MGP Database

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MGP004133

UniProt Annotations

Entry Information
Gene NameRAS guanyl releasing protein 1 (calcium and DAG-regulated)
Protein EntryGRP1_HUMAN
UniProt IDO95267
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=5; Comment=Additional isoforms seem to exist. Several splicing events may be used independently in a modular way.; Name=1; IsoId=O95267-1; Sequence=Displayed; Name=2; Synonyms=A; IsoId=O95267-2; Sequence=VSP_030836; Name=3; Synonyms=B; IsoId=O95267-3; Sequence=VSP_030836, VSP_030841, VSP_030842; Name=4; Synonyms=C; IsoId=O95267-4; Sequence=VSP_030836, VSP_030837, VSP_030838; Name=5; Synonyms=D; IsoId=O95267-5; Sequence=VSP_030836, VSP_030839, VSP_030840; Note=No experimental confirmation available.;
Developmental StageExpressed in fetal brain and kidney. {ECO:0000269|PubMed:9789079}.
DiseaseSystemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17878389}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Aberrantly spliced isoforms and/or diminished levels of RASGRP1 are found in a cohort of SLE patients raising the possibility that dysregulation of this signaling protein contributes to the development of autoimmunity in a subset of SLE patients.
DomainThe phorbol-ester/DAG-type zinc finger is the principal mediator of the targeting to membranes and is required for functional activation through DAG-binding.
DomainTwo EF-hand domains are present. However, only EF-hand 1 (and not EF-hand 2) binds calcium. {ECO:0000269|PubMed:23908768}.
Enzyme RegulationAutoinhibited. Activated by diacylglycerol and calcium binding, which induces a conformational change releasing the autoinhibitory state (PubMed:23908768). Regulated by DGKA (PubMed:11919165). Regulated by DGKZ (PubMed:11257115). Regulated by PLC gamma and F-actin polymerization (PubMed:12839994). {ECO:0000269|PubMed:11257115, ECO:0000269|PubMed:11919165, ECO:0000269|PubMed:12839994, ECO:0000269|PubMed:23908768}.
FunctionFunctions as a calcium- and diacylglycerol (DAG)- regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP (PubMed:15899849, PubMed:23908768). Activates the Erk/MAP kinase cascade (PubMed:15899849). Regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B- lymphocyte antigen receptors to Ras (PubMed:10807788, PubMed:12839994). Regulates NK cell cytotoxicity and ITAM- dependent cytokine production by activation of Ras-mediated ERK and JNK pathways (PubMed:19933860). Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (By similarity). May also function in differentiation of other cell types (PubMed:12845332). {ECO:0000250|UniProtKB:Q9Z1S3, ECO:0000269|PubMed:10807788, ECO:0000269|PubMed:12782630, ECO:0000269|PubMed:12839994, ECO:0000269|PubMed:12845332, ECO:0000269|PubMed:15060167, ECO:0000269|PubMed:15184873, ECO:0000269|PubMed:15899849, ECO:0000269|PubMed:19933860, ECO:0000269|PubMed:23908768}.
Sequence CautionSequence=AAH67298.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
SimilarityBelongs to the RASGRP family. {ECO:0000305}.
SimilarityContains 1 N-terminal Ras-GEF domain. {ECO:0000255|PROSITE-ProRule:PRU00135}.
SimilarityContains 1 phorbol-ester/DAG-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00226}.
SimilarityContains 1 Ras-GEF domain. {ECO:0000255|PROSITE- ProRule:PRU00168}.
SimilarityContains 2 EF-hand domains. {ECO:0000255|PROSITE- ProRule:PRU00448}.
Subcellular LocationCytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Found both in the cytosol and associated with membranes. Relocalization to the cell membrane upon activation is F-actin-dependent. Translocates to the Golgi in response to phorbol ester or nerve growth factor. Localizes to somata and dendrites but not to axons of hippocampal pyramidal cells (By similarity). {ECO:0000250}.
SubunitHomodimer (PubMed:23908768). Forms a signaling complex with DGKZ and HRAS (PubMed:11257115). Interacts with F-actin (PubMed:12839994). Interacts with SKAP1 (PubMed:17658605). {ECO:0000269|PubMed:11257115, ECO:0000269|PubMed:12839994, ECO:0000269|PubMed:17658605, ECO:0000269|PubMed:23908768}.
Tissue SpecificityExpressed in brain with higher expression in cerebellum, cerebral cortex and amygdala. Expressed in the hematopoietic system. Expressed in T-cells (at protein level). Expressed in NK cells (at protein level) (PubMed:19933860). {ECO:0000269|PubMed:10807788, ECO:0000269|PubMed:17878389, ECO:0000269|PubMed:19933860, ECO:0000269|PubMed:9789079}.
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