DOCK8_HUMAN
ID DOCK8_HUMAN Reviewed; 2099 AA.
AC Q8NF50; A2A350; A2BDF2; A4FU78; B7ZLP0; E9PH09; Q3MV16; Q5JPJ1; Q8TEP1;
AC Q8WUY2; Q9BYJ5; Q9H1Q2; Q9H1Q3; Q9H308; Q9H7P2;
DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Dedicator of cytokinesis protein 8;
GN Name=DOCK8;
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), AND VARIANT THR-97.
RC TISSUE=Lung;
RA Takahashi K., Kohno T., Yokota J.;
RT "DOCK8, a candidate tumor suppressor gene.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 53-2099 (ISOFORM 2), AND VARIANT SER-413.
RC TISSUE=Brain, Muscle, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 53-2099 (ISOFORM 1).
RC TISSUE=Lymph node;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 301-2099 (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=12693554; DOI=10.1093/dnares/10.1.49;
RA Jikuya H., Takano J., Kikuno R., Hirosawa M., Nagase T., Nomura N.,
RA Ohara O.;
RT "Characterization of long cDNA clones from human adult spleen. II. The
RT complete sequences of 81 cDNA clones.";
RL DNA Res. 10:49-57(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 591-2099 (ISOFORM 1).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 920-2099 (ISOFORM 1).
RC TISSUE=Spleen;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1775-2099, AND VARIANT PRO-1970.
RX PubMed=10729223; DOI=10.1006/geno.2000.6121;
RA Ottolenghi C., Veitia R., Quintana-Murci L., Torchard D., Scapoli L.,
RA Souleyreau-Therville N., Beckmann J., Fellous M., McElreavey K.;
RT "The region on 9p associated with 46,XY sex reversal contains several
RT transcripts expressed in the urogenital system and a novel doublesex-
RT related domain.";
RL Genomics 64:170-178(2000).
RN [9]
RP NOMENCLATURE.
RX PubMed=12432077; DOI=10.1242/jcs.00219;
RA Cote J.-F., Vuori K.;
RT "Identification of an evolutionarily conserved superfamily of DOCK180-
RT related proteins with guanine nucleotide exchange activity.";
RL J. Cell Sci. 115:4901-4913(2002).
RN [10]
RP CHROMOSOMAL TRANSLOCATION, AND INVOLVEMENT IN MRD2.
RX PubMed=18060736; DOI=10.1016/j.ygeno.2007.10.011;
RA Griggs B.L., Ladd S., Saul R.A., DuPont B.R., Srivastava A.K.;
RT "Dedicator of cytokinesis 8 is disrupted in two patients with mental
RT retardation and developmental disabilities.";
RL Genomics 91:195-202(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP FUNCTION, INTERACTION WITH CDC42, AND DOMAIN.
RX PubMed=22461490; DOI=10.1182/blood-2012-01-407098;
RA Harada Y., Tanaka Y., Terasawa M., Pieczyk M., Habiro K., Katakai T.,
RA Hanawa-Suetsugu K., Kukimoto-Niino M., Nishizaki T., Shirouzu M., Duan X.,
RA Uruno T., Nishikimi A., Sanematsu F., Yokoyama S., Stein J.V., Kinashi T.,
RA Fukui Y.;
RT "DOCK8 is a Cdc42 activator critical for interstitial dendritic cell
RT migration during immune responses.";
RL Blood 119:4451-4461(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20; SER-139; SER-451;
RP SER-936; SER-1145 AND SER-2087, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [16]
RP FUNCTION, AND INTERACTION WITH CCDC88B.
RX PubMed=25762780; DOI=10.4049/jimmunol.1402897;
RA Ham H., Huynh W., Schoon R.A., Vale R.D., Billadeau D.D.;
RT "HkRP3 is a microtubule-binding protein regulating lytic granule clustering
RT and NK cell killing.";
RL J. Immunol. 194:3984-3996(2015).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP FUNCTION, INTERACTION WITH LRCH1 AND CDC42, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DOMAIN, PHOSPHORYLATION, AND MUTAGENESIS OF SER-2077; SER-2082
RP AND SER-2087.
