ID CASP2_HUMAN Reviewed; 452 AA. AC P42575; A8K5F9; D3DXD6; E9PDN0; P42576; Q59F21; Q7KZL6; Q86UJ3; Q9BUP7; AC Q9BZK9; Q9BZL0; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 2. DT 27-MAR-2024, entry version 224. 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, NEDD2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE [MRNA] OF RP 14-452 (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=8087842; DOI=10.1016/s0092-8674(94)90422-7; RA Wang L., Miura M., Bergeron L., Zhu H., Yuan J.; RT "Ich-1, an Ice/ced-3-related gene, encodes both positive and negative RT regulators of programmed cell death."; RL Cell 78:739-750(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF RP 32-108 (ISOFORMS 1/2), AND ALTERNATIVE SPLICING. RX PubMed=11156409; RA Droin N., Beauchemin M., Solary E., Bertrand R.; RT "Identification of a caspase-2 isoform that behaves as an endogenous RT inhibitor of the caspase cascade."; RL Cancer Res. 60:7039-7047(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-172; ALA-178 AND RP GLY-441. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-172. RC TISSUE=Skin; 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-452 (ISOFORM 1), AND VARIANT RP LEU-172. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 194-452. RC TISSUE=Spleen; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP CLEAVAGE SITES. RX PubMed=8654923; DOI=10.1101/gad.10.9.1073; RA Xue D., Shaham S., Horvitz H.R.; RT "The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease RT with substrate specificities similar to those of the human CPP32 RT protease."; RL Genes Dev. 10:1073-1083(1996). RN [12] RP INTERACTION WITH CRADD. RX PubMed=9044836; RA Ahmad M., Srinivasula S.M., Wang L., Talanian R.V., Litwack G., RA Fernandes-Alnemri T., Alnemri E.S.; RT "CRADD, a novel human apoptotic adaptor molecule for caspase-2, and RT FasL/tumor necrosis factor receptor-interacting protein RIP."; RL Cancer Res. 57:615-619(1997). RN [13] RP INTERACTION WITH CRADD, DOMAIN, AND MUTAGENESIS OF LEU-57; GLY-95; PHE-99; RP ASP-100; PHE-102; GLU-104 AND LEU-106. RX PubMed=8985253; DOI=10.1038/385086a0; RA Duan H., Dixit V.M.; RT "RAIDD is a new 'death' adaptor molecule."; RL Nature 385:86-89(1997). RN [14] RP INTERACTION WITH NOL3. RX PubMed=9560245; DOI=10.1073/pnas.95.9.5156; RA Koseki T., Inohara N., Chen S., Nunez G.; RT "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that RT interacts selectively with caspases."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5156-5160(1998). RN [15] RP FUNCTION, AND IDENTIFICATION IN PIDDOSOME COMPLEX. RX PubMed=15073321; DOI=10.1126/science.1095432; RA Tinel A., Tschopp J.; RT "The PIDDosome, a protein complex implicated in activation of caspase-2 in RT response to genotoxic stress."; RL Science 304:843-846(2004). RN [16] RP INTERACTION WITH PIDD1. RX PubMed=16652156; DOI=10.1038/sj.onc.1209569; RA Vakifahmetoglu H., Olsson M., Orrenius S., Zhivotovsky B.; RT "Functional connection between p53 and caspase-2 is essential for apoptosis RT induced by DNA damage."; RL Oncogene 25:5683-5692(2006). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 167-452 IN COMPLEX WITH RP INHIBITOR, SUBUNIT, AND DISULFIDE BOND. RX PubMed=12920126; DOI=10.1074/jbc.m304895200; RA Schweizer A., Briand C., Grutter M.G.; RT "Crystal structure of caspase-2, apical initiator of the intrinsic RT apoptotic pathway."; RL J. Biol. Chem. 278:42441-42447(2003). 