Dedicator of cytokinesis protein 6

Protein found in humans

DOCK6
Identifiers
AliasesDOCK6, AOS2, ZIR1, Dock6, dedicator of cytokinesis 6
External IDsOMIM: 614194; MGI: 1914789; HomoloGene: 83291; GeneCards: DOCK6; OMA:DOCK6 - orthologs
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for DOCK6
Genomic location for DOCK6
Band19p13.2Start11,199,295 bp[1]
End11,262,524 bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]
Chromosome 9 (mouse)
Genomic location for DOCK6
Genomic location for DOCK6
Band9|9 A3Start21,711,156 bp[2]
End21,763,931 bp[2]
RNA expression pattern
Bgee
HumanMouse (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
SpeciesHumanMouse
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 MbChr 9: 21.71 – 21.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

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.

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130158 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032198 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez gene: DOCK6 dedicator of cytokinesis 6".
  6. ^ Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". J. Cell Sci. 115 (Pt 24): 4901–13. doi:10.1242/jcs.00219. PMID 12432077.
  7. ^ Meller N, Merlot S, Guda C (November 2005). "CZH proteins: a new family of Rho-GEFs". J. Cell Sci. 118 (Pt 21): 4937–46. doi:10.1242/jcs.02671. PMID 16254241.
  8. ^ Côté JF, Motoyama AB, Bush JA, Vuori K (August 2005). "A novel and evolutionarily conserved PtdIns(3,4,5)P3-binding domain is necessary for DOCK180 signaling". Nat. Cell Biol. 7 (8): 797–807. doi:10.1038/ncb1280. PMC 1352170. PMID 16025104.
  9. ^ Côté JF, Vuori K (2006). "In Vitro Guanine Nucleotide Exchange Activity of DHR-2/DOCKER/CZH2 Domains". Regulators and Effectors of Small GTPases: Rho Family. Methods in Enzymology. Vol. 406. pp. 41–57. doi:10.1016/S0076-6879(06)06004-6. ISBN 978-0-12-182811-0. PMID 16472648.
  10. ^ Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A (February 2007). "Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth". Exp. Cell Res. 313 (4): 791–804. doi:10.1016/j.yexcr.2006.11.017. PMID 17196961.

Further reading

  • Côté JF, Vuori K (2007). "GEF what? Dock180 and related proteins help Rac to polarize cells in new ways". Trends Cell Biol. 17 (8): 383–93. doi:10.1016/j.tcb.2007.05.001. PMC 2887429. PMID 17765544.
  • Kwofie MA, Skowronski J (2008). "Specific recognition of Rac2 and Cdc42 by DOCK2 and DOCK9 guanine nucleotide exchange factors". J. Biol. Chem. 283 (6): 3088–96. doi:10.1074/jbc.M705170200. PMID 18056264.
  • Katoh H, Negishi M (2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature. 424 (6947): 461–64. Bibcode:2003Natur.424..461K. doi:10.1038/nature01817. PMID 12879077. S2CID 4411133.


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