ID CASP7_HUMAN Reviewed; 303 AA.
AC P55210; B4DQU7; B5BU45; D3DRB8; Q13364; Q53YD5; Q5SVL0; Q5SVL3; Q96BA0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 27-MAR-2024, entry version 229.
DE RecName: Full=Caspase-7 {ECO:0000303|PubMed:9070923};
DE Short=CASP-7 {ECO:0000303|PubMed:9070923};
DE EC=3.4.22.60 {ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230, ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:18723680};
DE AltName: Full=Apoptotic protease Mch-3 {ECO:0000303|PubMed:8521391};
DE AltName: Full=CMH-1 {ECO:0000303|PubMed:8567622};
DE AltName: Full=ICE-like apoptotic protease 3 {ECO:0000303|PubMed:8576161};
DE Short=ICE-LAP3 {ECO:0000303|PubMed:8576161};
DE Contains:
DE RecName: Full=Caspase-7 subunit p20;
DE Contains:
DE RecName: Full=Caspase-7 subunit p11;
DE Flags: Precursor;
GN Name=CASP7 {ECO:0000303|PubMed:9070923, ECO:0000312|HGNC:HGNC:1508};
GN Synonyms=MCH3 {ECO:0000303|PubMed:8521391};
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] (ISOFORMS ALPHA AND BETA), AND FUNCTION.
RC TISSUE=T-cell;
RX PubMed=8521391;
RA Fernandes-Alnemri T., Takahashi A., Armstrong R.C., Krebs J., Fritz L.C.,
RA Tomaselli K.J., Wang L., Yu Z., Croce C.M., Salveson G., Earnshaw W.C.,
RA Litwack G., Alnemri E.S.;
RT "Mch3, a novel human apoptotic cysteine protease highly related to CPP32.";
RL Cancer Res. 55:6045-6052(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF CYS-186.
RX PubMed=8576161; DOI=10.1074/jbc.271.3.1621;
RA Duan H., Chinnaiyan A.M., Hudson P.L., Wing J.P., He W.-W., Dixit V.M.;
RT "ICE-LAP3, a novel mammalian homologue of the Caenorhabditis elegans cell
RT death protein Ced-3 is activated during Fas- and tumor necrosis factor-
RT induced apoptosis.";
RL J. Biol. Chem. 271:1621-1625(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), AND FUNCTION.
RC TISSUE=Spleen;
RX PubMed=8567622; DOI=10.1074/jbc.271.4.1825;
RA Lippke J.A., Gu Y., Sarnecki C., Caron P.R., Su M.S.-S.;
RT "Identification and characterization of CPP32/Mch2 homolog 1, a novel
RT cysteine protease similar to CPP32.";
RL J. Biol. Chem. 271:1825-1828(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND ALPHA'), AND FUNCTION.
RC TISSUE=Fetal lung, and Fetal spleen;
RX PubMed=9070923; DOI=10.1006/geno.1996.4548;
RA Juan T.S.-C., McNiece I.K., Argento J.M., Jenkins N.A., Gilbert D.J.,
RA Copeland N.G., Fletcher F.A.;
RT "Identification and mapping of Casp7, a cysteine protease resembling CPP32
RT beta, interleukin-1 beta converting enzyme, and CED-3.";
RL Genomics 40:86-93(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), AND VARIANT GLU-4.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA').
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), AND VARIANT GLU-4.
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 [11]
RP FUNCTION.
RX PubMed=8643593; DOI=10.1073/pnas.93.11.5437;
RA Pai J.-T., Brown M.S., Goldstein J.L.;
RT "Purification and cDNA cloning of a second apoptosis-related cysteine
RT protease that cleaves and activates sterol regulatory element binding
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5437-5442(1996).
RN [12]
RP PROTEOLYTIC PROCESSING.
RX PubMed=8755496; DOI=10.1073/pnas.93.15.7464;
RA Fernandes-Alnemri T., Armstrong R.C., Krebs J.F., Srinivasula S.M.,
RA Wang L., Bullrich F., Fritz L.C., Trapani J.A., Tomaselli K.J., Litwack G.,
RA Alnemri E.S.;
RT "In vitro activation of CPP32 and Mch3 by Mch4, a novel human apoptotic
RT cysteine protease containing two FADD-like domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7464-7469(1996).
RN [13]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=9852092; DOI=10.1074/jbc.273.51.34278;
RA Yang X., Stennicke H.R., Wang B., Green D.R., Jaenicke R.U., Srinivasan A.,
RA Seth P., Salvesen G.S., Froelich C.J.;
RT "Granzyme B mimics apical caspases. Description of a unified pathway for
RT trans-activation of executioner caspase-3 and -7.";
RL J. Biol. Chem. 273:34278-34283(1998).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10497198; DOI=10.1074/jbc.274.40.28379;
RA Germain M., Affar E.B., D'Amours D., Dixit V.M., Salvesen G.S.,
RA Poirier G.G.;
RT "Cleavage of automodified poly(ADP-ribose) polymerase during apoptosis.
RT Evidence for involvement of caspase-7.";
RL J. Biol. Chem. 274:28379-28384(1999).
RN [15]
RP ACTIVITY REGULATION.
RX PubMed=10821855; DOI=10.1074/jbc.275.21.16007;
RA Lee D., Long S.A., Adams J.L., Chan G., Vaidya K.S., Francis T.A.,
RA Kikly K., Winkler J.D., Sung C.-M., Debouck C., Richardson S., Levy M.A.,
RA DeWolf W.E. Jr., Keller P.M., Tomaszek T., Head M.S., Ryan M.D.,
RA Haltiwanger R.C., Liang P.-H., Janson C.A., McDevitt P.J., Johanson K.,
RA Concha N.O., Chan W., Abdel-Meguid S.S., Badger A.M., Lark M.W.,
RA Nadeau D.P., Suva L.J., Gowen M., Nuttall M.E.;
RT "Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit
RT apoptosis and maintain cell functionality.";
RL J. Biol. Chem. 275:16007-16014(2000).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF ASP-23; CYS-186; ASP-198 AND ASP-206.
RX PubMed=12824163; DOI=10.1074/jbc.m305110200;
RA Denault J.B., Salvesen G.S.;
RT "Human caspase-7 activity and regulation by its N-terminal peptide.";
RL J. Biol. Chem. 278:34042-34050(2003).
RN [17]
RP INTERACTION WITH BIRC6/BRUCE.
