ARHGEF26
Identifiers
Aliases	ARHGEF26, CSGEF, HMFN1864, SGEF, Rho guanine nucleotide exchange factor 26
External IDs	OMIM: 617552; MGI: 1918053; GeneCards: ARHGEF26
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.2 Start 154,121,003 bp[1] End 154,257,827 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 E1 Start 62,245,765 bp[2] End 62,369,642 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibial nerve muscle layer of sigmoid colon testicle sural nerve right lung Descending thoracic aorta right lobe of liver upper lobe of left lung gonad ascending aorta Top expressed in otolith organ utricle neural layer of retina right lung vestibular sensory epithelium subdivision of hippocampus Region I of hippocampus proper deep cerebellar nuclei right lung lobe retinal pigment epithelium More reference expression data BioGPS n/a
Gene ontology Molecular function guanyl-nucleotide exchange factor activity Cellular component cell projection ruffle cytosol Biological process ruffle assembly regulation of Rho protein signal transduction endothelial cell morphogenesis positive regulation of apoptotic process regulation of small GTPase mediated signal transduction G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 26084 622434 Ensembl ENSG00000114790 ENSG00000277101 ENSMUSG00000036885 UniProt Q96DR7 n/a RefSeq (mRNA) NM_001251962 NM_001251963 NM_015595 NM_001081295 RefSeq (protein) NP_001238891 NP_001238892 NP_056410 n/a Location (UCSC) Chr 3: 154.12 – 154.26 Mb Chr 3: 62.25 – 62.37 Mb PubMed search [3] [4]
Wikidata
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SGEF (Src homology 3 domain-containing Guanine nucleotide Exchange Factor) is a 97 kDa protein involved in intracellular signalling networks. It functions as a guanine nucleotide exchange factor (GEF) for RhoG, a small G protein of the Rho family.^[5]

SGEF was discovered during a screen for androgen-responsive genes in human prostate cancer cells.^[6] Subsequent northern blot analysis revealed expression of SGEF in tissues of the heart, brain, placenta, lung, liver, kidney, pancreas, prostate, testis, small intestine and colon. SGEF is also expressed in endothelial cells of the vasculature.^[7] Several widely used cell lines express this protein, these include A431, HeLa, HUT78, HEK-293, Jurkat, THP, PC12, RAJI, U937 and Meg-01.^[8] SGEF was identified to contribute to the formation of atherosclerosis through promoting endothelial docking structures that resulted in retention of leukocytes at athero-prone sites of inflammation.^[9] Genetic variants in SGEF have been associated with coronary artery disease^[10]

SGEF is part of a large class of proteins (GEFs) that function to activate small G proteins. In their resting state G proteins are bound to guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting nucleotide exchange.

SGEF has the canonical GEF structure of tandem DH and PH domains, which elicit nucleotide exchange and, in addition, contains an N-terminal proline-rich motif and a C-terminal SH3 domain.^[6] Proline regions and SH3 domains often mediate recruitment and binding to adaptor proteins suggesting that SGEF is probably involved in the formation of heteromultimeric protein complexes.

Data from several studies suggest that SGEF is regulated by its recruitment to transmembrane receptor-linked adaptor proteins via its SH3 domain. In one study, mutation of the SH3 domain disrupted SGEF-dependent functions in NIH-3T3 fibroblasts.^[8] In endothelial cells SGEF was recruited to the intracellular domain of the transmembrane adhesion molecule ICAM-1 upon leukocyte adhesion to the endothelium.^[7]