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RASA4 RAS p21 protein activator 4 [ Homo sapiens (human) ]

Gene ID: 10156, updated on 3-Apr-2024

Summary

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Official Symbol
RASA4provided by HGNC
Official Full Name
RAS p21 protein activator 4provided by HGNC
Primary source
HGNC:HGNC:23181
See related
Ensembl:ENSG00000105808 MIM:607943; AllianceGenome:HGNC:23181
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GAPL; CAPRI
Summary
This gene encodes a member of the GAP1 family of GTPase-activating proteins that suppresses the Ras/mitogen-activated protein kinase pathway in response to Ca(2+). Stimuli that increase intracellular Ca(2+) levels result in the translocation of this protein to the plasma membrane, where it activates Ras GTPase activity. Consequently, Ras is converted from the active GTP-bound state to the inactive GDP-bound state and no longer activates downstream pathways that regulate gene expression, cell growth, and differentiation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in endometrium (RPKM 14.7), spleen (RPKM 11.8) and 24 other tissues See more
Orthologs
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Genomic context

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Location:
7q22.1
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (102579646..102616758, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (103897145..103934456, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (102220093..102257205, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene POLR2J3-UPK3BL2 readthrough Neighboring gene speedy/RINGO cell cycle regulator family member E2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:102212169-102212830 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:102213197-102213370 Neighboring gene uncharacterized LOC124901712 Neighboring gene RNA polymerase II subunit J3 Neighboring gene uncharacterized LOC124901714 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:102250895-102251509 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:102252774-102253416 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:102253600-102254568 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:102255538-102256506 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:102264455-102264956 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:102264957-102265456 Neighboring gene POLR2J2-UPK3BL1 readthrough Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:102281267-102281768 Neighboring gene uroplakin 3B like 1 Neighboring gene speedy/RINGO cell cycle regulator family member E2B

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. RASA4 inhibits the HIFα signaling pathway to suppress proliferation of cervical cancer cells. Chen J, et al. Bioengineered, 2021 Dec. PMID 34752201, Free PMC Article
  2. Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients. Xu X, et al. Proc Natl Acad Sci U S A, 2021 Oct 26. PMID 34675073, Free PMC Article
  3. RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia. Poetsch AR, et al. Epigenetics, 2014 Sep. PMID 25147919, Free PMC Article
  4. Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts. Malone ET, et al. Front Cell Infect Microbiol, 2021. PMID 34094999, Free PMC Article
  5. Distinct phosphoinositide binding specificity of the GAP1 family proteins: characterization of the pleckstrin homology domains of MRASAL and KIAA0538. Minagawa T, et al. Biochem Biophys Res Commun, 2001 Oct 19. PMID 11594756

See all (21) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RASA4 inhibits the HIFalpha signaling pathway to suppress proliferation of cervical cancer cells.
    Title: RASA4 inhibits the HIFα signaling pathway to suppress proliferation of cervical cancer cells.
  2. Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.
    Title: Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients.
  3. Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts.
    Title: Treponema denticola-Induced RASA4 Upregulation Mediates Cytoskeletal Dysfunction and MMP-2 Activity in Periodontal Fibroblasts.
  4. RASA4 isoform 2 promoter methylation correlated with clinical parameters predicting poor prognosis (older age, elevated fetal hemoglobin), with higher risk of relapse after hematopoietic stem cell transplantation, and with PTPN11 mutation.
    Title: RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia.
  5. Ca2+-dependent monomer and dimer formation switches CAPRI Protein between Ras GTPase-activating protein (GAP) and RapGAP activities
    Title: Ca2+-dependent monomer and dimer formation switches CAPRI Protein between Ras GTPase-activating protein (GAP) and RapGAP activities.
  6. CAPRI seems to low-pass filter the Ca2+ signal, converting different intensities of stimulation into different durations of Ras activity.
    Title: CAPRI and RASAL impose different modes of information processing on Ras due to contrasting temporal filtering of Ca2+.
  7. CAPRI (Ca2+-promoted Ras inactivator) a Ca2+-dependent Ras GTPase-activating protein (Ras GAP). Switches off the Ras-MAPK pathway following G protein-coupled receptor stimulated intracellular Ca2+ elevation that recruits CAPRI to the plasma membrane.
    Title: CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway.
Submit: New GeneRIF Correction

