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Aliases for RASGRP4 Gene

Aliases for RASGRP4 Gene

  • RAS Guanyl Releasing Protein 4 2 3 5

External Ids for RASGRP4 Gene

Previous GeneCards Identifiers for RASGRP4 Gene

  • GC19M039514
  • GC19M039291
  • GC19M043575
  • GC19M043591
  • GC19M038899
  • GC19M035347

Summaries for RASGRP4 Gene

Entrez Gene Summary for RASGRP4 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]

GeneCards Summary for RASGRP4 Gene

RASGRP4 (RAS Guanyl Releasing Protein 4) is a Protein Coding gene. Diseases associated with RASGRP4 include Mast-Cell Leukemia and Mastocytosis. Among its related pathways are RET signaling and Immune System. GO annotations related to this gene include calcium ion binding and GTP-dependent protein binding. An important paralog of this gene is RASGRP1.

UniProtKB/Swiss-Prot for RASGRP4 Gene

  • Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. May function in mast cells differentiation.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RASGRP4 Gene

Genomics for RASGRP4 Gene

Regulatory Elements for RASGRP4 Gene

Enhancers for RASGRP4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19F038426 0.3 FANTOM5 19.1 +0.8 802 0.1 ZMYM3 ZIC2 HIC1 ZFHX2 GLIS2 POLR2A PRDM10 KDM1A EGR2 ZBTB20 RASGRP4 NFKBIB RINL GC19P038425
GH19F038385 0.7 ENCODE 11.4 +41.4 41440 0.2 ZNF263 CTCF ZNF654 GLIS2 POLR2A GLIS1 SMC3 PRDM10 RAD21 SUPT5H CATSPERG RASGRP4 RYR1 ENSG00000267090 PSMD8
GH19F038386 0.5 ENCODE 11.4 +39.8 39810 0.2 ZNF202 ZNF121 ZBTB33 ZNF573 RASGRP4 RYR1 ZNF571 ENSG00000267090 SPRED3
GH19F038527 0.8 ENCODE 11.3 -101.6 -101631 0.0 OSR2 SP3 RNF2 IRF1 ZBTB7A RYR1 RASGRP4 ENSG00000269445 GC19P038502
GH19F038538 0.8 Ensembl ENCODE 10.9 -112.5 -112485 0.9 ZBTB10 ZNF121 ZNF362 MTA2 ETV6 TBX21 FAM98C RYR1 RASGRP4 FBXO27 FBXO17 ENSG00000268055 GC19P038542
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around RASGRP4 on UCSC Golden Path with GeneCards custom track

Promoters for RASGRP4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000216431 405 601 EBF1 ZIC2 ZNF121 GLIS2 EED PRDM10 ZNF740 RNF2 ZBTB11 JUNB

Genomic Location for RASGRP4 Gene

Chromosome:
19
Start:
38,409,051 bp from pter
End:
38,426,305 bp from pter
Size:
17,255 bases
Orientation:
Minus strand

Genomic View for RASGRP4 Gene

Genes around RASGRP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RASGRP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RASGRP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RASGRP4 Gene

Proteins for RASGRP4 Gene

  • Protein details for RASGRP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TDF6-GRP4_HUMAN
    Recommended name:
    RAS guanyl-releasing protein 4
    Protein Accession:
    Q8TDF6
    Secondary Accessions:
    • A6H8M4
    • C0LTP2
    • C0LTP3
    • C0LTP4
    • C0LTP5
    • C0LTP7
    • C9J416
    • C9JHZ1
    • Q8N858
    • Q96QN5
    • Q96QN6
    • Q96QN7

    Protein attributes for RASGRP4 Gene

    Size:
    673 amino acids
    Molecular mass:
    74882 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for RASGRP4 Gene

neXtProt entry for RASGRP4 Gene

Post-translational modifications for RASGRP4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

No data available for DME Specific Peptides for RASGRP4 Gene

Domains & Families for RASGRP4 Gene

Gene Families for RASGRP4 Gene

Graphical View of Domain Structure for InterPro Entry

Q8TDF6

UniProtKB/Swiss-Prot:

GRP4_HUMAN :
  • The phorbol-ester/DAG-type zinc finger mediates the binding and the functional activation by DAG.
  • Belongs to the RASGRP family.
  • Contains 1 phorbol-ester/DAG-type zinc finger.
Domain:
  • The phorbol-ester/DAG-type zinc finger mediates the binding and the functional activation by DAG.
  • Contains 1 EF-hand domain.
  • Contains 1 N-terminal Ras-GEF domain.
  • Contains 1 Ras-GEF domain.
Family:
  • Belongs to the RASGRP family.
Similarity:
  • Contains 1 phorbol-ester/DAG-type zinc finger.
genes like me logo Genes that share domains with RASGRP4: view

Function for RASGRP4 Gene

Molecular function for RASGRP4 Gene

UniProtKB/Swiss-Prot Function:
Functions as a cation- and diacylglycerol (DAG)-regulated nucleotide exchange factor activating Ras through the exchange of bound GDP for GTP. May function in mast cells differentiation.

