My NCBISign In

Display Settings:

Format

Send to:

Choose Destination

    CASP2 caspase 2, apoptosis-related cysteine peptidase [ Homo sapiens ]

    Gene ID: 835, updated on 11-May-2012
    Help top of page

    Summary

    Official Symbol
    CASP2provided by HGNC
    Official Full Name
    caspase 2, apoptosis-related cysteine peptidaseprovided by HGNC
    Primary source
    HGNC:1503
    See related
    Ensembl:ENSG00000106144; HPRD:02800; MIM:600639; Vega:OTTHUMG00000023641
    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
    ICH1; NEDD2; CASP-2; NEDD-2; PPP1R57
    Summary
    This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Caspases mediate cellular apoptosis through the proteolytic cleavage of specific protein substrates. The encoded protein may function in stress-induced cell death pathways, cell cycle maintenance, and the suppression of tumorigenesis. Increased expression of this gene may play a role in neurodegenerative disorders including Alzheimer's disease, Huntington's disease and temporal lobe epilepsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]
    Help top of page

    Genomic context

    Location :
    7q34-q35
    Sequence :
    Chromosome: 7; NC_000007.13 (142985308..143004789)
    See CASP2 in Epigenomics, MapViewer

    Chromosome 7 - NC_000007.13Genomic Context describing neighboring genes Neighboring gene glutathione S-transferase kappa 1 Neighboring gene transmembrane protein 139 Neighboring gene histidine triad nucleotide binding protein 1 pseudogene 1 Neighboring gene chloride channel, voltage-sensitive 1

    Help top of page

    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
    Helptop of page

    Bibliography

    Related articles in PubMed

    1. Nucleotide excision repair factor XPC enhances DNA damage-induced apoptosis by downregulating the antiapoptotic short isoform of caspase-2. Wang QE, et al. Cancer Res, 2012 Feb 1. PMID 22174370.
    2. Induction of caspase-2 activation by a DNA enzyme evokes tumor cell apoptosis. Kim SH, et al. DNA Cell Biol, 2012 Jan. PMID 22077397.
    3. Somatic mutations of caspase-2 gene in gastric and colorectal cancers. Kim MS, et al. Pathol Res Pract, 2011 Oct 15. PMID 21940110.
    4. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    5. Oncogenic ras-induced down-regulation of pro-apoptotic protease caspase-2 is required for malignant transformation of intestinal epithelial cells. Yoo BH, et al. J Biol Chem, 2011 Nov 11. PMID 21903589.

    See all (118) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Data suggest that this novel role of caspase-2 as a translational regulator of p21 expression occurs not only independently of its enzymatic activity but also does not require known caspase-2-activating platforms.
      Title: Caspase-2 is required for DNA damage-induced expression of the CDK inhibitor p21(WAF1/CIP1).
    2. Findings suggest that XPC enhances DNA damage-induced apoptosis through inhibition of caspase-2 (casp-2S) transcription.
      Title: Nucleotide excision repair factor XPC enhances DNA damage-induced apoptosis by downregulating the antiapoptotic short isoform of caspase-2.
    3. Studies indicate that DNA damage may trigger caspase 2 activation.
      Title: Induction of caspase-2 activation by a DNA enzyme evokes tumor cell apoptosis.
    4. somatic mutation of caspase-2 is rare in gastric and colorectal carcinomas.
      Title: Somatic mutations of caspase-2 gene in gastric and colorectal cancers.
    5. ras-induced down-regulation of caspase-2 represents a novel mechanism by which oncogenic Ras protects malignant intestinal epithelial cells from anoikis
      Title: Oncogenic ras-induced down-regulation of pro-apoptotic protease caspase-2 is required for malignant transformation of intestinal epithelial cells.
    6. Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis.
      Title: Structural and enzymatic insights into caspase-2 protein substrate recognition and catalysis.
    7. Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination.
      Title: Caspase-2-mediated cleavage of Mdm2 creates a p53-induced positive feedback loop.
    8. analyzed cancer tissues from acute leukemias, breast cancers, lung cancers, and liver cancers for the detection of caspase-2 somatic mutations
      Title: Somatic mutation of proapoptotic caspase-2 gene is rare in acute leukemias and common solid cancers.
    9. The changes of caspase-2 and caspase-5 activities could be indicative of their involvement in the cervical malignancy mechanisms.
      Title: Indication of participation of caspase-2 and caspase-5 in mechanisms of human cervical malignancy.
    10. Activation of caspase-9, but not caspase-2 or caspase-8, is essential for heat-induced apoptosis in Jurkat cells.
      Title: Activation of caspase-9, but not caspase-2 or caspase-8, is essential for heat-induced apoptosis in Jurkat cells.
    Submit: New GeneRIF Correction See all (63)
    Help top of page

