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    CASP9 caspase 9 [ Homo sapiens (human) ]

    Gene ID: 842, updated on 3-Dec-2024

    Summary

    Official Symbol
    CASP9provided by HGNC
    Official Full Name
    caspase 9provided by HGNC
    Primary source
    HGNC:HGNC:1511
    See related
    Ensembl:ENSG00000132906 MIM:602234; AllianceGenome:HGNC:1511
    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
    MCH6; APAF3; APAF-3; PPP1R56; ICE-LAP6
    Summary
    This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
    Expression
    Ubiquitous expression in adrenal (RPKM 10.2), ovary (RPKM 6.7) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See CASP9 in Genome Data Viewer
    Location:
    1p36.21
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (15491401..15524912, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (14936101..14969610, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (15817896..15851285, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376767 Neighboring gene chymotrypsin like elastase 2A Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:15809342-15809842 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:15809843-15810343 Neighboring gene chymotrypsin like elastase 2B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:15826802-15827302 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:15831890-15832390 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:15835827-15836756 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 304 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 305 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:15852999-15853502 Neighboring gene Sharpr-MPRA regulatory region 4011 Neighboring gene DnaJ heat shock protein family (Hsp40) member C16 Neighboring gene small Cajal body-specific RNA 21B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 239 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 308 Neighboring gene agmatinase (putative)

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV-1 subtype C activates CASP9, which induces apoptosis of cardiomyocytes and can be inhibited with the HIV-1 neutralizing aptamer UCLA1 PubMed
    HIV-1 activates CASP9 (Caspase-9) in CD4+ T lymphocytes as observed in clinical samples collected from HIV-1 infected patients PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env The interaction of cell-associated HIV-1 gp120 with CXCR4-expressing target cells triggers apoptotic processes by activating caspase-9 and -3 PubMed
    env Treatment of human retinal capillary endothelial cells (HRCECs) with HIV-1 gp120 increases the numbers of apoptotic cells and expression of cleaved caspase-9 protein, but decreases mitochondrial membrane potential PubMed
    env Treatment of HIV-1 Env-pseudotyped virus-infected MDM cells with both soluble TRAIL and an agonistic anti-DR5 antibody AD5-10 induces activation of caspase-3, -8, and -9 PubMed
    env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    Envelope transmembrane glycoprotein gp41 env Siva-1 sensitizes CD4-positive T-cells to HIV-1 gp120/gp41-induced apoptosis. The Siva-1-mediated sensitization on CD4-positive T-cells shows significant activation of caspase-3, -8, and -9 PubMed
    Nef nef HIV-1 Nef inhibits cleavage of the 45-kDa procaspase-9 to a 35-kDa fragment in BFA-treated MDMs PubMed
    nef Microarray analyses have shown HIV-1 Nef-induced upregulation of caspase-9 in primary human brain micro vascular endothelial cells PubMed
    Tat tat FasL-induced release of cytochrome c and activation of caspase-9 are inhibited in HIV-1 Tat101-expressing Jurkat cells due to high stability of the mitochondrial inner membrane electrochemical potential PubMed
    tat HIV-1 Tat activates caspase 9 to induce apoptotic cell death in retinal pigment epithelial cells PubMed
    tat HIV-1 Tat-induced apoptosis through increased expression of anti-apoptotic protein Bcl-2, proapoptotic protein Bax and activation of caspases CASP3 and CASP9 is inhibited by estrogen receptor beta (ER)-mediated estrogen treatment PubMed
    Vpr vpr HIV-1 Vpr carboxy-terminally truncated form C81, which does not contain the arginine-rich domain (amino acids 82-96), induces apoptosis via the activation of caspase 9 PubMed
    vpr Virion-associated Vpr activates caspase 3/7, 8, and 9 in Fas-mediated apoptosis in Jurkat T cells and human activated PBMCs PubMed
    vpr Virion-associated Vpr triggers apoptosis through caspases 3/7 and 9 in human T cells independently of other HIV de novo-expressed proteins and also activates caspase 8, the initiator caspase of the death receptor pathway PubMed
    vpr Overproduction of EEF2 blocks HIV-1 Vpr-induced cell death both in fission yeast and human cells, suppresses caspase 9 and caspase 3-mediated apoptosis induced by Vpr, and reduces cytochrome c release induced by Vpr PubMed
    vpr HIV-1 Vpr-induced apoptosis through caspase activation and Smac release from mitochondria is dependent on G2 cell cycle arrest , but is lost in cells synchronized in G1/S PubMed
    vpr HIV-1 Vpr induces apoptosis through activation of caspase 9 as well as by increasing the overall expression level of caspase 9 PubMed
    retropepsin gag-pol HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, and cleavage of DFF and PARP PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH3 domain binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables cysteine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables cysteine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
     
