Dedicator of cytokinesis protein 6

Dedicator of cytokinesis protein 6 (Dock6), also known as Zir1 is a large (~200 kDa) protein encoded in the human by the DOCK6 gene, involved in intracellular signalling networks.^[5] It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G-proteins.

DOCK6
Identifiers
Aliases	DOCK6, AOS2, ZIR1, Dock6, dedicator of cytokinesis 6
External IDs	OMIM: 614194; MGI: 1914789; HomoloGene: 83291; GeneCards: DOCK6; OMA:DOCK6 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 11,199,295 bp[1] End 11,262,524 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A3 Start 21,711,156 bp[2] End 21,763,931 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in epithelium of colon right lung apex of heart upper lobe of left lung left lobe of thyroid gland right lobe of thyroid gland skin of leg skin of abdomen subcutaneous adipose tissue gastric mucosa Top expressed in interventricular septum tail of embryo lip ascending aorta left lung semi-lunar valve aortic valve left lung lobe internal carotid artery muscle of thigh More reference expression data BioGPS n/a
Gene ontology Molecular function guanyl-nucleotide exchange factor activity Cellular component perinuclear region of cytoplasm cytoplasm cytosol Biological process small GTPase mediated signal transduction blood coagulation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57572 319899 Ensembl ENSG00000130158 ENSMUSG00000032198 UniProt Q96HP0 Q8VDR9 RefSeq (mRNA) NM_020812 NM_001367830 NM_177030 RefSeq (protein) NP_065863 NP_001354759 NP_796004 Location (UCSC) Chr 19: 11.2 – 11.26 Mb Chr 9: 21.71 – 21.76 Mb PubMed search [3] [4]
Wikidata
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Discovery

Dock6 was identified as one of a family of proteins which share high sequence similarity with Dock180, the archetypal member of the DOCK family.^[6] It has a similar domain arrangement to other DOCK proteins,^[7] with a DHR1 domain known in other proteins to bind phospholipids,^[8] and a DHR2 domain containing the GEF activity.^[9]

Function

There is currently very little information about the cellular role of this protein. However, Dock6 has been reported to exhibit dual GEF specificity towards the small G proteins Rac1 and Cdc42.^[10] It is the only DOCK family member reported to activate both of these G proteins. The same study also showed that transfection of the Dock6 DHR2 domain into N1E-115 neuroblastoma cells promoted Rac- and Cdc42-dependent neurite outgrowth, although the physiological significance of this has yet to be demonstrated.