Gene Ontology (GO) - Molecular Function for RASGRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS --
GO:0005509 calcium ion binding IEA --
GO:0019992 diacylglycerol binding TAS 11880369
GO:0030742 GTP-dependent protein binding NAS 11880369
genes like me logo Genes that share ontologies with RASGRP4: view
genes like me logo Genes that share phenotypes with RASGRP4: view

Animal Models for RASGRP4 Gene

MGI Knock Outs for RASGRP4:

Animal Model Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for RASGRP4 Gene

Localization for RASGRP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RASGRP4 Gene

Cytoplasm. Cell membrane. Note=Recruited to membranes upon activation by DAG.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RASGRP4 Gene COMPARTMENTS Subcellular localization image for RASGRP4 gene
Compartment Confidence
cytosol 5
plasma membrane 5
nucleus 2

Gene Ontology (GO) - Cellular Components for RASGRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS 11880369
GO:0016020 membrane IEA,IDA 11880369
genes like me logo Genes that share ontologies with RASGRP4: view

Pathways & Interactions for RASGRP4 Gene

SuperPathways for RASGRP4 Gene

SuperPathway Contained pathways
1 RET signaling
2 MAPK signaling pathway
3 Developmental Biology
4 Cytokine Signaling in Immune system
5 Immune System
genes like me logo Genes that share pathways with RASGRP4: view

Pathways by source for RASGRP4 Gene

1 GeneGo (Thomson Reuters) pathway for RASGRP4 Gene

Gene Ontology (GO) - Biological Process for RASGRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway NAS 11880369
GO:0007202 activation of phospholipase C activity NAS 11880369
GO:0007264 small GTPase mediated signal transduction IEA --
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway NAS 11880369
genes like me logo Genes that share ontologies with RASGRP4: view

No data available for SIGNOR curated interactions for RASGRP4 Gene

Drugs & Compounds for RASGRP4 Gene

(1) Drugs for RASGRP4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Guanosine triphosphate Experimental Pharma 0

(4) Additional Compounds for RASGRP4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Diglycerides Group A
  • 1,2-Dimyristoyl-rac-glycerol
  • DAG(14:0/14:0)
  • DAG(28:0)
  • DG(14:0/14:0)
  • DG(28:0)
Diglycerides Group B
  • 1-Palmitoleoyl-2-arachidonyl-sn-glycerol
  • DAG(16:1/20:0)
  • DAG(16:1n7/20:0)
  • DAG(16:1w7/20:0)
  • DAG(36:1)
Diglycerides Group C
  • 1-Myristoyl-3-stearoyl-sn-glycerol
  • 1-Tetradecanoyl-3-octadecanoyl-sn-glycerol
  • DAG(14:0/0:0/18:0)
  • DAG(32:0)
  • DG(32:0)
Diglycerides Group D
  • 1,2-Didocosahexaenoyl-rac-glycerol
  • DAG(22:6/22:6)
  • DAG(22:6n3/22:6n3)
  • DAG(22:6w3/22:6w3)
  • DAG(44:12)
genes like me logo Genes that share compounds with RASGRP4: view

Transcripts for RASGRP4 Gene

Unigene Clusters for RASGRP4 Gene

RAS guanyl releasing protein 4:
Representative Sequences:

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RASGRP4 Gene

No ASD Table

Relevant External Links for RASGRP4 Gene

GeneLoc Exon Structure for
RASGRP4
ECgene alternative splicing isoforms for
RASGRP4

Expression for RASGRP4 Gene

mRNA expression in normal human tissues for RASGRP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for RASGRP4 Gene

This gene is overexpressed in Whole Blood (x41.3).

