ID   CASP2_RAT               Reviewed;         452 AA.
AC   P55215; O35398; O55194; Q9WUI6;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   06-DEC-2005, sequence version 3.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Caspase-2;
DE            Short=CASP-2;
DE            EC=3.4.22.55;
DE   AltName: Full=Protease ICH-1;
DE   Contains:
DE     RecName: Full=Caspase-2 subunit p18;
DE   Contains:
DE     RecName: Full=Caspase-2 subunit p13;
DE   Contains:
DE     RecName: Full=Caspase-2 subunit p12;
DE   Flags: Precursor;
GN   Name=Casp2; Synonyms=Ich1;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=9427555; DOI=10.1016/s0378-1119(97)00463-0;
RA   Sato N., Milligan C.E., Uchiyama Y., Oppenheim R.W.;
RT   "Cloning and expression of the cDNA encoding rat caspase-2.";
RL   Gene 202:127-132(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=12067235; DOI=10.1046/j.1471-4159.2002.00781.x;
RA   Jin K., Nagayama T., Mao X., Kawaguchi K., Hickey R.W., Greenberg D.A.,
RA   Simon R.P., Graham S.H.;
RT   "Two caspase-2 transcripts are expressed in rat hippocampus after global
RT   cerebral ischemia.";
RL   J. Neurochem. 81:25-35(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 67-324.
RC   STRAIN=Sprague-Dawley; TISSUE=Kidney cortex;
RX   PubMed=9530276; DOI=10.1152/ajprenal.1998.274.3.f587;
RA   Kaushal G.P., Singh A.B., Shah S.V.;
RT   "Identification of gene family of caspases in rat kidney and altered
RT   expression in ischemia-reperfusion injury.";
RL   Am. J. Physiol. 274:F587-F595(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 198-379.
RC   TISSUE=Ovary;
RX   PubMed=7588240; DOI=10.1210/endo.136.11.7588240;
RA   Flaws J.A., Kugu K., Trbovich A.M., Desanti A., Tilly K.I.,
RA   Hirshfield A.N., Tilly J.L.;
RT   "Interleukin-1 beta-converting enzyme-related proteases (IRPs) and
RT   mammalian cell death: dissociation of IRP-induced oligonucleosomal
RT   endonuclease activity from morphological apoptosis in granulosa cells of
RT   the ovarian follicle.";
RL   Endocrinology 136:5042-5053(1995).
RN   [5]
RP   INTERACTION WITH NOL3.
RX   PubMed=16639714; DOI=10.1002/jcb.20946;
RA   Zhang Y.Q., Herman B.;
RT   "ARC protects rat cardiomyocytes against oxidative stress through
RT   inhibition of caspase-2 mediated mitochondrial pathway.";
RL   J. Cell. Biochem. 99:575-588(2006).
CC   -!- FUNCTION: Involved in the activation cascade of caspases responsible
CC       for apoptosis execution. Might function by either activating some
CC       proteins required for cell death or inactivating proteins necessary for
CC       cell survival (By similarity). Associates with PIDD1 and CRADD to form
CC       the PIDDosome, a complex that activates CASP2 and triggers apoptosis in
CC       response to genotoxic stress (By similarity).
CC       {ECO:0000250|UniProtKB:P42575}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Strict requirement for an Asp residue at P1, with 316-Asp
CC         being essential for proteolytic activity and has a preferred cleavage
CC         sequence of Val-Asp-Val-Ala-Asp-|-.; EC=3.4.22.55;
CC   -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC       heterodimers, each one formed by a p18 subunit and a p12 subunit. Forms
CC       a complex named the PIDDosome with PIDD1 and CRADD (By similarity).
CC       Interacts with NOL3 (via CARD domain); inhibits CASP2 activity in a
CC       phosphorylation-dependent manner (PubMed:16639714).
CC       {ECO:0000250|UniProtKB:P42575, ECO:0000269|PubMed:16639714}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=caspase-2L;
CC         IsoId=P55215-1; Sequence=Displayed;
CC       Name=2; Synonyms=caspase-2S;
CC         IsoId=P55215-2; Sequence=VSP_016555, VSP_016556;
CC   -!- DOMAIN: The CARD domain mediates a direct interaction with CRADD.
