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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
    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
    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
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine     Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines pheochromocytoma cell line
    at STAGE
  • 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
    interspecies homolog to murine Rasgrp1
    homolog to rattus Rasgrp1
    intraspecies homolog to RASGRP2
  • RAS superfamily
  • guanine nucleotide exchange factor (GEF) domain family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • 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
    signaling signal transduction
    RAS protein signal transduction
    a component
    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
    activated by T-cell receptor (TCR) and promotes TCR-dependent positive selection of thymocytes (Klinger 2005)
    Other calcium Ca2+ and DAG-regulated
    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
  • 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
    Therapy target