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   27-MAR-2024, entry version 187.
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; 112.
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; 9606-ENSP00000276420; -.
DR   PeptideAtlas; O60496; -.
DR   ProteomicsDB; 49433; -.
DR   Antibodypedia; 3823; 822 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   AGR; HGNC:2991; -.
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; YDSIEDH; -.
DR   OrthoDB; 2996885at2759; -.
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; 8 hits in 1151 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 140 other cell types or tissues.
DR   ExpressionAtlas; O60496; baseline and differential.
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:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
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; cd14676; PH_DOK1_2_3; 1.
DR   CDD; cd01203; PTB_DOK1_DOK2_DOK3; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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   PANTHER; PTHR21258:SF14; DOCKING PROTEIN 2; 1.
DR   PANTHER; PTHR21258; DOCKING PROTEIN RELATED; 1.
DR   Pfam; PF02174; IRS; 1.
DR   SMART; SM01244; IRS; 1.
DR   SMART; SM00233; PH; 1.
DR   SMART; SM00310; PTBI; 1.
DR   SUPFAM; SSF50729; PH domain-like; 2.
DR   PROSITE; PS51064; IRS_PTB; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   Genevisible; O60496; HS.
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
//