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Target has curated data in GtoImmuPdb
Target id: 3016
Nomenclature: RAS guanyl releasing protein 1
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 797 | 15q14 | RASGRP1 | RAS guanyl releasing protein 1 | |
Mouse | - | 795 | 2 59.19 cM | Rasgrp1 | RAS guanyl releasing protein 1 | |
Rat | - | 795 | 3q35 | Rasgrp1 | RAS guanyl releasing protein 1 | |
Gene and Protein Information Comments | ||||||
The human gene gives rise to alternatively spliced transcript variants that encode different protein isoforms. Isoform a is the longest at 797 amino acids, and isoforms b and c are shorter proteins. |
Previous and Unofficial Names |
calcium- and diacylglycerol-regulated guanine nucleotide exchange factor II | CalDAG-GEFII | RASGRP | RAS guanyl releasing protein 1 (calcium and DAG-regulated) |
Database Links | |
Alphafold | O95267 (Hs), Q9Z1S3 (Mm), Q9R1K8 (Rn) |
ChEMBL Target | CHEMBL5953 (Hs), CHEMBL3109 (Rn) |
Ensembl Gene | ENSG00000172575 (Hs), ENSMUSG00000027347 (Mm), ENSRNOG00000005404 (Rn) |
Entrez Gene | 10125 (Hs), 19419 (Mm), 29434 (Rn) |
Human Protein Atlas | ENSG00000172575 (Hs) |
KEGG Gene | hsa:10125 (Hs), mmu:19419 (Mm), rno:29434 (Rn) |
OMIM | 603962 (Hs) |
Pharos | O95267 (Hs) |
RefSeq Nucleotide | NM_005739 (Hs), NM_011246 (Mm), NM_019211 (Rn) |
RefSeq Protein | NP_005730 (Hs), NP_035376 (Mm), NP_062084 (Rn) |
UniProtKB | O95267 (Hs), Q9Z1S3 (Mm), Q9R1K8 (Rn) |
Wikipedia | RASGRP1 (Hs) |
Download all structure-activity data for this target as a CSV file
Activators | |||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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Immunopharmacology Comments |
RAS guanyl releasing protein 1 (RASGRP1) functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor. It activates Ras and the downstream Erk/MAP kinase cascade. RASGRP1 regulates the development, homeostasis and differentiation of T aand B cells [2,7,10], and has been linked to NK cell development and function [4,10]. Loss-of-function mutations in RASGRP1 have been identified in patients with early onset primary immunodeficiency and a predisposition to lymphoproliferative disease [5-6,11-12]. Autoimmune pathology has also been reported as a consequence of defective RASGRP1 function [3,13].[9]. |
Immuno Process Associations | ||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Gene Expression and Pathophysiology Comments | |
Biallelic loss-of-function mutations in RASGRP1 have been identified in patients presenting with early onset primary immunodeficiency and a predisposition to lymphoproliferative disease ( e.g. Epstein-Barr virus (EBV)-associated B cell lymphoma) [5-6,11-12]. |
1. Garcia LC, Donadío LG, Mann E, Kolusheva S, Kedei N, Lewin NE, Hill CS, Kelsey JS, Yang J, Esch TE et al.. (2014) Synthesis, biological, and biophysical studies of DAG-indololactones designed as selective activators of RasGRP. Bioorg Med Chem, 22 (12): 3123-40. [PMID:24794745]
2. Golec DP, Henao Caviedes LM, Baldwin TA. (2016) RasGRP1 and RasGRP3 Are Required for Efficient Generation of Early Thymic Progenitors. J Immunol, 197 (5): 1743-53. [PMID:27465532]
3. Layer K, Lin G, Nencioni A, Hu W, Schmucker A, Antov AN, Li X, Takamatsu S, Chevassut T, Dower NA et al.. (2003) Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity, 19 (2): 243-55. [PMID:12932358]
4. Lee SH, Yun S, Lee J, Kim MJ, Piao ZH, Jeong M, Chung JW, Kim TD, Yoon SR, Greenberg PD et al.. (2009) RasGRP1 is required for human NK cell function. J Immunol, 183 (12): 7931-8. [PMID:19933860]
5. Mao H, Yang W, Latour S, Yang J, Winter S, Zheng J, Ni K, Lv M, Liu C, Huang H et al.. (2018) RASGRP1 mutation in autoimmune lymphoproliferative syndrome-like disease. J Allergy Clin Immunol, 142 (2): 595-604.e16. [PMID:29155103]
6. Platt CD, Fried AJ, Hoyos-Bachiloglu R, Usmani GN, Schmidt B, Whangbo J, Chiarle R, Chou J, Geha RS. (2017) Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1. Clin Immunol, 183: 142-144. [PMID:28822832]
7. Priatel JJ, Chen X, Huang YH, Chow MT, Zenewicz LA, Coughlin JJ, Shen H, Stone JC, Tan R, Teh HS. (2010) RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells. J Immunol, 184 (2): 666-76. [PMID:20007535]
8. Priatel JJ, Chen X, Zenewicz LA, Shen H, Harder KW, Horwitz MS, Teh HS. (2007) Chronic immunodeficiency in mice lacking RasGRP1 results in CD4 T cell immune activation and exhaustion. J Immunol, 179 (4): 2143-52. [PMID:17675473]
9. Rapoport MJ, Bloch O, Amit-Vasina M, Yona E, Molad Y. (2011) Constitutive abnormal expression of RasGRP-1 isoforms and low expression of PARP-1 in patients with systemic lupus erythematosus. Lupus, 20 (14): 1501-9. [PMID:21976405]
10. Shen S, Chen Y, Gorentla BK, Lu J, Stone JC, Zhong XP. (2011) Critical roles of RasGRP1 for invariant NKT cell development. J Immunol, 187 (9): 4467-73. [PMID:21957144]
11. Somekh I, Marquardt B, Liu Y, Rohlfs M, Hollizeck S, Karakukcu M, Unal E, Yilmaz E, Patiroglu T, Cansever M et al.. (2018) Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma. J Clin Immunol, 38 (6): 699-710. [PMID:30030704]
12. Winter S, Martin E, Boutboul D, Lenoir C, Boudjemaa S, Petit A, Picard C, Fischer A, Leverger G, Latour S. (2018) Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility. EMBO Mol Med, 10 (2): 188-199. [PMID:29282224]
13. Yasuda S, Stevens RL, Terada T, Takeda M, Hashimoto T, Fukae J, Horita T, Kataoka H, Atsumi T, Koike T. (2007) Defective expression of Ras guanyl nucleotide-releasing protein 1 in a subset of patients with systemic lupus erythematosus. J Immunol, 179 (7): 4890-900. [PMID:17878389]
EF-hand domain containing proteins: RAS guanyl releasing protein 1. Last modified on 28/08/2018. Accessed on 02/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=3016.