RASGRP1

Expressed in fetal brain and kidney.

The phorbol-ester/DAG-type zinc finger is the principal mediator of the targeting to membranes and is required for functional activation through DAG-binding.

Two EF-hand domains are present. However, only EF-hand 1 (and not EF-hand 2) binds calcium.

Functions 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, PubMed:27776107, PubMed:29155103). 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, PubMed:27776107, PubMed:29155103). 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. May also function in differentiation of other cell types (PubMed:12845332).

Systemic lupus erythematosus

SLE

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.

None

Disease susceptibility is associated with variants 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.

Immunodeficiency 64 with lymphoproliferation

IMD64

An autosomal recessive primary immunodeficiency characterized by recurrent bacterial, viral and fungal infections, variably decreased numbers of T cells, deficiencies of B and NK cells, and increased susceptibility to Epstein-Barr virus (EBV) infection. Patients may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity.

None

The disease is caused by variants affecting the gene represented in this entry.

Belongs to the RASGRP family.

Expressed 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).

• Cytoplasm
• Cytosol
• Cell membrane
• Peripheral membrane protein
• Golgi apparatus membrane
• Peripheral membrane protein
• Endoplasmic reticulum membrane
• Peripheral membrane protein
• 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).

RASGRP, RAS guanyl-releasing protein 1, Calcium and DAG-regulated guanine nucleotide exchange factor II, Ras guanyl-releasing protein, CalDAG-GEFII

• swissprot:O95267

Proteins

Oncology

90402Da