RX PubMed=15200957; DOI=10.1016/j.molcel.2004.05.018;
RA Bartke T., Pohl C., Pyrowolakis G., Jentsch S.;
RT "Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin
RT ligase.";
RL Mol. Cell 14:801-811(2004).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16123041; DOI=10.1074/jbc.m506460200;
RA Clarke C.A., Bennett L.N., Clarke P.R.;
RT "Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1
RT pathway.";
RL J. Biol. Chem. 280:35337-35345(2005).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16374543; DOI=10.1007/s10495-005-3276-y;
RA Rodriguez-Hernandez A., Brea-Calvo G., Fernandez-Ayala D.J., Cordero M.,
RA Navas P., Sanchez-Alcazar J.A.;
RT "Nuclear caspase-3 and caspase-7 activation, and poly(ADP-ribose)
RT polymerase cleavage are early events in camptothecin-induced apoptosis.";
RL Apoptosis 11:131-139(2006).
RN [20]
RP ACTIVITY REGULATION, INTERACTION WITH XIAP, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=16352606; DOI=10.1074/jbc.m507393200;
RA Twiddy D., Cohen G.M., Macfarlane M., Cain K.;
RT "Caspase-7 is directly activated by the approximately 700-kDa apoptosome
RT complex and is released as a stable XIAP-caspase-7 approximately 200-kDa
RT complex.";
RL J. Biol. Chem. 281:3876-3888(2006).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, INTERACTION
RP WITH XIAP, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF CYS-186; ASP-192;
RP ASP-198 AND ASP-206.
RX PubMed=16916640; DOI=10.1016/j.molcel.2006.06.020;
RA Denault J.B., Bekes M., Scott F.L., Sexton K.M., Bogyo M., Salvesen G.S.;
RT "Engineered hybrid dimers: tracking the activation pathway of caspase-7.";
RL Mol. Cell 23:523-533(2006).
RN [22]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=17646170; DOI=10.1074/jbc.m705265200;
RA Young J.E., Gouw L., Propp S., Sopher B.L., Taylor J., Lin A., Hermel E.,
RA Logvinova A., Chen S.F., Chen S., Bredesen D.E., Truant R., Ptacek L.J.,
RA La Spada A.R., Ellerby L.M.;
RT "Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity
RT and transcriptional dysregulation.";
RL J. Biol. Chem. 282:30150-30160(2007).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18723680; DOI=10.1073/pnas.0707715105;
RA Walsh J.G., Cullen S.P., Sheridan C., Luethi A.U., Gerner C., Martin S.J.;
RT "Executioner caspase-3 and caspase-7 are functionally distinct proteases.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12815-12819(2008).
RN [24]
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 [25]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND
RP ACTIVITY REGULATION.
RX PubMed=19617626; DOI=10.1074/jbc.m109.038174;
RA Gafni J., Cong X., Chen S.F., Gibson B.W., Ellerby L.M.;
RT "Calpain-1 cleaves and activates caspase-7.";
RL J. Biol. Chem. 284:25441-25449(2009).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF ARG-187; TYR-223; TYR-229 AND CYS-290.
RX PubMed=19581639; DOI=10.1074/jbc.m109.001826;
RA Hardy J.A., Wells J.A.;
RT "Dissecting an allosteric switch in caspase-7 using chemical and mutational
RT probes.";
RL J. Biol. Chem. 284:26063-26069(2009).
RN [27]
RP FUNCTION.
RX PubMed=20159985; DOI=10.1074/jbc.m109.068221;
RA Majerciak V., Kruhlak M., Dagur P.K., McCoy J.P. Jr., Zheng Z.M.;
RT "Caspase-7 cleavage of Kaposi sarcoma-associated herpesvirus ORF57 confers
RT a cellular function against viral lytic gene expression.";
RL J. Biol. Chem. 285:11297-11307(2010).
RN [28]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=20566630; DOI=10.1074/jbc.m110.126573;
RA Nakatsumi H., Yonehara S.;
RT "Identification of functional regions defining different activity in
RT caspase-3 and caspase-7 within cells.";
RL J. Biol. Chem. 285:25418-25425(2010).
RN [29]
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 [30]
RP FUNCTION.
RX PubMed=21157428; DOI=10.1038/emboj.2010.326;
RA Edelmann B., Bertsch U., Tchikov V., Winoto-Morbach S., Perrotta C.,
RA Jakob M., Adam-Klages S., Kabelitz D., Schuetze S.;
RT "Caspase-8 and caspase-7 sequentially mediate proteolytic activation of
RT acid sphingomyelinase in TNF-R1 receptosomes.";
RL EMBO J. 30:379-394(2011).
RN [31]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-30; THR-173 AND SER-239, AND MUTAGENESIS OF SER-30; THR-173 AND
RP SER-239.
RX PubMed=21555521; DOI=10.1074/jbc.m111.236596;
RA Li X., Wen W., Liu K., Zhu F., Malakhova M., Peng C., Li T., Kim H.G.,
RA Ma W., Cho Y.Y., Bode A.M., Dong Z., Dong Z.;
RT "Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2
RT inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell
RT lines.";
RL J. Biol. Chem. 286:22291-22299(2011).
RN [32]
RP FUNCTION.
RX PubMed=22464733; DOI=10.1016/j.molcel.2012.02.016;
RA Erener S., Petrilli V., Kassner I., Minotti R., Castillo R., Santoro R.,
RA Hassa P.O., Tschopp J., Hottiger M.O.;
RT "Inflammasome-activated caspase 7 cleaves PARP1 to enhance the expression
RT of a subset of NF-kappaB target genes.";
RL Mol. Cell 46:200-211(2012).
RN [33]
RP FUNCTION.
RX PubMed=22184066; DOI=10.1128/mcb.06466-11;
RA Riman S., Rizkallah R., Kassardjian A., Alexander K.E., Luescher B.,
RA Hurt M.M.;
RT "Phosphorylation of the transcription factor YY1 by CK2alpha prevents
RT cleavage by caspase 7 during apoptosis.";
RL Mol. Cell. Biol. 32:797-807(2012).
RN [34]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF ASP-23;
RP 38-LYS--LYS-41; 39-LYS-LYS-40 AND LYS-39.
RX PubMed=22451931; DOI=10.1073/pnas.1200934109;
RA Boucher D., Blais V., Denault J.B.;
RT "Caspase-7 uses an exosite to promote poly(ADP ribose) polymerase 1
RT proteolysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:5669-5674(2012).
RN [35]
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=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [37]
RP INTERACTION WITH HSPA5.
RX PubMed=26045166; DOI=10.1158/0008-5472.can-14-3751;
RA Kang J.M., Park S., Kim S.J., Kim H., Lee B., Kim J., Park J., Kim S.T.,
RA Yang H.K., Kim W.H., Kim S.J.;
RT "KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the
RT Oncoprotein GRP78.";
RL Cancer Res. 75:3087-3097(2015).
RN [38]
RP FUNCTION, AND MUTAGENESIS OF 38-LYS--LYS-41.
