GEFT

Rho guanine nucleotide exchange factor 25, also known as guanine nucleotide exchange factor (GEFT), is a protein that in humans is encoded by the ARHGEF25 gene.^[5]

ARHGEF25
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RGN
Identifiers
Aliases	ARHGEF25, GEFT, p63RhoGEF, Rho guanine nucleotide exchange factor 25
External IDs	OMIM: 610215; MGI: 1277173; HomoloGene: 32691; GeneCards: ARHGEF25; OMA:ARHGEF25 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.3 Start 57,610,180 bp[1] End 57,617,245 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 D3|10 74.5 cM Start 127,018,394 bp[2] End 127,025,952 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right hemisphere of cerebellum right coronary artery gastric mucosa body of uterus muscle layer of sigmoid colon popliteal artery tibial arteries left uterine tube myometrium thoracic aorta Top expressed in dentate gyrus of hippocampal formation granule cell hippocampus proper CA3 field primary visual cortex primary motor cortex superior frontal gyrus vas deferens Region I of hippocampus proper umbilical cord lateral septal nucleus More reference expression data BioGPS n/a
Gene ontology Molecular function guanyl-nucleotide exchange factor activity Cellular component cytoplasm cytosol plasma membrane myofibril sarcomere membrane Biological process regulation of Rho protein signal transduction G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 115557 52666 Ensembl ENSG00000240771 ENSMUSG00000019467 UniProt Q86VW2 Q9CWR0 RefSeq (mRNA) NM_001111270 NM_133483 NM_182947 NM_001347933 NM_001166413 NM_028027 NM_001358557 NM_001358558 RefSeq (protein) NP_001104740 NP_891992 NP_001334862 NP_001159885 NP_082303 NP_001345486 NP_001345487 Location (UCSC) Chr 12: 57.61 – 57.62 Mb Chr 10: 127.02 – 127.03 Mb PubMed search [3] [4]
Wikidata
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Nomenclature

The human gene encoding GEFT is officially named ARHGEF25 (Rho guanine nucleotide exchange factor 25) . The full length version (containing an N-terminus) of which is known as p63RhoGEF.^[6]

Tissue distribution

GEFT is primarily expressed in tissues that are excitable, these include, the brain, heart, as well as muscle. In nonexcitable tissues however little expression is found. Overexpression of GEFT was found to lead to change in cell morphology and re-organization of the actin cytoskeleton. In addition expression of GEFT in NIH3T3 cells promotes foci formation as well as cell proliferation, translation, and migration.^[7]

Function

GEFT is an N-Terminally truncated protein isoformen coded by the ARHGEF25 gene in humans. It belongs to the Dbl family of guanine exchange factors (GEFs), a group of proteins which activate Rho family GTPases.^[8] GEFT is a member of the Dbl family of guanine GEFT has been characterized as an activator of Rac1, Cdc42, and some contexts of RhoA, and plays roles in cytoskeletal organization, neurite development and cell morphology.^[9]

Interactions

GEFT has shown to interact with multiple members of the Rho family of small GTPases. Biochemical characterization shoes GEFT functions primarily as an exchange factor for Rac1 and Cdc42, displaying strong guanine exchange activity toward both the proteins. Through these interactions, GEFT promotes the formation of lamellipodia, filopodia , and microspikes in the membrane, which are consistent Rac1- and Cdc43- directed cytoskeletal remodeling. GEFT also activates downstream transcriptional pathways associated with many GTPases, including SRE, Elk1, SAP1. As well as significantly activating c-Jun, and AP-1 transcription factors. By activating all of these small GTPases (Rac1 and Cdc42), it strongly stimulates JNK signaling pathways and its transcriptional factors. GEFT can also bind and interact with RhoA, however, the exchange activity between the two is substantially weaker, resulting in only moderate stimulation of RhoA dependent SRE activity.^[8][10]