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   24-JAN-2024, entry version 180.
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; 9606-ENSP00000262593; -.
DR   PeptideAtlas; Q9P104; -.
DR   ProteomicsDB; 83627; -. [Q9P104-1]
DR   ProteomicsDB; 83628; -. [Q9P104-2]
DR   Antibodypedia; 28805; 437 antibodies from 34 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   AGR; HGNC:16173; -.
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; MECIGTR; -.
DR   OrthoDB; 2996885at2759; -.
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 1135 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 174 other cell types or tissues.
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:0007265; P:Ras protein signal transduction; 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   CDD; cd13164; PTB_DOK4_DOK5_DOK6; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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   PANTHER; PTHR21258:SF45; DOCKING PROTEIN 5; 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   Genevisible; Q9P104; HS.
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
//