DOK2_MOUSE
ID DOK2_MOUSE Reviewed; 412 AA.
AC O70469; O70272; Q99KL1;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Docking protein 2;
DE AltName: Full=Dok-related protein;
DE Short=Dok-R;
DE AltName: Full=Downstream of tyrosine kinase 2;
DE AltName: Full=IL-four receptor-interacting protein;
DE Short=FRIP;
DE AltName: Full=p56(dok-2);
GN Name=Dok2; Synonyms=Frip;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION AT TYROSINE RESIDUES.
RX PubMed=9697832; DOI=10.1016/s1074-7613(00)80584-1;
RA Nelms K., Snow A.L., Hu-Li J., Paul W.E.;
RT "FRIP, a hematopoietic cell-specific rasGAP-interacting protein
RT phosphorylated in response to cytokine stimulation.";
RL Immunity 9:13-24(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9764820; DOI=10.1038/sj.onc.1202115;
RA Jones N., Dumont D.J.;
RT "The Tek/Tie2 receptor signals through a novel Dok-related docking protein,
RT Dok-R.";
RL Oncogene 17:1097-1108(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP INTERACTION WITH EGFR; NCK AND RASGAP, PHOSPHORYLATION AT TYR-276; TYR-304
RP AND TYR-351, AND MUTAGENESIS OF TYR-276; TYR-304 AND TYR-351.
RX PubMed=10508618; DOI=10.1016/s0960-9822(99)80458-8;
RA Jones N., Dumont D.J.;
RT "Recruitment of Dok-R to the EGF receptor through its PTB domain is
RT required for attenuation of Erk MAP kinase activation.";
RL Curr. Biol. 9:1057-1060(1999).
RN [6]
RP INTERACTION WITH RET, PHOSPHORYLATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11470823; DOI=10.1083/jcb.200102032;
RA Grimm J., Sachs M., Britsch S., Di Cesare S., Schwarz-Romond T.,
RA Alitalo K., Birchmeier W.;
RT "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret
RT receptor tyrosine kinase and mediate neuronal differentiation.";
RL J. Cell Biol. 154:345-354(2001).
RN [7]
RP INTERACTION WITH TEK/TIE2, AND PHOSPHORYLATION.
RX PubMed=12665569; DOI=10.1128/mcb.23.8.2658-2668.2003;
RA Jones N., Chen S.H., Sturk C., Master Z., Tran J., Kerbel R.S.,
RA Dumont D.J.;
RT "A unique autophosphorylation site on Tie2/Tek mediates Dok-R
RT phosphotyrosine binding domain binding and function.";
RL Mol. Cell. Biol. 23:2658-2668(2003).
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.
CC -!- SUBUNIT: Interacts with phosphorylated RASGAP and EGFR. Interacts with
CC RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine
CC phosphorylated). {ECO:0000269|PubMed:10508618,
CC ECO:0000269|PubMed:11470823, ECO:0000269|PubMed:12665569}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen and lung.
CC {ECO:0000269|PubMed:11470823, ECO:0000269|PubMed:9478921}.
CC -!- DEVELOPMENTAL STAGE: During embryonic liver development, expressed in
CC the islands of cells, consistent with an expression in hematopoietic
CC precursors. {ECO:0000269|PubMed:11470823}.
CC -!- DOMAIN: PTB domain mediates receptor interaction.
CC -!- PTM: On immunoreceptor stimulation, phosphorylated on C-terminal
CC tyrosine residues. Phosphorylation on Tyr-351 is required for binding
CC to the SH2 domain of NCK. Phosphorylation on both Tyr-276 and Tyr-304
CC is required for interaction with RASGAP. Phosphorylated on tyrosine
CC residues by TEK/TIE2. {ECO:0000269|PubMed:10508618,
CC ECO:0000269|PubMed:11470823, ECO:0000269|PubMed:12665569,
CC ECO:0000269|PubMed:9697832}.
CC -!- SIMILARITY: Belongs to the DOK family. Type A subfamily. {ECO:0000305}.
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DR EMBL; AF030627; AAC31315.1; -; mRNA.
DR EMBL; AF035117; AAC13266.1; -; mRNA.
DR EMBL; AF059583; AAC78606.1; -; mRNA.
DR EMBL; BC004590; AAH04590.1; -; mRNA.
DR CCDS; CCDS27262.1; -.