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:15073321). Associates with PIDD1 and CRADD to CC form the PIDDosome, a complex that activates CASP2 and triggers CC apoptosis in response to genotoxic stress (PubMed:15073321). CC {ECO:0000269|PubMed:15073321}. 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 CC (PubMed:12920126). Forms a complex named the PIDDosome with PIDD1 and CC CRADD (PubMed:9044836, PubMed:8985253, PubMed:15073321, CC PubMed:16652156). Interacts with NOL3 (via CARD domain); inhibits CASP2 CC activity in a phosphorylation-dependent manner (PubMed:9560245). CC {ECO:0000269|PubMed:12920126, ECO:0000269|PubMed:15073321, CC ECO:0000269|PubMed:16652156, ECO:0000269|PubMed:8985253, CC ECO:0000269|PubMed:9044836, ECO:0000269|PubMed:9560245}. CC -!- INTERACTION: CC P42575; O95429: BAG4; NbExp=3; IntAct=EBI-520342, EBI-2949658; CC P42575; P42575: CASP2; NbExp=11; IntAct=EBI-520342, EBI-520342; CC P42575; P42575-1: CASP2; NbExp=2; IntAct=EBI-520342, EBI-520357; CC P42575; P78560: CRADD; NbExp=23; IntAct=EBI-520342, EBI-520375; CC P42575; O43741: PRKAB2; NbExp=3; IntAct=EBI-520342, EBI-1053424; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Isoforms differ in the N- and C-termini.; CC Name=1; Synonyms=ICH-1L; CC IsoId=P42575-1; Sequence=Displayed; CC Name=2; Synonyms=ICH-1S; CC IsoId=P42575-2; Sequence=VSP_000801, VSP_000802; CC Name=3; Synonyms=Casp-2L-Pro; CC IsoId=P42575-3; Sequence=VSP_046280, VSP_046281, VSP_046282; CC -!- TISSUE SPECIFICITY: Expressed at higher levels in the embryonic lung, CC liver and kidney than in the heart and brain. In adults, higher level CC expression is seen in the placenta, lung, kidney, and pancreas than in CC the heart, brain, liver and skeletal muscle. CC -!- DOMAIN: The CARD domain mediates a direct interaction with CRADD. CC {ECO:0000269|PubMed:8985253}. CC -!- PTM: The mature protease can process its own propeptide, but not that CC of other caspases. {ECO:0000269|PubMed:8654923}. CC -!- MISCELLANEOUS: [Isoform 1]: Acts as a positive regulator of apoptosis. CC -!- MISCELLANEOUS: [Isoform 2]: Acts as a negative regulator of apoptosis. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: May function as an endogenous apoptosis CC inhibitor that antagonizes caspase activation and cell death. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA58959.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAO25653.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAP22346.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAP22349.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAD92877.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/casp2/"; 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; U13021; AAA58959.1; ALT_INIT; mRNA. DR EMBL; U13022; AAA58960.1; -; mRNA. DR EMBL; AF314174; AAK00299.1; -; mRNA. DR EMBL; AF314175; AAK00300.1; -; mRNA. DR EMBL; CR541748; CAG46548.1; -; mRNA. DR EMBL; AK291274; BAF83963.1; -; mRNA. DR EMBL; AY219042; AAO25653.1; ALT_INIT; Genomic_DNA. DR EMBL; AC073342; AAP22346.1; ALT_INIT; Genomic_DNA. DR EMBL; AC073342; AAP22347.1; -; Genomic_DNA. DR