ARHGEF11

Last updated
ARHGEF11
Protein ARHGEF11 PDB 1htj.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases ARHGEF11 , GTRAP48, PDZ-RHOGEF, Rho guanine nucleotide exchange factor 11
External IDs OMIM: 605708; MGI: 2441869; HomoloGene: 11409; GeneCards: ARHGEF11; OMA:ARHGEF11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_014784
NM_198236
NM_001377418
NM_001377419

NM_001003912
NM_001360195
NM_001360197

RefSeq (protein)

NP_055599
NP_937879
NP_001364347
NP_001364348

n/a

Location (UCSC) Chr 1: 156.93 – 157.05 Mb Chr 3: 87.52 – 87.65 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. [5] [6] [7] This protein is also called RhoGEF11 or PDZ-RhoGEF.

Contents

Function

Rho guanine nucleotide exchange factor 11 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. [8] 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. [9] In particular, active Rho is a major regulator of the cell actin cytoskeleton. [9]

RhoGEF11 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. [8] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). [10] [11] GPCR-regulated RhoGEF11 (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. [12]

Two alternative transcripts encoding different isoforms have been described. [7]

Interactions

ARHGEF11 has been shown to interact with:

See also

Related Research Articles

<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.

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">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">PLXNB1</span> Protein-coding gene in the species Homo sapiens

Plexin B1 is a protein of the plexin family that in humans is encoded by the PLXNB1 gene.

<span class="mw-page-title-main">ARHGEF1</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. This protein is also called RhoGEF1 or p115-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">Rnd1</span> Protein-coding gene in the species Homo sapiens

Rnd1 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND1.

<span class="mw-page-title-main">PLXNB2</span> Protein-coding gene in the species Homo sapiens

Plexin-B2 is a protein that in humans is encoded by the PLXNB2 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">PLXNB3</span> Protein-coding gene in the species Homo sapiens

Plexin-B3 is a protein that in humans is encoded by the PLXNB3 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">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: ENSG00000132694 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000041977 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 Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs KH (Oct 1999). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member". FEBS Letters. 459 (3): 313–8. doi:10.1016/S0014-5793(99)01270-3. PMID   10526156. S2CID   8529412.
  6. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 4 (2): 141–50. doi: 10.1093/dnares/4.2.141 . PMID   9205841.
  7. 1 2 "Entrez Gene: ARHGEF11 Rho guanine nucleotide exchange factor (GEF) 11".
  8. 1 2 Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS (Feb 1999). "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho". The Journal of Biological Chemistry. 274 (9): 5868–79. doi: 10.1074/jbc.274.9.5868 . PMID   10026210.
  9. 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): 303–315. doi:10.1016/j.ejcb.2013.09.002. PMID   24183240.
  10. Fukuhara S, Chikumi H, Gutkind JS (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.
  11. Diviani, D; Soderling, J; Scott, JD (Nov 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". Journal of Biological Chemistry. 276 (47): 44247–44257. doi: 10.1074/jbc.M106629200 . PMID   11546812.
  12. Kozasa T (2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sci. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID   11358341.
  13. 1 2 Chen, Z; Singer, WD; Danesh, SM; Sternweis, PC; Sprang, SR (Oct 2008). "Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF". Structure. 16 (10): 1532–1543. doi:10.1016/j.str.2008.07.009. PMC   2586972 . PMID   18940608.
  14. 1 2 3 Perrot V, Vazquez-Prado J, Gutkind JS (Nov 2002). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF". The Journal of Biological Chemistry. 277 (45): 43115–20. doi: 10.1074/jbc.M206005200 . PMID   12183458.
  15. 1 2 Swiercz JM, Kuner R, Behrens J, Offermanns S (Jul 2002). "Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology". Neuron. 35 (1): 51–63. doi: 10.1016/S0896-6273(02)00750-X . PMID   12123608. S2CID   18981429.
  16. Oinuma I, Katoh H, Harada A, Negishi M (Jul 2003). "Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells". The Journal of Biological Chemistry. 278 (28): 25671–7. doi: 10.1074/jbc.M303047200 . PMID   12730235.
  17. Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S (Sep 2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochemical and Biophysical Research Communications. 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. PMID   12220504.

Further reading