ARHGEF4

Rho guanine nucleotide exchange factor (GEF) 4
PDB rendering based on 2dx1.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2DX1​, 2PZ1​, 3NMX​, 3NMZ​
Identifiers
Symbols	ARHGEF4 ; ASEF; ASEF1; GEF4; STM6
External IDs	OMIM: 605216 MGI: 2442507 HomoloGene: 49414 GeneCards: ARHGEF4 Gene
Gene ontology Molecular function • guanyl-nucleotide exchange factor activity • protein binding • protein domain specific binding • Rac guanyl-nucleotide exchange factor activity Cellular component • cytosol • ruffle membrane Biological process • small GTPase mediated signal transduction • lamellipodium assembly • regulation of Rho protein signal transduction • positive regulation of apoptotic process • positive regulation of GTPase activity • filopodium assembly • neurotrophin TRK receptor signaling pathway • regulation of small GTPase mediated signal transduction • apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	50649	226970
Ensembl	ENSG00000136002	ENSMUSG00000037509
UniProt	Q9NR80	Q7TNR9
RefSeq (mRNA)	NM_015320	NM_183019
RefSeq (protein)	NP_056135	NP_898840
Location (UCSC)	Chr 2: 130.84 – 131.05 Mb	Chr 1: 34.68 – 34.81 Mb
PubMed search

Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.^[1][2]

Function

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein-coupled receptors. The encoded protein may form complex with G proteins and stimulate Rho-dependent signals. This protein is similar to rat collybistin protein. Alternative splicing of this gene generates two transcript variants that encode different isoforms. Also, there is possibility for the usage of multiple polyadenylation sites for this gene.^[2]

Model organisms

Arhgef4 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal[3]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal[4]
Peripheral blood lymphocytes	Abnormal[5]
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal[6]
Citrobacter infection	Normal[7]
All tests and analysis from[8][9]

Model organisms have been used in the study of ARHGEF4 function. A conditional knockout mouse line, called Arhgef4^{tm1a(KOMP)Wtsi[10][11]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[8][15] Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: males has atypical peripheral blood lymphocyte parameters, including a decreased B cell number and an increased granulocyte number.^[8]

Interactions

ARHGEF4 has been shown to interact with APC.^[16]

References

1. Thiesen S, Kübart S, Ropers HH, Nothwang HG (Jul 2000). "Isolation of two novel human RhoGEFs, ARHGEF3 and ARHGEF4, in 3p13-21 and 2q22". Biochem Biophys Res Commun 273 (1): 364–9. doi:10.1006/bbrc.2000.2925. PMID 10873612.
2. "Entrez Gene: ARHGEF4 Rho guanine nucleotide exchange factor (GEF) 4".
3. "Dysmorphology data for Arhgef4". Wellcome Trust Sanger Institute.
4. "Haematology data for Arhgef4". Wellcome Trust Sanger Institute.
5. "Peripheral blood lymphocytes data for Arhgef4". Wellcome Trust Sanger Institute.
6. "Salmonella infection data for Arhgef4". Wellcome Trust Sanger Institute.
7. "Citrobacter infection data for Arhgef4". Wellcome Trust Sanger Institute.
8. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
9. Mouse Resources Portal, Wellcome Trust Sanger Institute.
10. "International Knockout Mouse Consortium".
11. "Mouse Genome Informatics".
12. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
13. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
14. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
15. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
16. Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y, Higuchi O, Akiyama T (2000). "Asef, a link between the tumor suppressor APC and G-protein signaling". Science 289 (5482): 1194–7. doi:10.1126/science.289.5482.1194. PMID 10947987.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Kuraguchi M, Wang XP, Bronson RT, et al. (2006). "Adenomatous polyposis coli (APC) is required for normal development of skin and thymus". PLoS Genet. 2 (9): e146. doi:10.1371/journal.pgen.0020146. PMC 1564426. PMID 17002498.
• Watanabe T, Wang S, Noritake J, et al. (2005). "Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration". Dev. Cell 7 (6): 871–83. doi:10.1016/j.devcel.2004.10.017. PMID 15572129.
• Kawasaki Y, Sato R, Akiyama T (2003). "Mutated APC and Asef are involved in the migration of colorectal tumour cells". Nat. Cell Biol. 5 (3): 211–5. doi:10.1038/ncb937. PMID 12598901.
• Kawasaki Y, Senda T, Ishidate T, et al. (2000). "Asef, a link between the tumor suppressor APC and G-protein signaling". Science 289 (5482): 1194–7. doi:10.1126/science.289.5482.1194. PMID 10947987.