RhoGEF domain

Last updated
DH/PH RhoGEF domain
PDB 1dbh EBI.jpg
Structure of the RhoGEF domain from the human Son of sevenless protein, an example of a DH/PH domain RhoGEF. [1]
Identifiers
SymbolRhoGEF
Pfam PF00621
InterPro IPR035899 IPR000219, IPR035899
SMART RhoGEF
SCOP2 1dbh / SCOPe / SUPFAM
OPM protein 1xd4
CDD cd00160
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1foe E:1044-1233 1f5x A:198-372 1ki1 D:1241-1422

1nty A:1237-1407 1kzg C:636-811 1lb1 C:636-811 1kz7 C:636-811 1rj2 D:511-686 1xcg E:738-922 1txd A:791-976 1x86 E:791-976 1by1 A:275-450

Contents

1dbh A:204-389 1xdv B:204-389 1xd4 A:204-389
Dedicator of cytokinesis (DOCK) RhoGEF domain
Identifiers
SymbolRhoGEF
Pfam PF06920
InterPro IPR010703 IPR026791, IPR010703
SCOP2 1wg7 / SCOPe / SUPFAM
CDD cd11684
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1wg7

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.

The largest class of RhoGEFs is composed of proteins containing the "Dbl-homology" (DH) domain, which almost always is found together with a pleckstrin-homology (PH) domain to form a combined DH/PH domain structure. [2] [3]

A distinct class of RhoGEFs is those proteins containing the DOCK/CZH/DHR-2 domain. This structure has no sequence similarity with DBL-homology domains. [4]

Human proteins containing DH/PH RhoGEF domain

ABR; AKAP13/ARHGEF13/Lbc; ALS2; ALS2CL; ARHGEF1/p115-RhoGEF; ARHGEF10; ARHGEF10L; ARHGEF11/PDZ-RhoGEF.; ARHGEF12/LARG; ARHGEF15; ARHGEF16; ARHGEF17; ARHGEF18; ARHGEF19; ARHGEF2; ARHGEF25; ARHGEF26; ARHGEF28; ARHGEF3; ARHGEF33; ARHGEF35; ARHGEF37; ARHGEF38; ARHGEF39; ARHGEF4; ARHGEF40; ARHGEF5; ARHGEF6/alpha-PIX; ARHGEF7/beta-PIX; ARHGEF9; BCR; DNMBP; ECT2; ECT2L; FARP1; FARP2; FGD1; FGD2; FGD3; FGD4; FGD5; FGD6; ITSN1/Intersectin 1; ITSN2/Intersectin 2; KALRN/Kalirin; MCF2; MCF2L; MCF2L2; NET1; NGEF; OBSCN; PLEKHG1; PLEKHG2; PLEKHG3; PLEKHG4; PLEKHG4B; PLEKHG5; PLEKHG6; PREX1; PREX2; RASGRF1; RASGRF2; SPATA13; TIAM1; TIAM2; TRIO; VAV1; VAV2; VAV3.

Human proteins containing DOCK/CZH RhoGEF domain

DOCK1/DOCK180; DOCK2; DOCK3/MOCA; DOCK4; DOCK5; DOCK6/ZIR1; DOCK7/ZIR2; DOCK8/ZIR3; DOCK9/Zizimin1; DOCK10/Zizimin2; DOCK11/Zizimin3

See also

Related Research Articles

In cell signalling, Son of Sevenless (SOS) refers to a set of genes encoding guanine nucleotide exchange factors that act on the Ras subfamily of small GTPases.

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> 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.

<span class="mw-page-title-main">FGD1</span> 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.

<span class="mw-page-title-main">ARHGEF7</span> 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">AKAP13</span> Protein-coding gene in the species Homo sapiens

A-kinase anchor protein 13 is a protein that in humans, is encoded by the AKAP13 gene. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.

<span class="mw-page-title-main">ARHGEF6</span> Protein-coding gene in humans

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

<span class="mw-page-title-main">Dedicator of cytokinesis protein 1</span> Protein found in humans

Dedicator of cytokinesis protein 1 (Dock1), also (DOCK180), is a large protein encoded in the human by the DOCK1 gene, 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).

<span class="mw-page-title-main">ARHGEF11</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. This protein is also called RhoGEF11 or PDZ-RhoGEF.

<span class="mw-page-title-main">ARHGEF12</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).

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

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.

<span class="mw-page-title-main">MCF2</span> Protein-coding gene in the humans

The DBL proto-oncogene is a protein that in humans is encoded by the MCF2 gene.

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

Triple functional domain protein is a protein that in humans is encoded by the TRIO gene.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 7</span> Protein found in humans

Dedicator of cytokinesis protein (Dock7) is a large protein encoded in the human by the DOCK7 gene, 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.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 4</span> Protein found in humans

Dedicator of cytokinesis protein 4 (Dock4), is a large protein encoded in the human by the DOCK4 gene, 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.

ELMO is a family of related proteins involved in intracellular signalling networks. These proteins have no intrinsic catalytic activity and instead function as adaptors which can regulate the activity of other proteins through their ability to mediate protein-protein interactions.

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.

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.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 11</span> Protein-coding gene in humans

Dedicator of cytokinesis protein 11 (Dock11), also known as Zizimin2, is a large protein encoded in the human by the DOCK11 gene, involved in intracellular signalling networks. 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.

<span class="mw-page-title-main">PLEKHG5</span> Protein-coding gene in the species Homo sapiens

Pleckstrin homology domain containing, family G member 5 (PLEKHG5) is a protein that in humans is encoded by the PLEKHG5 gene. Eight transcript variants encoding different isoforms have been found for this gene.

<span class="mw-page-title-main">PLEKHG2</span> 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. Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J (October 1998). "Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein". Cell. 95 (2): 259–68. doi: 10.1016/S0092-8674(00)81756-0 . PMID   9790532. S2CID   11868669.
  2. Fort P, Blangy A (June 2017). "The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals". Genome Biology and Evolution. 9 (6): 1471–1486. doi:10.1093/gbe/evx100. PMC   5499878 . PMID   28541439.
  3. Cerione RA, Zheng Y (April 1996). "The Dbl family of oncogenes". Current Opinion in Cell Biology. 8 (2): 216–22. doi: 10.1016/s0955-0674(96)80068-8 . PMID   8791419.
  4. 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.

Further reading