RX PubMed=28863261; DOI=10.1021/acs.biochem.7b00298;
RA Martini C., Bedard M., Lavigne P., Denault J.B.;
RT "Characterization of Hsp90 co-chaperone p23 cleavage by caspase-7 uncovers
RT a peptidase-substrate interaction involving intrinsically disordered
RT regions.";
RL Biochemistry 56:5099-5111(2017).
RN [39]
RP INTERACTION WITH ATXN3.
RX PubMed=30455355; DOI=10.1074/jbc.ra118.005801;
RA Weishaeupl D., Schneider J., Peixoto Pinheiro B., Ruess C., Dold S.M.,
RA von Zweydorf F., Gloeckner C.J., Schmidt J., Riess O., Schmidt T.;
RT "Physiological and pathophysiological characteristics of ataxin-3
RT isoforms.";
RL J. Biol. Chem. 294:644-661(2019).
RN [40]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, RNA-BINDING, AND MUTAGENESIS OF
RP 38-LYS--LYS-41 AND 39-LYS-LYS-40.
RX PubMed=31586028; DOI=10.1073/pnas.1909283116;
RA Desroches A., Denault J.B.;
RT "Caspase-7 uses RNA to enhance proteolysis of poly(ADP-ribose) polymerase 1
RT and other RNA-binding proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:21521-21528(2019).
RN [41]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, RNA-BINDING, AND MUTAGENESIS OF
RP ASP-23 AND 39-LYS-LYS-40.
RX PubMed=34156061; DOI=10.1042/bcj20210366;
RA Desroches A., Denault J.B.;
RT "Characterization of caspase-7 interaction with RNA.";
RL Biochem. J. 478:2681-2696(2021).
RN [42]
RP FUNCTION, PROTEOLYTIC CLEAVAGE, AND ADP-RIBOXANATION AT ARG-233 (MICROBIAL
RP INFECTION).
RX PubMed=35338844; DOI=10.1016/j.molcel.2022.03.010;
RA Peng T., Tao X., Xia Z., Hu S., Xue J., Zhu Q., Pan X., Zhang Q., Li S.;
RT "Pathogen hijacks programmed cell death signaling by arginine ADPR-
RT deacylization of caspases.";
RL Mol. Cell 82:1806-1820(2022).
RN [43] {ECO:0007744|PDB:1I51}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 51-198 AND 199-303 IN COMPLEX
RP WITH XIAP, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP INTERACTION WITH XIAP.
RX PubMed=11257230; DOI=10.1016/s0092-8674(01)00272-0;
RA Chai J., Shiozaki E., Srinivasula S.M., Wu Q., Datta P., Alnemri E.S.,
RA Shi Y., Dataa P.;
RT "Structural basis of caspase-7 inhibition by XIAP.";
RL Cell 104:769-780(2001).
RN [44] {ECO:0007744|PDB:1I4O}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 24-303 IN COMPLEX WITH XIAP,
RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH XIAP.
RX PubMed=11257231; DOI=10.1016/s0092-8674(02)02075-5;
RA Huang Y., Park Y.C., Rich R.L., Segal D., Myszka D.G., Wu H.;
RT "Structural basis of caspase inhibition by XIAP: differential roles of the
RT linker versus the BIR domain.";
RL Cell 104:781-790(2001).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 51-303, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, ACTIVE SITE, AND MUTAGENESIS OF CYS-186.
RX PubMed=11701129; DOI=10.1016/s0092-8674(01)00544-x;
RA Chai J., Wu Q., Shiozaki E., Srinivasula S.M., Alnemri E.S., Shi Y.;
RT "Crystal structure of a procaspase-7 zymogen: mechanisms of activation and
RT substrate binding.";
RL Cell 107:399-407(2001).
RN [46] {ECO:0007744|PDB:1GQF}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 47-303, SUBUNIT, AND MUTAGENESIS
RP OF CYS-186.
RX PubMed=11752425; DOI=10.1073/pnas.221580098;
RA Riedl S.J., Fuentes-Prior P., Renatus M., Kairies N., Krapp S., Huber R.,
RA Salvesen G.S., Bode W.;
RT "Structural basis for the activation of human procaspase-7.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:14790-14795(2001).
RN [47] {ECO:0007744|PDB:1SHJ, ECO:0007744|PDB:1SHL}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 50-303 IN COMPLEX WITH DICA AND
RP FICA ALLOSTERIC INHIBITORS, FUNCTION, ACTIVITY REGULATION, AND ACTIVE
RP SITES.
RX PubMed=15314233; DOI=10.1073/pnas.0404781101;
RA Hardy J.A., Lam J., Nguyen J.T., O'Brien T., Wells J.A.;
RT "Discovery of an allosteric site in the caspases.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12461-12466(2004).
RN [48] {ECO:0007744|PDB:2QL5, ECO:0007744|PDB:2QL7, ECO:0007744|PDB:2QL9, ECO:0007744|PDB:2QLB, ECO:0007744|PDB:2QLF, ECO:0007744|PDB:2QLJ}
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 24-196 AND 207-303, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17697120; DOI=10.1111/j.1742-4658.2007.05994.x;
RA Agniswamy J., Fang B., Weber I.T.;
RT "Plasticity of S2-S4 specificity pockets of executioner caspase-7 revealed
RT by structural and kinetic analysis.";
RL FEBS J. 274:4752-4765(2007).
RN [49] {ECO:0007744|PDB:4HQ0, ECO:0007744|PDB:4HQR}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 47-303 OF MUTANT IV IN COMPLEX
RP WITH AC-DEVD-CHO INHIBITOR, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF 195-ILE--ASP-204; 195-ILE--ASP-206 AND 195-ILE--GLY-200.
RX PubMed=23897474; DOI=10.1107/s0907444913010196;
RA Kang H.J., Lee Y.M., Bae K.H., Kim S.J., Chung S.J.;
RT "Structural asymmetry of procaspase-7 bound to a specific inhibitor.";
RL Acta Crystallogr. D 69:1514-1521(2013).
RN [50] {ECO:0007744|PDB:4JR1, ECO:0007744|PDB:4JR2}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 57-303 IN COMPLEX WITH COVALENT
RP INHIBITORS, AND MUTAGENESIS OF ASP-23 AND ASP-198.
RX PubMed=23650375; DOI=10.1073/pnas.1306759110;
RA Thomsen N.D., Koerber J.T., Wells J.A.;
RT "Structural snapshots reveal distinct mechanisms of procaspase-3 and -7
RT activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:8477-8482(2013).
RN [51] {ECO:0007744|PDB:4LSZ}
RP X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 24-198 AND 207-303 IN COMPLEX
RP WITH DARPIN D7.18, AND ACTIVITY REGULATION.
