ID   DOK4_HUMAN              Reviewed;         326 AA.
AC   Q8TEW6; O75209; Q9BTP2; Q9NVV3;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 2.
DT   24-JAN-2024, entry version 151.
DE   RecName: Full=Docking protein 4;
DE   AltName: Full=Downstream of tyrosine kinase 4;
DE   AltName: Full=Insulin receptor substrate 5;
DE            Short=IRS-5;
DE            Short=IRS5;
GN   Name=DOK4;
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], AND TISSUE SPECIFICITY.
RC   TISSUE=T-cell;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND PHOSPHORYLATION AT
RP   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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA   Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA   Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA   Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA   Adams M.D.;
RT   "Genome duplications and other features in 12 Mb of DNA sequence from human
RT   chromosome 16p and 16q.";
RL   Genomics 60:295-308(1999).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon, and Pancreas;
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).
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. DOK4 functions in RET-mediated
CC       neurite outgrowth and plays a positive role in activation of the MAP
CC       kinase pathway (By similarity). Putative link with downstream effectors
CC       of RET in neuronal differentiation. May be involved in the regulation
CC       of the immune response induced by T-cells. {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with RET and TEK/TIE2. Interaction with RET is
CC       mediated through the PTB domain and requires phosphorylation of RET
CC       'Tyr-1062' (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q8TEW6; Q9BSQ5: CCM2; NbExp=3; IntAct=EBI-6918542, EBI-1573056;
CC       Q8TEW6; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-6918542, EBI-742054;
CC       Q8TEW6; Q7L591-3: DOK3; NbExp=3; IntAct=EBI-6918542, EBI-10694655;
CC       Q8TEW6; P04626: ERBB2; NbExp=2; IntAct=EBI-6918542, EBI-641062;
CC       Q8TEW6; Q0VD86: INCA1; NbExp=3; IntAct=EBI-6918542, EBI-6509505;
CC       Q8TEW6; P35372: OPRM1; NbExp=4; IntAct=EBI-6918542, EBI-2624570;
CC       Q8TEW6; Q06710: PAX8; NbExp=3; IntAct=EBI-6918542, EBI-2683132;
CC       Q8TEW6; Q99471: PFDN5; NbExp=3; IntAct=EBI-6918542, EBI-357275;
CC   -!- TISSUE SPECIFICITY: Widely expressed. High expression in skeletal
CC       muscle, heart, kidney and liver. Weaker expression in spleen, lung and
CC       small intestine, brain, heart and. Expressed in both resting and
CC       activated peripheral blood T-cells. {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       or RET stimulation. {ECO:0000269|PubMed:12730241}.
CC   -!- SIMILARITY: Belongs to the DOK family. Type B subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC24310.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AF466369; AAL74195.1; -; mRNA.
DR   EMBL; AK001350; BAA91642.1; -; mRNA.
DR   EMBL; AC004382; AAC24310.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BC001540; AAH01540.1; -; mRNA.
DR   EMBL; BC003541; AAH03541.1; -; mRNA.
DR   CCDS; CCDS10783.1; -.
DR   RefSeq; NP_060580.2; NM_018110.3.
DR   RefSeq; XP_005256100.1; XM_005256043.2.
DR   AlphaFoldDB; Q8TEW6; -.
DR   SMR; Q8TEW6; -.
DR   BioGRID; 120837; 74.
DR   IntAct; Q8TEW6; 34.
DR   MINT; Q8TEW6; -.
DR   STRING; 9606.ENSP00000455566; -.
DR   iPTMnet; Q8TEW6; -.
DR   PhosphoSitePlus; Q8TEW6; -.
DR   SwissPalm; Q8TEW6; -.
DR   BioMuta; DOK4; -.
DR   DMDM; 84029600; -.
DR   MassIVE; Q8TEW6; -.
DR   PaxDb; 9606-ENSP00000344277; -.
DR   PeptideAtlas; Q8TEW6; -.
DR   ProteomicsDB; 74516; -.
DR   Antibodypedia; 28881; 270 antibodies from 29 providers.
DR   DNASU; 55715; -.