    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Help top of page

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_116764.2 NP_003796.1 CRADD    BIND  PubMed The CARD domain of Casp2 interacts with the death domain (DD) of RAIDD. 
    NP_116764.2     BIND  PubMed Casp2 interacts with VAD-fmk. 
    P42575 P18509 ADCYAP1    HPRD  PubMed  
    P42575 P55957 BID    HPRD  PubMed  
    P42575 Q92851 CASP10    HPRD  PubMed  
    P42575 P31944 CASP14    HPRD  PubMed  
    P42575 P42575 CASP2    HPRD  PubMed  
    P42575 P55210 CASP7    HPRD  PubMed  
    P42575 P30281 CCND3    HPRD  PubMed  
    P42575 O15519 CFLAR    HPRD  PubMed  
    P42575 P78560 CRADD    HPRD  PubMed  
    P42575 P68400 CSNK2A1    HPRD  PubMed  
    P42575 Q14203 DCTN1    HPRD  PubMed  
    P42575 P15924 DSP    HPRD  PubMed  
    P42575 Q08378 GOLGA3    HPRD  PubMed  
    P42575 NP_002102.2 HTT    BIND  PubMed Htt interacts with caspase 2. 
    P42575 P52292 KPNA2    HPRD  PubMed  
    P42575 Proapoptotic caspase adaptor protein MZB1    HPRD  PubMed  
    P42575 Q9C000 NLRP1    HPRD  PubMed  
    P42575 Q9Y239 NOD1    HPRD  PubMed  
    P42575 O60936 NOL3    HPRD  PubMed  
    P42575 Q9HB75 PIDD    HPRD  PubMed  
    P42575 NP_000312.1 RB1    BIND  PubMed CASP2 (caspase-2) cleaves RB-1 (hRB) at the DEAD consensus site into the p100 form. 
    P42575 P06400 RB1    HPRD  PubMed  
    BioGRID:107285 BioGRID:107068 BCL2    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:107285 BioGRID:107070 BCL2L1    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:107285 BioGRID:107106 BID    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:107293 CASP10    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:117116 CASP14    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107285 BioGRID:107285 CASP2    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:107286 CASP3    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:107290 CASP7    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:107291 CASP8    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:107292 CASP9    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:107285 BioGRID:107336 CCND3    BioGRID  PubMed Two-hybrid 
    BioGRID:107285 BioGRID:114275 CRADD    BioGRID  PubMed Affinity Capture-Western; Phenotypic Suppression; Reconstituted Complex; Two-hybrid 
    BioGRID:107285 BioGRID:108237 EEF1A1    BioGRID  PubMed Two-hybrid 
    BioGRID:107285 BioGRID:109142 GRB2    BioGRID  PubMed Two-hybrid 
    BioGRID:107285 BioGRID:110358 MDM2    BioGRID  PubMed Biochemical Activity 
    BioGRID:107285 BioGRID:116529 NLRP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107285 BioGRID:115664 NOD1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107285 BioGRID:114477 NOL3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107285 BioGRID:120645 PIDD    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107285 BioGRID:115966 RAI1    BioGRID  PubMed Two-hybrid 
    BioGRID:107285 BioGRID:112168 RXRA    BioGRID  PubMed Two-hybrid 
    BioGRID:107285 BioGRID:112986 TNFRSF1A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107285 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107285 BioGRID:106828 XIAP    BioGRID  PubMed Phenotypic Suppression 
    Help top of page

