DOK2_HUMAN
ID DOK2_HUMAN Reviewed; 412 AA.
AC O60496; Q8N5A4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Docking protein 2;
DE AltName: Full=Downstream of tyrosine kinase 2;
DE AltName: Full=p56(dok-2);
GN Name=DOK2;
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], PROTEIN SEQUENCE OF 8-21; 30-49; 59-89 AND
RP 128-149, TISSUE SPECIFICITY, INTERACTION WITH RASGAP, AND VARIANT PRO-152.
RX PubMed=9478921; DOI=10.1074/jbc.273.9.4827;
RA Di Cristofano A., Carpino N., Dunant N., Friedland G., Kobayashi R.,
RA Strife A., Wisniewski D., Clarkson B., Pandolfi P.P., Resh M.D.;
RT "Molecular cloning and characterization of p56dok-2 defines a new family of
RT RasGAP-binding proteins.";
RL J. Biol. Chem. 273:4827-4830(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, AND IDENTIFICATION BY
RP 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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, AND IDENTIFICATION BY
RP 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-299, AND IDENTIFICATION BY
RP 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 [7]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN UL46.
RX PubMed=28841444; DOI=10.1016/j.virol.2017.08.018;
RA Lahmidi S., Strunk U., Smiley J.R., Pearson A., Duplay P.;
RT "Herpes simplex virus 1 infection of T cells causes VP11/12-dependent
RT phosphorylation and degradation of the cellular protein Dok-2.";
RL Virology 511:66-73(2017).
RN [8]
RP STRUCTURE BY NMR OF 1-247.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PH and IRS domains of human docking protein 2,
RT isoform A.";
RL Submitted (OCT-2006) to the PDB data bank.
CC -!- FUNCTION: DOK proteins are enzymatically inert adaptor or scaffolding
CC proteins. They provide a docking platform for the assembly of
CC multimolecular signaling complexes. DOK2 may modulate the cellular
CC proliferation induced by IL-4, as well as IL-2 and IL-3. May be
CC involved in modulating Bcr-Abl signaling. Attenuates EGF-stimulated MAP
CC kinase activation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with phosphorylated RASGAP and EGFR. Interacts with
CC RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine
CC phosphorylated) (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Herpes simplex virus 1
CC (HHV-1) protein UL46; this interaction induces DOK2 phosphorylation and
CC subsequent degradation. {ECO:0000269|PubMed:28841444}.
CC -!- INTERACTION:
CC O60496; Q9NUX5: POT1; NbExp=2; IntAct=EBI-1046024, EBI-752420;
CC O60496; P42681: TXK; NbExp=3; IntAct=EBI-1046024, EBI-7877438;
CC O60496; P07947: YES1; NbExp=3; IntAct=EBI-1046024, EBI-515331;
CC -!- TISSUE SPECIFICITY: Highly expressed in peripheral blood leukocytes,
CC lymph nodes and spleen. Lower expression in thymus, bone marrow and
CC fetal liver. {ECO:0000269|PubMed:9478921}.
CC -!- DOMAIN: PTB domain mediates receptor interaction.
CC -!- PTM: On immunoreceptor stimulation, phosphorylated on C-terminal
CC tyrosine residues. Phosphorylation on Tyr-345 is required for binding
CC to the SH2 domain of NCK. Phosphorylation on both Tyr-271 and Tyr-299
CC is required for interaction with RASGAP. Phosphorylated on tyrosine
CC residues by TEK/TIE2 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DOK family. Type A subfamily. {ECO:0000305}.
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DR EMBL; AF034970; AAC13265.1; -; mRNA.
DR EMBL; BC032623; AAH32623.1; -; mRNA.
DR CCDS; CCDS6016.1; -.
DR RefSeq; NP_003965.2; NM_003974.3.
DR PDB; 2D9W; NMR; -; A=1-114.
DR PDB; 2DLW; NMR; -; A=148-247.
DR PDBsum; 2D9W; -.
DR PDBsum; 2DLW; -.
DR AlphaFoldDB; O60496; -.
DR BMRB; O60496; -.
DR SMR; O60496; -.
DR BioGRID; 114508; 111.
DR IntAct; O60496; 81.
DR MINT; O60496; -.
DR STRING; 9606.ENSP00000276420; -.
DR iPTMnet; O60496; -.
DR PhosphoSitePlus; O60496; -.
DR BioMuta; DOK2; -.
DR OGP; O60496; -.
DR jPOST; O60496; -.
DR MassIVE; O60496; -.
DR MaxQB; O60496; -.
DR PaxDb; O60496; -.
DR PeptideAtlas; O60496; -.
DR PRIDE; O60496; -.
DR ProteomicsDB; 49433; -.
