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FLASH GENE
Symbol RASGRP1 contributors: mct/npt/pgu - updated : 14-09-2017
HGNC name RAS guanyl releasing protein 1 (calcium and DAG-regulated)
HGNC id 9878
Location 15q14      Physical location : 38.780.302 - 38.857.007
Synonym name
  • ras activator RasGRP
  • calcium and DAG-regulated guanine nucleotide exchange factor II
  • guanine nucleotide exchange factor, calcium- and DAG-regulated, Rap1A
  • Synonym symbol(s) RASGRP, CALDAG-GEFI, CALDAG-GEFII, EVI18, MGC129998, MGC129999, V
    DNA
    TYPE functioning gene
    STRUCTURE 76.71 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    HH114 15q13.3 hypothetical protein HH114 LOC390575 15 similar to casein kinase 1, alpha 1 MEIS2 15q14 Meis1, myeloid ecotropic viral integration site 1 homolog 2 (mouse) LOC145846 15q13.3 hypothetical LOC145846 LOC390576 15 similar to ribosomal protein S15 MGC35118 15q13.3 hypothetical protein MGC35118 SPRED1 15q13.3 sprouty-related, EVH1 domain containing 1 FLJ38426 15q13.3 hypothetical protein FLJ38426 RASGRP1 15q15 RAS guanyl releasing protein 1 (calcium and DAG-regulated) THBS1 15q15 thrombospondin 1 FLJ35989 15q14 hypothetical protein FLJ35989 GPR 15q14 putative G protein coupled receptor LOC388113 15 hypothetical gene supported by BC035481 MGC10997 15q13-q14 pseudogene MGC10997 SRP14 15q15.1-q21.1 signal recognition particle 14kDa (homologous Alu RNA binding protein) BMF 15q14 Bcl2 modifying factor BUB1B 15q15 BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) PAK6 15q14 p21(CDKN1A)-activated kinase 6 LOC390577 15 similar to KIAA1728 protein PLCB2 15q15 phospholipase C, beta 2 LOC390578 15 similar to BLOCK 23 LOC388114 15 LOC388114 LOC388115 15 similar to RIKEN cDNA 2600011L02
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 4943 86.5 762 - 1999 10087292
    17 - 5048 90.3 797 - 1999 10087292
    15 - 4538 - 597 - 1999 10087292
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Epithelial    
    Lymphoid    
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines pheochromocytoma cell line
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • besides the catalytic domain
  • an atypical pair of "EF hands" that bind calcium (EF1, is required for receptor-induced translocation of RasGRP1 to the plasma membrane in B cell lines) (Tazmini 2009)
  • a diacylglycerol (DAG)-binding domain
  • HOMOLOGY
    interspecies homolog to murine Rasgrp1
    homolog to rattus Rasgrp1
    intraspecies homolog to RASGRP2
    Homologene
    FAMILY
  • RAS superfamily
  • guanine nucleotide exchange factor (GEF) domain family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    text
  • peripheral plasma membrane protein
  • activation of RasGRP1 requires its translocation to membranes, which can be directly mediated by either its PT or C1 domains
  • basic FUNCTION
  • guanine nucleotide releasing (exchange) protein 1, RAS activator
  • involved in Ras activation crucial for lymphocyte development and effector function (Roose 2007)
  • orchestrates Ras signaling in two ways, by activating Ras directly andby facilitating priming of SOS1 with RasGTP that binds the allosteric pocket (Roose 2007)
  • essential in T cell receptor-mediated Ras-Erk activation (Liu 2007)
  • essential regulator of mast cell function (Liu 2007)
  • plays an essential role in NK cell effector functions (Lee 2009)
  • might act as an important bridge between phospholipase-gamma activation and NK cell effector functions via the Ras-MAPK pathway (Lee 2009)
  • RASGRP1 and GRB2/SOS1 are insulators of signals that lead to RAS activation induced by different stimuli, rather than cooperating downstream of the TCRA
  • physiological relevance of the tail domain in RASGRP1 function and control of ERK signaling
  • required for ERK activation downstream of CXCR4 signaling
  • important regulator of proliferation and differentiation at the thymic beta-selection checkpoint and functions downstream of CXCR4 to activate the Ras/MAPK pathway
  • RASGRP1 and SOS1 are RAS-specific nucleotide exchange factors that have distinct roles in lymphocyte development
  • RASGRP1 upregulates signaling from RAS and contributes to epidermal tumorigenesis by increasing the total dosage of active RAS
  • creates a negative feedback loop that limits proliferative EGFR-SOS1-RAS signals in colorectal carcinoma cells
  • is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling
  • is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    RAS protein signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • Ca2+
  • lipid
  • protein
  • binding to SKAP1 required the C-terminus of SKAP1 and was enhanced by tyrosine phosphorylation of SKAP1 (Kosko 2008)
  • inetracting with SOS1 for Ras activation (unusual RASGRP1-SOS1 interplay results in sensitive and robust Ras activation that cannot be achieved with either activator alone) (Roose 2007)
  • GNAI2 and ZAP70 mediate RASGRP1 membrane localization and activation of CXCL12-induced T cell functions
  • RASGRP1, RASGRP3 may regulate progenitor entry into the thymus through a CCR9-dependent mechanism
  • RASGRP1-deficient cells showed decreased activation of the GTPase RHOA
  • cell & other
    REGULATION
    activated by T-cell receptor (TCR) and promotes TCR-dependent positive selection of thymocytes (Klinger 2005)
    Other calcium Ca2+ and DAG-regulated
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    contributes to the development of autoimmunity in a subset of SLE patients
    tumoral     --over  
    on most T lymphocytic leukemias and is a common site of proviral insertion in retrovirus-induced murine T-cell lymphomas
    tumoral     --other  
    deregulated expression of RasGRP1 promotes lymphomagenesis by expanding the pool of thymocytes which are susceptible to transformation
    constitutional       loss of function
    resulted in defective proliferation, activation and motility of T cells and B cells, and causes immunodeficiency with impaired cytoskeletal dynamics
    constitutional germinal mutation      
    in combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis
    Susceptibility
  • to systemic lupus erythematosus
  • type 1 diabetes
  • to IgA nephropathy (IgAN)
  • Variant & Polymorphism SNP
  • rs17574546 and rs7171171 associated to type 1 diabetes
  • rs7170151 in RASGRP1 showed novel associations in IgAN
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS