Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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Rho guanine nucleotide exchange factor 12(ARHGEF12) Rho guanine nucleotide exchange factor 12(ARHGEF12) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11q23.3,
ENSEMBL_GENE_ID ENSG00000196914,
GENERIF_SUMMARY Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation, Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated protein and PDZ-RhoGEF., LARG plays a critical role in plexin-B1 signaling to stimulate Rho activation and cytoskeletal reorganization., Rho activation through Galpha12 and the regulation of RhoGEFs by heterotrimeric G proteins G1213 is further modulated by tyrosine phosphorylated leukemia-associated RhoGEF., Data show that different rho guanine nucleotide exchange factors (rhoGEFs; p115rhoGEF, LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and lysophosphatidic acid receptors., analysis of LARG RhoA binding and nucleotide exchange structure, CD44 interaction with LARG and EGFR plays a pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up-regulation required for CaMKII-mediated cytoskeleton function and in head and neck squamous cell carcinoma progression, Tyr1306Cys substitution in LARG, through its differential activation of RhoA, increases insulin sensitivity in nondiabetic Pima Indians., There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for type 2 diabetes, insulin sensitivity, or the metabolic syndrome, Analysis of the (15)N relaxation data using reduced spectral density mapping shows that the apo LARG PDZ is flexible and exhibits internal motions on both picosecond to nanosecond and microsecond to millisecond timescales, LARG activation is regulated by an induced-fit mechanism through the GAP interface of Galpha(13)., Moreover, leukemia-associated guanine nucleotide exchange factor (LARG) associates with Unc5B to transduce the RhoA signal., mutations in the hydrophobic patch do not have a significant effect on in vitro activity, but abolished the ability of LARG to activate RhoA and to induce stress fiber formation in cultured cells., LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer, a novel physical and functional interaction between ABCA1 and PDZ-RhoGEF/LARG, which activates RhoA, resulting in ABCA1 stabilization and cholesterol efflux activity., Mechanistic insights into specificity, activity, and regulatory elements of the regulator of G-protein signaling (RGS)-containing Rho-specific guanine nucleotide exchange factors (GEFs) p115, PDZ-RhoGEF (PRG), and leukemia-associated RhoGEF (LARG)., The PDZ domain of LARG is required HRH1-mediated activation of the strictly Rho-dependent transcriptional activity of serum response factor and can be mimicked by activated Galpha(q)(Q209L)., NIS enhanced cell migration and invasion by binding to leukemia-associated RhoA guanine exchange factor, RhoGEF activity of p210 BCR/ABL directly contributes to transforming activity, and may account for the difference in disease outcome associated with p190 BCR/ABL and p210 BCR/ABL., LARG is a novel and temporally distinct Rho Guanine Nucleotide Exchange Factor required for completion of abscission., Agonist-induced Ca2+ sensitization in smooth muscle, Data indicate that ICAM-1 signaling activates leukemia-associated Rho guanine nucleotide exchange factor (LARG), also known as Rho GEF 12 (ARHGEF12)., TGF-beta regulates LARG and GEF-H1 during epithelial-mesenchymal transition to affect stiffening response to force and cell invasion., this study identified a novel association between IOP and ARHGEF12., that leukemia-associated Rho guanine-nucleotide exchange factor can be directly phosphorylated by cyclin-dependent kinase 1, Two related guanine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling.,
OFFICIAL_GENE_SYMBOL ARHGEF12,
SP_COMMENT disease:A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with MLL., function:May play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13). Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase and may act as GTPase-activating protein (GAP) for GNA12 and GNA13., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR., sequence caution:Contaminating sequence. Potential poly-A sequence., similarity:Contains 1 DH (DBL-homology) domain., similarity:Contains 1 PDZ (DHR) domain., similarity:Contains 1 PH domain., similarity:Contains 1 RGSL (RGS-like) domain., subcellular location:Translocated to the membrane upon stimulation., subunit:Interacts with GNA12 and GNA13, probably through the RGS-like domain. Interacts with RHOA, PLXNB1 and PLXNB2. Interacts through its PDZ domain with IGF1R beta subunit., tissue specificity:Ubiquitously expressed. Isoform 2 is found in jejunum and testis.,