DOK3_HUMAN
ID DOK3_HUMAN Reviewed; 496 AA.
AC Q7L591; E9PAT0; H7BXS0; Q8N864; Q9BQB3; Q9H666;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Docking protein 3;
DE AltName: Full=Downstream of tyrosine kinase 3;
GN Name=DOK3;
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] (ISOFORMS 1 AND 4).
RC TISSUE=Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=B-cell, and Lymph;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=12595900; DOI=10.1038/sj.gene.6363891;
RA Favre C., Gerard A., Clauzier E., Pontarotti P., Olive D., Nunes J.A.;
RT "DOK4 and DOK5: new Dok-related genes expressed in human T cells.";
RL Genes Immun. 4:40-45(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-194 AND SER-330, AND
RP 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 [8]
RP IDENTIFICATION BY 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).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: On tyrosine phosphorylation, interacts with CSK and
CC INPP5D/SHIP1 via their SH2 domains. Both Tyr-381 and Tyr-398 are
CC required for interaction with INPP5D. Only Tyr-381 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 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q7L591; Q93062: RBPMS; NbExp=3; IntAct=EBI-2834978, EBI-740322;
CC Q7L591; Q13077: TRAF1; NbExp=4; IntAct=EBI-2834978, EBI-359224;
CC Q7L591; Q07883: GRB2; Xeno; NbExp=3; IntAct=EBI-2834978, EBI-7061573;
CC Q7L591-3; Q9NQ94: A1CF; NbExp=3; IntAct=EBI-10694655, EBI-2809489;
CC Q7L591-3; Q49AR9: ANKS1A; NbExp=3; IntAct=EBI-10694655, EBI-11954519;
CC Q7L591-3; P10606: COX5B; NbExp=3; IntAct=EBI-10694655, EBI-1053725;
CC Q7L591-3; Q8TEW6: DOK4; NbExp=3; IntAct=EBI-10694655, EBI-6918542;
CC Q7L591-3; Q86UW9: DTX2; NbExp=3; IntAct=EBI-10694655, EBI-740376;
CC Q7L591-3; O75603: GCM2; NbExp=3; IntAct=EBI-10694655, EBI-10188645;
CC Q7L591-3; P49639: HOXA1; NbExp=3; IntAct=EBI-10694655, EBI-740785;
CC Q7L591-3; P04792: HSPB1; NbExp=3; IntAct=EBI-10694655, EBI-352682;
CC Q7L591-3; O60333-2: KIF1B; NbExp=3; IntAct=EBI-10694655, EBI-10975473;
CC Q7L591-3; Q99750: MDFI; NbExp=3; IntAct=EBI-10694655, EBI-724076;
CC Q7L591-3; Q9HB20: PLEKHA3; NbExp=3; IntAct=EBI-10694655, EBI-11079894;
CC Q7L591-3; O43447: PPIH; NbExp=5; IntAct=EBI-10694655, EBI-1055615;
CC Q7L591-3; O43741: PRKAB2; NbExp=3; IntAct=EBI-10694655, EBI-1053424;
CC Q7L591-3; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-10694655, EBI-396669;
CC Q7L591-3; Q92529: SHC3; NbExp=3; IntAct=EBI-10694655, EBI-79084;
CC Q7L591-3; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-10694655, EBI-11959123;
CC Q7L591-3; Q13077: TRAF1; NbExp=3; IntAct=EBI-10694655, EBI-359224;
CC Q7L591-3; O76024: WFS1; NbExp=3; IntAct=EBI-10694655, EBI-720609;
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=4;
CC Name=1;
CC IsoId=Q7L591-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7L591-2; Sequence=VSP_013713, VSP_013715, VSP_013716;
CC Name=3;
CC IsoId=Q7L591-3; Sequence=VSP_013712, VSP_013715, VSP_013716;
CC Name=4;
CC IsoId=Q7L591-4; Sequence=VSP_013712, VSP_013714, VSP_013715,
CC VSP_013716;
CC -!- TISSUE SPECIFICITY: Expressed in spleen. {ECO:0000269|PubMed:12595900}.
CC -!- DOMAIN: PTB domain mediates receptor interaction. {ECO:0000250}.
CC -!- PTM: Constitutively tyrosine-phosphorylated. {ECO:0000250}.
CC -!- PTM: On IL2 stimulation, phosphorylated on C-terminal tyrosine residues
CC possibly by Src kinases. Can also be phosphorylated by ABL1 kinase (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the DOK family. Type A subfamily. {ECO:0000305}.
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DR EMBL; AK026223; BAB15399.1; -; mRNA.
DR EMBL; AK097258; BAC04986.1; -; mRNA.
DR EMBL; AC145098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004564; AAH04564.2; -; mRNA.
DR EMBL; BC004867; AAH04867.1; -; mRNA.
DR CCDS; CCDS47349.1; -. [Q7L591-4]
DR CCDS; CCDS47350.1; -. [Q7L591-3]
DR RefSeq; NP_001138347.1; NM_001144875.1. [Q7L591-3]
DR RefSeq; NP_001138348.1; NM_001144876.1. [Q7L591-4]
DR RefSeq; NP_001295164.1; NM_001308235.1.
DR RefSeq; NP_001295165.1; NM_001308236.1.
DR RefSeq; NP_079148.2; NM_024872.2.
DR RefSeq; XP_005266044.1; XM_005265987.1.
DR AlphaFoldDB; Q7L591; -.
DR SMR; Q7L591; -.
DR BioGRID; 123005; 42.
DR IntAct; Q7L591; 60.
DR MINT; Q7L591; -.
DR STRING; 9606.ENSP00000349727; -.
DR iPTMnet; Q7L591; -.
DR PhosphoSitePlus; Q7L591; -.
DR BioMuta; DOK3; -.