RX PubMed=24779913; DOI=10.1042/bj20131456;
RA Fluetsch A., Ackermann R., Schroeder T., Lukarska M., Hausammann G.J.,
RA Weinert C., Briand C., Gruetter M.G.;
RT "Combined inhibition of caspase 3 and caspase 7 by two highly selective
RT DARPins slows down cellular demise.";
RL Biochem. J. 461:279-290(2014).
RN [52] {ECO:0007744|PDB:4ZVO, ECO:0007744|PDB:4ZVP, ECO:0007744|PDB:4ZVQ, ECO:0007744|PDB:4ZVR, ECO:0007744|PDB:4ZVS, ECO:0007744|PDB:4ZVT, ECO:0007744|PDB:4ZVU}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-198 AND 199-303, FUNCTION,
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF 230-TYR--SER-234; 232-TRP--SER-234
RP AND GLN-276.
RX PubMed=27032039; DOI=10.1021/acschembio.5b00971;
RA Hill M.E., MacPherson D.J., Wu P., Julien O., Wells J.A., Hardy J.A.;
RT "Reprogramming caspase-7 specificity by regio-specific mutations and
RT selection provides alternate solutions for substrate recognition.";
RL ACS Chem. Biol. 11:1603-1612(2016).
RN [53] {ECO:0007744|PDB:5K20}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-198 AND 199-303, ACTIVITY
RP REGULATION, PROTEOLYTIC CLEAVAGE, PHOSPHORYLATION AT SER-30; THR-173 AND
RP SER-239, AND MUTAGENESIS OF SER-30; CYS-186; SER-239 AND CYS-290.
RX PubMed=27889207; DOI=10.1016/j.str.2016.11.001;
RA Eron S.J., Raghupathi K., Hardy J.A.;
RT "Dual site phosphorylation of caspase-7 by PAK2 blocks apoptotic activity
RT by two distinct mechanisms.";
RL Structure 25:27-39(2017).
RN [54] {ECO:0007744|PDB:7WZS}
RP X-RAY CRYSTALLOGRAPHY (3.60 ANGSTROMS) OF 24-303 IN COMPLEX WITH
RP C.VIOLACEUM COPC TOXIN, FUNCTION, PROTEOLYTIC CLEAVAGE, ADP-RIBOXANATION AT
RP ARG-233 (MICROBIAL INFECTION), AND MUTAGENESIS OF ARG-233.
RX PubMed=35446120; DOI=10.1128/mbio.00690-22;
RA Liu Y., Zeng H., Hou Y., Li Z., Li L., Song X., Ding J., Shao F., Xu Y.;
RT "Calmodulin binding activates chromobacterium CopC effector to ADP-
RT riboxanate host apoptotic caspases.";
RL MBio 0:0-0(2022).
CC -!- FUNCTION: Thiol protease involved in different programmed cell death
CC processes, such as apoptosis, pyroptosis or granzyme-mediated
CC programmed cell death, by proteolytically cleaving target proteins
CC (PubMed:8521391, PubMed:8567622, PubMed:8576161, PubMed:9070923,
CC PubMed:16916640, PubMed:17646170, PubMed:18723680, PubMed:19581639,
CC PubMed:11257230, PubMed:11257231, PubMed:11701129, PubMed:15314233).
CC Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences,
CC with some plasticity for alternate non-canonical sequences
CC (PubMed:12824163, PubMed:19581639, PubMed:20566630, PubMed:15314233,
CC PubMed:17697120, PubMed:23897474, PubMed:23650375, PubMed:27032039).
CC Its involvement in the different programmed cell death processes is
CC probably determined by upstream proteases that activate CASP7 (By
CC similarity). Acts as an effector caspase involved in the execution
CC phase of apoptosis: following cleavage and activation by initiator
CC caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis
CC by catalyzing cleavage of proteins, such as CLSPN, PARP1, PTGES3 and
CC YY1 (PubMed:10497198, PubMed:16123041, PubMed:16374543,
CC PubMed:16916640, PubMed:18723680, PubMed:20566630, PubMed:21555521,
CC PubMed:22184066, PubMed:22451931, PubMed:28863261, PubMed:31586028,
CC PubMed:34156061, PubMed:27889207, PubMed:35338844, PubMed:35446120).
CC Compared to CASP3, acts as a minor executioner caspase and cleaves a
CC limited set of target proteins (PubMed:18723680). Acts as a key
CC regulator of the inflammatory response in response to bacterial
CC infection by catalyzing cleavage and activation of the sphingomyelin
CC phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting
CC membrane repair (PubMed:21157428). Regulates pyroptosis in intestinal
CC epithelial cells: cleaved and activated by CASP1 in response to
CC S.typhimurium infection, promoting its secretion to the extracellular
CC milieu, where it catalyzes activation of SMPD1, generating ceramides
CC that repair membranes and counteract the action of gasdermin-D (GSDMD)
CC pores (By similarity). Regulates granzyme-mediated programmed cell
CC death in hepatocytes: cleaved and activated by granzyme B (GZMB) in
CC response to bacterial infection, promoting its secretion to the
CC extracellular milieu, where it catalyzes activation of SMPD1,
CC generating ceramides that repair membranes and counteract the action of
CC perforin (PRF1) pores (By similarity). Following cleavage by CASP1 in
CC response to inflammasome activation, catalyzes processing and
CC inactivation of PARP1, alleviating the transcription repressor activity
CC of PARP1 (PubMed:22464733). Acts as an inhibitor of type I interferon
CC production during virus-induced apoptosis by mediating cleavage of
CC antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine
CC overproduction (By similarity). Cleaves and activates sterol regulatory
CC element binding proteins (SREBPs) (PubMed:8643593). Cleaves
CC phospholipid scramblase proteins XKR4, XKR8 and XKR9 (By similarity).
CC In case of infection, catalyzes cleavage of Kaposi sarcoma-associated
CC herpesvirus protein ORF57, thereby preventing expression of viral lytic
CC genes (PubMed:20159985). {ECO:0000250|UniProtKB:P97864,
CC ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230,
CC ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129,
CC ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:15314233,
CC ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543,
CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170,
CC ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680,
CC ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:20159985,
CC ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:21157428,
CC ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:22184066,
CC ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:22464733,
CC ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474,
CC ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:27889207,
CC ECO:0000269|PubMed:28863261, ECO:0000269|PubMed:31586028,
CC ECO:0000269|PubMed:34156061, ECO:0000269|PubMed:35338844,
CC ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8521391,
CC ECO:0000269|PubMed:8567622, ECO:0000269|PubMed:8576161,
CC ECO:0000269|PubMed:8643593, ECO:0000269|PubMed:9070923}.
CC -!- FUNCTION: [Isoform Beta]: Lacks enzymatic activity.
