Caspase 2

Protein-coding gene in the species Homo sapiens

CASP2
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1PYO, 2P2C, 3R5J, 3R6G, 3R6L, 3R7B, 3R7N, 3R7S, 3RJM

Identifiers
AliasesCASP2, CASP-2, ICH1, NEDD-2, NEDD2, PPP1R57, caspase 2
External IDsOMIM: 600639; MGI: 97295; HomoloGene: 7254; GeneCards: CASP2; OMA:CASP2 - orthologs
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for CASP2
Genomic location for CASP2
Band7q34Start143,288,215 bp[1]
End143,307,696 bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for CASP2
Genomic location for CASP2
Band6 B2.1|6 20.54 cMStart42,241,919 bp[2]
End42,259,442 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • buccal mucosa cell

  • tendon of biceps brachii

  • trabecular bone

  • skin of hip

  • skin of thigh

  • tonsil

  • ganglionic eminence

  • blood

  • mucosa of sigmoid colon

  • testicle
Top expressed in
  • saccule

  • otic placode

  • otic vesicle

  • endocardial cushion

  • fetal liver hematopoietic progenitor cell

  • maxillary prominence

  • mandibular prominence

  • thymus

  • hair follicle

  • Gonadal ridge
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
  • cysteine-type peptidase activity
  • protein domain specific binding
  • peptidase activity
  • protein binding
  • enzyme binding
  • hydrolase activity
  • identical protein binding
  • cysteine-type endopeptidase activity involved in apoptotic process
  • cysteine-type endopeptidase activity
  • cysteine-type endopeptidase activity involved in execution phase of apoptosis
Cellular component
  • cytoplasm
  • cytosol
  • membrane
  • mitochondrion
  • nucleus
Biological process
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
  • execution phase of apoptosis
  • protein processing
  • human ageing
  • positive regulation of apoptotic signaling pathway
  • luteolysis
  • cellular response to mechanical stimulus
  • positive regulation of neuron apoptotic process
  • brain development
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • extrinsic apoptotic signaling pathway in absence of ligand
  • positive regulation of apoptotic process
  • ectopic germ cell programmed cell death
  • apoptotic signaling pathway
  • neural retina development
  • apoptotic process
  • regulation of apoptotic process
  • proteolysis
  • negative regulation of apoptotic process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

835

12366

Ensembl

ENSG00000106144

ENSMUSG00000029863

UniProt

P42575

P29594

RefSeq (mRNA)

NM_032983
NM_001224
NM_032982
NM_032984

NM_007610

RefSeq (protein)

NP_001215
NP_116764
NP_116765

NP_031636

Location (UCSC)Chr 7: 143.29 – 143.31 MbChr 6: 42.24 – 42.26 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Caspase 2 also known as CASP2 is an enzyme that, in humans, is encoded by the CASP2 gene.[5] CASP2 orthologs[6] have been identified in nearly all mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts.

Function

Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The proteolytic cleavage of this protein is induced by a variety of apoptotic stimuli.[7]

Caspase 2 proteolytically cleaves other proteins. It belongs to a family of cysteine proteases called caspases that cleave proteins only at an amino acid following an aspartic acid residue. Within this family, caspase 2 is part of the Ich-1 subfamily. It is one of the most conserved caspases in different species of animal. Caspase 2 has a similar amino acid sequence to initiator caspases, including caspase 1, caspase 4, caspase 5, and caspase 9. It is produced as a zymogen, which contains a long pro-domain that is similar to that of caspase 9 and contains a protein interaction domain known as a CARD domain. Pro-caspase-2 contains two subunits, p19 and p12.

It has been shown to associate with several proteins involved in apoptosis using its CARD domain, including RIP-associated Ich-1/Ced-3-homologue protein with a death domain (RAIDD), apoptosis repressor with caspase recruitment domain (ARC), and death effector filament-forming Ced-4-like apoptosis protein (DEFCAP).[8] Together with RAIDD and p53-induced protein with a death domain ([PIDD])(LRDD), caspase 2 has been shown to form the so-called PIDDosome,[9] which may serve as an activation platform for the protease, although it may also be activated in the absence of PIDD.[10] Overall, caspase 2 appears to be a very versatile caspase with multiple functions beyond cell death induction.[11][12]

Interactions

Caspase 2 has been shown to interact with:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000106144 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029863 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Kumar S, White DL, Takai S, Turczynowicz S, Juttner CA, Hughes TP (June 1995). "Apoptosis regulatory gene NEDD2 maps to human chromosome segment 7q34-35, a region frequently affected in haematological neoplasms". Hum. Genet. 95 (6): 641–4. doi:10.1007/bf00209480. PMID 7789948. S2CID 22813779.
  6. ^ "OrthoMaM phylogenetic marker: CASP2 coding sequence". Archived from the original on 24 September 2015. Retrieved 20 December 2009.
  7. ^ "Entrez Gene: CASP2".
  8. ^ Zhivotovsky B, Orrenius S (2005). "Caspase-2 function in response to DNA damage". Biochem. Biophys. Res. Commun. 331 (3): 859–67. doi:10.1016/j.bbrc.2005.03.191. PMID 15865942.
  9. ^ a b Tinel A, Tschopp J (May 2004). "The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress". Science. 304 (5672): 843–6. Bibcode:2004Sci...304..843T. doi:10.1126/science.1095432. PMID 15073321. S2CID 6583298.
  10. ^ Manzl C, Krumschnabel G, Bock F, Sohm B, Labi V, Baumgartner F, Logette E, Tschopp J, Villunger A (April 2009). "Caspase-2 activation in the absence of PIDDosome formation". J. Cell Biol. 185 (2): 291–303. doi:10.1083/jcb.200811105. PMC 2700374. PMID 19364921.
  11. ^ Krumschnabel G, Manzl C, Villunger A (September 2009). "Caspase-2: killer, savior and safeguard--emerging versatile roles for an ill-defined caspase". Oncogene. 28 (35): 3093–6. doi:10.1038/onc.2009.173. PMC 3272399. PMID 19581929.
  12. ^ Krumschnabel G, Sohm B, Bock F, Manzl C, Villunger A (February 2009). "The enigma of caspase-2: the laymen's view". Cell Death Differ. 16 (2): 195–207. doi:10.1038/cdd.2008.170. PMC 3272397. PMID 19023332.
  13. ^ a b Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478.
  14. ^ Paroni G, Henderson C, Schneider C, Brancolini C (June 2001). "Caspase-2-induced apoptosis is dependent on caspase-9, but its processing during UV- or tumor necrosis factor-dependent cell death requires caspase-3". J. Biol. Chem. 276 (24): 21907–15. doi:10.1074/jbc.M011565200. PMID 11399776.
  15. ^ Droin N, Beauchemin M, Solary E, Bertrand R (December 2000). "Identification of a caspase-2 isoform that behaves as an endogenous inhibitor of the caspase cascade". Cancer Res. 60 (24): 7039–47. PMID 11156409.
  16. ^ Duan H, Dixit VM (January 1997). "RAIDD is a new 'death' adaptor molecule" (PDF). Nature. 385 (6611): 86–9. Bibcode:1997Natur.385...86D. doi:10.1038/385086a0. hdl:2027.42/62739. PMID 8985253. S2CID 4317538.
  17. ^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.

External links

  • The MEROPS online database for peptidases and their inhibitors: C14.006[permanent dead link]
  • Overview of all the structural information available in the PDB for UniProt: P42575 (Human Caspase-2) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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