| Src homology 3 domain-containing Guanine nucleotide Exchange Factor) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | SGEF | ||||||
| Alt. symbols | CSGEF, HMFN1864 | ||||||
| NCBI gene | 26084 | ||||||
| RefSeq | NM_015595 | ||||||
| UniProt | Q96DR7 | ||||||
| Other data | |||||||
| Locus | Chr. 3q25.2 | ||||||
| |||||||
SGEF (Src homology 3 domain-containingGuanine nucleotideExchangeFactor) is a 97 kDaprotein involved inintracellularsignalling networks. It functions as aguanine nucleotide exchange factor (GEF) forRhoG, a smallG protein of theRho family.[1]
SGEF was discovered during a screen forandrogen-responsive genes in humanprostate cancer cells.[2] Subsequentnorthern blot analysis revealed expression of SGEF in tissues of theheart,brain,placenta,lung,liver,kidney,pancreas,prostate,testis,small intestine andcolon. SGEF is also expressed inendothelial cells of thevasculature.[3] Several widely usedcell lines express this protein, these includeA431,HeLa,HUT78,HEK-293,Jurkat,THP,PC12,RAJI,U937 andMeg-01.[4]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.[5] Genetic variants in SGEF have been associated withcoronary artery disease[6]
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 toguanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding ofguanosine triphosphate (GTP). GEFs activate G proteins by promoting nucleotide exchange.
SGEF has the canonical GEF structure of tandemDH andPH domains, which elicit nucleotide exchange and, in addition, contains anN-terminalproline-rich motif and aC-terminalSH3 domain.[2] Proline regions and SH3 domains often mediate recruitment and binding toadaptor proteins suggesting that SGEF is probably involved in the formation of heteromultimericprotein complexes.
Data from several studies suggest that SGEF is regulated by its recruitment totransmembrane receptor-linked adaptor proteins via its SH3 domain. In one study, mutation of the SH3 domain disrupted SGEF-dependent functions inNIH-3T3 fibroblasts.[4] In endothelial cells SGEF was recruited to the intracellular domain of the transmembraneadhesion moleculeICAM-1 uponleukocyte adhesion to the endothelium.[3]