CC {ECO:0000269|PubMed:8521391}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for an Asp residue at position P1 and has a
CC preferred cleavage sequence of Asp-Glu-Val-Asp-|-.; EC=3.4.22.60;
CC Evidence={ECO:0000269|PubMed:10497198, ECO:0000269|PubMed:11257230,
CC ECO:0000269|PubMed:11701129, ECO:0000269|PubMed:12824163,
CC ECO:0000269|PubMed:16123041, ECO:0000269|PubMed:16374543,
CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:17646170,
CC ECO:0000269|PubMed:17697120, ECO:0000269|PubMed:18723680,
CC ECO:0000269|PubMed:19581639, ECO:0000269|PubMed:19617626,
CC ECO:0000269|PubMed:20566630, ECO:0000269|PubMed:22451931,
CC ECO:0000269|PubMed:23650375, ECO:0000269|PubMed:23897474,
CC ECO:0000269|PubMed:27032039, ECO:0000269|PubMed:31586028,
CC ECO:0000269|PubMed:34156061};
CC -!- ACTIVITY REGULATION: During activation, the N-terminal disordered
CC prodomain is removed by cleavage (PubMed:12824163, PubMed:16916640).
CC Concomitantly, double cleavage gives rise to a large Caspase-7 subunit
CC p20 and a small Caspase-7 subunit p11 (PubMed:16916640). The two large
CC and two small subunits then assemble to form the active CASP7 complex
CC (PubMed:16916640). Can be cleaved and activated by different caspases,
CC depending on the context (PubMed:16916640). Cleaved and activated by
CC initiator caspases (CASP8, CASP9 and/or CASP10), leading to execution
CC phase of apoptosis (PubMed:16352606, PubMed:16916640). Inhibited by
CC XIAP, which directly binds to the active site pocket and obstructs
CC substrate entry (PubMed:16352606, PubMed:16916640, PubMed:11257230,
CC PubMed:11257231). Cleavage and maturation by GZMB regulates granzyme-
CC mediated programmed cell death (By similarity). Cleavage and maturation
CC by CASP1 regulates pyroptosis (By similarity). Phosphorylation at Ser-
CC 30 and Ser-239 by PAK2 inhibits its activity (PubMed:21555521,
CC PubMed:27889207). Inhibited by isatin sulfonamides (PubMed:10821855).
CC Inhibited by 2-(2,4-Dichlorophenoxy)- N-(2-mercapto-ethyl)-acetamide
CC (DICA) and 5-Fluoro-1H-indole-2- carboxylic acid (2-mercapto-ethyl)-
CC amide (FICA) allosteric inhibitors, which disrupt an interaction
CC between Arg-187 and Tyr-223 (PubMed:15314233, PubMed:19581639).
CC Specifically inhibited by DARPin D7.18 and D7.43, which specifically
CC bind to the precursor CASP7 and prevent its processing and activation
CC (PubMed:24779913). {ECO:0000250|UniProtKB:P97864,
CC ECO:0000269|PubMed:10821855, ECO:0000269|PubMed:11257230,
CC ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:12824163,
CC ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16352606,
CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:19581639,
CC ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:24779913,
CC ECO:0000269|PubMed:27889207}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for a DEVD peptide {ECO:0000269|PubMed:19581639};
CC Note=kcat is 0.51 sec(-1) for a DEVD peptide.
CC {ECO:0000269|PubMed:19581639};
CC -!- SUBUNIT: Heterotetramer that consists of two anti-parallel arranged
CC heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11)
CC subunit (PubMed:16916640, PubMed:20566630, PubMed:11701129,
CC PubMed:11752425). Interacts with XIAP (via its second BIR domain);
CC inhibiting CASP7 activity (PubMed:16916640, PubMed:11257230,
CC PubMed:11257231). Interacts with BIRC6/bruce (PubMed:15200957).
CC Interacts with ATXN3 (short isoform 1) (PubMed:30455355). Interacts
CC with HSPA5 (PubMed:26045166). {ECO:0000269|PubMed:11257230,
CC ECO:0000269|PubMed:11257231, ECO:0000269|PubMed:11701129,
CC ECO:0000269|PubMed:11752425, ECO:0000269|PubMed:15200957,
CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:20566630,
CC ECO:0000269|PubMed:26045166, ECO:0000269|PubMed:30455355}.
CC -!- INTERACTION:
CC P55210; Q13490: BIRC2; NbExp=2; IntAct=EBI-523958, EBI-514538;
CC P55210; P83105: HTRA4; NbExp=6; IntAct=EBI-523958, EBI-21776319;
CC P55210; P42858: HTT; NbExp=12; IntAct=EBI-523958, EBI-466029;
CC P55210; Q8N4N3-2: KLHL36; NbExp=3; IntAct=EBI-523958, EBI-10973851;
CC P55210; P43364: MAGEA11; NbExp=3; IntAct=EBI-523958, EBI-739552;
CC P55210; Q16236: NFE2L2; NbExp=2; IntAct=EBI-523958, EBI-2007911;
CC P55210; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-523958, EBI-740897;
CC P55210; Q13177: PAK2; NbExp=6; IntAct=EBI-523958, EBI-1045887;
CC P55210; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-523958, EBI-9090282;
CC P55210; P21673: SAT1; NbExp=6; IntAct=EBI-523958, EBI-711613;
CC P55210; Q86WV1-2: SKAP1; NbExp=3; IntAct=EBI-523958, EBI-11995314;
CC P55210; P17405: SMPD1; NbExp=6; IntAct=EBI-523958, EBI-7095800;
CC P55210; P98170: XIAP; NbExp=3; IntAct=EBI-523958, EBI-517127;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12824163,
CC ECO:0000305|PubMed:21555521, ECO:0000305|PubMed:8576161}. Nucleus
CC {ECO:0000269|PubMed:19617626, ECO:0000269|PubMed:21555521}. Secreted,
CC extracellular space {ECO:0000250|UniProtKB:P97864}. Note=Following
CC cleavage and activation by CASP1 or granzyme B (GZMB), secreted into
CC the extracellular milieu by passing through the gasdermin-D (GSDMD)
CC pores or perforin (PRF1) pore, respectively.
CC {ECO:0000250|UniProtKB:P97864}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=Alpha {ECO:0000303|PubMed:8521391};
CC IsoId=P55210-1; Sequence=Displayed;
CC Name=Beta {ECO:0000303|PubMed:8521391};
CC IsoId=P55210-2; Sequence=VSP_000807;
CC Name=Alpha' {ECO:0000303|PubMed:9070923}; Synonyms=Beta
CC {ECO:0000303|PubMed:9070923};
CC IsoId=P55210-3; Sequence=VSP_000806;
CC Name=4;
CC IsoId=P55210-4; Sequence=VSP_045325;
CC -!- TISSUE SPECIFICITY: Highly expressed in lung, skeletal muscle, liver,
CC kidney, spleen and heart, and moderately in testis. No expression in
CC the brain. {ECO:0000269|PubMed:8576161}.
