CASP2_RAT
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 03-AUG-2022, entry version 181.
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; P55215; -.
DR PRIDE; P55215; -.
DR Ensembl; ENSRNOT00000022672; ENSRNOP00000022672; ENSRNOG00000016707. [P55215-1]
DR GeneID; 64314; -.
DR KEGG; rno:64314; -.
DR UCSC; RGD:69274; rat. [P55215-1]
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; 1092723at2759; -.
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 tissues.
DR ExpressionAtlas; P55215; baseline and differential.
DR Genevisible; P55215; RN.
DR GO; GO:0008303; C:caspase complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:1905369; C:endopeptidase complex; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA: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; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006915; P:apoptotic process; IMP:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP: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:0060546; P:negative regulation of necroptotic process; ISO: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 GO; GO:0097752; P:regulation of DNA stability; ISO:RGD.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:RGD.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR035702; Caspase_2.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF151; PTHR10454:SF151; 1.
DR Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 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.
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
