DOK3_MOUSE
ID DOK3_MOUSE Reviewed; 444 AA.
AC Q9QZK7;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Docking protein 3;
DE AltName: Full=Downstream of tyrosine kinase 3;
DE AltName: Full=p62(dok)-like protein;
DE Short=DOK-L;
GN Name=Dok3; Synonyms=Dokl;
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], INTERACTION WITH ABL1, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF ARG-209 AND ARG-224.
RC STRAIN=BALB/cJ;
RX PubMed=10567556; DOI=10.1128/mcb.19.12.8314;
RA Cong F., Yuan B., Goff S.P.;
RT "Characterization of a novel member of the DOK family that binds and
RT modulates Abl signaling.";
RL Mol. Cell. Biol. 19:8314-8325(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, PHOSPHORYLATION, AND
RP INTERACTION WITH CSK AND INPP5D.
RX PubMed=10733577; DOI=10.1128/mcb.20.8.2743-2754.2000;
RA Lemay S., Davidson D., Latour S., Veillette A.;
RT "Dok-3, a novel adapter molecule involved in the negative regulation of
RT immunoreceptor signaling.";
RL Mol. Cell. Biol. 20:2743-2754(2000).
RN [3]
RP INTERACTION WITH INPP5D, FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF
RP TYR-325; TYR-343; TYR-378 AND TYR-399.
RX PubMed=14993273; DOI=10.1128/mcb.24.6.2332-2343.2004;
RA Robson J.D., Davidson D., Veillette A.;
RT "Inhibition of the Jun N-terminal protein kinase pathway by SHIP-1, a lipid
RT phosphatase that interacts with the adaptor molecule Dok-3.";
RL Mol. Cell. Biol. 24:2332-2343(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND TYR-325, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-274; SER-308 AND SER-371, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. DOK3 is a negative regulator of JNK
CC signaling in B-cells through interaction with INPP5D/SHIP1. May
CC modulate ABL1 function. {ECO:0000269|PubMed:14993273}.
CC -!- SUBUNIT: On tyrosine phosphorylation, interacts with CSK and
CC INPP5D/SHIP1 via their SH2 domains. Both Tyr-325 and Tyr-343 are
CC required for interaction with INPP5D. Only Tyr-325 is required for
CC interaction with CSK. Binds ABL1 through the PTB domain and in a
CC kinase-dependent manner. Does not interact with RasGAP.
CC {ECO:0000269|PubMed:10567556, ECO:0000269|PubMed:10733577,
CC ECO:0000269|PubMed:14993273}.
CC -!- INTERACTION:
CC Q9QZK7; P03332: gag; Xeno; NbExp=3; IntAct=EBI-2906753, EBI-935477;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced.;
CC Name=1;
CC IsoId=Q9QZK7-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in bone marrow, spleen and
CC lung. Low levels in heart, brain, liver, muscle, thymus, kidney and
CC testis. Highly expressed in B-cells and macrophages.
CC {ECO:0000269|PubMed:10567556, ECO:0000269|PubMed:10733577}.
CC -!- DOMAIN: PTB domain mediates receptor interaction. {ECO:0000250}.
CC -!- PTM: Constitutively tyrosine-phosphorylated.
CC -!- PTM: On IL2 stimulation, phosphorylated on C-terminal tyrosine residues
CC possibly by Src kinases. Can also be phosphorylated by ABL1 kinase.
CC -!- MISCELLANEOUS: Overexpression of DOK3 inhibits the transforming
CC activity of v-ABL, the ABL oncogene.
CC -!- MISCELLANEOUS: [Isoform 1]: Major, and shortest isoform.
CC -!- SIMILARITY: Belongs to the DOK family. Type A subfamily. {ECO:0000305}.
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DR EMBL; AF179242; AAF14285.1; -; mRNA.
DR EMBL; AF237580; AAF61309.1; -; mRNA.
DR CCDS; CCDS26548.1; -. [Q9QZK7-1]
DR RefSeq; NP_038767.1; NM_013739.2. [Q9QZK7-1]
DR RefSeq; XP_017171013.1; XM_017315524.1. [Q9QZK7-1]
DR AlphaFoldDB; Q9QZK7; -.
DR SMR; Q9QZK7; -.
DR BioGRID; 205149; 7.
DR IntAct; Q9QZK7; 4.
DR MINT; Q9QZK7; -.
DR STRING; 10090.ENSMUSP00000046695; -.
DR iPTMnet; Q9QZK7; -.
DR PhosphoSitePlus; Q9QZK7; -.
DR jPOST; Q9QZK7; -.
DR MaxQB; Q9QZK7; -.
DR PaxDb; Q9QZK7; -.