CC -!- DOMAIN: The exosite polybasic region mediates non-specific RNA-binding,
CC acting as a bridge for RNA-binding target proteins, such as PARP1
CC (PubMed:22451931, PubMed:31586028, PubMed:34156061). The exosite is
CC also required for interaction with non-RNA-binding proteins, such as
CC Hsp90 co-chaperone PTGES3 (PubMed:34156061).
CC {ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:31586028,
CC ECO:0000269|PubMed:34156061}.
CC -!- PTM: Cleavage by different proteases, such as granzyme B (GZMB),
CC caspase-1 (CASP1), caspase-8 (CASP8), caspase-9 (CASP9) or caspase-10
CC (CASP10) generate the two active subunits (PubMed:9852092,
CC PubMed:12824163, PubMed:16352606, PubMed:16916640, PubMed:35338844,
CC PubMed:35446120). Its involvement in different programmed cell death
CC processes is probably specified by the protease that activates CASP7
CC (PubMed:9852092, PubMed:16916640). Cleaved and activated by initiator
CC caspases (CASP8, CASP9 and/or CASP10), leading to execution phase of
CC apoptosis (PubMed:16352606, PubMed:16916640, PubMed:21555521,
CC PubMed:27889207). Cleavage and maturation by GZMB regulates granzyme-
CC mediated programmed cell death (By similarity). Cleaved and activated
CC by CASP1 in response to bacterial infection (By similarity). Propeptide
CC domains can also be cleaved efficiently by CASP3 (PubMed:8755496).
CC Active heterodimers between the small subunit of caspase-7 and the
CC large subunit of CASP3, and vice versa, also occur (PubMed:8755496).
CC Also cleaved at the N-terminus at alternative sites by CAPN1, leading
CC to its activation (PubMed:19617626). {ECO:0000250|UniProtKB:P97864,
CC ECO:0000269|PubMed:12824163, ECO:0000269|PubMed:16352606,
CC ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:19617626,
CC ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:27889207,
CC ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120,
CC ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:9852092}.
CC -!- PTM: Phosphorylation at Ser-30 and Ser-239 by PAK2 inhibits its
CC activity (PubMed:21555521, PubMed:27889207). Phosphorylation at Ser-30
CC prevents cleavage and activation by initiator caspase CASP9, while
CC phosphorylation at Ser-239 prevents thiol protease activity by
CC preventing substrate-binding (PubMed:21555521, PubMed:27889207).
CC {ECO:0000269|PubMed:21555521, ECO:0000269|PubMed:27889207}.
CC -!- PTM: (Microbial infection) ADP-riboxanation by C.violaceum CopC blocks
CC CASP7 processing, preventing CASP7 activation and ability to recognize
CC and cleave substrates. {ECO:0000269|PubMed:35338844,
CC ECO:0000269|PubMed:35446120}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Delayed - Issue 252 of
CC November 2022;
CC URL="https://www.proteinspotlight.org/back_issues/252/";
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DR EMBL; U37448; AAC50303.1; -; mRNA.
DR EMBL; U37449; AAC50304.1; -; mRNA.
DR EMBL; U39613; AAC50346.1; -; mRNA.
DR EMBL; U40281; AAC50352.1; -; mRNA.
DR EMBL; U67319; AAC51152.1; -; mRNA.
DR EMBL; U67320; AAC51153.1; -; mRNA.
DR EMBL; U67206; AAF21460.1; -; mRNA.
DR EMBL; BT006683; AAP35329.1; -; mRNA.
DR EMBL; AB451281; BAG70095.1; -; mRNA.
DR EMBL; AB451413; BAG70227.1; -; mRNA.
DR EMBL; AK298964; BAG61059.1; -; mRNA.
DR EMBL; AL592546; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49494.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49495.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49498.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49496.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49497.1; -; Genomic_DNA.
DR EMBL; BC015799; AAH15799.1; -; mRNA.
DR CCDS; CCDS58096.1; -. [P55210-4]
DR CCDS; CCDS7580.1; -. [P55210-3]
DR CCDS; CCDS7581.1; -. [P55210-1]
DR CCDS; CCDS7582.1; -. [P55210-2]
DR RefSeq; NP_001218.1; NM_001227.4. [P55210-1]
DR RefSeq; NP_001253985.1; NM_001267056.1. [P55210-1]
DR RefSeq; NP_001253986.1; NM_001267057.1.
DR RefSeq; NP_001253987.1; NM_001267058.1. [P55210-4]
DR RefSeq; NP_001307840.1; NM_001320911.1.
DR RefSeq; NP_203124.1; NM_033338.5. [P55210-3]
DR RefSeq; NP_203125.1; NM_033339.4. [P55210-1]
DR RefSeq; NP_203126.1; NM_033340.3. [P55210-2]
DR PDB; 1F1J; X-ray; 2.35 A; A/B=2-303.
DR PDB; 1GQF; X-ray; 2.90 A; A/B=47-303.
DR PDB; 1I4O; X-ray; 2.40 A; A/B=24-303.
DR PDB; 1I51; X-ray; 2.45 A; A/C=51-198, B/D=199-303.
DR PDB; 1K86; X-ray; 2.60 A; A/B=51-303.
DR PDB; 1K88; X-ray; 2.70 A; A/B=51-303.
DR PDB; 1KMC; X-ray; 2.90 A; A/B=1-303.
DR PDB; 1SHJ; X-ray; 2.80 A; A/B=50-303.
DR PDB; 1SHL; X-ray; 3.00 A; A/B=57-303.
DR PDB; 2QL5; X-ray; 2.34 A; A/C=24-196, B/D=207-303.
DR PDB; 2QL7; X-ray; 2.40 A; A/C=24-196, B/D=207-303.
DR PDB; 2QL9; X-ray; 2.14 A; A/C=24-196, B/D=207-303.
DR PDB; 2QLB; X-ray; 2.25 A; A/C=24-196, B/D=207-303.
DR PDB; 2QLF; X-ray; 2.80 A; A/C=24-196, B/D=207-303.
DR PDB; 2QLJ; X-ray; 2.60 A; A/C=24-196, B/D=207-303.
DR PDB; 3EDR; X-ray; 2.45 A; A/C=24-196, B/D=207-303.
DR PDB; 3H1P; X-ray; 2.61 A; A/B=50-303.
DR PDB; 3IBC; X-ray; 2.75 A; A/C=24-196, B/D=207-303.
DR PDB; 3IBF; X-ray; 2.50 A; A/C=24-196, B/D=207-303.
DR PDB; 3R5K; X-ray; 2.86 A; A/B=1-303.
