 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; SSF48371; ARM repeat; 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; Q92608; HS. 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 //