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CASP9 caspase 9 [ Homo sapiens (human) ]

Gene ID: 842, updated on 17-Dec-2019

Summary

Official Symbol
CASP9provided by HGNC
Official Full Name
caspase 9provided by HGNC
Primary source
HGNC:HGNC:1511
See related
Ensembl:ENSG00000132906 MIM:602234
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

Genomic context

See CASP9 in Genome Data Viewer
Location:
1p36.21
Exon count:
11
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 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 2A Neighboring gene chymotrypsin like elastase 2B Neighboring gene DnaJ heat shock protein family (Hsp40) member C16 Neighboring gene small Cajal body-specific RNA 21B Neighboring gene agmatinase

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

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 IDA
Inferred from Direct Assay
more info
PubMed 
cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
 
cysteine-type endopeptidase activity involved in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cysteine-type endopeptidase activity involved in apoptotic signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cysteine-type endopeptidase activity involved in apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
PubMed 
kidney development IEA
Inferred from Electronic Annotation
more info
 
leukocyte apoptotic process IEA
Inferred from Electronic Annotation
more info
 
platelet formation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
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 ischemia 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 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
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
 
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

NCBI Reference Sequences (RefSeq)

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_001229.5NP_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
    P55211
    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_001278054.1NP_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
    ENSP00000255256.7, 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/Swiss-Prot
    P55211
    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_102732.1 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 Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

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

mRNA and Protein(s)

  1. XM_005246014.2XP_005246071.1  caspase-9 isoform X1

    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_011542273.3XP_011540575.1  caspase-9 isoform X2

    UniProtKB/TrEMBL
    F8VVS7
    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 ...
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