DR PDB; 4FDL; X-ray; 2.80 A; A/B=2-303.
DR PDB; 4FEA; X-ray; 3.79 A; A/B=57-303.
DR PDB; 4HQ0; X-ray; 3.00 A; A/B=47-303.
DR PDB; 4HQR; X-ray; 3.00 A; A/B=47-303.
DR PDB; 4JB8; X-ray; 1.70 A; A=24-198, B=207-303.
DR PDB; 4JJ8; X-ray; 2.94 A; A/B=57-303.
DR PDB; 4JR1; X-ray; 2.15 A; A/B=57-303.
DR PDB; 4JR2; X-ray; 1.65 A; A/B=57-303.
DR PDB; 4LSZ; X-ray; 2.26 A; A/C=24-198, B/D=207-303.
DR PDB; 4ZVO; X-ray; 2.85 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVP; X-ray; 2.50 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVQ; X-ray; 2.50 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVR; X-ray; 2.30 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVS; X-ray; 2.50 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVT; X-ray; 2.85 A; A/C=1-198, B/D=199-303.
DR PDB; 4ZVU; X-ray; 2.60 A; A/C=1-198, B/D=199-303.
DR PDB; 5IC6; X-ray; 2.70 A; A/C=1-198, B/D=199-303.
DR PDB; 5K20; X-ray; 2.20 A; A/C=1-198, B/D=199-303.
DR PDB; 5V6U; X-ray; 2.80 A; A/B=1-303.
DR PDB; 5V6Z; X-ray; 2.60 A; A/B=1-303.
DR PDB; 7WZS; X-ray; 3.60 A; B=24-303.
DR PDB; 8DGZ; X-ray; 2.80 A; A/B=2-303.
DR PDB; 8DJ3; X-ray; 3.20 A; A/B=2-303.
DR PDBsum; 1F1J; -.
DR PDBsum; 1GQF; -.
DR PDBsum; 1I4O; -.
DR PDBsum; 1I51; -.
DR PDBsum; 1K86; -.
DR PDBsum; 1K88; -.
DR PDBsum; 1KMC; -.
DR PDBsum; 1SHJ; -.
DR PDBsum; 1SHL; -.
DR PDBsum; 2QL5; -.
DR PDBsum; 2QL7; -.
DR PDBsum; 2QL9; -.
DR PDBsum; 2QLB; -.
DR PDBsum; 2QLF; -.
DR PDBsum; 2QLJ; -.
DR PDBsum; 3EDR; -.
DR PDBsum; 3H1P; -.
DR PDBsum; 3IBC; -.
DR PDBsum; 3IBF; -.
DR PDBsum; 3R5K; -.
DR PDBsum; 4FDL; -.
DR PDBsum; 4FEA; -.
DR PDBsum; 4HQ0; -.
DR PDBsum; 4HQR; -.
DR PDBsum; 4JB8; -.
DR PDBsum; 4JJ8; -.
DR PDBsum; 4JR1; -.
DR PDBsum; 4JR2; -.
DR PDBsum; 4LSZ; -.
DR PDBsum; 4ZVO; -.
DR PDBsum; 4ZVP; -.
DR PDBsum; 4ZVQ; -.
DR PDBsum; 4ZVR; -.
DR PDBsum; 4ZVS; -.
DR PDBsum; 4ZVT; -.
DR PDBsum; 4ZVU; -.
DR PDBsum; 5IC6; -.
DR PDBsum; 5K20; -.
DR PDBsum; 5V6U; -.
DR PDBsum; 5V6Z; -.
DR PDBsum; 7WZS; -.
DR PDBsum; 8DGZ; -.
DR PDBsum; 8DJ3; -.
DR AlphaFoldDB; P55210; -.
DR EMDB; EMD-27839; -.
DR SMR; P55210; -.
DR BioGRID; 107290; 67.
DR ComplexPortal; CPX-2862; Caspase-7 complex.
DR DIP; DIP-29973N; -.
DR ELM; P55210; -.
DR IntAct; P55210; 25.
DR MINT; P55210; -.
DR STRING; 9606.ENSP00000358327; -.
DR BindingDB; P55210; -.
DR ChEMBL; CHEMBL3468; -.
DR DrugBank; DB05408; Emricasan.
DR DrugBank; DB03384; Fica.
DR DrugBank; DB06255; Incadronic acid.
DR DrugCentral; P55210; -.
DR GuidetoPHARMACOLOGY; 1623; -.
DR MEROPS; C14.004; -.
DR TCDB; 8.A.217.1.1; the apoptosis cell death regulator (acdr) family.
DR iPTMnet; P55210; -.
DR PhosphoSitePlus; P55210; -.
DR BioMuta; CASP7; -.
DR DMDM; 1730092; -.
DR EPD; P55210; -.
DR jPOST; P55210; -.
DR MassIVE; P55210; -.
DR MaxQB; P55210; -.
DR PaxDb; 9606-ENSP00000358327; -.
DR PeptideAtlas; P55210; -.
DR ProteomicsDB; 56811; -. [P55210-1]
DR ProteomicsDB; 56812; -. [P55210-2]
DR ProteomicsDB; 56813; -. [P55210-3]
DR Pumba; P55210; -.
DR Antibodypedia; 18528; 1167 antibodies from 45 providers.
DR DNASU; 840; -.
DR Ensembl; ENST00000345633.8; ENSP00000298701.7; ENSG00000165806.21. [P55210-1]
DR Ensembl; ENST00000369315.5; ENSP00000358321.1; ENSG00000165806.21. [P55210-1]
DR Ensembl; ENST00000369318.8; ENSP00000358324.4; ENSG00000165806.21. [P55210-1]
DR Ensembl; ENST00000369331.8; ENSP00000358337.3; ENSG00000165806.21. [P55210-2]
DR Ensembl; ENST00000452490.3; ENSP00000398107.2; ENSG00000165806.21. [P55210-4]
DR Ensembl; ENST00000614447.4; ENSP00000478285.1; ENSG00000165806.21. [P55210-2]
DR Ensembl; ENST00000621345.4; ENSP00000480584.1; ENSG00000165806.21. [P55210-1]
DR Ensembl; ENST00000621607.4; ENSP00000478999.1; ENSG00000165806.21. [P55210-3]
DR GeneID; 840; -.
DR KEGG; hsa:840; -.
DR MANE-Select; ENST00000369318.8; ENSP00000358324.4; NM_001227.5; NP_001218.1.
DR UCSC; uc001lam.5; human. [P55210-1]
DR AGR; HGNC:1508; -.
DR CTD; 840; -.
DR DisGeNET; 840; -.
DR GeneCards; CASP7; -.
DR HGNC; HGNC:1508; CASP7.
DR HPA; ENSG00000165806; Low tissue specificity.