RX PubMed=28028151; DOI=10.1084/jem.20160068;
RA Xu X., Han L., Zhao G., Xue S., Gao Y., Xiao J., Zhang S., Chen P.,
RA Wu Z.Y., Ding J., Hu R., Wei B., Wang H.;
RT "LRCH1 interferes with DOCK8-Cdc42-induced T cell migration and ameliorates
RT experimental autoimmune encephalomyelitis.";
RL J. Exp. Med. 214:209-226(2017).
RN [19]
RP VARIANT HIES2 ARG-473.
RX PubMed=19776401; DOI=10.1056/nejmoa0905506;
RA Zhang Q., Davis J.C., Lamborn I.T., Freeman A.F., Jing H., Favreau A.J.,
RA Matthews H.F., Davis J., Turner M.L., Uzel G., Holland S.M., Su H.C.;
RT "Combined immunodeficiency associated with DOCK8 mutations.";
RL N. Engl. J. Med. 361:2046-2055(2009).
RN [20]
RP VARIANT VAL-652.
RX PubMed=24169519; DOI=10.1038/ejhg.2013.243;
RA Piton A., Poquet H., Redin C., Masurel A., Lauer J., Muller J.,
RA Thevenon J., Herenger Y., Chancenotte S., Bonnet M., Pinoit J.M., Huet F.,
RA Thauvin-Robinet C., Jaeger A.S., Le Gras S., Jost B., Gerard B., Peoc'h K.,
RA Launay J.M., Faivre L., Mandel J.L.;
RT "20 ans apres: a second mutation in MAOA identified by targeted high-
RT throughput sequencing in a family with altered behavior and cognition.";
RL Eur. J. Hum. Genet. 22:776-783(2014).
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) which specifically
CC activates small GTPase CDC42 by exchanging bound GDP for free GTP
CC (PubMed:28028151, PubMed:22461490). During immune responses, required
CC for interstitial dendritic cell (DC) migration by locally activating
CC CDC42 at the leading edge membrane of DC (By similarity). Required for
CC CD4(+) T-cell migration in response to chemokine stimulation by
CC promoting CDC42 activation at T cell leading edge membrane
CC (PubMed:28028151). Is involved in NK cell cytotoxicity by controlling
CC polarization of microtubule-organizing center (MTOC), and possibly
CC regulating CCDC88B-mediated lytic granule transport to MTOC during cell
CC killing (PubMed:25762780). {ECO:0000250|UniProtKB:Q8C147,
CC ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:25762780,
CC ECO:0000269|PubMed:28028151}.
CC -!- SUBUNIT: Interacts (via DOCKER domain) with GTPase CDC42; the
CC interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490,
CC PubMed:28028151). The unphosphorylated form interacts (via DOCKER
CC domain) with LRCH1 (via LRR repeats); the interaction prevents the
CC association between DOCK8 and CDC42 (PubMed:28028151). Interacts with
CC CCDC88B (PubMed:25762780). {ECO:0000269|PubMed:22461490,
CC ECO:0000269|PubMed:25762780, ECO:0000269|PubMed:28028151}.