CC       {ECO:0000250|UniProtKB:P42575}.
CC   -!- PTM: The mature protease can process its own propeptide, but not that
CC       of other caspases. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB82567.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; U77933; AAB96379.1; -; mRNA.
DR   EMBL; AF136231; AAD33684.1; -; mRNA.
DR   EMBL; AF136232; AAD33685.1; -; mRNA.
DR   EMBL; AF025671; AAB82567.1; ALT_FRAME; mRNA.
DR   EMBL; U34684; AAC52260.1; -; mRNA.
DR   PIR; I67436; I67436.
DR   PIR; JC6507; JC6507.
DR   RefSeq; NP_071967.2; NM_022522.2. [P55215-1]
DR   AlphaFoldDB; P55215; -.
DR   SMR; P55215; -.
DR   DIP; DIP-48602N; -.
DR   IntAct; P55215; 3.
DR   STRING; 10116.ENSRNOP00000022672; -.
DR   MEROPS; C14.006; -.
DR   iPTMnet; P55215; -.
DR   PhosphoSitePlus; P55215; -.
DR   PaxDb; 10116-ENSRNOP00000022672; -.
DR   Ensembl; ENSRNOT00000022672.7; ENSRNOP00000022672.2; ENSRNOG00000016707.8. [P55215-1]
DR   Ensembl; ENSRNOT00055048741; ENSRNOP00055040054; ENSRNOG00055028158. [P55215-1]
DR   Ensembl; ENSRNOT00060014286; ENSRNOP00060010969; ENSRNOG00060008547. [P55215-1]
DR   Ensembl; ENSRNOT00065026675; ENSRNOP00065020922; ENSRNOG00065016049. [P55215-1]
DR   GeneID; 64314; -.
DR   KEGG; rno:64314; -.
DR   UCSC; RGD:69274; rat. [P55215-1]
DR   AGR; RGD:69274; -.
DR   CTD; 835; -.
DR   RGD; 69274; Casp2.
DR   eggNOG; KOG3573; Eukaryota.
DR   GeneTree; ENSGT00940000156657; -.
DR   HOGENOM; CLU_036904_5_2_1; -.
DR   InParanoid; P55215; -.
DR   OMA; VMVLMTH; -.
DR   OrthoDB; 2873736at2759; -.
DR   PhylomeDB; P55215; -.
DR   TreeFam; TF102023; -.
DR   BRENDA; 3.4.22.55; 5301.
DR   Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR   Reactome; R-RNO-205025; NADE modulates death signalling.
DR   Reactome; R-RNO-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR   PRO; PR:P55215; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000016707; Expressed in thymus and 20 other cell types or tissues.
DR   ExpressionAtlas; P55215; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:1905369; C:endopeptidase complex; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:RGD.
DR   GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR   GO; GO:0097199; F:cysteine-type endopeptidase activity involved in apoptotic signaling pathway; IBA:GO_Central.
DR   GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IEA:InterPro.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR   GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR   GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISO:RGD.
DR   GO; GO:0035234; P:ectopic germ cell programmed cell death; ISO:RGD.
DR   GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR   GO; GO:0001554; P:luteolysis; IEP:RGD.
DR   GO; GO:0003407; P:neural retina development; IEP:RGD.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR   GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:0012501; P:programmed cell death; TAS:RGD.
DR   GO; GO:0016485; P:protein processing; ISO:RGD.
DR   GO; GO:0006508; P:proteolysis; TAS:RGD.
DR   CDD; cd08332; CARD_CASP2; 1.
DR   CDD; cd00032; CASc; 1.
DR   Gene3D; 3.40.50.1460; -; 1.
DR   Gene3D; 3.30.70.1470; Caspase-like; 1.
DR   Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR   InterPro; IPR001315; CARD.
DR   InterPro; IPR035702; CASP2_CARD.
DR   InterPro; IPR029030; Caspase-like_dom_sf.
DR   InterPro; IPR033139; Caspase_cys_AS.
DR   InterPro; IPR016129; Caspase_his_AS.
DR   InterPro; IPR011029; DEATH-like_dom_sf.
DR   InterPro; IPR011600; Pept_C14_caspase.
