DOK6_HUMAN
ID DOK6_HUMAN Reviewed; 331 AA.
AC Q6PKX4; A6NNG3; Q4V9S3; Q8WUZ8; Q96HI2; Q96LU2;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Docking protein 6;
DE AltName: Full=Downstream of tyrosine kinase 6;
GN Name=DOK6; Synonyms=DOK5L;
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], FUNCTION, INTERACTION WITH RET, PHOSPHORYLATION
RP AT TYROSINE RESIDUES, AND TISSUE SPECIFICITY.
RX PubMed=15286081; DOI=10.1074/jbc.m403726200;
RA Crowder R.J., Enomoto H., Yang M., Johnson E.M. Jr., Milbrandt J.;
RT "Dok-6, a novel p62 Dok family member, promotes Ret-mediated neurite
RT outgrowth.";
RL J. Biol. Chem. 279:42072-42081(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Eye, and Hippocampus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 33-331.
RC TISSUE=Cerebellum;
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).
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. DOK6 promotes Ret-mediated neurite
CC growth. May have a role in brain development and/or maintenance.
CC {ECO:0000269|PubMed:15286081}.
CC -!- SUBUNIT: Interacts via its PTB domain with phosphorylated RET.
CC {ECO:0000269|PubMed:15286081}.
CC -!- INTERACTION:
CC Q6PKX4; Q8NFV4-4: ABHD11; NbExp=3; IntAct=EBI-2880244, EBI-12318443;
CC Q6PKX4; Q03989: ARID5A; NbExp=3; IntAct=EBI-2880244, EBI-948603;
CC Q6PKX4; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-2880244, EBI-946029;
CC Q6PKX4; P26998: CRYBB3; NbExp=3; IntAct=EBI-2880244, EBI-1965681;
CC Q6PKX4; P00533: EGFR; NbExp=2; IntAct=EBI-2880244, EBI-297353;
CC Q6PKX4; Q9NVL1-2: FAM86C1P; NbExp=3; IntAct=EBI-2880244, EBI-12845222;
CC Q6PKX4; Q14847-2: LASP1; NbExp=3; IntAct=EBI-2880244, EBI-9088686;
CC Q6PKX4; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-2880244, EBI-10274069;
CC Q6PKX4; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-2880244, EBI-8487781;
CC Q6PKX4; Q16288: NTRK3; NbExp=3; IntAct=EBI-2880244, EBI-3936704;
CC Q6PKX4; Q93062: RBPMS; NbExp=3; IntAct=EBI-2880244, EBI-740322;
CC Q6PKX4; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-2880244, EBI-6257312;
CC Q6PKX4; Q6NXT4-4: SLC30A6; NbExp=3; IntAct=EBI-2880244, EBI-13046630;
CC Q6PKX4; Q96SF7: TBX15; NbExp=3; IntAct=EBI-2880244, EBI-10191361;
CC Q6PKX4; Q08117-2: TLE5; NbExp=3; IntAct=EBI-2880244, EBI-11741437;
CC Q6PKX4; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-2880244, EBI-11975223;
CC -!- TISSUE SPECIFICITY: Highly expressed in fetal and adult brain. Highly
CC expressed in the cerebellum. Weak expression in kidney, spinal cord and
CC testis. {ECO:0000269|PubMed:15286081}.
CC -!- DOMAIN: PTB domain mediates receptor interaction. {ECO:0000250}.
CC -!- PTM: On Ret activation, phosphorylated on one or more C-terminal
CC tyrosine residues by an Src family kinase.
CC {ECO:0000269|PubMed:15286081}.
CC -!- SIMILARITY: Belongs to the DOK family. Type B subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB71577.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY599248; AAT09770.1; -; mRNA.
DR EMBL; AC026585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471117; EAW66514.1; -; Genomic_DNA.
DR EMBL; BC008583; AAH08583.3; -; mRNA.
DR EMBL; BC019045; AAH19045.2; -; mRNA.
DR EMBL; BC096744; AAH96744.1; -; mRNA.
DR EMBL; AK057795; BAB71577.1; ALT_INIT; mRNA.