CC -!- INTERACTION:
CC Q8NF50; Q9Y2V2: CARHSP1; NbExp=3; IntAct=EBI-2548605, EBI-718719;
CC Q8NF50; Q6A162: KRT40; NbExp=3; IntAct=EBI-2548605, EBI-10171697;
CC Q8NF50; Q9Y2L9: LRCH1; NbExp=3; IntAct=EBI-2548605, EBI-2797324;
CC Q8NF50; Q5VUJ6: LRCH2; NbExp=4; IntAct=EBI-2548605, EBI-2659666;
CC Q8NF50; P50222: MEOX2; NbExp=3; IntAct=EBI-2548605, EBI-748397;
CC Q8NF50; Q99836: MYD88; NbExp=3; IntAct=EBI-2548605, EBI-447677;
CC Q8NF50; Q9BSJ6: PIMREG; NbExp=3; IntAct=EBI-2548605, EBI-2568609;
CC Q8NF50-2; Q13895: BYSL; NbExp=5; IntAct=EBI-10174653, EBI-358049;
CC Q8NF50-2; Q9Y2V2: CARHSP1; NbExp=3; IntAct=EBI-10174653, EBI-718719;
CC Q8NF50-2; O43633: CHMP2A; NbExp=3; IntAct=EBI-10174653, EBI-2692789;
CC Q8NF50-2; Q9NQT4: EXOSC5; NbExp=3; IntAct=EBI-10174653, EBI-371876;
CC Q8NF50-2; Q86V42: FAM124A; NbExp=3; IntAct=EBI-10174653, EBI-744506;
CC Q8NF50-2; Q3B820: FAM161A; NbExp=3; IntAct=EBI-10174653, EBI-719941;
CC Q8NF50-2; Q9NW38: FANCL; NbExp=3; IntAct=EBI-10174653, EBI-2339898;
CC Q8NF50-2; Q9NXK8: FBXL12; NbExp=3; IntAct=EBI-10174653, EBI-719790;
CC Q8NF50-2; P02008: HBZ; NbExp=3; IntAct=EBI-10174653, EBI-719843;
CC Q8NF50-2; Q9Y2L9: LRCH1; NbExp=5; IntAct=EBI-10174653, EBI-2797324;
CC Q8NF50-2; Q96II8: LRCH3; NbExp=3; IntAct=EBI-10174653, EBI-8795942;
CC Q8NF50-2; Q96HR3: MED30; NbExp=3; IntAct=EBI-10174653, EBI-394659;
CC Q8NF50-2; B2R894: MRPL38; NbExp=3; IntAct=EBI-10174653, EBI-7825143;
CC Q8NF50-2; Q14D33: RTP5; NbExp=3; IntAct=EBI-10174653, EBI-10217913;
CC Q8NF50-2; G3V1X1: ZFC3H1; NbExp=3; IntAct=EBI-10174653, EBI-6448783;
CC Q8NF50-2; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-10174653, EBI-745520;
CC Q8NF50-2; A8K900; NbExp=3; IntAct=EBI-10174653, EBI-10174650;
CC Q8NF50-3; O75427: LRCH4; NbExp=2; IntAct=EBI-25409271, EBI-718707;
CC Q8NF50-4; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-12021848, EBI-3866319;
CC Q8NF50-4; O75031: HSF2BP; NbExp=3; IntAct=EBI-12021848, EBI-7116203;
CC Q8NF50-4; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12021848, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28028151}. Cell
CC membrane {ECO:0000269|PubMed:28028151}; Peripheral membrane protein
CC {ECO:0000305|PubMed:28028151}; Cytoplasmic side {ECO:0000305}. Cell
CC projection, lamellipodium membrane {ECO:0000269|PubMed:28028151};
CC Peripheral membrane protein {ECO:0000305|PubMed:28028151}; Cytoplasmic
CC side {ECO:0000305}. Note=Enriched and co-localizes with GTPase CDC42 at
CC the immunological synapse formed during T cell/antigen presenting cell
CC cognate interaction. Translocates from the cytoplasm to the plasma
CC membrane in response to chemokine CXCL12/SDF-1-alpha stimulation.
CC {ECO:0000269|PubMed:28028151}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q8NF50-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8NF50-2; Sequence=VSP_027373;
CC Name=3;
CC IsoId=Q8NF50-3; Sequence=VSP_039838;
CC Name=4;
CC IsoId=Q8NF50-4; Sequence=VSP_039838, VSP_027373;
CC -!- TISSUE SPECIFICITY: Expressed in peripheral blood mononuclear cells
CC (PBMCs). {ECO:0000269|PubMed:28028151}.
CC -!- DOMAIN: The DOCKER domain is necessary and sufficient for the GEF
CC activity. {ECO:0000269|PubMed:22461490, ECO:0000269|PubMed:28028151}.
CC -!- PTM: In response to chemokine CXCL12/SDF-1-alpha stimulation,
CC phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation
CC from LRCH1. {ECO:0000269|PubMed:28028151}.
CC -!- DISEASE: Hyper-IgE recurrent infection syndrome 2, autosomal recessive
CC (HIES2) [MIM:243700]: A rare disorder characterized by
CC immunodeficiency, recurrent infections, eczema, increased serum IgE,
CC eosinophilia and lack of connective tissue and skeletal involvement.