    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Apoptosis, organism-specific biosystem (from WikiPathways)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Apoptosis Modulation by HSP70, organism-specific biosystem (from WikiPathways)
      Apoptosis Modulation by HSP70, organism-specific biosystem
      Apoptosis Modulation by HSP70
    • Caspase cascade in apoptosis, organism-specific biosystem (from Pathway Interaction Database)
      Caspase cascade in apoptosis, organism-specific biosystem
      Caspase cascade in apoptosis
    • Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystem (from REACTOME)
      Cell death signalling via NRAGE, NRIF and NADE, organism-specific biosystemp75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNG...
    • HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem (from Pathway Interaction Database)
      HIV-1 Nef: Negative effector of Fas and TNF-alpha, organism-specific biosystem
      HIV-1 Nef: Negative effector of Fas and TNF-alpha
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • MAPK signaling pathway, organism-specific biosystem (from WikiPathways)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • NADE modulates death signalling, organism-specific biosystem (from REACTOME)
      NADE modulates death signalling, organism-specific biosystemNADE protein (p75NTR-associated cell death executor) may induce cell death upon NGF binding, but not BDNF, NT3, or NT4/5 binding, to p75NTR. The NADE-dependent apoptosis is modulated by the 14-3-3-ep...
    • NOD1/2 Signaling Pathway, organism-specific biosystem (from REACTOME)
      NOD1/2 Signaling Pathway, organism-specific biosystemNOD1 is ubiquitously expressed, while NOD2 expression is restricted to monocytes, macrophages, dendritic cells, and intestinal Paneth cells (Inohara et al. 2005). NOD1 and NOD2 activation induces tra...
    • Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystem (from REACTOME)
      Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystemThe innate immune system is the first line of defense against invading microorganisms, a broad specificity response characterized by the recruitment and activation of phagocytes and the release of an...
    • 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...
    • 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...
    • TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TNF-alpha/NF-kB Signaling Pathway, organism-specific biosystem"The Tumor Necrosis Factor alpha is a proinflammatory cytokine belonging to the TNF superfamily. It signals through 2 separate receptors - TNFRSF1A and TNFRSF1B, both members of the TNF receptor supe...
    • p75 NTR receptor-mediated signalling, organism-specific biosystem (from REACTOME)
      p75 NTR receptor-mediated signalling, organism-specific biosystemBesides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a ...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    cysteine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enzyme binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein domain specific binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest IMP
    Inferred from Mutant Phenotype
    more info
    		  
    aging IEA
    Inferred from Electronic Annotation
    more info
    		  
    apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    apoptotic process TAS
    Traceable Author Statement
    more info
    		  
    apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    brain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    execution phase of apoptosis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    induction of apoptosis by extracellular signals TAS
    Traceable Author Statement
    more info
    		  
    luteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    neural retina development IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of neuron apoptosis IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    membrane fraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    soluble fraction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    caspase-2
    Names
    caspase-2
    protease ICH-1
    protein phosphatase 1, regulatory subunit 57
    neural precursor cell expressed developmentally down-regulated protein 2
    NP_001215.1
    NP_116764.2
    NP_116765.2
    Help top of page

