DOK5_HUMAN
ID DOK5_HUMAN Reviewed; 306 AA.
AC Q9P104; Q5T7Y0; Q5TE53; Q8TEW7; Q96H13; Q9BZ24; Q9NQF4; Q9Y411;
DT 06-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2002, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Docking protein 5;
DE AltName: Full=Downstream of tyrosine kinase 5;
DE AltName: Full=Insulin receptor substrate 6;
DE Short=IRS-6;
DE Short=IRS6;
GN Name=DOK5; Synonyms=C20orf180;
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] (ISOFORM 1).
RA Luo W.Q., Chen J.H., Huang X.W., Zhou Y., Zhou H.J., Hu S.N., Yuan J.G.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION AT TYROSINE RESIDUES.
RC TISSUE=Skeletal muscle;
RX PubMed=12730241; DOI=10.1074/jbc.m212430200;
RA Cai D., Dhe-Paganon S., Melendez P.A., Lee J., Shoelson S.E.;
RT "Two new substrates in insulin signaling, IRS5/DOK4 and IRS6/DOK5.";
RL J. Biol. Chem. 278:25323-25330(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-306 (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP CRYSTALLIZATION.
RX PubMed=12454490; DOI=10.1107/s090744490201644x;
RA Shi N., Zhou W., Tang K., Gao Y., Jin J., Gao F., Peng X., Bartlam M.,
RA Qiang B., Yuan J., Rao Z.;
RT "Expression, crystallization and preliminary X-ray studies of the
RT recombinant PTB domain of human dok-5 protein.";
RL Acta Crystallogr. D 58:2170-2172(2002).
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. DOK5 functions in RET-mediated
CC neurite outgrowth and plays a positive role in activation of the MAP
CC kinase pathway. Putative link with downstream effectors of RET in
CC neuronal differentiation.
CC -!- SUBUNIT: Interacts with phosphorylated RET. In contrast to other DOK
CC proteins, it does not interact with RASGAP (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q9P104-2; Q99471: PFDN5; NbExp=3; IntAct=EBI-10692909, EBI-357275;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9P104-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9P104-2; Sequence=VSP_003854;
CC -!- TISSUE SPECIFICITY: Highest expression in skeletal muscle, lower in
CC brain, heart and kidney. Also detected in activated peripheral blood T-
CC lymphocytes. {ECO:0000269|PubMed:12595900,
CC ECO:0000269|PubMed:12730241}.
CC -!- DOMAIN: PTB domain mediates receptor interaction. {ECO:0000250}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to insulin, IGF1
CC and GDNF. {ECO:0000269|PubMed:12730241}.
CC -!- SIMILARITY: Belongs to the DOK family. Type B subfamily. {ECO:0000305}.
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DR EMBL; AF132732; AAF66443.1; -; mRNA.
DR EMBL; AF466368; AAL74194.1; -; mRNA.
DR EMBL; AL118501; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008992; AAH08992.1; -; mRNA.
DR EMBL; AL050069; CAB43255.3; -; mRNA.
DR CCDS; CCDS13446.1; -. [Q9P104-1]
DR CCDS; CCDS13447.1; -. [Q9P104-2]
DR PIR; T08731; T08731.
DR RefSeq; NP_060901.2; NM_018431.4. [Q9P104-1]
DR RefSeq; NP_808874.1; NM_177959.2. [Q9P104-2]
DR RefSeq; XP_011527206.1; XM_011528904.1. [Q9P104-2]
DR PDB; 1J0W; X-ray; 2.50 A; A/B=133-232.
DR PDBsum; 1J0W; -.
DR AlphaFoldDB; Q9P104; -.
DR SMR; Q9P104; -.
DR BioGRID; 120926; 16.
DR IntAct; Q9P104; 15.
DR MINT; Q9P104; -.
DR STRING; 9606.ENSP00000262593; -.
DR iPTMnet; Q9P104; -.
DR PhosphoSitePlus; Q9P104; -.
DR BioMuta; DOK5; -.
DR DMDM; 26393190; -.
DR MassIVE; Q9P104; -.