CC {ECO:0000269|PubMed:19776401}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 2
CC (MRD2) [MIM:614113]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:18060736}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. A chromosomal aberration
CC disrupting DOCK8 has been found in a patient with intellectual
CC disability and ectodermal dysplasia. A balanced translocation, t(X;9)
CC (q13.1;p24). A genomic deletion of approximately 230 kb in subtelomeric
CC 9p has been detected in a patient with intellectual disability.
CC -!- SIMILARITY: Belongs to the DOCK family. {ECO:0000255|PROSITE-
CC ProRule:PRU00983}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG42221.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB84907.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAI46160.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB191037; BAE45254.1; -; mRNA.
DR EMBL; AL158832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161725; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019102; AAH19102.2; -; mRNA.
DR EMBL; BC112894; AAI12895.1; -; mRNA.
DR EMBL; BC130518; AAI30519.1; -; mRNA.
DR EMBL; BC143929; AAI43930.1; -; mRNA.
DR EMBL; AL583913; CAC29497.1; -; mRNA.
DR EMBL; AL832270; CAI46160.1; ALT_INIT; mRNA.
DR EMBL; AK090429; BAC03410.1; -; mRNA.
DR EMBL; AK074081; BAB84907.1; ALT_FRAME; mRNA.
DR EMBL; AK024436; BAB15726.1; -; mRNA.
DR EMBL; AF194407; AAG42221.1; ALT_FRAME; mRNA.
DR CCDS; CCDS55283.1; -. [Q8NF50-3]
DR CCDS; CCDS55284.1; -. [Q8NF50-4]
DR CCDS; CCDS6440.2; -. [Q8NF50-1]
DR RefSeq; NP_001177387.1; NM_001190458.1. [Q8NF50-4]
DR RefSeq; NP_001180465.1; NM_001193536.1. [Q8NF50-3]
DR RefSeq; NP_982272.2; NM_203447.3. [Q8NF50-1]
DR RefSeq; XP_011516347.1; XM_011518045.2. [Q8NF50-4]
DR RefSeq; XP_011516349.1; XM_011518047.2. [Q8NF50-3]
DR RefSeq; XP_011516350.1; XM_011518048.2. [Q8NF50-3]
DR RefSeq; XP_016870662.1; XM_017015173.1. [Q8NF50-3]
DR AlphaFoldDB; Q8NF50; -.
DR SMR; Q8NF50; -.
DR BioGRID; 123577; 120.
DR CORUM; Q8NF50; -.
DR IntAct; Q8NF50; 107.
DR MINT; Q8NF50; -.
DR STRING; 9606.ENSP00000394888; -.
DR GlyGen; Q8NF50; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8NF50; -.
DR PhosphoSitePlus; Q8NF50; -.
DR BioMuta; DOCK8; -.
DR DMDM; 158937439; -.
DR EPD; Q8NF50; -.
DR jPOST; Q8NF50; -.
DR MassIVE; Q8NF50; -.
DR MaxQB; Q8NF50; -.
DR PaxDb; Q8NF50; -.
DR PeptideAtlas; Q8NF50; -.
DR PRIDE; Q8NF50; -.
DR ProteomicsDB; 20435; -.
DR ProteomicsDB; 73260; -. [Q8NF50-1]
DR ProteomicsDB; 73261; -. [Q8NF50-2]
DR ProteomicsDB; 73262; -. [Q8NF50-3]
DR Antibodypedia; 758; 311 antibodies from 27 providers.
DR DNASU; 81704; -.
DR Ensembl; ENST00000432829.7; ENSP00000394888.3; ENSG00000107099.18. [Q8NF50-1]
DR Ensembl; ENST00000453981.5; ENSP00000408464.2; ENSG00000107099.18. [Q8NF50-3]
DR Ensembl; ENST00000469391.5; ENSP00000419438.1; ENSG00000107099.18. [Q8NF50-4]
DR GeneID; 81704; -.
DR KEGG; hsa:81704; -.
DR MANE-Select; ENST00000432829.7; ENSP00000394888.3; NM_203447.4; NP_982272.2.