DR CCDS; CCDS32841.1; -.
DR RefSeq; NP_689934.2; NM_152721.5.
DR AlphaFoldDB; Q6PKX4; -.
DR SMR; Q6PKX4; -.
DR BioGRID; 128636; 23.
DR IntAct; Q6PKX4; 20.
DR MINT; Q6PKX4; -.
DR STRING; 9606.ENSP00000372160; -.
DR iPTMnet; Q6PKX4; -.
DR PhosphoSitePlus; Q6PKX4; -.
DR BioMuta; DOK6; -.
DR DMDM; 84029601; -.
DR MassIVE; Q6PKX4; -.
DR PaxDb; Q6PKX4; -.
DR PeptideAtlas; Q6PKX4; -.
DR PRIDE; Q6PKX4; -.
DR Antibodypedia; 23216; 178 antibodies from 26 providers.
DR DNASU; 220164; -.
DR Ensembl; ENST00000382713.10; ENSP00000372160.5; ENSG00000206052.11.
DR GeneID; 220164; -.
DR KEGG; hsa:220164; -.
DR MANE-Select; ENST00000382713.10; ENSP00000372160.5; NM_152721.6; NP_689934.2.
DR UCSC; uc002lkl.4; human.
DR CTD; 220164; -.
DR DisGeNET; 220164; -.
DR GeneCards; DOK6; -.
DR HGNC; HGNC:28301; DOK6.
DR HPA; ENSG00000206052; Tissue enhanced (brain, parathyroid gland, retina).
DR MIM; 611402; gene.
DR neXtProt; NX_Q6PKX4; -.
DR OpenTargets; ENSG00000206052; -.
DR PharmGKB; PA134866995; -.
DR VEuPathDB; HostDB:ENSG00000206052; -.
DR eggNOG; KOG4047; Eukaryota.
DR GeneTree; ENSGT00940000158760; -.
DR HOGENOM; CLU_057256_0_0_1; -.
DR InParanoid; Q6PKX4; -.
DR OMA; NIFRRCW; -.
DR OrthoDB; 1224728at2759; -.
DR PhylomeDB; Q6PKX4; -.
DR TreeFam; TF324994; -.
DR PathwayCommons; Q6PKX4; -.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q6PKX4; -.
DR SIGNOR; Q6PKX4; -.
DR BioGRID-ORCS; 220164; 6 hits in 1064 CRISPR screens.
DR ChiTaRS; DOK6; human.
DR GenomeRNAi; 220164; -.
DR Pharos; Q6PKX4; Tbio.
DR PRO; PR:Q6PKX4; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q6PKX4; protein.
DR Bgee; ENSG00000206052; Expressed in cortical plate and 152 other tissues.
DR ExpressionAtlas; Q6PKX4; baseline and differential.
DR Genevisible; Q6PKX4; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; 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 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 Phosphoprotein; Reference proteome.
FT CHAIN 1..331
FT /note="Docking protein 6"
FT /id="PRO_0000187279"
FT DOMAIN 8..112
FT /note="PH"
FT DOMAIN 132..237
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 293..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 263..273
FT /note="DKFBH motif"
FT CONFLICT 238
FT /note="M -> V (in Ref. 5; BAB71577)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 38318 MW; 0C5EF2BF247091C1 CRC64;
MASNFNDIVK QGYVKIRSRK LGIFRRCWLV FKKASSKGPR RLEKFPDEKA AYFRNFHKVT
ELHNIKNITR LPRETKKHAV AIIFHDETSK TFACESELEA EEWCKHLCME CLGTRLNDIS
LGEPDLLAAG VQREQNERFN VYLMPTPNLD IYGECTMQIT HENIYLWDIH NAKVKLVMWP
LSSLRRYGRD STWFTFESGR MCDTGEGLFT FQTREGEMIY QKVHSATLAI AEQHERLMLE
MEQKARLQTS LTEPMTLSKS ISLPRSAYWH HITRQNSVGE IYSLQGHGFG SSKMSRAQTF
PSYAPEQSEE AQQPLSRSSS YGFSYSSSLI Q