RASGRP1

Protein identityUniProt · HPA

UniProt accession

O95267

Gene

RASGRP1

Ensembl

ENSG00000172575

Chromosome

15

Canonical length

797 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene is a member of a family of genes characterized by the presence of a Ras superfamily guanine nucleotide exchange factor (GEF) domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cells and B-cells development, homeostasis and differentiation. Alternatively spliced transcript variants encoding different isoforms have been identified. Altered expression of the different isoforms of this protein may be a cause of susceptibility to systemic lupus erythematosus (SLE). [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

797 residues, UniProt reviewed canonical sequence.

>O95267|RASGRP1
     1  MGTLGKAREA PRKPSHGCRA ASKARLEAKP ANSPFPSHPS LAHITQFRMM VSLGHLAKGA
    61  SLDDLIDSCI QSFDADGNLC RSNQLLQVML TMHRIVISSA ELLQKVITLY KDALAKNSPG
   121  LCLKICYFVR YWITEFWVMF KMDASLTDTM EEFQELVKAK GEELHCRLID TTQINARDWS
   181  RKLTQRIKSN TSKKRKVSLL FDHLEPEELS EHLTYLEFKS FRRISFSDYQ NYLVNSCVKE
   241  NPTMERSIAL CNGISQWVQL MVLSRPTPQL RAEVFIKFIQ VAQKLHQLQN FNTLMAVIGG
   301  LCHSSISRLK ETSSHVPHEI NKVLGEMTEL LSSSRNYDNY RRAYGECTDF KIPILGVHLK
   361  DLISLYEAMP DYLEDGKVNV HKLLALYNHI SELVQLQEVA PPLEANKDLV HLLTLSLDLY
   421  YTEDEIYELS YAREPRNHRA PPLTPSKPPV VVDWASGVSP KPDPKTISKH VQRMVDSVFK
   481  NYDHDQDGYI SQEEFEKIAA SFPFSFCVMD KDREGLISRD EITAYFMRAS SIYSKLGLGF
   541  PHNFQETTYL KPTFCDNCAG FLWGVIKQGY RCKDCGMNCH KQCKDLVVFE CKKRAKNPVA
   601  PTENNTSVGP VSNLCSLGAK DLLHAPEEGP FTFPNGEAVE HGEESKDRTI MLMGVSSQKI
   661  SLRLKRAVAH KATQTESQPW IGSEGPSGPF VLSSPRKTAQ DTLYVLPSPT SPCPSPVLVR
   721  KRAFVKWENK DSLIKSKEEL RHLRLPTYQE LEQEINTLKA DNDALKIQLK YAQKKIESLQ
   781  LEKSNHVLAQ MEQGDCS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RASGRP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

36 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RASGRP1.

Disease | AllUniProt

Conditions RASGRP1 is implicated in, by any mechanism.

• Systemic lupus erythematosus (SLE) MIM:152700
• Immunodeficiency 64 with lymphoproliferation (IMD64) MIM:618534

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 511 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency 64

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.32

gnomAD pLI

0.97

gnomAD missense Z

2.74

DepMap mean gene effect

0

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of GTPase activity
• B cell activation
• B cell proliferation
• cell differentiation
• inflammatory response to antigenic stimulus
• mast cell degranulation
• natural killer cell activation
• positive regulation of MAP kinase activity
• positive regulation of natural killer cell differentiation
• positive regulation of natural killer cell mediated cytotoxicity
• positive regulation of protein phosphorylation
• positive regulation of Ras protein signal transduction
• positive regulation of T cell differentiation in thymus
• Ras protein signal transduction
• regulation of ERK1 and ERK2 cascade
• regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• secretory granule localization
• signal transduction
• T cell activation
• T cell proliferation
• vesicle transport along microtubule

Molecular functions

• calcium ion binding
• diacylglycerol binding
• guanyl-nucleotide exchange factor activity
• identical protein binding
• lipid binding
• phosphatidylcholine binding
• zinc ion binding

Cellular components

• cytosol
• endoplasmic reticulum membrane
• Golgi apparatus
• Golgi membrane
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Ras-like guanine nucleotide exchange factor, N-terminal
• Ras guanine-nucleotide exchange factors catalytic domain
• EF-hand domain
• Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
• Ras-like guanine nucleotide exchange factor
• EF-hand domain pair
• EF-Hand 1, calcium-binding site
• Diacylglycerol/phorbol-ester binding
• Ras guanine nucleotide exchange factor domain superfamily
• Ras guanine-nucleotide exchange factor, catalytic domain superfamily
• C1-like domain superfamily
• Phorbol esters/diacylglycerol binding domain (C1 domain)
• RasGEF domain
• RasGEF N-terminal motif

KeywordsUniProt

• Calcium
• Cell membrane
• Coiled coil
• Cytoplasm
• Differentiation
• Endoplasmic reticulum
• Golgi apparatus
• Guanine-nucleotide releasing factor
• Membrane
• Metal-binding
• Phosphoprotein
• Repeat
• Systemic lupus erythematosus
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of RASGRP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SKAP1