ARHGEF4

Rho guanine nucleotide exchange factor 4 is a protein that in humans is encoded by the ARHGEF4 gene.[5][6]

ARHGEF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DX1, 2PZ1, 3NMX, 3NMZ
Identifiers
Aliases	ARHGEF4, ASEF, ASEF1, GEF4, STM6, Rho guanine nucleotide exchange factor 4, SMIM39
External IDs	OMIM: 605216 MGI: 2442507 HomoloGene: 49414 GeneCards: ARHGEF4
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q21.1 Start 130,836,916 bp[1] End 131,047,263 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 B Start 34,678,188 bp[2] End 34,813,309 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • Rac guanyl-nucleotide exchange factor activity • GO:0001948 protein binding • protein domain specific binding • guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity Cellular component • cytoplasm • ruffle membrane • cytosol • cell membrane • cell projection • membrane Biological process • filopodium assembly • regulation of Rho protein signal transduction • GO:0007243 intracellular signal transduction • regulation of small GTPase mediated signal transduction • lamellipodium assembly • positive regulation of apoptotic process • G-protein coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	50649	226970
Ensembl	ENSG00000136002	ENSMUSG00000037509
UniProt	Q9NR80	Q7TNR9
RefSeq (mRNA)	NM_015320 NM_032995 NM_001367493 NM_001375900 NM_001375901 NM_001375902 NM_001375903 NM_001375904	NM_183019 NM_001368773
RefSeq (protein)	NP_056135 NP_001354422 NP_001362829 NP_001362830 NP_001362831 NP_001362832 NP_001362833	NP_898840 NP_001355702
Location (UCSC)	Chr 2: 130.84 – 131.05 Mb	Chr 1: 34.68 – 34.81 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

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[7]
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[8]
Peripheral blood lymphocytes	Abnormal[9]
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal[10]
Citrobacter infection	Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of ARHGEF4 function. A conditional knockout mouse line, called Arhgef4^{tm1a(KOMP)Wtsi}[14][15] 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.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] 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.[12]

Interactions

ARHGEF4 has been shown to interact with APC.[20]

References

1. GRCh38: Ensembl release 89: ENSG00000136002 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000037509 - 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. 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.
6. "Entrez Gene: ARHGEF4 Rho guanine nucleotide exchange factor (GEF) 4".
7. "Dysmorphology data for Arhgef4". Wellcome Trust Sanger Institute.
8. "Haematology data for Arhgef4". Wellcome Trust Sanger Institute.
9. "Peripheral blood lymphocytes data for Arhgef4". Wellcome Trust Sanger Institute.
10. "Salmonella infection data for Arhgef4". Wellcome Trust Sanger Institute.
11. "Citrobacter infection data for Arhgef4". Wellcome Trust Sanger Institute.
12. 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.
13. Mouse Resources Portal, Wellcome Trust Sanger Institute.
14. "International Knockout Mouse Consortium".
15. "Mouse Genome Informatics".
16. 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.
17. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
18. 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.
19. 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.
20. 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.

External links

• Human ARHGEF4 genome location and ARHGEF4 gene details page in the UCSC Genome Browser.

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.