Seroatlas · Human Serome Atlas

RASGRP4

RAS guanyl-releasing protein 4

Also known as: GRP4_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
Q8TDF6
Gene
RASGRP4
Ensembl
ENSG00000171777
Chromosome
19
Canonical length
673 aa
Protein class
Predicted intracellular proteins, RAS pathway related proteins
Subcellular location
Nucleoplasm,Plasma membrane,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors. It contains a Ras exchange motif, a diacylglycerol-binding domain, and two calcium-binding EF hands. This protein was shown to activate H-Ras in a cation-dependent manner in vitro. Expression of this protein in myeloid cell lines was found to be correlated with elevated level of activated RAS protein, and the RAS activation can be greatly enhanced by phorbol ester treatment, which suggested a role of this protein in diacylglycerol regulated cell signaling pathways. Studies of a mast cell leukemia cell line expressing substantial amounts of abnormal transcripts of this gene indicated that this gene may play an important role in the final stages of mast cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

Canonical amino-acid sequenceUniProt

673 residues, UniProt reviewed canonical sequence.

>Q8TDF6|RASGRP4
     1  MNRKDSKRKS HQECTGKIGG RGRPRQVRRH KTCPSPREIS KVMASMNLGL LSEGGCSEDE
    61  LLEKCIQSFD SAGSLCHEDH MLNMVLAMHS WVLPSADLAA RLLTSYQKAT GDTQELRRLQ
   121  ICHLVRYWLM RHPEVMHQDP QLEEVIGRFW ATVAREGNSA QRRLGDSSDL LSPGGPGPPL
   181  PMSSPGLGKK RKVSLLFDHL ETGELAQHLT YLEFRSFQAI TPQDLRSYVL QGSVRGCPAL
   241  EGSVGLSNSV SRWVQVMVLS RPGPLQRAQV LDKFIHVAQR LHQLQNFNTL MAVTGGLCHS
   301  AISRLKDSHA HLSPDSTKAL LELTELLASH NNYARYRRTW AGCAGFRLPV LGVHLKDLVS
   361  LHEAQPDRLP DGRLHLPKLN NLYLRLQELV ALQGQHPPCS ANEDLLHLLT LSLDLFYTED
   421  EIYELSYARE PRCPKSLPPS PFNAPLVVEW APGVTPKPDR VTLGRHVEQL VESVFKNYDP
   481  EGRGTISQED FERLSGNFPF ACHGLHPPPR QGRGSFSREE LTGYLLRASA ICSKLGLAFL
   541  HTFHEVTFRK PTFCDSCSGF LWGVTKQGYR CRECGLCCHK HCRDQVKVEC KKRPGAKGDA
   601  GPPGAPVPST PAPHASCGSE ENHSYTLSLE PETGCQLRHA WTQTESPHPS WETDTVPCPV
   661  MDPPSTASSK LDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RASGRP4 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)
0.35
Highest tissue expression
20 nTPM

Expression across tissuesHPA

Tissue

  • bone marrow: 20 nTPM
  • spleen: 9.4 nTPM
  • appendix: 6.3 nTPM
  • lung: 3.1 nTPM
  • adipose tissue: 3 nTPM
  • urinary bladder: 2.3 nTPM

Single-cell type

  • neutrophils: 219 nCPM
  • neutrophil progenitors: 52 nCPM
  • mast cells: 39 nCPM
  • monocytes: 37 nCPM
  • hofbauer cells: 35 nCPM
  • kupffer cells: 20 nCPM

Immune cell

  • neutrophil: 40 nTPM
  • eosinophil: 20 nTPM
  • non-classical monocyte: 18 nTPM
  • intermediate monocyte: 15 nTPM
  • classical monocyte: 13 nTPM
  • basophil: 13 nTPM

Brain region

  • thalamus: 3.3 nTPM
  • white matter: 3.2 nTPM
  • medulla oblongata: 2.8 nTPM
  • spinal cord: 2.5 nTPM
  • pons: 2.2 nTPM
  • cerebral cortex: 1.9 nTPM

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)
0.46
gnomAD pLI
0.04
gnomAD missense Z
2.05
DepMap mean gene effect
-0.06
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads RASGRP4 as an antibody target. Whether an autoantibody or antibody against RASGRP4 could matter depends on whether native RASGRP4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

RASGRP4 is annotated at the cell surface, where native RASGRP4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label RASGRP4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/RASGRP4. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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