DR UCSC; uc003zgf.2; human. [Q8NF50-1]
DR CTD; 81704; -.
DR DisGeNET; 81704; -.
DR GeneCards; DOCK8; -.
DR HGNC; HGNC:19191; DOCK8.
DR HPA; ENSG00000107099; Tissue enhanced (lymphoid).
DR MalaCards; DOCK8; -.
DR MIM; 243700; phenotype.
DR MIM; 611432; gene.
DR MIM; 614113; phenotype.
DR neXtProt; NX_Q8NF50; -.
DR OpenTargets; ENSG00000107099; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 217390; Combined immunodeficiency due to DOCK8 deficiency.
DR PharmGKB; PA134918866; -.
DR VEuPathDB; HostDB:ENSG00000107099; -.
DR eggNOG; KOG1997; Eukaryota.
DR GeneTree; ENSGT00940000155876; -.
DR HOGENOM; CLU_000624_0_0_1; -.
DR InParanoid; Q8NF50; -.
DR OMA; VIAGQTX; -.
DR OrthoDB; 20156at2759; -.
DR PhylomeDB; Q8NF50; -.
DR TreeFam; TF313629; -.
DR PathwayCommons; Q8NF50; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q8NF50; -.
DR SIGNOR; Q8NF50; -.
DR BioGRID-ORCS; 81704; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; DOCK8; human.
DR GeneWiki; Dock8; -.
DR GenomeRNAi; 81704; -.
DR Pharos; Q8NF50; Tbio.
DR PRO; PR:Q8NF50; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8NF50; protein.
DR Bgee; ENSG00000107099; Expressed in bone marrow cell and 166 other tissues.
DR ExpressionAtlas; Q8NF50; baseline and differential.
DR Genevisible; Q8NF50; HS.
DR GO; GO:0031252; C:cell leading edge; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031258; C:lamellipodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031256; C:leading edge membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:UniProtKB.
DR GO; GO:0036336; P:dendritic cell migration; IEA:Ensembl.
DR GO; GO:0001771; P:immunological synapse formation; IEA:Ensembl.
DR GO; GO:0061485; P:memory T cell proliferation; IMP:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:2000406; P:positive regulation of T cell migration; IMP:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd08696; C2_Dock-C; 1.
DR Gene3D; 1.20.58.740; -; 1.
DR Gene3D; 1.25.40.410; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR037808; C2_Dock-C.
DR InterPro; IPR027007; C2_DOCK-type_domain.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR026791; DOCK.
DR InterPro; IPR021816; DOCK_C/D_N.
DR InterPro; IPR043161; DOCK_C_lobe_A.
DR InterPro; IPR043162; DOCK_C_lobe_C.
DR InterPro; IPR027357; DOCKER_dom.
DR PANTHER; PTHR23317; PTHR23317; 1.
DR Pfam; PF06920; DHR-2; 1.
DR Pfam; PF14429; DOCK-C2; 1.
DR Pfam; PF11878; DUF3398; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS51650; C2_DOCK; 1.
DR PROSITE; PS51651; DOCKER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection;
KW Chromosomal rearrangement; Cytoplasm; Disease variant;
KW Guanine-nucleotide releasing factor; Intellectual disability; Membrane;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..2099
FT /note="Dedicator of cytokinesis protein 8"
FT /id="PRO_0000189997"
FT DOMAIN 560..729
FT /note="C2 DOCK-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00983"
FT DOMAIN 1632..2066
FT /note="DOCKER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00984"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 904
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C147"
FT MOD_RES 936
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C147"
FT MOD_RES 2087
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039838"
FT VAR_SEQ 927..958
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027373"
FT VARIANT 97
FT /note="P -> T (in dbSNP:rs529208)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_033888"
FT VARIANT 169
FT /note="E -> K (in dbSNP:rs11789099)"
FT /id="VAR_059972"
FT VARIANT 237
FT /note="E -> K (in dbSNP:rs11789099)"
FT /id="VAR_033889"
FT VARIANT 413
FT /note="N -> S (in dbSNP:rs10970979)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_033890"
FT VARIANT 473
FT /note="K -> R (in HIES2; dbSNP:rs112321280)"
FT /evidence="ECO:0000269|PubMed:19776401"
FT /id="VAR_063753"
FT VARIANT 597
FT /note="A -> V (in dbSNP:rs17673268)"
FT /id="VAR_033891"
FT VARIANT 652
FT /note="I -> V (in dbSNP:rs1381340726)"
FT /evidence="ECO:0000269|PubMed:24169519"
FT /id="VAR_071964"
FT VARIANT 1008
FT /note="R -> W (in dbSNP:rs16937932)"
FT /id="VAR_033892"
FT VARIANT 1970
FT /note="A -> P (in dbSNP:rs34908836)"
FT /evidence="ECO:0000269|PubMed:10729223"
FT /id="VAR_033893"
FT MUTAGEN 2077
FT /note="S->A: Abolishes phosphorylation. No migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation; when
FT associated with A-2082 and A-2087."