DR PRIDE; Q9QZK7; -.
DR ProteomicsDB; 277370; -. [Q9QZK7-1]
DR Antibodypedia; 29319; 395 antibodies from 37 providers.
DR DNASU; 27261; -.
DR Ensembl; ENSMUST00000047877; ENSMUSP00000046695; ENSMUSG00000035711. [Q9QZK7-1]
DR Ensembl; ENSMUST00000223563; ENSMUSP00000153308; ENSMUSG00000035711. [Q9QZK7-1]
DR GeneID; 27261; -.
DR KEGG; mmu:27261; -.
DR UCSC; uc007qrm.1; mouse. [Q9QZK7-1]
DR CTD; 79930; -.
DR MGI; MGI:1351490; Dok3.
DR VEuPathDB; HostDB:ENSMUSG00000035711; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000161724; -.
DR HOGENOM; CLU_569310_0_0_1; -.
DR InParanoid; Q9QZK7; -.
DR OMA; YENLCML; -.
DR PhylomeDB; Q9QZK7; -.
DR TreeFam; TF324994; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 27261; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q9QZK7; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9QZK7; protein.
DR Bgee; ENSMUSG00000035711; Expressed in granulocyte and 122 other tissues.
DR ExpressionAtlas; Q9QZK7; baseline and differential.
DR Genevisible; Q9QZK7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:MGI.
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.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..444
FT /note="Docking protein 3"
FT /id="PRO_0000187273"
FT DOMAIN 7..123
FT /note="PH"
FT DOMAIN 157..261
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 278..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L591"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 308
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 325
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 209
FT /note="R->A: Greatly reduced ABL1-binding; reduced tyrosine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10567556"
FT MUTAGEN 224
FT /note="R->A: Greatly reduced ABL1-binding; reduced tyrosine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:10567556"
FT MUTAGEN 325
FT /note="Y->F: Enhanced reduction of BCR-induced IL2
FT secretion. No effect on interaction with INPP5D SH2 domain.
FT Abolishes interaction with CSK SH2 domain. No effect on
FT BCR-triggered tyrosine phosphorylation. Abolishes reduction
FT of BCR-induced IL2 secretion, the interaction with INPP5D
FT SH2 domain and BCR-triggered tyrosine phosphorylation; when
FT associated with F-343."
FT /evidence="ECO:0000269|PubMed:14993273"
FT MUTAGEN 343
FT /note="Y->F: Some reduction of BCR-induced IL2 secretion.
FT Some interaction with INPP5D SH2 domain. Some decrease in
FT BCR-triggered tyrosine phosphorylation. Abolishes reduction
FT of BCR-induced IL2 secretion, the interaction with INPP5D
FT SH2 domain and BCR-triggered tyrosine phosphorylation; when
FT associated with F-325."
FT /evidence="ECO:0000269|PubMed:14993273"
FT MUTAGEN 378
FT /note="Y->F: No effect on the reduction of BCR-induced IL2
FT secretion, nor on the interaction with the SH2 domain of
FT INPP5D or CSK nor on BCR-triggered tyrosine
FT phosphorylation; when associated with F-399."
FT /evidence="ECO:0000269|PubMed:14993273"
FT MUTAGEN 399
FT /note="Y->F: No effect on the reduction of BCR-induced IL2
FT secretion, nor on the interaction with the SH2 domain of
FT INPP5D or CSK nor on BCR-triggered tyrosine
FT phosphorylation; when associated with F-378."
FT /evidence="ECO:0000269|PubMed:14993273"
SQ SEQUENCE 444 AA; 48027 MW; 124B705712202D9B CRC64;
MESVEPPVKD GILYQQHVKF GKKCWRKVWA LLYAGGPSGV ARLESWDVRD GGLGPAGDRS
TGPSRRGERR VIRLADCVSV LPADGESCPR DTGAFLITTT ERSHLLAAQH RQSWVDPICQ
LAFPGTGECS SGSGQAESPK RGFVPMEENS IYSSWQEVTE FPVIVQRTEA TSRCQLKGPY
LLVLGQDDIQ LRETSKPQAC FSWPYRFLRK YGSDKGVFSF EAGRRCDSGE GLFAFSSPRA
PDICGVVAAA IARQRERLPE LAMSPPCPLP RALSLPSLEP PGELREVAPG FELPTPRKLP
LTDPGPQSLP LLLSPTQEGP ASGLYASVCK QTSKHTGTAE HLYENVCMLE ASPGLTNGGP
EAQEGPPGGR SPLGSPIYHN TEDLSWPGSA QDSNLEAQYR RLLELELDEA GSAGRSGAQA
GIKAKLVTLL TRERKKGPAP CDRP
