CASP2_HUMAN
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 03-AUG-2022, entry version 215.
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/";
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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; 54.
DR ComplexPortal; CPX-3905; Caspase-2 PIDDosome.
DR ComplexPortal; CPX-969; Caspase-2 complex.
DR CORUM; P42575; -.
DR IntAct; P42575; 14.
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; P42575; -.
DR PeptideAtlas; P42575; -.
DR PRIDE; P42575; -.
DR ProteomicsDB; 19708; -.
DR ProteomicsDB; 55519; -. [P42575-1]
DR ProteomicsDB; 55520; -. [P42575-2]
DR Antibodypedia; 3198; 821 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 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; 1092723at2759; -.
DR PhylomeDB; P42575; -.
DR TreeFam; TF102023; -.
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; 11 hits in 1093 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 179 other tissues.
DR ExpressionAtlas; P42575; baseline and differential.
DR Genevisible; P42575; HS.
DR GO; GO:0008303; C:caspase complex; IPI:ComplexPortal.
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:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IC:ComplexPortal.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IBA:GO_Central.
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: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: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; IBA:GO_Central.
DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:UniProtKB.
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; IEP:UniProtKB.
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:0060546; P:negative regulation of necroptotic process; IDA:ComplexPortal.
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; 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 GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:ComplexPortal.
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 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