FT /evidence="ECO:0000269|PubMed:28028151"
FT MUTAGEN 2077
FT /note="S->E: Phosphomimetic mutant. Enhances migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation and
FT reduces interaction with LRCH1; when associated with E-2082
FT and E-2087."
FT /evidence="ECO:0000269|PubMed:28028151"
FT MUTAGEN 2082
FT /note="S->A: Abolishes phosphorylation. No migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation; when
FT associated with A-2077 and A-2087."
FT /evidence="ECO:0000269|PubMed:28028151"
FT MUTAGEN 2082
FT /note="S->E: Phosphomimetic mutant. Enhances migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation and
FT reduces interaction with LRCH1; when associated with E-2077
FT and E-2087."
FT /evidence="ECO:0000269|PubMed:28028151"
FT MUTAGEN 2087
FT /note="S->A: Abolishes phosphorylation. No migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation; when
FT associated with A-2077 and A-2082."
FT /evidence="ECO:0000269|PubMed:28028151"
FT MUTAGEN 2087
FT /note="S->E: Phosphomimetic mutant. Enhances migration in
FT response to chemokine CXCL12/SDF-1-alpha stimulation and
FT reduces interaction with LRCH1; when associated with E-2077
FT and E-2082."
FT /evidence="ECO:0000269|PubMed:28028151"
FT CONFLICT 22
FT /note="A -> V (in Ref. 1; BAE45254)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="S -> I (in Ref. 3; AAI30519/AAI43930)"
FT /evidence="ECO:0000305"
FT CONFLICT 600
FT /note="V -> VV (in Ref. 4; CAI46160)"
FT /evidence="ECO:0000305"
FT CONFLICT 1751
FT /note="V -> F (in Ref. 6; BAB84907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1755
FT /note="V -> F (in Ref. 6; BAB84907)"
FT /evidence="ECO:0000305"
FT CONFLICT 1927
FT /note="Y -> F (in Ref. 3; AAI30519/AAI43930)"
FT /evidence="ECO:0000305"
FT CONFLICT 2029
FT /note="E -> K (in Ref. 8; AAG42221)"
FT /evidence="ECO:0000305"
FT CONFLICT 2046
FT /note="L -> F (in Ref. 8; AAG42221)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2099 AA; 238529 MW; AF651C26E2D8E73E CRC64;
MATLPSAERR AFALKINRYS SAEIRKQFTL PPNLGQYHRQ SISTSGFPSL QLPQFYDPVE
PVDFEGLLMT HLNSLDVQLA QELGDFTDDD LDVVFTPKEC RTLQPSLPEE GVELDPHVRD