DR Antibodypedia; 3823; 725 antibodies from 38 providers.
DR DNASU; 9046; -.
DR Ensembl; ENST00000276420.9; ENSP00000276420.4; ENSG00000147443.13.
DR GeneID; 9046; -.
DR KEGG; hsa:9046; -.
DR MANE-Select; ENST00000276420.9; ENSP00000276420.4; NM_003974.4; NP_003965.2.
DR UCSC; uc003wzy.2; human.
DR CTD; 9046; -.
DR DisGeNET; 9046; -.
DR GeneCards; DOK2; -.
DR HGNC; HGNC:2991; DOK2.
DR HPA; ENSG00000147443; Tissue enhanced (lung, lymphoid tissue).
DR MIM; 604997; gene.
DR neXtProt; NX_O60496; -.
DR OpenTargets; ENSG00000147443; -.
DR PharmGKB; PA27457; -.
DR VEuPathDB; HostDB:ENSG00000147443; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000159868; -.
DR HOGENOM; CLU_030101_2_0_1; -.
DR InParanoid; O60496; -.
DR OMA; RPDHIYD; -.
DR OrthoDB; 378139at2759; -.
DR PhylomeDB; O60496; -.
DR TreeFam; TF324994; -.
DR PathwayCommons; O60496; -.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; O60496; -.
DR SIGNOR; O60496; -.
DR BioGRID-ORCS; 9046; 5 hits in 1073 CRISPR screens.
DR ChiTaRS; DOK2; human.
DR EvolutionaryTrace; O60496; -.
DR GeneWiki; DOK2; -.
DR GenomeRNAi; 9046; -.
DR Pharos; O60496; Tbio.
DR PRO; PR:O60496; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O60496; protein.
DR Bgee; ENSG00000147443; Expressed in granulocyte and 139 other tissues.
DR ExpressionAtlas; O60496; baseline and differential.
DR Genevisible; O60496; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IEA:Ensembl.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd01203; PTB_DOK1_DOK2_DOK3; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR037751; Dok1/2/3_PTB.
DR InterPro; IPR002404; IRS_PTB.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR Pfam; PF02174; IRS; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00310; PTBI; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Host-virus interaction;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..412
FT /note="Docking protein 2"
FT /id="PRO_0000187270"
FT DOMAIN 4..114
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 147..252
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 246..296
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 359..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 254..290
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 271
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O70469"
FT MOD_RES 299
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:15592455, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 345
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O70469"
FT VARIANT 152
FT /note="A -> P (in dbSNP:rs1140295)"
FT /evidence="ECO:0000269|PubMed:9478921"
FT /id="VAR_030951"
FT VARIANT 274
FT /note="P -> L (in dbSNP:rs34215892)"
FT /id="VAR_053068"
FT VARIANT 394
FT /note="S -> A (in dbSNP:rs2242241)"
FT /id="VAR_030952"
FT CONFLICT 166
FT /note="L -> R (in Ref. 1; AAC13265)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="A -> S (in Ref. 1; AAC13265)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="E -> K (in Ref. 1; AAC13265)"
FT /evidence="ECO:0000305"
FT CONFLICT 374
FT /note="A -> R (in Ref. 1; AAC13265)"
FT /evidence="ECO:0000305"
FT STRAND 5..13
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 25..31
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:2D9W"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 82..90
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:2D9W"
FT HELIX 99..113
FT /evidence="ECO:0007829|PDB:2D9W"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:2DLW"
FT HELIX 159..164
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 168..174
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:2DLW"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:2DLW"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:2DLW"
FT HELIX 231..247
FT /evidence="ECO:0007829|PDB:2DLW"
SQ SEQUENCE 412 AA; 45379 MW; EFAEDBA68439757F CRC64;
MGDGAVKQGF LYLQQQQTFG KKWRRFGASL YGGSDCALAR LELQEGPEKP RRCEAARKVI
RLSDCLRVAE AGGEASSPRD TSAFFLETKE RLYLLAAPAA ERGDWVQAIC LLAFPGQRKE
LSGPEGKQSR PCMEENELYS SAVTVGPHKE FAVTMRPTEA SERCHLRGSY TLRAGESALE
LWGGPEPGTQ LYDWPYRFLR RFGRDKVTFS FEAGRRCVSG EGNFEFETRQ GNEIFLALEE
AISAQKNAAP ATPQPQPATI PASLPRPDSP YSRPHDSLPP PSPTTPVPAP RPRGQEGEYA
VPFDAVARSL GKNFRGILAV PPQLLADPLY DSIEETLPPR PDHIYDEPEG VAALSLYDSP
QEPRGEAWRR QATADRDPAG LQHVQPAGQD FSASGWQPGT EYDNVVLKKG PK
