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

    Gene ID: 10156, updated on 2-Nov-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
    mouse all
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    Genomic context

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    See RASA4 in Genome Data Viewer
    Location:
    7q22.1
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (102579646..102616758, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (103897145..103934456, complement)
    RS_2024_09 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 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. CAPRI regulates Ca(2+)-dependent inactivation of the Ras-MAPK pathway. Lockyer PJ, et al. Curr Biol, 2001 Jun 26. PMID 11448776

    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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    NEW Try the new Transcript table

    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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