CASP2_MOUSE
ID CASP2_MOUSE Reviewed; 452 AA.
AC P29594; O08737; Q3TCM0; Q8C9H7; Q8K241;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 5.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Caspase-2;
DE Short=CASP-2;
DE EC=3.4.22.55;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 2;
DE Short=NEDD-2;
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, Nedd-2, Nedd2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF CYS-320.
RC STRAIN=BALB/cJ;
RX PubMed=7958843; DOI=10.1101/gad.8.14.1613;
RA Kumar S., Kinoshita M., Noda M., Copeland N.G., Jenkins N.A.;
RT "Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein
RT similar to the product of the Caenorhabditis elegans cell death gene ced-3
RT and the mammalian IL-1 beta-converting enzyme.";
RL Genes Dev. 8:1613-1626(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C3H/An;
RX PubMed=9038361; DOI=10.1016/s0014-5793(97)00026-4;
RA van de Craen M., Vandenabeele P., Declercq W., van den Brande I.,
RA van Loo G., Molemans F., Schotte P., van Criekinge W., Beyaert R.,
RA Fiers W.;
RT "Characterization of seven murine caspase family members.";
RL FEBS Lett. 403:61-69(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE.
RC TISSUE=Brain;
RX PubMed=1378265; DOI=10.1016/0006-291x(92)91747-e;
RA Kumar S., Tomooka Y., Noda M.;
RT "Identification of a set of genes with developmentally down-regulated
RT expression in the mouse brain.";
RL Biochem. Biophys. Res. Commun. 185:1155-1161(1992).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (PubMed:7958843). 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, ECO:0000269|PubMed:7958843}.
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. Interacts with NOL3
CC (via CARD domain); inhibits CASP2 activity in a phosphorylation-
CC dependent manner. {ECO:0000250|UniProtKB:P42575}.
CC -!- TISSUE SPECIFICITY: High level expression seen in the embryonic CNS,
CC liver, lung, kidney, small intestine, and hair follicles of vibrissae.
CC Moderate expression seen in the skin, oral mucosa, skeletal muscle,
CC submandibular gland and thymus. In the adult, it is highly expressed in
CC spleen, lung and kidney. Moderately in the brain, heart, testis, liver.
CC Low levels in the thymus, skeletal muscle, ovary and gut.
CC -!- DEVELOPMENTAL STAGE: During embryonic development is highly expressed
CC in several types of mouse tissue undergoing high rates of programmed
CC cell death such as central nervous system and kidney.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D28492; BAA25876.1; -; mRNA.
DR EMBL; Y13085; CAA73527.1; -; mRNA.
DR EMBL; AK042072; BAC31153.1; -; mRNA.
DR EMBL; AK170649; BAE41936.1; -; mRNA.
DR EMBL; BC034262; AAH34262.1; -; mRNA.
DR CCDS; CCDS20064.1; -.
DR RefSeq; NP_031636.1; NM_007610.2.
DR AlphaFoldDB; P29594; -.
DR SMR; P29594; -.
DR BioGRID; 198496; 2.
DR ComplexPortal; CPX-3901; Caspase-2 complex.
DR ComplexPortal; CPX-3963; Caspase-2 PIDDosome.
DR CORUM; P29594; -.
DR STRING; 10090.ENSMUSP00000031895; -.
DR MEROPS; C14.006; -.
DR iPTMnet; P29594; -.
DR PhosphoSitePlus; P29594; -.
DR EPD; P29594; -.
DR MaxQB; P29594; -.
DR PaxDb; P29594; -.
DR PeptideAtlas; P29594; -.
DR PRIDE; P29594; -.
DR ProteomicsDB; 265535; -.
DR Antibodypedia; 3198; 821 antibodies from 43 providers.
DR DNASU; 12366; -.
DR Ensembl; ENSMUST00000031895; ENSMUSP00000031895; ENSMUSG00000029863.
DR GeneID; 12366; -.
DR KEGG; mmu:12366; -.
DR UCSC; uc009bqq.2; mouse.
DR CTD; 835; -.
DR MGI; MGI:97295; Casp2.
DR VEuPathDB; HostDB:ENSMUSG00000029863; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000156657; -.
DR HOGENOM; CLU_036904_5_2_1; -.
DR InParanoid; P29594; -.
DR OMA; VMVLMTH; -.
DR OrthoDB; 1092723at2759; -.
DR PhylomeDB; P29594; -.
DR TreeFam; TF102023; -.
DR BRENDA; 3.4.22.55; 3474.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-205025; NADE modulates death signalling.
DR Reactome; R-MMU-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR BioGRID-ORCS; 12366; 1 hit in 61 CRISPR screens.
DR PRO; PR:P29594; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P29594; protein.
DR Bgee; ENSMUSG00000029863; Expressed in saccule of membranous labyrinth and 253 other tissues.
DR ExpressionAtlas; P29594; baseline and differential.
DR Genevisible; P29594; MM.
DR GO; GO:0008303; C:caspase complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:1905369; C:endopeptidase complex; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISO:MGI.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
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:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:MGI.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISO:MGI.
DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IGI:MGI.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0001554; P:luteolysis; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0060546; P:negative regulation of necroptotic process; ISO:MGI.
DR GO; GO:0003407; P:neural retina development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ComplexPortal.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:0097752; P:regulation of DNA stability; IDA:ComplexPortal.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISO:MGI.
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; Apoptosis; Hydrolase; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Zymogen.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P42575"
FT PROPEP 2..169
FT /evidence="ECO:0000250"
FT /id="PRO_0000004546"
FT CHAIN 170..333
FT /note="Caspase-2 subunit p18"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004547"
FT CHAIN 334..452
FT /note="Caspase-2 subunit p13"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004548"
FT CHAIN 348..452
FT /note="Caspase-2 subunit p12"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004549"
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 MUTAGEN 320
FT /note="C->G: Loss of function."
FT /evidence="ECO:0000269|PubMed:7958843"
FT CONFLICT 85..102
FT /note="VELLNLLPKRGPQAFDAF -> EGCGGWRGPAFVCFVGGA (in Ref. 3;
FT BAE41936)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="Missing (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="K -> R (in Ref. 3; BAC31153)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 452 AA; 50661 MW; A4DE25A712FAB855 CRC64;
MAAPSGRSQS SLHRKGLMAA DRRSRILAVC GMHPDHQETL KKNRVVLAKQ LLLSELLEHL
LEKDIITLEM RELIQAKGGS FSQNVELLNL LPKRGPQAFD AFCEALRETR QGHLEDLLLT
TLSDIQHVLP PLSCDYDTSL PFSVCESCPP HKQLRLSTDA TEHSLDNGDG PPCLLVKPCT
PEFYQAHYQL AYRLQSQPRG LALVLSNVHF TGEKDLEFRS GGDVDHTTLV TLFKLLGYNV
HVLHDQTAQE MQEKLQNFAQ LPAHRVTDSC VVALLSHGVE GGIYGVDGKL LQLQEVFRLF
DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHTQS PGCEESDAGK EELMKMRLPT
RSDMICGYAC LKGNAAMRNT KRGSWYIEAL TQVFSERACD MHVADMLVKV NALIKEREGY
APGTEFHRCK EMSEYCSTLC QQLYLFPGYP PT