    enables enzyme activator activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables peptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in DNA damage response IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cellular response to UV IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to dexamethasone stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in epithelial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in fibroblast apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in glial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in intrinsic apoptotic signaling pathway IC
    Inferred by Curator
    more info
    PubMed 
    involved_in intrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in intrinsic apoptotic signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in kidney development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in leukocyte apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in platelet formation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of neuron apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein maturation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein processing IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to cobalt ion IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to ischemia IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in signal transduction in response to DNA damage IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of apoptosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of apoptosome IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of caspase complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    is_active_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    caspase-9
    Names
    ICE-like apoptotic protease 6
    apoptotic protease MCH-6
    apoptotic protease activating factor 3
    caspase 9, apoptosis-related cysteine peptidase
    protein phosphatase 1, regulatory subunit 56
    NP_001220.2
    NP_001264983.1
    NP_127463.2
    XP_005246071.1
    XP_011540575.1
    XP_047287990.1
    XP_054195099.1
    XP_054195100.1
    XP_054195101.1

    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_029188.1 RefSeqGene

      Range
      5576..38390
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001229.5NP_001220.2  caspase-9 isoform alpha precursor

      See identical proteins and their annotated locations for NP_001220.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (alpha) encodes the longest isoform (alpha).
      Source sequence(s)
      AL512883, BC006463
      Consensus CDS
      CCDS158.1
      UniProtKB/Swiss-Prot
      B4E1A3, O95348, P55211, Q53Y70, Q5JRU9, Q5UGI1, Q92852, Q9BQ62, Q9UEQ3, Q9UIJ8
      UniProtKB/TrEMBL
      A8K7U6
      Related
      ENSP00000330237.5, ENST00000333868.10
      Conserved Domains (2) summary
      cd08326
      Location:1790
      CARD_CASP9; Caspase activation and recruitment domain of Caspase-9
      cd00032
      Location:152414
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
    2. NM_001278054.2NP_001264983.1  caspase-9 isoform beta

      See identical proteins and their annotated locations for NP_001264983.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (beta) lacks several alternate in-frame exons in the coding region compared to variant alpha. It encodes isoform beta (also known as caspase-9S, caspase-9 beta, caspase-9b) which is shorter compared to isoform alpha.
      Source sequence(s)
      AB015653, AL512883
      Consensus CDS
      CCDS59995.1
      UniProtKB/Swiss-Prot
      P55211
      Related
      ENSP00000255256.7, ENST00000348549.9
      Conserved Domains (2) summary
      cd08326
      Location:1790
      CARD_CASP9; Caspase activation and recruitment domain of Caspase-9
      cl00042
      Location:140264
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
    3. NM_032996.3NP_127463.2  caspase-9 isoform 3

      See identical proteins and their annotated locations for NP_127463.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant alpha. The encoded isoform (3) has a shorter N-terminus, compared to isoform alpha.
      Source sequence(s)
      AK303743, AL512883, DA078665
      Consensus CDS
      CCDS159.2
      UniProtKB/TrEMBL
      A8K7R5, A8K7U6
      Related
      ENSP00000365051.4, ENST00000375890.8
      Conserved Domains (1) summary
      cd00032
      Location:69331
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...

    RNA

    1. NR_102732.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant alpha, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL512883, AY732490, HY027003
    2. NR_102733.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in an internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant alpha, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AJ781267, AL512883

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      15491401..15524912 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005246014.3XP_005246071.1  caspase-9 isoform X1

      See identical proteins and their annotated locations for XP_005246071.1

      UniProtKB/TrEMBL
      A8K7R5, A8K7U6
      Conserved Domains (1) summary
      cd00032
      Location:69331
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...
    2. XM_047432034.1XP_047287990.1  caspase-9 isoform X2

    3. XM_011542273.4XP_011540575.1  caspase-9 isoform X3

      UniProtKB/TrEMBL
      F8VVS7, Q59GG2
      Related
      ENSP00000449584.1, ENST00000546424.5
      Conserved Domains (2) summary
      cd08326
      Location:1790
      CARD_CASP9; Caspase activation and recruitment domain of Caspase-9
      cd00032
      Location:152397
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues; Cysteine-dependent aspartate-directed proteases that mediate programmed cell death (apoptosis). Caspases are synthesized as inactive zymogens and activated by proteolysis of the peptide ...

    RNA

    1. XR_007064158.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      14936101..14969610 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054339124.1XP_054195099.1  caspase-9 isoform X1

      UniProtKB/TrEMBL
      A8K7R5, A8K7U6
    2. XM_054339125.1XP_054195100.1  caspase-9 isoform X2

    3. XM_054339126.1XP_054195101.1  caspase-9 isoform X3

      UniProtKB/TrEMBL
      F8VVS7, Q59GG2

    RNA

    1. XR_008486177.1 RNA Sequence