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RAS guanyl-releasing protein 1 (Ras guanyl-releasing protein, Ca+2 & DAG-regulated guanine nucleotide exchange factor II, calDAG-GEFII, RASGRP1, RASGRP)
Function:
- diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP
- activates the Erk/MAP kinase cascade
- couples T-lymphocytes & B-lymphocytes antigen receptors to the activation of Ras
- hence, regulates T-cells & B-cells development, homeostasis & differentiation
- functions also in FcERI-evoked degranulation & cytokine secretion by mast cells, regulating allergic response
- may also function in other cell types differentiation forms a signaling complex with DGKZ & HRAS
- interacts with F-actin
- interacts with SKAP1
- probably regulated by Ca+2 (putative)
- regulated by PLC gamma, DGKA, DGKZ & by F-actin polymerization
Structure:
- phorbol-ester/DAG-type Zn+2 finger is the principal mediator of the targeting to membranes & is required for functional activation through DAG-binding
- belongs to the RASGRP family
- contains 2 EF-hand domains
- contains 1 N-terminal Ras-GEF domain
- contains 1 phorbol-ester/DAG-type Zn+2 finger
- contains 1 Ras-GEF domain
Compartment:
- cytoplasm, peripheral membrane, cell membrane
- Golgi apparatus, endoplasmic reticulum
- found both in the cytosol & 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 & dendrites but not to axons of hippocampal pyramidal cells
Alternative splicing:
- named isoforms=5
- additional isoforms seem to exist
- several splicing events may be used independently in a modular way
Expression:
- expressed in brain with higher expression cerebellum, cerebral cortex & amygdala
- expressed in the hematopoietic system
- expressed in T-cells (at protein level)
- expressed in fetal brain & kidney
Pathology:
- altered expression of the different RASGRP1 isoforms may be a cause of susceptibility to systemic lupus erythematosus
General
Ca+2 binding protein
guanine nucleotide exchange factor (GDP/GTP dissociation stimulator, guanine nucleotide-releasing factor/protein, GNEF, GNDS, GDS)
phosphoprotein
zinc finger protein
Properties
SIZE: entity length = 797 aa
MW = 90 kD
COMPARTMENT: cytoplasm
golgi
endoplasmic reticulum
MOTIF: guanine nucleotide exchange domain
NAME: guanine nucleotide exchange domain
SITE: 53-176
MOTIF: Ras exchanger motif region; required for transforming activity {57-110}
Thr phosphorylation site {T184}
guanine nucleotide exchange domain
NAME: guanine nucleotide exchange domain
SITE: 205-436
EF hand
SITE: 470-505
MOTIF: Ca+2-binding site
SITE: 483-494
EF hand
SITE: 497-532
MOTIF: Ca+2-binding site
SITE: 510-521
Zinc finger
NAME: Zinc finger
SITE: 541-591
EFFECTOR-BOUND: Zn+2
Suppress the PT region-mediated translocation to plasma membrane {686-694}
PT region; mediates the BCR-dependent translocation to plasma membrane {718-797}
MOTIF: coiled coil {746-786}
Database Correlations
OMIM correlations
UniProt O95267
PFAM correlations
Kegg hsa:1012
References
UniProt :accession O95267