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    CASP9 caspase 9 [ Homo sapiens (human) ]

    Gene ID: 842, updated on 22-Sep-2016
    Official Symbol
    CASP9provided by HGNC
    Official Full Name
    caspase 9provided by HGNC
    Primary source
    HGNC:HGNC:1511
    See related
    Ensembl:ENSG00000132906 HPRD:03756; MIM:602234; Vega:OTTHUMG00000002256
    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]
    Orthologs
    Location:
    1p36.21
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 1 NC_000001.11 (15491401..15524912, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (15817896..15851407, complement)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376767 Neighboring gene chymotrypsin like elastase family member 2A Neighboring gene chymotrypsin like elastase family member 2B Neighboring gene DnaJ heat shock protein family (Hsp40) member C16 Neighboring gene agmatinase Neighboring gene uncharacterized LOC107985735

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

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      Prostate cancer, organism-specific biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...
    • Prostate cancer, conserved biosystem (from KEGG)
      Prostate cancer, conserved biosystemProstate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of...
    • Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystem (from REACTOME)
      Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...
    • SMAC binds to IAPs, organism-specific biosystem (from REACTOME)
      SMAC binds to IAPs, organism-specific biosystemSMAC binds to the XIAP:caspase complexes.
    • SMAC-mediated apoptotic response, organism-specific biosystem (from REACTOME)
      SMAC-mediated apoptotic response, organism-specific biosystemOnce released from the mitochondria, SMAC binds to IAP family proteins displacing them from Caspase:IAP complexes liberating the active caspases.
    • SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystem (from REACTOME)
      SMAC-mediated dissociation of IAP:caspase complexes, organism-specific biosystemSmac/DIABLO regulates IAP function. Residues 56-59 of Smac/DIABLO are homologous to the amino-terminal motif that is used by caspase-9 to bind to the BIR3 domain of XIAP. Binding of Smac/DIABLO to ...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
    • Signaling by FGFR, organism-specific biosystem (from REACTOME)
      Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by FGFR1, organism-specific biosystem (from REACTOME)
      Signaling by FGFR1, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by FGFR2, organism-specific biosystem (from REACTOME)
      Signaling by FGFR2, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by FGFR3, organism-specific biosystem (from REACTOME)
      Signaling by FGFR3, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by FGFR4, organism-specific biosystem (from REACTOME)
      Signaling by FGFR4, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • Small cell lung cancer, organism-specific biosystem (from KEGG)
      Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
    • Small cell lung cancer, conserved biosystem (from KEGG)
      Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
    • Thyroid hormone signaling pathway, organism-specific biosystem (from KEGG)
      Thyroid hormone signaling pathway, organism-specific biosystemThe thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) a...
    • Toxoplasmosis, organism-specific biosystem (from KEGG)
      Toxoplasmosis, organism-specific biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
    • Toxoplasmosis, conserved biosystem (from KEGG)
      Toxoplasmosis, conserved biosystemToxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechan...
    • Tuberculosis, organism-specific biosystem (from KEGG)
      Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • Tuberculosis, conserved biosystem (from KEGG)
      Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • VEGF signaling pathway, organism-specific biosystem (from KEGG)
      VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGF signaling pathway, conserved biosystem (from KEGG)
      VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • Viral myocarditis, organism-specific biosystem (from KEGG)
      Viral myocarditis, organism-specific biosystemMyocarditis is a cardiac disease associated with inflammation and injury of the myocardium. It results from various etiologies, both noninfectious and infectious, but coxsackievirus B3 (CVB3) is stil...
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p75(NTR)-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
      p75(NTR)-mediated signaling, organism-specific biosystem
      p75(NTR)-mediated signaling
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    SH3 domain binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cysteine-type endopeptidase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    cysteine-type endopeptidase activity involved in apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enzyme activator activity TAS
    Traceable Author Statement
    more info
    PubMed 
    peptidase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c TAS
    Traceable Author Statement
    more info
     
    aging IEA
    Inferred from Electronic Annotation
    more info
     
    apoptotic process TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to DNA damage stimulus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to UV IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular response to dexamethasone stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    extrinsic apoptotic signaling pathway in absence of ligand TAS
    Traceable Author Statement
    more info
     
    glial cell apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    intrinsic apoptotic signaling pathway in response to DNA damage IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    platelet formation TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    proteolysis IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of response to DNA damage stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to antibiotic IEA
    Inferred from Electronic Annotation
    more info
     
    response to cobalt ion IEA
    Inferred from Electronic Annotation
    more info
     
    response to estradiol IEA
    Inferred from Electronic Annotation
    more info
     
    response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    signal transduction in response to DNA damage IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Component Evidence Code Pubs
    apoptosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    nucleus IEA
    Inferred from Electronic Annotation
    more info
     
    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

    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
      5001..38390
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001229.4NP_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
      P55211
      Related
      ENSP00000330237, OTTHUMP00000002322, ENST00000333868, OTTHUMT00000006438
      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_001278054.1NP_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, OTTHUMP00000002323, ENST00000348549, OTTHUMT00000006439
      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/Swiss-Prot
      P55211
      Related
      ENSP00000365051, OTTHUMP00000242819, ENST00000375890, OTTHUMT00000407261
      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_102732.1 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_102733.1 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: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p7 Primary Assembly

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

    mRNA and Protein(s)

    1. XM_005246014.2XP_005246071.1  

      See identical proteins and their annotated locations for XP_005246071.1

      UniProtKB/Swiss-Prot
      P55211
      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_011542273.2XP_011540575.1  

      UniProtKB/TrEMBL
      F8VVS7
      Related
      ENSP00000449584, OTTHUMP00000242817, ENST00000546424, OTTHUMT00000407260
      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 ...

    Alternate CHM1_1.1

    Genomic

    1. NC_018912.2 Alternate CHM1_1.1

      Range
      15616531..15649948 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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