{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q8NF50","secondaryAccessions":["A2A350","A2BDF2","A4FU78","B7ZLP0","E9PH09","Q3MV16","Q5JPJ1","Q8TEP1","Q8WUY2","Q9BYJ5","Q9H1Q2","Q9H1Q3","Q9H308","Q9H7P2"],"uniProtkbId":"DOCK8_HUMAN","entryAudit":{"firstPublicDate":"2003-07-03","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-08-21","entryVersion":194,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Dedicator of cytokinesis protein 8"}}},"genes":[{"geneName":{"value":"DOCK8"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8C147"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22461490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25762780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Guanine nucleotide exchange factor (GEF) which specifically activates small GTPase CDC42 by exchanging bound GDP for free GTP (PubMed:22461490, PubMed:28028151). During immune responses, required for interstitial dendritic cell (DC) migration by locally activating CDC42 at the leading edge membrane of DC (By similarity). Required for CD4(+) T-cell migration in response to chemokine stimulation by promoting CDC42 activation at T cell leading edge membrane (PubMed:28028151). Is involved in NK cell cytotoxicity by controlling polarization of microtubule-organizing center (MTOC), and possibly regulating CCDC88B-mediated lytic granule transport to MTOC during cell killing (PubMed:25762780)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22461490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25762780"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Interacts (via DOCKER domain) with GTPase CDC42; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490, PubMed:28028151). The unphosphorylated form interacts (via DOCKER domain) with LRCH1 (via LRR repeats); the interaction prevents the association between DOCK8 and CDC42 (PubMed:28028151). Interacts with CCDC88B 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Translocates from the cytoplasm to the plasma membrane in response to chemokine CXCL12/SDF-1-alpha stimulation"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28028151"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cytoplasmic side","id":"SL-9910"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Cell projection, lamellipodium membrane","id":"SL-0292"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"28028151"}],"value":"Peripheral membrane protein","id":"SL-9903"},"orientation":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cytoplasmic side","id":"SL-9910"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q8NF50-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q8NF50-2"],"sequenceIds":["VSP_027373"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q8NF50-3"],"sequenceIds":["VSP_039838"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q8NF50-4"],"sequenceIds":["VSP_039838","VSP_027373"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"Expressed in peripheral blood mononuclear cells (PBMCs)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22461490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"The DOCKER domain is necessary and sufficient for the GEF activity"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28028151"}],"value":"In response to chemokine CXCL12/SDF-1-alpha stimulation, phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation from LRCH1"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Hyper-IgE syndrome 2, autosomal recessive, with recurrent infections","diseaseAccession":"DI-02809","acronym":"HIES2","description":"A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement.","diseaseCrossReference":{"database":"MIM","id":"243700"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19776401"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Intellectual developmental disorder, autosomal dominant 2","diseaseAccession":"DI-03185","acronym":"MRD2","description":"A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.","diseaseCrossReference":{"database":"MIM","id":"614113"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18060736"}]},"note":{"texts":[{"value":"The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration disrupting DOCK8 has been found in a patient with intellectual disability and ectodermal dysplasia. A balanced translocation, t(X;9) (q13.1;p24). A genomic deletion of approximately 230 kb in subtelomeric 9p has been detected in a patient with intellectual disability"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00983"}],"value":"Belongs to the DOCK family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAG42221.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"BAB84907.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"CAI46160.1","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":2099,"modifier":"EXACT"}},"description":"Dedicator of cytokinesis protein 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