Dock11

Last updated
DOCK11
Identifiers
Aliases DOCK11 , ACG, ZIZ2, bB128O4.1, Dock11, dedicator of cytokinesis 11
External IDs OMIM: 300681 MGI: 1923224 HomoloGene: 70950 GeneCards: DOCK11
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_144658

NM_001009947
NM_177745

RefSeq (protein)

NP_653259

NP_001009947

Location (UCSC) Chr X: 118.5 – 118.69 Mb Chr X: 35.15 – 35.34 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa) protein involved in intracellular signalling networks. [5] [6] It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock11 activates the small G protein Cdc42.

Contents

Discovery

Dock11 was identified as a protein which is highly expressed in Germinal center B lymphocytes. [7] Subsequent RT-PCR analysis revealed expression of this protein in the spleen, thymus, bone marrow and in peripheral blood lymphocytes. Dock11 is expressed at lower levels in NIH-3T3 fibroblasts, C2C12 myoblasts and Neuro-2A neuroblastoma cells. Dock11 mRNA has also been detected in the pars intermedia. [8]

Structure and function

Dock11 exhibits the same domain arrangement as other members of the DOCK-D/Zizimin subfamily and shares the highest level of sequence identity with Dock9. [7] It contains a DHR2 domain which mediates GEF activity and a DHR1 domain which may interact with membrane phospholipids. It also contains an N-terminal PH domain which may be involved in its recruitment to the plasma membrane. Dock11 binds and activates nucleotide-free Cdc42 via its DHR2 domain [7] and has also been reported to mediate positive feedback on active, GTP-bound Cdc42, [9] although this interaction required a small N-terminal region of Dock11 in addition to the DHR2 domain. Cdc42 in turn regulates signaling pathways that control diverse cellular functions including morphology, migration, endocytosis and cell cycle progression. [10] Gene expression studies have suggested that Dock11 may have a role in the development of pituitary and testicular tumours. [8] [11]

Related Research Articles

Guanine nucleotide exchange factor Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

FGD1 Protein-coding gene in the species Homo sapiens

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

RhoGEF domain

RhoGEF domain describes two distinct structural domains with guanine nucleotide exchange factor (GEF) activity to regulate small GTPases in the Rho family. Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF domains in proteins are able to promote GDP release and GTP binding to activate specific Rho family members, including RhoA, Rac1 and Cdc42.

ARHGEF7 Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">ARHGEF6</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene.

Dock180

Dock180, also known as DOCK1, is a large protein involved in intracellular signalling networks. It is the mammalian ortholog of the C. elegans protein CED-5 and belongs to the DOCK family of Guanine nucleotide exchange factors (GEFs).

RhoG

RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.

Dock2

Dock2, also known as DOCK2, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac.

Dock7

Dock7, also known as Zir2, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock7 activates isoforms of the small G protein Rac.

Dedicator of cytokinesis protein 10 Protein-coding gene in the species Homo sapiens

Dedicator of cytokinesis protein 10 (Dock10), also known as Zizimin3, is a large protein involved in intracellular signalling networks that in humans is encoded by the DOCK10 gene. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors, which function as activators of small G proteins.

Dock4 Protein-coding gene in the species Homo sapiens

Dock4, also known as DOCK4, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock4 activates the small G proteins Rac and Rap1.

Dock8 Protein-coding gene in the species Homo sapiens

DOCK8, also known as Zir3, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins.

Dock3

Dock3, also known as MOCA and PBP, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-B subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock3 specifically activates the small G protein Rac.

Dock9

Dock9, also known as Zizimin1, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-D subfamily of the DOCK family of guanine nucleotide exchange factors that function as activators of small G proteins. Dock9 activates the small G protein Cdc42.

DOCK is a family of related proteins involved in intracellular signalling networks. DOCK family members contain a RhoGEF domain to function as guanine nucleotide exchange factors to promote GDP release and GTP binding to specific Small GTPases of the Rho family, leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP.

DHR1, also known as CZH1 or Docker1, is a protein domain of approximately 200–250 amino acids that is present in the DOCK family of signalling proteins. This domain binds phospholipids and so may assist in recruitment to cellular membranes. There is evidence that this domain may also mediate protein–protein interactions.

DHR2, also known as CZH2 or Docker2, is a protein domain of approximately 450-550 amino acids that is present in the DOCK family of proteins. This domain functions as a guanine nucleotide exchange factor (GEF) domain for small G proteins of the Rho family. DHR2 domains bear no significant similarity to the well described DH domain present in other RhoGEFs such as Vav, P-Rex and TRIO. Indeed, the most divergent mammalian DHR2 domains share only 16-17% sequence similarity.

Dock5 Protein-coding gene in the species Homo sapiens

Dock5, also known as DOCK5, is a large protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock5 is predicted to activate the small G protein Rac.

Dock6 Protein-coding gene in the species Homo sapiens

Dock6, also known as Zir1 is a large protein involved in intracellular signalling networks. 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.

PLEKHG2 Protein-coding gene in the species Homo sapiens

Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000147251 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031093 - 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: DOCK11 dedicator of cytokinesis 11".
  6. Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". Journal of Cell Science. 115 (Pt 24): 4901–13. doi: 10.1242/jcs.00219 . PMID   12432077.
  7. 1 2 3 Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz MA, Maruyama M (February 2005). "Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes". FEBS Letters. 579 (5): 1039–46. doi:10.1016/j.febslet.2005.01.006. PMID   15710388. S2CID   36721405.
  8. 1 2 Chien WM, Garrison K, Caufield E, Orthel J, Dill J, Fero ML (March 2007). "Differential gene expression of p27Kip1 and Rb knockout pituitary tumors associated with altered growth and angiogenesis". Cell Cycle. 6 (6): 750–7. doi:10.4161/cc.6.6.3986. PMC   2040307 . PMID   17361101.
  9. Lin Q, Yang W, Baird D, Feng Q, Cerione RA (November 2006). "Identification of a DOCK180-related guanine nucleotide exchange factor that is capable of mediating a positive feedback activation of Cdc42". The Journal of Biological Chemistry. 281 (46): 35253–62. doi: 10.1074/jbc.M606248200 . PMID   16968698.
  10. Sinha S, Yang W (November 2008). "Cellular signaling for activation of Rho GTPase Cdc42". Cellular Signalling. 20 (11): 1927–34. doi:10.1016/j.cellsig.2008.05.002. PMID   18558478.
  11. Almstrup K, Leffers H, Lothe RA, Skakkebaek NE, Sonne SB, Nielsen JE, Rajpert-De Meyts E, Skotheim RI (August 2007). "Improved gene expression signature of testicular carcinoma in situ". International Journal of Andrology. 30 (4): 292–302, discussion 303. doi:10.1111/j.1365-2605.2007.00758.x. PMID   17488342.

Further reading