    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_029248.1 RefSeqGene

      Range
      5001..24482
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001224.4 → NP_001215.1  caspase-2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternative 5' terminal exon (resulting in translation initiation from an in-frame downstream AUG), and an additional internal exon compared to variant 1. The latter causes a frame-shift, and early translation termination, rendering this transcript a candidate for nonsense-mediated mRNA decay (NMD). However, this variant is represented as protein-coding as the encoded short isoform (2, also known as ICH-1S) has been shown to be expressed in vivo (PMID:12598307), and to function as a negative regulator of apoptosis (PMID:8087842).
      Source sequence(s)
      AC073342, BC002427, BQ447606, U13022
      UniProtKB/TrEMBL
      D3DXD9
      UniProtKB/Swiss-Prot
      P42575
      Conserved Domains (2) summary
      cd08332
      Location:1 – 90
      Blast Score: 332
      CARD_CASP2; Caspase activation and recruitment domain of Caspase-2
      cl00042
      Location:160 – 295
      Blast Score: 438
      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_032982.3 → NP_116764.2  caspase-2 isoform 1 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1, also known as ICH-1L), which has been shown to function as a positive regulator of apoptosis (PMID:8087842).
      Source sequence(s)
      AC073342, AK291274, BQ447606, DA505883, DB455837
      Consensus CDS
      CCDS5879.1
      UniProtKB/Swiss-Prot
      P42575
      Related
      ENSP00000312664, OTTHUMP00000025259, ENST00000310447, OTTHUMT00000059962
      Conserved Domains (2) summary
      cd00032
      Location:191 – 446
      Blast Score: 703
      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 ...
      cd08332
      Location:32 – 121
      Blast Score: 342
      CARD_CASP2; Caspase activation and recruitment domain of Caspase-2

    3. NM_032983.3 → NP_116765.2  caspase-2 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon and uses an alternate splice site in the coding region, which results in a frameshift and early stop codon, compared to variant 1. The encoded isoform (3) is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC073342, AF314174, BC002427, BQ447606, DA505883, DB455840
      Consensus CDS
      CCDS47733.1
      UniProtKB/TrEMBL
      E9PDN0
      UniProtKB/Swiss-Prot
      P42575
      UniProtKB/TrEMBL
      Q9BZL0
      Related
      ENSP00000340030, OTTHUMP00000202227, ENST00000350623, OTTHUMT00000327426
      Conserved Domains (1) summary
      cl14633
      Location:32 – 108
      Blast Score: 275
      DD_superfamily; The Death Domain Superfamily of protein-protein interaction domains

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000007.13 Reference GRCh37.p5 Primary Assembly

      Range
      142985308..143004789
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000139.1 Alternate HuRef

      Range
      137322670..137342153
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CRA_TCAGchr7v2

    Genomic

    1. AC_000068.1 Alternate CRA_TCAGchr7v2

      Range
      142387424..142406906
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC073342.3 AAP22346.1
      AAP22347.1
      AAP22348.1
      AAP22349.1
    genomic AY219042.1 AAO25653.1
    genomic CH236959.1 (1263712..1283096) None
    genomic CH471198.2 EAW51860.1
      EAW51862.1
      EAW51863.1
      EAW51864.1
      EAW51867.1
      EAW51869.1
      EAW51870.1
    mRNA AB209640.1 BAD92877.1
    mRNA AF314174.1 AAK00299.1
    mRNA AF314175.1 AAK00300.1
    mRNA AK096245.1 None
    mRNA AK291274.1 BAF83963.1
    mRNA AK303265.1 BAG64347.1
    mRNA AK303391.1 BAG64447.1
    mRNA BC002427.2 AAH02427.2
    mRNA BG397039.1 None
    mRNA BM998653.1 None
    mRNA BQ447606.1 None
    mRNA BT007240.1 AAP35904.1
    mRNA BX537669.1 None
    mRNA CB988674.1 None
    mRNA CR541748.1 CAG46548.1
    mRNA DA505883.1 None
    mRNA DB455837.1 None
    mRNA DB455840.1 None
    mRNA U13021.1 AAA58959.1
    mRNA U13022.1 AAA58960.1
    other-genetic DQ893820.2 ABM84746.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42575.2 GenPept UniProtKB/Swiss-Prot:P42575
    Q9BZL0 GenPept UniProtKB/TrEMBL:Q9BZL0
    Help top of page

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Links

      Links to other resources

      General information

      Related sites

      Feedback

      Subscription

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...