Protein differential expression in normal tissues from HIPED for RASGRP4 Gene

This gene is overexpressed in Cervix (25.5), Monocytes (13.0), Tlymphocyte (10.3), Heart (9.4), and Neutrophil (7.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for RASGRP4 Gene



Protein tissue co-expression partners for RASGRP4 Gene

NURSA nuclear receptor signaling pathways regulating expression of RASGRP4 Gene:

RASGRP4

SOURCE GeneReport for Unigene cluster for RASGRP4 Gene:

Hs.130434

mRNA Expression by UniProt/SwissProt for RASGRP4 Gene:

Q8TDF6-GRP4_HUMAN
Tissue specificity: Expressed by mast cells and their progenitors (at protein level). Specifically expressed in mononuclear leukocytes. Highly expressed in myeloid cells compared to lymphoid cells. Also detected in heart, skeletal muscle, spleen, liver, placenta and lung. Not detected in brain. Isoform 1 is the major isoform in normal individuals. Isoform 2 is more significantly expressed in a patient with asthma. Isoform 3 is more significantly expressed in a patient with asthma and a mastocytosis patient.
genes like me logo Genes that share expression patterns with RASGRP4: view

Primer Products

Orthologs for RASGRP4 Gene

This gene was present in the common ancestor of animals.

Orthologs for RASGRP4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RASGRP4 34 35
  • 99.26 (n)
dog
(Canis familiaris)
Mammalia RASGRP4 34 35
  • 88.96 (n)
cow
(Bos Taurus)
Mammalia RASGRP4 34 35
  • 88.16 (n)
mouse
(Mus musculus)
Mammalia Rasgrp4 34 16 35
  • 83.78 (n)
rat
(Rattus norvegicus)
Mammalia Rasgrp4 34
  • 82.64 (n)
oppossum
(Monodelphis domestica)
Mammalia RASGRP4 35
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RASGRP4 35
  • 52 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RASGRP4 35
  • 55 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii rasgrp4 35
  • 45 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea rgef-1 35
  • 29 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 35 (a)
OneToMany
Species where no ortholog for RASGRP4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for RASGRP4 Gene

ENSEMBL:
Gene Tree for RASGRP4 (if available)
TreeFam:
Gene Tree for RASGRP4 (if available)

Paralogs for RASGRP4 Gene

Paralogs for RASGRP4 Gene

(4) SIMAP similar genes for RASGRP4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with RASGRP4: view

Variants for RASGRP4 Gene

Sequence variations from dbSNP and Humsavar for RASGRP4 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs10411128 -- 38,414,364(+) cccag(C/G)ctggg intron-variant
rs10411217 -- 38,414,599(+) GGGAT(C/T)ACAGG intron-variant
rs10412098 -- 38,415,043(+) CGGAA(A/G)CCCGC intron-variant, nc-transcript-variant, reference, synonymous-codon
rs10413428 -- 38,424,102(+) TCTCC(A/G)GGGAT intron-variant
rs10419454 -- 38,424,280(+) acgcc(C/G)agcta intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RASGRP4 Gene

Variant ID Type Subtype PubMed ID
dgv3525n100 CNV gain 25217958
nsv1064275 CNV loss 25217958
nsv470140 CNV gain 18288195
nsv833822 CNV loss 17160897
nsv833823 CNV loss 17160897
nsv833824 CNV loss 17160897

Variation tolerance for RASGRP4 Gene

Residual Variation Intolerance Score: 92.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.07; 68.92% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RASGRP4 Gene

Human Gene Mutation Database (HGMD)
RASGRP4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RASGRP4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RASGRP4 Gene

Disorders for RASGRP4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RASGRP4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
mast-cell leukemia
  • leukemia mast cell
mastocytosis
  • mast cell disease
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for RASGRP4

Genetic Association Database (GAD)
RASGRP4
Human Genome Epidemiology (HuGE) Navigator
RASGRP4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RASGRP4
genes like me logo Genes that share disorders with RASGRP4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RASGRP4 Gene

Publications for RASGRP4 Gene

  1. The diacylglycerol-dependent translocation of ras guanine nucleotide- releasing protein 4 inside a human mast cell line results in substantial phenotypic changes, including expression of interleukin 13 receptor alpha2. (PMID: 18024961) Katsoulotos G.P. … Krilis S.A. (J. Biol. Chem. 2008) 3 4 22 64
  2. RasGRP4 regulates the expression of prostaglandin D2 in human and rat mast cell lines. (PMID: 12493770) Li L. … Stevens R.L. (J. Biol. Chem. 2003) 3 4 22 64
  3. RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. (PMID: 11956218) Yang Y. … Stevens R.L. (J. Biol. Chem. 2002) 2 3 4 64
  4. RasGRP4 is a novel Ras activator isolated from acute myeloid leukemia. (PMID: 11880369) Reuther G.W. … Der C.J. (J. Biol. Chem. 2002) 3 4 22 64
  5. Aberrant splicing of the hRasGRP4 transcript and decreased levels of this signaling protein in the peripheral blood mononuclear cells in a subset of patients with rheumatoid arthritis. (PMID: 21933395) Hashimoto T. … Koike T. (Arthritis Res. Ther. 2011) 3 4 64

Products for RASGRP4 Gene

Sources for RASGRP4 Gene