DR PaxDb; Q9P104; -.
DR PeptideAtlas; Q9P104; -.
DR PRIDE; Q9P104; -.
DR ProteomicsDB; 83627; -. [Q9P104-1]
DR ProteomicsDB; 83628; -. [Q9P104-2]
DR Antibodypedia; 28805; 387 antibodies from 33 providers.
DR DNASU; 55816; -.
DR Ensembl; ENST00000262593.10; ENSP00000262593.5; ENSG00000101134.12. [Q9P104-1]
DR Ensembl; ENST00000395939.5; ENSP00000379270.1; ENSG00000101134.12. [Q9P104-2]
DR GeneID; 55816; -.
DR KEGG; hsa:55816; -.
DR MANE-Select; ENST00000262593.10; ENSP00000262593.5; NM_018431.5; NP_060901.2.
DR UCSC; uc002xwy.4; human. [Q9P104-1]
DR CTD; 55816; -.
DR DisGeNET; 55816; -.
DR GeneCards; DOK5; -.
DR HGNC; HGNC:16173; DOK5.
DR HPA; ENSG00000101134; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 608334; gene.
DR neXtProt; NX_Q9P104; -.
DR OpenTargets; ENSG00000101134; -.
DR PharmGKB; PA25724; -.
DR VEuPathDB; HostDB:ENSG00000101134; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000160725; -.
DR HOGENOM; CLU_057256_1_0_1; -.
DR InParanoid; Q9P104; -.
DR OMA; ITYECIC; -.
DR OrthoDB; 1224728at2759; -.
DR PhylomeDB; Q9P104; -.
DR TreeFam; TF324994; -.
DR PathwayCommons; Q9P104; -.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q9P104; -.
DR SIGNOR; Q9P104; -.
DR BioGRID-ORCS; 55816; 12 hits in 1063 CRISPR screens.
DR ChiTaRS; DOK5; human.
DR EvolutionaryTrace; Q9P104; -.
DR GeneWiki; DOK5; -.
DR GenomeRNAi; 55816; -.
DR Pharos; Q9P104; Tbio.
DR PRO; PR:Q9P104; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9P104; protein.
DR Bgee; ENSG00000101134; Expressed in ventricular zone and 172 other tissues.
DR Genevisible; Q9P104; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0051386; P:regulation of neurotrophin TRK receptor signaling pathway; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd14678; PH_DOK4_DOK5_DOK6; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR037816; DOK4/5/6_PH.
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 3D-structure; Alternative splicing; Phosphoprotein; Reference proteome.
FT CHAIN 1..306
FT /note="Docking protein 5"
FT /id="PRO_0000187277"
FT DOMAIN 8..112
FT /note="PH"
FT DOMAIN 132..237
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT MOTIF 263..273
FT /note="DKFBH motif"
FT VAR_SEQ 1..108
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_003854"
FT CONFLICT 225..234
FT /note="SAALAIAEQH -> LLQMKMSERA (in Ref. 1; AAF66443)"
FT /evidence="ECO:0000305"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 161..171
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 174..180
FT /evidence="ECO:0007829|PDB:1J0W"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:1J0W"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:1J0W"
FT HELIX 216..229
FT /evidence="ECO:0007829|PDB:1J0W"
SQ SEQUENCE 306 AA; 35464 MW; 2F259529E8B068DB CRC64;
MASNFNDIVK QGYVRIRSRR LGIYQRCWLV FKKASSKGPK RLEKFSDERA AYFRCYHKVT
ELNNVKNVAR LPKSTKKHAI GIYFNDDTSK TFACESDLEA DEWCKVLQME CVGTRINDIS
LGEPDLLATG VEREQSERFN VYLMPSPNLD VHGECALQIT YEYICLWDVQ NPRVKLISWP
LSALRRYGRD TTWFTFEAGR MCETGEGLFI FQTRDGEAIY QKVHSAALAI AEQHERLLQS
VKNSMLQMKM SERAASLSTM VPLPRSAYWQ HITRQHSTGQ LYRLQDVSSP LKLHRTETFP
AYRSEH
