ARHGEF1

Last updated
ARHGEF1
Protein ARHGEF1 PDB 1iap.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ARHGEF1 , GEF1, LBCL2, LSC, P115-RHOGEF, SUB1.5, Rho guanine nucleotide exchange factor 1, IMD62
External IDs OMIM: 601855; MGI: 1353510; HomoloGene: 3454; GeneCards: ARHGEF1; OMA:ARHGEF1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004706
NM_198977
NM_199002

NM_001130150
NM_001130151
NM_001130152
NM_001130153
NM_008488

Contents

RefSeq (protein)

NP_004697
NP_945328
NP_945353

NP_001123622
NP_001123623
NP_001123624
NP_001123625
NP_032514

Location (UCSC) Chr 19: 41.88 – 41.93 Mb Chr 7: 24.6 – 24.63 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. [5] [6] [7] This protein is also called RhoGEF1 or p115-RhoGEF.

Function

Rho guanine nucleotide exchange factor 1 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. [5] Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. [8] In particular, active Rho is a major regulator of the cell actin cytoskeleton. [8]

RhoGEF1 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. [9] [10] The others are ARHGEF11 (also known as PDZ-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). [11] [12] GPCR-regulated RhoGEF1 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. In addition to being activated by G12 or G13 G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins (which are themselves GTPase proteins). This action increases the rate of G protein deactivation, limiting the time during which these RhoGEFs activate Rho. [13]

Multiple alternatively spliced transcript variants have been identified for this gene, but the full-length nature and function of some variants has not been defined. [7]

Interactions

ARHGEF1 has been shown to interact with:

See also

Related Research Articles

GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a protein domain common to many GTPases.

G12/G13 alpha subunits are alpha subunits of heterotrimeric G proteins that link cell surface G protein-coupled receptors primarily to guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. Together, these two proteins comprise one of the four classes of G protein alpha subunits. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP. G12/G13 are not targets of pertussis toxin or cholera toxin, as are other classes of G protein alpha subunits.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">T-cell lymphoma invasion and metastasis-inducing protein 1</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.

<span class="mw-page-title-main">GNAI1</span> Protein-coding gene in humans

Guanine nucleotide-binding protein G(i), alpha-1 subunit is a protein that in humans is encoded by the GNAI1 gene.

<span class="mw-page-title-main">RhoGEF domain</span> Protein 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.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in humans

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">RAP2A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rap-2a is a protein that in humans is encoded by the RAP2A gene. RAP2A is a member of the Ras-related protein family.

<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">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">VAV3</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.

<span class="mw-page-title-main">RAPGEF2</span> Protein-coding gene in the species Homo sapiens

Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene.

<span class="mw-page-title-main">MCF2L</span> Gene found in humans

Guanine nucleotide exchange factor DBS is a protein that in humans is encoded by the MCF2L gene.

<span class="mw-page-title-main">GNA13</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the GNA13 gene.

<span class="mw-page-title-main">GNAI3</span> Protein-coding gene in humans

Guanine nucleotide-binding protein G(k) subunit alpha is a protein that in humans is encoded by the GNAI3 gene.

<span class="mw-page-title-main">GNA12</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000076928 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000040940 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. 1 2 Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, et al. (October 1996). "Identification of a novel guanine nucleotide exchange factor for the Rho GTPase". The Journal of Biological Chemistry. 271 (41): 25452–8. doi: 10.1074/jbc.271.41.25452 . PMID   8810315.
  6. Aasheim HC, Pedeutour F, Smeland EB (April 1997). "Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues". Oncogene. 14 (14): 1747–52. doi:10.1038/sj.onc.1200994. PMID   9135076. S2CID   24528606.
  7. 1 2 "Entrez Gene: ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1".
  8. 1 2 Thumkeo D, Watanabe S, Narumiya S (Oct–Nov 2013). "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology. 92 (10–11): 303–15. doi:10.1016/j.ejcb.2013.09.002. PMID   24183240.
  9. Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, et al. (June 1998). "p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13". Science. 280 (5372): 2109–11. doi:10.1126/science.280.5372.2109. PMID   9641915.
  10. 1 2 Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, et al. (June 1998). "Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13". Science. 280 (5372): 2112–4. doi:10.1126/science.280.5372.2112. PMID   9641916.
  11. Fukuhara S, Chikumi H, Gutkind JS (March 2001). "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?". Oncogene. 20 (13): 1661–8. doi: 10.1038/sj.onc.1204182 . PMID   11313914.
  12. Diviani D, Soderling J, Scott JD (November 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". The Journal of Biological Chemistry. 276 (47): 44247–57. doi: 10.1074/jbc.M106629200 . PMID   11546812.
  13. Kozasa T (April 2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID   11358341.
  14. 1 2 Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, et al. (December 2003). "RGS16 inhibits signalling through the G alpha 13-Rho axis". Nature Cell Biology. 5 (12): 1095–103. doi:10.1038/ncb1065. PMID   14634662. S2CID   6798899.
  15. Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (August 2003). "Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement". The Journal of Biological Chemistry. 278 (31): 28793–8. doi: 10.1074/jbc.M303900200 . PMID   12754211.

Further reading