DR RefSeq; NP_034201.1; NM_010071.2.
DR AlphaFoldDB; O70469; -.
DR SMR; O70469; -.
DR BioGRID; 199268; 9.
DR IntAct; O70469; 10.
DR MINT; O70469; -.
DR STRING; 10090.ENSMUSP00000022698; -.
DR iPTMnet; O70469; -.
DR PhosphoSitePlus; O70469; -.
DR EPD; O70469; -.
DR jPOST; O70469; -.
DR PaxDb; O70469; -.
DR PeptideAtlas; O70469; -.
DR PRIDE; O70469; -.
DR ProteomicsDB; 277369; -.
DR Antibodypedia; 3823; 725 antibodies from 38 providers.
DR DNASU; 13449; -.
DR Ensembl; ENSMUST00000022698; ENSMUSP00000022698; ENSMUSG00000022102.
DR GeneID; 13449; -.
DR KEGG; mmu:13449; -.
DR UCSC; uc007uoy.1; mouse.
DR CTD; 9046; -.
DR MGI; MGI:1332623; Dok2.
DR VEuPathDB; HostDB:ENSMUSG00000022102; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000159868; -.
DR HOGENOM; CLU_030101_2_0_1; -.
DR InParanoid; O70469; -.
DR OMA; RPDHIYD; -.
DR OrthoDB; 378139at2759; -.
DR PhylomeDB; O70469; -.
DR TreeFam; TF324994; -.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-8853659; RET signaling.
DR BioGRID-ORCS; 13449; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Dok2; mouse.
DR PRO; PR:O70469; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; O70469; protein.
DR Bgee; ENSMUSG00000022102; Expressed in granulocyte and 117 other tissues.
DR ExpressionAtlas; O70469; baseline and differential.
DR Genevisible; O70469; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; IPI:MGI.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; TAS:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IPI:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IPI:MGI.
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 Pfam; PF00169; PH; 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 Phosphoprotein; Reference proteome.
FT CHAIN 1..412
FT /note="Docking protein 2"
FT /id="PRO_0000187271"
FT DOMAIN 7..117
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 149..254
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 250..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 322..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 366..412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..282
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 366..398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 276
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10508618"
FT MOD_RES 304
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10508618"
FT MOD_RES 351
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10508618"
FT MUTAGEN 276
FT /note="Y->F: No loss of binding to SH2 domain of RASGAP or
FT NCK. Complete loss of binding to SH2 domain of RASGAP; when
FT associated with F-304."
FT /evidence="ECO:0000269|PubMed:10508618"
FT MUTAGEN 304
FT /note="Y->F: No loss of binding to SH2 domain of RASGAP.
FT Complete loss of binding to SH2 domain of RASGAP; when
FT associated with F-276."
FT /evidence="ECO:0000269|PubMed:10508618"
FT MUTAGEN 351
FT /note="Y->F: No loss of binding to SH2 domain of RASGAP.
FT Complete loss of binding to SH2 domain of NCK."
FT /evidence="ECO:0000269|PubMed:10508618"
FT CONFLICT 245
FT /note="A -> T (in Ref. 4; AAH04590)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="L -> F (in Ref. 2; AAC13266)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="P -> T (in Ref. 2; AAC13266)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="Missing (in Ref. 4; AAH04590)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 45522 MW; 02AC02530DBED053 CRC64;
MVRMEEPAVK QGFLHLQQQQ TFGKKWRRFA AVLYGESGCA LARLELQDVP EKTRRGEATR
KVVRLSDCLR VAEVGSEASS PRDTSAFILE TKERLYLLAA PSAERSDWIQ AICLLAFPGQ
RKGSPGLEEK SGSPCMEENE LYSSSTTGLC KEYMVTIRPT EASERCRLRG SYTLRTGVSA
LELWGGPEPG TQLYDWPYRF LRRFGRDKAT FSFEAGRRCL SGEGNFEFET RHGNEIFQAL
EKVIAVQKNA TPSGPPSLPA TGPMMPTVLP RPESPYSRPH DSLPSPSPGT LVPGMRPGAP
EGEYAVPFDT VAHSLRKSFR GLLTGPPPHL PDPLYDSIQE DPGAPLPDHI YDEPEGVAAL
SLYDRTQRPS GETWREQATA DGGPSSLQQD SSVPDWPQAT EYDNVILKKG PK