EMBL; AC073342; AAP22348.1; -; Genomic_DNA. DR EMBL; AC073342; AAP22349.1; ALT_INIT; Genomic_DNA. DR EMBL; CH471198; EAW51863.1; -; Genomic_DNA. DR EMBL; CH471198; EAW51867.1; -; Genomic_DNA. DR EMBL; CH471198; EAW51870.1; -; Genomic_DNA. DR EMBL; BC002427; AAH02427.2; -; mRNA. DR EMBL; BT007240; AAP35904.1; -; mRNA. DR EMBL; AB209640; BAD92877.1; ALT_INIT; mRNA. DR CCDS; CCDS5879.1; -. [P42575-1] DR PIR; A54821; A54821. DR RefSeq; NP_001215.1; NM_001224.4. DR RefSeq; NP_116764.2; NM_032982.3. [P42575-1] DR RefSeq; NP_116765.2; NM_032983.3. DR PDB; 1PYO; X-ray; 1.65 A; A/C=167-333, B/D=348-452. DR PDB; 2P2C; X-ray; 3.24 A; A/C/E/G/I/K=167-333, B/D/F/H/J/L=348-452. DR PDB; 3R5J; X-ray; 1.77 A; A/C=175-333, B/D=349-452. DR PDB; 3R6G; X-ray; 2.07 A; A/C=175-333, B/D=349-452. DR PDB; 3R6L; X-ray; 1.90 A; A/C=175-333, B/D=349-452. DR PDB; 3R7B; X-ray; 1.80 A; A/C=175-333, B/D=349-452. DR PDB; 3R7N; X-ray; 2.33 A; A/C=175-333, B/D=349-452. DR PDB; 3R7S; X-ray; 2.25 A; A/C=175-333, B/D=349-452. DR PDB; 3RJM; X-ray; 2.55 A; A/C=167-333, B/D=348-452. DR PDB; 6GKF; X-ray; 2.60 A; I/J/K/L/M/N/O/P=136-143. DR PDB; 6GKG; X-ray; 2.85 A; I/J/K/L/M/N=161-168. DR PDB; 6S9K; X-ray; 1.60 A; B=135-168. DR PDB; 6SAD; X-ray; 2.75 A; C=135-168. DR PDB; 6Y8B; X-ray; 1.54 A; P=136-143. DR PDB; 6Y8D; X-ray; 1.51 A; B=161-168. DR PDBsum; 1PYO; -. DR PDBsum; 2P2C; -. DR PDBsum; 3R5J; -. DR PDBsum; 3R6G; -. DR PDBsum; 3R6L; -. DR PDBsum; 3R7B; -. DR PDBsum; 3R7N; -. DR PDBsum; 3R7S; -. DR PDBsum; 3RJM; -. DR PDBsum; 6GKF; -. DR PDBsum; 6GKG; -. DR PDBsum; 6S9K; -. DR PDBsum; 6SAD; -. DR PDBsum; 6Y8B; -. DR PDBsum; 6Y8D; -. DR AlphaFoldDB; P42575; -. DR SMR; P42575; -. DR BioGRID; 107285; 58. DR ComplexPortal; CPX-3905; Caspase-2 PIDDosome. DR ComplexPortal; CPX-969; Caspase-2 complex. DR CORUM; P42575; -. DR IntAct; P42575; 15. DR MINT; P42575; -. DR STRING; 9606.ENSP00000312664; -. DR BindingDB; P42575; -. DR ChEMBL; CHEMBL4884; -. DR DrugCentral; P42575; -. DR GuidetoPHARMACOLOGY; 1618; -. DR MEROPS; C14.006; -. DR iPTMnet; P42575; -. DR PhosphoSitePlus; P42575; -. DR BioMuta; CASP2; -. DR DMDM; 83300977; -. DR EPD; P42575; -. DR jPOST; P42575; -. DR MassIVE; P42575; -. DR MaxQB; P42575; -. DR PaxDb; 9606-ENSP00000312664; -. DR PeptideAtlas; P42575; -. DR ProteomicsDB; 19708; -. DR ProteomicsDB; 55519; -. [P42575-1] DR ProteomicsDB; 55520; -. [P42575-2] DR Pumba; P42575; -. DR Antibodypedia; 3198; 901 antibodies from 43 providers. DR DNASU; 835; -. DR Ensembl; ENST00000310447.10; ENSP00000312664.5; ENSG00000106144.20. [P42575-1] DR GeneID; 835; -. DR KEGG; hsa:835; -. DR MANE-Select; ENST00000310447.10; ENSP00000312664.5; NM_032982.4; NP_116764.2. DR UCSC; uc003wco.3; human. [P42575-1] DR AGR; HGNC:1503; -. DR CTD; 835; -. DR DisGeNET; 835; -. DR GeneCards; CASP2; -. DR HGNC; HGNC:1503; CASP2. DR HPA; ENSG00000106144; Low tissue specificity. DR MIM; 600639; gene. DR neXtProt; NX_P42575; -. DR OpenTargets; ENSG00000106144; -. DR PharmGKB; PA26086; -. DR VEuPathDB; HostDB:ENSG00000106144; -. DR eggNOG; KOG3573; Eukaryota. DR GeneTree; ENSGT00940000156657; -. DR HOGENOM; CLU_036904_5_2_1; -. DR InParanoid; P42575; -. DR OMA; VMVLMTH; -. DR OrthoDB; 2873736at2759; -. DR PhylomeDB; P42575; -. DR TreeFam; TF102023; -. DR BioCyc; MetaCyc:HS02869-MONOMER; -. DR BRENDA; 3.4.22.55; 2681. DR PathwayCommons; P42575; -. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-205025; NADE modulates death signalling. DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases. DR SignaLink; P42575; -. DR SIGNOR; P42575; -. DR BioGRID-ORCS; 835; 14 hits in 1174 CRISPR screens. DR ChiTaRS; CASP2; human. DR EvolutionaryTrace; P42575; -. DR GeneWiki; Caspase_2; -. DR GenomeRNAi; 835; -. DR Pharos; P42575; Tchem. DR PRO; PR:P42575; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P42575; Protein. DR Bgee; ENSG00000106144; Expressed in buccal mucosa cell and 181 other cell types or tissues. DR ExpressionAtlas; P42575; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:1905369; C:endopeptidase complex; IPI:ComplexPortal. DR GO; GO:0005730; C:nucleolus; NAS:ComplexPortal. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB. 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:0019899; F:enzyme binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0006974; P:DNA damage response; NAS:ComplexPortal. DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB. DR GO; GO:0035234; P:ectopic germ cell programmed cell death; IEA:Ensembl. DR GO; GO:0097194; P:execution phase of apoptosis; TAS:UniProtKB. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central. 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; NAS:UniProtKB. DR GO; GO:0003407; P:neural retina development; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0016485; P:protein processing; IDA:BHF-UCL. 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; P42575; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Hydrolase; KW Phosphoprotein; Protease; Reference proteome; Thiol protease; Zymogen. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT PROPEP 2..169 FT /id="PRO_0000004541" FT CHAIN 170..325 FT /note="Caspase-2 subunit p18" FT /id="PRO_0000004542" FT PROPEP 326..333 FT /id="PRO_0000004543" FT CHAIN 334..452 FT /note="Caspase-2 subunit p13" FT /id="PRO_0000004544" FT CHAIN 348..452 FT /note="Caspase-2 subunit p12" FT /id="PRO_0000004545" FT DOMAIN 32..121 FT /note="CARD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT REGION 327..354 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:0007744|PubMed:19413330" FT MOD_RES 157 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 340 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VAR_SEQ 1..31 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8087842, ECO:0000303|Ref.3" FT /id="VSP_000801" FT VAR_SEQ 1..17 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11156409" FT /id="VSP_046280" FT VAR_SEQ 107..108 FT /note="RE -> HS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11156409" FT /id="VSP_046281" FT VAR_SEQ 109..452 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11156409" FT /id="VSP_046282" FT VAR_SEQ 323..452 FT /note="DETDRGVDQQDGKNHAGSPGCEESDAGKEKLPKMRLPTRSDMICGYACLKGT FT AAMRNTKRGSWYIEALAQVFSERACDMHVADMLVKVNALIKDREGYAPGTEFHRCKEMS FT EYCSTLCRHLYLFPGHPPT -> GGAIGSLGHLLLFTAATASLAL (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:8087842, ECO:0000303|Ref.3" FT /id="VSP_000802" FT VARIANT 105 FT /note="A -> G (in dbSNP:rs762263774)" FT /id="VAR_055621" FT VARIANT 172 FT /note="V -> L (in dbSNP:rs4647297)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5, FT ECO:0000269|Ref.9" FT /id="VAR_016334" FT VARIANT 178 FT /note="P -> A (in dbSNP:rs4647298)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_016335" FT VARIANT 441 FT /note="R -> G (in dbSNP:rs4647338)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_016336" FT MUTAGEN 57 FT /note="L->F: Loss of interaction with CRADD." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 95 FT /note="G->R: Loss of interaction with CRADD." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 99 FT /note="F->A: Loss of interaction with CRADD." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 100 FT /note="D->A: No effect on interaction with CRADD. Loss of FT interaction with CRADD; when associated A-104." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 102 FT /note="F->A: Loss of interaction with CRADD." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 104 FT /note="E->A: No effect on interaction with CRADD. Loss of FT interaction with CRADD; when associated A-100." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 106 FT /note="L->A: Loss of interaction with CRADD." FT /evidence="ECO:0000269|PubMed:8985253" FT MUTAGEN 320 FT /note="C->S: Loss of function." FT MUTAGEN 369 FT /note="A->T: Loss of function." FT CONFLICT 309..322 FT /note="QNKPKMFFIQACRG -> EEVTSLSILSAFVT (in Ref. 10; FT BAD92877)" FT /evidence="ECO:0000305" FT HELIX 150..157 FT /evidence="ECO:0007829|PDB:6S9K" FT HELIX 181..187 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 197..206 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 222..235 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 238..245 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 248..259 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 262..265 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 267..276 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 293..299 FT /evidence="ECO:0007829|PDB:1PYO" FT TURN 302..304 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 306..308 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 313..319 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 321..324 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 363..370 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:3R5J" FT TURN 380..382 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 385..397 FT /evidence="ECO:0007829|PDB:1PYO" FT TURN 398..400 FT /evidence="ECO:0007829|PDB:1PYO" FT HELIX 403..415 FT /evidence="ECO:0007829|PDB:1PYO" FT TURN 425..428 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 434..437 FT /evidence="ECO:0007829|PDB:1PYO" FT STRAND 440..442 FT /evidence="ECO:0007829|PDB:3R7S" SQ SEQUENCE 452 AA; 50685 MW; 6EF0ED05EF808385 CRC64; MAAPSAGSWS TFQHKELMAA DRGRRILGVC GMHPHHQETL KKNRVVLAKQ LLLSELLEHL LEKDIITLEM RELIQAKVGS FSQNVELLNL LPKRGPQAFD AFCEALRETK QGHLEDMLLT TLSGLQHVLP PLSCDYDLSL PFPVCESCPL YKKLRLSTDT VEHSLDNKDG PVCLQVKPCT PEFYQTHFQL AYRLQSRPRG LALVLSNVHF TGEKELEFRS GGDVDHSTLV TLFKLLGYDV HVLCDQTAQE MQEKLQNFAQ LPAHRVTDSC IVALLSHGVE GAIYGVDGKL LQLQEVFQLF DNANCPSLQN KPKMFFIQAC RGDETDRGVD QQDGKNHAGS PGCEESDAGK EKLPKMRLPT RSDMICGYAC LKGTAAMRNT KRGSWYIEAL AQVFSERACD MHVADMLVKV NALIKDREGY APGTEFHRCK EMSEYCSTLC RHLYLFPGHP PT //