DR   InterPro; IPR002138; Pept_C14_p10.
DR   InterPro; IPR001309; Pept_C14_p20.
DR   InterPro; IPR015917; Pept_C14A.
DR   PANTHER; PTHR47901:SF7; CASPASE 2; 1.
DR   PANTHER; PTHR47901; CASPASE RECRUITMENT DOMAIN-CONTAINING PROTEIN 18; 1.
DR   Pfam; PF00619; CARD; 1.
DR   Pfam; PF00656; Peptidase_C14; 1.
DR   PIRSF; PIRSF038001; Caspase_ICE; 1.
DR   PRINTS; PR00376; IL1BCENZYME.
DR   SMART; SM00114; CARD; 1.
DR   SMART; SM00115; CASc; 1.
DR   SUPFAM; SSF52129; Caspase-like; 1.
DR   SUPFAM; SSF47986; DEATH domain; 1.
DR   PROSITE; PS50209; CARD; 1.
DR   PROSITE; PS01122; CASPASE_CYS; 1.
DR   PROSITE; PS01121; CASPASE_HIS; 1.
DR   PROSITE; PS50207; CASPASE_P10; 1.
DR   PROSITE; PS50208; CASPASE_P20; 1.
DR   Genevisible; P55215; RN.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Apoptosis; Hydrolase; Phosphoprotein;
KW   Protease; Reference proteome; Thiol protease; Zymogen.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P42575"
FT   PROPEP          2..169
FT                   /id="PRO_0000043403"
FT   CHAIN           170..325
FT                   /note="Caspase-2 subunit p18"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000044573"
FT   PROPEP          326..333
FT                   /id="PRO_0000044574"
FT   CHAIN           334..452
FT                   /note="Caspase-2 subunit p13"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004551"
FT   CHAIN           348..452
FT                   /note="Caspase-2 subunit p12"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000004552"
FT   DOMAIN          32..121
FT                   /note="CARD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT   REGION          327..349
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        277
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        320
FT                   /evidence="ECO:0000250"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P42575"
FT   MOD_RES         157
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P42575"
FT   MOD_RES         340
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P42575"
FT   VAR_SEQ         323..343
FT                   /note="DETDRGVDQQDGKNHAQSPGC -> GAIGSLGPLLLFTAATASLAL (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12067235"
FT                   /id="VSP_016555"
FT   VAR_SEQ         344..452
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12067235"
FT                   /id="VSP_016556"
FT   CONFLICT        145
FT                   /note="C -> Y (in Ref. 3; AAB82567)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        166
FT                   /note="D -> H (in Ref. 3; AAB82567)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        177
FT                   /note="K -> E (in Ref. 3; AAB82567)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        197
FT                   /note="Q -> R (in Ref. 3; AAB82567)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        340
FT                   /note="S -> P (in Ref. 4; AAC52260)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        348..349
FT                   /note="AG -> TV (in Ref. 4; AAC52260)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        367
FT                   /note="G -> V (in Ref. 4; AAC52260)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        373
FT                   /note="G -> D (in Ref. 4; AAC52260)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        376..377
FT                   /note="AM -> PI (in Ref. 4; AAC52260)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   452 AA;  50728 MW;  03F9D096BB741CE3 CRC64;
     MAASSGRSQS SLHRKGLMAA DRRSRILAVC GMHPDHQETL KKNRVVLAKQ LLLSELLEHL
     LEKDIITLEM RELIQAKGGS FSQNVELLNL LPKRGPQAFD AFCEALRETR QGHLEDLLLT
     TLSDIQHILP PLSCDYDSSL PFSVCESCPP HKQSRLSTDT MEHSLDNGDG PPCLQVKPCT
     PEFYQAHYQL AYRLQSQPRG LALVMSNVHF TGEKDLEFRS GGDVDHTTLV TLFKLLGYNV
     HVLYDQTAQE MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GGIYGVDGKL LQLQEVFRLF
     DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAQS PGCEESDAGK EELMKMRLPT
     RSDMICGYAC LKGNAAMRNT KRGSWYIEAL TQVFSERACD MHVADMLVKV NALIKEREGY
     APGTEFHRCK EMSEYCSTLC QQLYLFPGYP PT
//