DOCK8
Domain
The DOCKER domain is necessary and sufficient for the GEF activity.
Function
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).
Involvement in disease
Hyper-IgE syndrome 2, autosomal recessive, with recurrent infections
HIES2
A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement.
None
The disease is caused by variants affecting the gene represented in this entry.
Intellectual developmental disorder, autosomal dominant 2
MRD2
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
None
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.
Post-translational modifications
In response to chemokine CXCL12/SDF-1-alpha stimulation, phosphorylated by PRKCA/PKC-alpha which promotes DOCK8 dissociation from LRCH1.
Sequence Similarities
Belongs to the DOCK family.
Tissue Specificity
Expressed in peripheral blood mononuclear cells (PBMCs).
Cellular localization
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cell projection
- Lamellipodium membrane
- Peripheral membrane protein
- Cytoplasmic side
- Enriched and co-localizes with GTPase CDC42 at the immunological synapse formed during T cell/antigen presenting cell cognate interaction. Translocates from the cytoplasm to the plasma membrane in response to chemokine CXCL12/SDF-1-alpha stimulation.
Alternative names
Dedicator of cytokinesis protein 8, DOCK8