DR   Ensembl; ENST00000340099.10; ENSP00000344277.4; ENSG00000125170.11.
DR   Ensembl; ENST00000569548.5; ENSP00000455128.1; ENSG00000125170.11.
DR   GeneID; 55715; -.
DR   KEGG; hsa:55715; -.
DR   MANE-Select; ENST00000340099.10; ENSP00000344277.4; NM_018110.5; NP_060580.2.
DR   UCSC; uc002elv.5; human.
DR   AGR; HGNC:19868; -.
DR   CTD; 55715; -.
DR   DisGeNET; 55715; -.
DR   GeneCards; DOK4; -.
DR   HGNC; HGNC:19868; DOK4.
DR   HPA; ENSG00000125170; Low tissue specificity.
DR   MIM; 608333; gene.
DR   neXtProt; NX_Q8TEW6; -.
DR   OpenTargets; ENSG00000125170; -.
DR   PharmGKB; PA134892921; -.
DR   VEuPathDB; HostDB:ENSG00000125170; -.
DR   eggNOG; KOG4047; Eukaryota.
DR   GeneTree; ENSGT00940000160143; -.
DR   HOGENOM; CLU_057256_1_0_1; -.
DR   InParanoid; Q8TEW6; -.
DR   OMA; KMLSIEC; -.
DR   OrthoDB; 2996885at2759; -.
DR   PhylomeDB; Q8TEW6; -.
DR   TreeFam; TF324994; -.
DR   PathwayCommons; Q8TEW6; -.
DR   Reactome; R-HSA-8853659; RET signaling.
DR   SignaLink; Q8TEW6; -.
DR   SIGNOR; Q8TEW6; -.
DR   BioGRID-ORCS; 55715; 7 hits in 1152 CRISPR screens.
DR   ChiTaRS; DOK4; human.
DR   GeneWiki; DOK4; -.
DR   GenomeRNAi; 55715; -.
DR   Pharos; Q8TEW6; Tbio.
DR   PRO; PR:Q8TEW6; -.
DR   Proteomes; UP000005640; Chromosome 16.
DR   RNAct; Q8TEW6; Protein.
DR   Bgee; ENSG00000125170; Expressed in mucosa of transverse colon and 178 other cell types or tissues.
DR   ExpressionAtlas; Q8TEW6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0007399; P:nervous system development; 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: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:SF44; DOCKING PROTEIN 4; 1.
DR   PANTHER; PTHR21258; DOCKING PROTEIN RELATED; 1.
DR   Pfam; PF02174; IRS; 1.
DR   Pfam; PF00169; PH; 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; Q8TEW6; HS.
PE   1: Evidence at protein level;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..326
FT                   /note="Docking protein 4"
FT                   /id="PRO_0000187274"
FT   DOMAIN          7..112
FT                   /note="PH"
FT   DOMAIN          132..237
FT                   /note="IRS-type PTB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT   MOTIF           265..275
FT                   /note="DKFBH motif"
FT   CONFLICT        64
FT                   /note="N -> S (in Ref. 2; no nucleotide entry and 3;
FT                   BAA91642)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        75
FT                   /note="T -> A (in Ref. 1; AAL74195)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   326 AA;  37028 MW;  1595B0CEC5584816 CRC64;
     MATNFSDIVK QGYVKMKSRK LGIYRRCWLV FRKSSSKGPQ RLEKYPDEKS VCLRGCPKVT
     EISNVKCVTR LPKETKRQAV AIIFTDDSAR TFTCDSELEA EEWYKTLSVE CLGSRLNDIS
     LGEPDLLAPG VQCEQTDRFN VFLLPCPNLD VYGECKLQIT HENIYLWDIH NPRVKLVSWP
     LCSLRRYGRD ATRFTFEAGR MCDAGEGLYT FQTQEGEQIY QRVHSATLAI AEQHKRVLLE
     MEKNVRLLNK GTEHYSYPCT PTTMLPRSAY WHHITGSQNI AEASSYAGEG YGAAQASSET
     DLLNRFILLK PKPSQGDSSE AKTPSQ
//