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Protein

Caspase-2

Gene

Casp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival (By similarity).By similarity

Catalytic activityi

Strict requirement for an Asp residue at P1, with 316-asp being essential for proteolytic activity and has a preferred cleavage sequence of Val-Asp-Val-Ala-Asp-|-.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei277 – 2771By similarity
Active sitei320 – 3201By similarity

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • aging Source: RGD
  • apoptotic process Source: RGD
  • brain development Source: RGD
  • cellular response to mechanical stimulus Source: Ensembl
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Ensembl
  • ectopic germ cell programmed cell death Source: Ensembl
  • extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
  • luteolysis Source: RGD
  • neural retina development Source: RGD
  • positive regulation of apoptotic signaling pathway Source: Ensembl
  • positive regulation of neuron apoptotic process Source: RGD
  • programmed cell death Source: RGD
  • proteolysis Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BRENDAi3.4.22.55. 5301.
ReactomeiREACT_309697. NADE modulates death signalling.

Protein family/group databases

MEROPSiC14.006.

Names & Taxonomyi

Protein namesi
Recommended name:
Caspase-2 (EC:3.4.22.55)
Short name:
CASP-2
Alternative name(s):
Protease ICH-1
Cleaved into the following 3 chains:
Gene namesi
Name:Casp2
Synonyms:Ich1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi69274. Casp2.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: RGD
  • mitochondrion Source: RGD
  • nucleus Source: Ensembl
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Propeptidei2 – 169168PRO_0000043403Add
BLAST
Chaini170 – 325156Caspase-2 subunit p18By similarityPRO_0000044573Add
BLAST
Propeptidei326 – 3338PRO_0000044574
Chaini334 – 452119Caspase-2 subunit p13By similarityPRO_0000004551Add
BLAST
Chaini348 – 452105Caspase-2 subunit p12By similarityPRO_0000004552Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei340 – 3401PhosphoserineBy similarity

Post-translational modificationi

The mature protease can process its own propeptide, but not that of other caspases.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

PaxDbiP55215.

PTM databases

PhosphoSiteiP55215.

Expressioni

Gene expression databases

ExpressionAtlasiP55215. baseline.
GenevestigatoriP55215.

Interactioni

Subunit structurei

Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit. Interacts with LRDD (By similarity). Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a phosphorylation-dependent manner.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-48602N.
STRINGi10116.ENSRNOP00000022672.

Structurei

3D structure databases

ProteinModelPortaliP55215.
SMRiP55215. Positions 173-333, 355-452.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 12190CARDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated
Contains 1 CARD domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG305976.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000290714.
HOVERGENiHBG103962.
InParanoidiP55215.
KOiK02186.
OMAiPCLQVKP.
OrthoDBiEOG7TTQ7K.
PhylomeDBiP55215.
TreeFamiTF102023.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProiIPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR017350. Caspase_ICE-type.
IPR011029. DEATH-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P55215-1) [UniParc]FASTAAdd to basket

Also known as: caspase-2L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAASSGRSQS SLHRKGLMAA DRRSRILAVC GMHPDHQETL KKNRVVLAKQ
60 70 80 90 100
LLLSELLEHL LEKDIITLEM RELIQAKGGS FSQNVELLNL LPKRGPQAFD
110 120 130 140 150
AFCEALRETR QGHLEDLLLT TLSDIQHILP PLSCDYDSSL PFSVCESCPP
160 170 180 190 200
HKQSRLSTDT MEHSLDNGDG PPCLQVKPCT PEFYQAHYQL AYRLQSQPRG
210 220 230 240 250
LALVMSNVHF TGEKDLEFRS GGDVDHTTLV TLFKLLGYNV HVLYDQTAQE
260 270 280 290 300
MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GGIYGVDGKL LQLQEVFRLF
310 320 330 340 350
DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAQS PGCEESDAGK
360 370 380 390 400
EELMKMRLPT RSDMICGYAC LKGNAAMRNT KRGSWYIEAL TQVFSERACD
410 420 430 440 450
MHVADMLVKV NALIKEREGY APGTEFHRCK EMSEYCSTLC QQLYLFPGYP

PT
Length:452
Mass (Da):50,728
Last modified:December 6, 2005 - v3
Checksum:i03F9D096BB741CE3
GO
Isoform 2 (identifier: P55215-2) [UniParc]FASTAAdd to basket

Also known as: caspase-2S

The sequence of this isoform differs from the canonical sequence as follows:
     323-343: DETDRGVDQQDGKNHAQSPGC → GAIGSLGPLLLFTAATASLAL
     344-452: Missing.