CVQTYIREWL IVNRKNQGSP EICGFKKTGS RKDFHKTLPK QTFESETLEC SEPAAQAGPR
HLNVLCDVSG KGPVTACDFD LRSLQPDKRL ENLLQQVSAE DFEKQNEEAR RTNRQAELFA
LYPSVDEEDA VEIRPVPECP KEHLGNRILV KLLTLKFEIE IEPLFASIAL YDVKERKKIS
ENFHCDLNSD QFKGFLRAHT PSVAASSQAR SAVFSVTYPS SDIYLVVKIE KVLQQGEIGD
CAEPYTVIKE SDGGKSKEKI EKLKLQAESF CQRLGKYRMP FAWAPISLSS FFNVSTLERE
VTDVDSVVGR SSVGERRTLA QSRRLSERAL SLEENGVGSN FKTSTLSVSS FFKQEGDRLS
DEDLFKFLAD YKRSSSLQRR VKSIPGLLRL EISTAPEIIN CCLTPEMLPV KPFPENRTRP
HKEILEFPTR EVYVPHTVYR NLLYVYPQRL NFVNKLASAR NITIKIQFMC GEDASNAMPV
IFGKSSGPEF LQEVYTAVTY HNKSPDFYEE VKIKLPAKLT VNHHLLFTFY HISCQQKQGA
SVETLLGYSW LPILLNERLQ TGSYCLPVAL EKLPPNYSMH SAEKVPLQNP PIKWAEGHKG
VFNIEVQAVS SVHTQDNHLE KFFTLCHSLE SQVTFPIRVL DQKISEMALE HELKLSIICL
NSSRLEPLVL FLHLVLDKLF QLSVQPMVIA GQTANFSQFA FESVVAIANS LHNSKDLSKD
QHGRNCLLAS YVHYVFRLPE VQRDVPKSGA PTALLDPRSY HTYGRTSAAA VSSKLLQARV
MSSSNPDLAG THSAADEEVK NIMSSKIADR NCSRMSYYCS GSSDAPSSPA APRPASKKHF
HEELALQMVV STGMVRETVF KYAWFFFELL VKSMAQHVHN MDKRDSFRRT RFSDRFMDDI
TTIVNVVTSE IAALLVKPQK ENEQAEKMNI SLAFFLYDLL SLMDRGFVFN LIRHYCSQLS
AKLSNLPTLI SMRLEFLRIL CSHEHYLNLN LFFMNADTAP TSPCPSISSQ NSSSCSSFQD
QKIASMFDLT SEYRQQHFLT GLLFTELAAA LDAEGEGISK VQRKAVSAIH SLLSSHDLDP
RCVKPEVKVK IAALYLPLVG IILDALPQLC DFTVADTRRY RTSGSDEEQE GAGAINQNVA
LAIAGNNFNL KTSGIVLSSL PYKQYNMLNA DTTRNLMICF LWIMKNADQS LIRKWIADLP
STQLNRILDL LFICVLCFEY KGKQSSDKVS TQVLQKSRDV KARLEEALLR GEGARGEMMR
RRAPGNDRFP GLNENLRWKK EQTHWRQANE KLDKTKAELD QEALISGNLA TEAHLIILDM
QENIIQASSA LDCKDSLLGG VLRVLVNSLN CDQSTTYLTH CFATLRALIA KFGDLLFEEE
VEQCFDLCHQ VLHHCSSSMD VTRSQACATL YLLMRFSFGA TSNFARVKMQ VTMSLASLVG
RAPDFNEEHL RRSLRTILAY SEEDTAMQMT PFPTQVEELL CNLNSILYDT VKMREFQEDP
EMLMDLMYRI AKSYQASPDL RLTWLQNMAE KHTKKKCYTE AAMCLVHAAA LVAEYLSMLE
DHSYLPVGSV SFQNISSNVL EESVVSEDTL SPDEDGVCAG QYFTESGLVG LLEQAAELFS
TGGLYETVNE VYKLVIPILE AHREFRKLTL THSKLQRAFD SIVNKDHKRM FGTYFRVGFF
GSKFGDLDEQ EFVYKEPAIT KLPEISHRLE AFYGQCFGAE FVEVIKDSTP VDKTKLDPNK
AYIQITFVEP YFDEYEMKDR VTYFEKNFNL RRFMYTTPFT LEGRPRGELH EQYRRNTVLT
TMHAFPYIKT RISVIQKEEF VLTPIEVAIE DMKKKTLQLA VAINQEPPDA KMLQMVLQGS
VGATVNQGPL EVAQVFLAEI PADPKLYRHH NKLRLCFKEF IMRCGEAVEK NKRLITADQR
EYQQELKKNY NKLKENLRPM IERKIPELYK PIFRVESQKR DSFHRSSFRK CETQLSQGS