DR DMDM; 84029599; -.
DR EPD; Q7L591; -.
DR jPOST; Q7L591; -.
DR MassIVE; Q7L591; -.
DR MaxQB; Q7L591; -.
DR PaxDb; Q7L591; -.
DR PeptideAtlas; Q7L591; -.
DR PRIDE; Q7L591; -.
DR ProteomicsDB; 19073; -.
DR ProteomicsDB; 43375; -.
DR ProteomicsDB; 68797; -. [Q7L591-1]
DR ProteomicsDB; 68798; -. [Q7L591-2]
DR ProteomicsDB; 68799; -. [Q7L591-3]
DR ProteomicsDB; 68800; -. [Q7L591-4]
DR Antibodypedia; 29319; 395 antibodies from 37 providers.
DR DNASU; 79930; -.
DR Ensembl; ENST00000312943.10; ENSP00000325174.6; ENSG00000146094.16. [Q7L591-3]
DR Ensembl; ENST00000377112.8; ENSP00000366316.4; ENSG00000146094.16. [Q7L591-4]
DR GeneID; 79930; -.
DR KEGG; hsa:79930; -.
DR UCSC; uc003mhi.5; human. [Q7L591-1]
DR CTD; 79930; -.
DR DisGeNET; 79930; -.
DR GeneCards; DOK3; -.
DR HGNC; HGNC:24583; DOK3.
DR HPA; ENSG00000146094; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 611435; gene.
DR neXtProt; NX_Q7L591; -.
DR OpenTargets; ENSG00000146094; -.
DR PharmGKB; PA128394725; -.
DR VEuPathDB; HostDB:ENSG00000146094; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000161724; -.
DR HOGENOM; CLU_030101_0_0_1; -.
DR InParanoid; Q7L591; -.
DR PhylomeDB; Q7L591; -.
DR TreeFam; TF324994; -.
DR PathwayCommons; Q7L591; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; Q7L591; -.
DR SIGNOR; Q7L591; -.
DR BioGRID-ORCS; 79930; 15 hits in 1075 CRISPR screens.
DR ChiTaRS; DOK3; human.
DR GeneWiki; DOK3; -.
DR GenomeRNAi; 79930; -.
DR Pharos; Q7L591; Tbio.
DR PRO; PR:Q7L591; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q7L591; protein.
DR Bgee; ENSG00000146094; Expressed in monocyte and 122 other tissues.
DR ExpressionAtlas; Q7L591; baseline and differential.
DR Genevisible; Q7L591; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0101003; C:ficolin-1-rich granule membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
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..496
FT /note="Docking protein 3"
FT /id="PRO_0000187272"
FT DOMAIN 63..179
FT /note="PH"
FT DOMAIN 213..317
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 18..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 408..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..446
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK7"
FT MOD_RES 381
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK7"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZK7"
FT VAR_SEQ 1..170
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013713"
FT VAR_SEQ 1..56
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013712"
FT VAR_SEQ 79..180
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013714"
FT VAR_SEQ 272..386
FT /note="GVFSFEAGRRCHSGEGLFAFSTPCAPDLCRAVAGAIARQRERLPELTRPQPC
FT PLPRATSLPSLDTPGELREMPPGPEPPTSRKMHLAEPGPQSLPLLLGPEPNDLASGLYA
FT SVCK -> ILLGTPGVSLLICKGERTDDVSGIILDESLLRAYSVPGAGGHSRVQDSLGP
FT VLREPTFQGERSFLKTSMLRSLLCSCSWRHPRSQPRTQASCLQGSDCPAPHRNSTSAAH
FT TLGTS (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013715"
FT VAR_SEQ 387..496
FT /note="Missing (in isoform 2, isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013716"
FT VARIANT 12
FT /note="R -> P (in dbSNP:rs3749728)"
FT /id="VAR_057525"
FT VARIANT 22
FT /note="G -> R (in dbSNP:rs41275297)"
FT /id="VAR_062002"
FT CONFLICT 267
FT /note="F -> L (in Ref. 1; BAB15399)"
FT /evidence="ECO:0000305"
FT CONFLICT Q7L591-2:188
FT /note="R -> C (in Ref. 2; AAH04867)"
FT /evidence="ECO:0000305"
FT CONFLICT Q7L591-3:302
FT /note="R -> C (in Ref. 3; AAH04564)"
FT /evidence="ECO:0000305"
FT CONFLICT Q7L591-4:200
FT /note="R -> C (in Ref. 1; BAC04986)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 496 AA; 53288 MW; 7E186B998F9F1E24 CRC64;
MTRGARLRSD ARAQLNQLSL DGGTGSGQKG KCEEFPSSLS SVSPGLEAAA LLLAVTMDPL
ETPIKDGILY QQHVKFGKKC WRKVWALLYA GGPSGVARLE SWEVRDGGLG AAGDRSAGPG
RRGERRVIRL ADCVSVLPAD GESCPRDTGA FLLTTTERSH LLAAQHRQAW MGPICQLAFP
GTGEASSGST DAQSPKRGLV PMEENSIYSS WQEVGEFPVV VQRTEAATRC QLKGPALLVL
GPDAIQLREA KGTQALYSWP YHFLRKFGSD KGVFSFEAGR RCHSGEGLFA FSTPCAPDLC
RAVAGAIARQ RERLPELTRP QPCPLPRATS LPSLDTPGEL REMPPGPEPP TSRKMHLAEP
GPQSLPLLLG PEPNDLASGL YASVCKRASG PPGNEHLYEN LCVLEASPTL HGGEPEPHEG
PGSRSPTTSP IYHNGQDLSW PGPANDSTLE AQYRRLLELD QVEGTGRPDP QAGFKAKLVT
LLSRERRKGP APCDRP