Show »
Length:343
Mass (Da):38,004
Checksum:i0292D6130C63F641
GO

Sequence cautioni

The sequence AAB82567.1 differs from that shown. Reason: Frameshift at positions 137 and 189. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti145 – 1451C → Y in AAB82567 (PubMed:9530276).Curated
Sequence conflicti166 – 1661D → H in AAB82567 (PubMed:9530276).Curated
Sequence conflicti177 – 1771K → E in AAB82567 (PubMed:9530276).Curated
Sequence conflicti197 – 1971Q → R in AAB82567 (PubMed:9530276).Curated
Sequence conflicti340 – 3401S → P in AAC52260 (PubMed:7588240).Curated
Sequence conflicti348 – 3492AG → TV in AAC52260 (PubMed:7588240).Curated
Sequence conflicti367 – 3671G → V in AAC52260 (PubMed:7588240).Curated
Sequence conflicti373 – 3731G → D in AAC52260 (PubMed:7588240).Curated
Sequence conflicti376 – 3772AM → PI in AAC52260 (PubMed:7588240).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei323 – 34321DETDR…QSPGC → GAIGSLGPLLLFTAATASLA L in isoform 2. 1 PublicationVSP_016555Add
BLAST
Alternative sequencei344 – 452109Missing in isoform 2. 1 PublicationVSP_016556Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77933 mRNA. Translation: AAB96379.1.
AF136231 mRNA. Translation: AAD33684.1.
AF136232 mRNA. Translation: AAD33685.1.
AF025671 mRNA. Translation: AAB82567.1. Frameshift.
U34684 mRNA. Translation: AAC52260.1.
PIRiI67436.
JC6507.
RefSeqiNP_071967.2. NM_022522.2. [P55215-1]
UniGeneiRn.1438.

Genome annotation databases

EnsembliENSRNOT00000022672; ENSRNOP00000022672; ENSRNOG00000016707. [P55215-1]
GeneIDi64314.
KEGGirno:64314.
UCSCiRGD:69274. rat. [P55215-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77933 mRNA. Translation: AAB96379.1.
AF136231 mRNA. Translation: AAD33684.1.
AF136232 mRNA. Translation: AAD33685.1.
AF025671 mRNA. Translation: AAB82567.1. Frameshift.
U34684 mRNA. Translation: AAC52260.1.
PIRiI67436.
JC6507.
RefSeqiNP_071967.2. NM_022522.2. [P55215-1]
UniGeneiRn.1438.

3D structure databases

ProteinModelPortaliP55215.
SMRiP55215. Positions 173-333, 355-452.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48602N.
STRINGi10116.ENSRNOP00000022672.

Protein family/group databases

MEROPSiC14.006.

PTM databases

PhosphoSiteiP55215.

Proteomic databases

PaxDbiP55215.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000022672; ENSRNOP00000022672; ENSRNOG00000016707. [P55215-1]
GeneIDi64314.
KEGGirno:64314.
UCSCiRGD:69274. rat. [P55215-1]

Organism-specific databases

CTDi835.
RGDi69274. Casp2.

Phylogenomic databases

eggNOGiNOG305976.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000290714.
HOVERGENiHBG103962.
InParanoidiP55215.
KOiK02186.
OMAiPCLQVKP.
OrthoDBiEOG7TTQ7K.
PhylomeDBiP55215.
TreeFamiTF102023.

Enzyme and pathway databases

BRENDAi3.4.22.55. 5301.
ReactomeiREACT_309697. NADE modulates death signalling.

Miscellaneous databases

NextBioi612988.
PROiP55215.

Gene expression databases

ExpressionAtlasiP55215. baseline.
GenevestigatoriP55215.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
3.40.50.1460. 1 hit.
InterProiIPR001315. CARD.
IPR029030. Caspase-like_dom.
IPR017350. Caspase_ICE-type.
IPR011029. DEATH-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00619. CARD. 1 hit.
PF00656. Peptidase_C14. 1 hit.
[Graphical view]
PIRSFiPIRSF038001. Caspase_ICE. 1 hit.
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00114. CARD. 1 hit.
SM00115. CASc. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
PROSITEiPS50209. CARD. 1 hit.
PS01122. CASPASE_CYS. 1 hit.
PS01121. CASPASE_HIS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and expression of the cDNA encoding rat caspase-2."
    Sato N., Milligan C.E., Uchiyama Y., Oppenheim R.W.
    Gene 202:127-132(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia."
    Jin K., Nagayama T., Mao X., Kawaguchi K., Hickey R.W., Greenberg D.A., Simon R.P., Graham S.H.
    J. Neurochem. 81:25-35(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "Identification of gene family of caspases in rat kidney and altered expression in ischemia-reperfusion injury."
    Kaushal G.P., Singh A.B., Shah S.V.
    Am. J. Physiol. 274:F587-F595(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 67-324.
    Strain: Sprague-Dawley.
    Tissue: Kidney cortex.
  4. "Interleukin-1 beta-converting enzyme-related proteases (IRPs) and mammalian cell death: dissociation of IRP-induced oligonucleosomal endonuclease activity from morphological apoptosis in granulosa cells of the ovarian follicle."
    Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I., Hirshfield A.N., Tilly J.L.
    Endocrinology 136:5042-5053(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 198-379.
    Tissue: Ovary.
  5. "ARC protects rat cardiomyocytes against oxidative stress through inhibition of caspase-2 mediated mitochondrial pathway."
    Zhang Y.Q., Herman B.
    J. Cell. Biochem. 99:575-588(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NOL3.

Entry informationi

Entry nameiCASP2_RAT
AccessioniPrimary (citable) accession number: P55215
Secondary accession number(s): O35398, O55194, Q9WUI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 6, 2005
Last modified: April 29, 2015
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.