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ59070, KIAA0538, MGC131890

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables GTPase activator activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables phospholipid binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in cellular response to calcium ion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of GTPase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of GTPase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of Ras protein signal transduction IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
colocalizes_with plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
ras GTPase-activating protein 4
Names
Ca2+-promoted Ras inactivator
calcium-promoted Ras inactivator
rasGAP-activating-like protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001079877.2 → NP_001073346.2  ras GTPase-activating protein 4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1.
    Source sequence(s)
    AC093668, AC105052
    Consensus CDS
    CCDS47674.1
    UniProtKB/TrEMBL
    Q2NL74
    Related
    ENSP00000412876.2, ENST00000449970.6
    Conserved Domains (5) summary
    cd04025
    Location:134 → 257
    C2B_RasA1_RasA4; C2 domain second repeat present in RasA1 and RasA4
    cd04054
    Location:6 → 126
    C2A_Rasal1_RasA4; C2 domain first repeat present in RasA1 and RasA4
    cd05395
    Location:265 → 550
    RasGAP_RASA4; Ras-GTPase Activating Domain of RASA4
    smart00323
    Location:244 → 605
    RasGAP; GTPase-activator protein for Ras-like GTPases
    cl17171
    Location:542 → 635
    PH-like; Pleckstrin homology-like domain

  2. NM_006989.6 → NP_008920.5  ras GTPase-activating protein 4 isoform 1

    See identical proteins and their annotated locations for NP_008920.5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC093668, AC105052
    Consensus CDS
    CCDS5725.1
    UniProtKB/Swiss-Prot
    O43374, O60286, Q14CQ4, Q86UW3, Q96QU0
    UniProtKB/TrEMBL
    Q2NL74
    Related
    ENSP00000262940.8, ENST00000262940.12
    Conserved Domains (7) summary
    cd04025
    Location:134 → 257
    C2B_RasA1_RasA4; C2 domain second repeat present in RasA1 and RasA4
    cd04054
    Location:6 → 126
    C2A_Rasal1_RasA4; C2 domain first repeat present in RasA1 and RasA4
    cd05395
    Location:265 → 550
    RasGAP_RASA4; Ras-GTPase Activating Domain of RASA4
    smart00323
    Location:244 → 605
    RasGAP; GTPase-activator protein for Ras-like GTPases
    cd13372
    Location:542 → 681
    PH_CAPRI; Ca2+ promoted Ras inactivator pleckstrin homology (PH) domain
    pfam00169
    Location:567 → 672
    PH; PH domain
    pfam00779
    Location:681 → 709
    BTK; BTK motif

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    102579646..102616758 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047419706.1 → XP_047275662.1  ras GTPase-activating protein 4 isoform X4

    UniProtKB/TrEMBL
    E7ERK1
    Related
    ENSP00000417395.1, ENST00000462172.5

  2. XM_047419707.1 → XP_047275663.1  ras GTPase-activating protein 4 isoform X9

  3. XM_047419709.1 → XP_047275665.1  ras GTPase-activating protein 4 isoform X8

  4. XM_047419702.1 → XP_047275658.1  ras GTPase-activating protein 4 isoform X2

  5. XM_047419703.1 → XP_047275659.1  ras GTPase-activating protein 4 isoform X3

  6. XM_047419701.1 → XP_047275657.1  ras GTPase-activating protein 4 isoform X1

  7. XM_047419708.1 → XP_047275664.1  ras GTPase-activating protein 4 isoform X7

    Related
    ENST00000523568.5

  8. XM_047419704.1 → XP_047275660.1  ras GTPase-activating protein 4 isoform X5

  9. XM_047419705.1 → XP_047275661.1  ras GTPase-activating protein 4 isoform X6

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    103897145..103934456 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047444983.1 → XP_047300939.1  ras GTPase-activating protein 4 isoform X4

  2. XM_047444990.1 → XP_047300946.1  ras GTPase-activating protein 4 isoform X8

  3. XM_047444985.1 → XP_047300941.1  ras GTPase-activating protein 4 isoform X10

  4. XM_047444981.1 → XP_047300937.1  ras GTPase-activating protein 4 isoform X2

  5. XM_047444982.1 → XP_047300938.1  ras GTPase-activating protein 4 isoform X3

  6. XM_047444980.1 → XP_047300936.1  ras GTPase-activating protein 4 isoform X1

  7. XM_047444989.1 → XP_047300945.1  ras GTPase-activating protein 4 isoform X7

  8. XM_047444987.1 → XP_047300943.1  ras GTPase-activating protein 4 isoform X12

  9. XM_047444984.1 → XP_047300940.1  ras GTPase-activating protein 4 isoform X5

  10. XM_047444986.1 → XP_047300942.1  ras GTPase-activating protein 4 isoform X11

  11. XM_047444988.1 → XP_047300944.1  ras GTPase-activating protein 4 isoform X6

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43374.2 GenPept UniProtKB/Swiss-Prot:O43374

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