DR MIM; 601761; gene.
DR neXtProt; NX_P55210; -.
DR OpenTargets; ENSG00000165806; -.
DR PharmGKB; PA26091; -.
DR VEuPathDB; HostDB:ENSG00000165806; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000153232; -.
DR HOGENOM; CLU_1098210_0_0_1; -.
DR InParanoid; P55210; -.
DR OMA; AKDTHYK; -.
DR OrthoDB; 2873736at2759; -.
DR PhylomeDB; P55210; -.
DR TreeFam; TF102023; -.
DR BioCyc; MetaCyc:HS09288-MONOMER; -.
DR BRENDA; 3.4.22.60; 2681.
DR PathwayCommons; P55210; -.
DR Reactome; R-HSA-111459; Activation of caspases through apoptosome-mediated cleavage.
DR Reactome; R-HSA-111463; SMAC (DIABLO) binds to IAPs.
DR Reactome; R-HSA-111464; SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-111469; SMAC, XIAP-regulated apoptotic response.
DR Reactome; R-HSA-264870; Caspase-mediated cleavage of cytoskeletal proteins.
DR SignaLink; P55210; -.
DR SIGNOR; P55210; -.
DR BioGRID-ORCS; 840; 17 hits in 1171 CRISPR screens.
DR ChiTaRS; CASP7; human.
DR EvolutionaryTrace; P55210; -.
DR GeneWiki; Caspase_7; -.
DR GenomeRNAi; 840; -.
DR Pharos; P55210; Tchem.
DR PRO; PR:P55210; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P55210; Protein.
DR Bgee; ENSG00000165806; Expressed in rectum and 181 other cell types or tissues.
DR ExpressionAtlas; P55210; baseline and differential.
DR Genevisible; P55210; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; TAS:UniProt.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:Ensembl.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0097153; F:cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0008233; F:peptidase activity; IDA:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProt.
DR GO; GO:0072734; P:cellular response to staurosporine; IMP:CAFA.
DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:UniProt.
DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0070227; P:lymphocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1905686; P:positive regulation of plasma membrane repair; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IDA:UniProt.
DR GO; GO:0051604; P:protein maturation; IDA:UniProt.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IEA:Ensembl.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 3.40.50.1460; -; 1.
DR Gene3D; 3.30.70.1470; Caspase-like; 1.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
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; PTHR10454; CASPASE; 1.
DR PANTHER; PTHR10454:SF31; CASPASE-7; 1.
DR Pfam; PF00656; Peptidase_C14; 1.
DR PIRSF; PIRSF038001; Caspase_ICE; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF52129; Caspase-like; 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; Allosteric enzyme; Alternative splicing;
KW Apoptosis; Cytoplasm; Hydrolase; Nucleus; Phosphoprotein; Protease;
KW Reference proteome; RNA-binding; Secreted; Thiol protease; Zymogen.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT PROPEP 2..23
FT /note="N-terminally processed"
FT /evidence="ECO:0000305|PubMed:12824163,
FT ECO:0000305|PubMed:16916640, ECO:0000305|PubMed:23650375,
FT ECO:0000305|PubMed:8755496"
FT /id="PRO_0000004616"
FT CHAIN 24..198
FT /note="Caspase-7 subunit p20"
FT /evidence="ECO:0000305|PubMed:12824163,
FT ECO:0000305|PubMed:16916640, ECO:0000305|PubMed:23650375,
FT ECO:0000305|PubMed:27889207, ECO:0000305|PubMed:8755496"
FT /id="PRO_0000004617"
FT PROPEP 199..206
FT /evidence="ECO:0000305|PubMed:12824163,
FT ECO:0000305|PubMed:16916640, ECO:0000305|PubMed:23650375,
FT ECO:0000305|PubMed:27889207"
FT /id="PRO_0000004618"
FT CHAIN 207..303
FT /note="Caspase-7 subunit p11"
FT /evidence="ECO:0000305|PubMed:12824163,
FT ECO:0000305|PubMed:16916640, ECO:0000305|PubMed:27889207,
FT ECO:0000305|PubMed:8755496"
FT /id="PRO_0000004619"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 38..41
FT /note="Exosite"
FT /evidence="ECO:0000269|PubMed:22451931,
FT ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061"
FT REGION 76..87
FT /note="Loop L1"
FT /evidence="ECO:0000303|PubMed:23897474"
FT REGION 187..196
FT /note="Loop L2"
FT /evidence="ECO:0000303|PubMed:23897474"
FT REGION 226..238
FT /note="Loop L3"
FT /evidence="ECO:0000303|PubMed:23897474"
FT REGION 274..288
FT /note="Loop L4"
FT /evidence="ECO:0000303|PubMed:23897474"
FT COMPBIAS 1..17
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 144
FT /evidence="ECO:0000269|PubMed:15314233"
FT ACT_SITE 186
FT /evidence="ECO:0000269|PubMed:11701129,
FT ECO:0000269|PubMed:15314233, ECO:0000269|PubMed:16916640"
FT SITE 36..37
FT /note="Cleavage; by CAPN1"
FT /evidence="ECO:0000269|PubMed:19617626"
FT SITE 45..46
FT /note="Cleavage; by CAPN1"
FT /evidence="ECO:0000269|PubMed:19617626"
FT SITE 47..48
FT /note="Cleavage; by CAPN1"
FT /evidence="ECO:0000269|PubMed:19617626"
FT SITE 187
FT /note="Involved in allosteric regulation"
FT /evidence="ECO:0000269|PubMed:15314233,
FT ECO:0000269|PubMed:19581639"
FT SITE 223
FT /note="Involved in allosteric regulation"
FT /evidence="ECO:0000269|PubMed:15314233,
FT ECO:0000269|PubMed:19581639"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895"
FT MOD_RES 30
FT /note="Phosphoserine; by PAK2"
FT /evidence="ECO:0000269|PubMed:21555521,
FT ECO:0000269|PubMed:27889207"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 173
FT /note="Phosphothreonine; by PAK2"
FT /evidence="ECO:0000269|PubMed:21555521,
FT ECO:0000269|PubMed:27889207"
FT MOD_RES 233
FT /note="(Microbial infection) ADP-riboxanated arginine"
FT /evidence="ECO:0000269|PubMed:35338844,
FT ECO:0000269|PubMed:35446120"
FT MOD_RES 239
FT /note="Phosphoserine; by PAK2"
FT /evidence="ECO:0000269|PubMed:21555521,
FT ECO:0000269|PubMed:27889207"
FT VAR_SEQ 1..36
FT /note="MADDQGCIEEQGVEDSANEDSVDAKPDRSSFVPSLF -> MQRGLFSDGDT
FT (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045325"
FT VAR_SEQ 1
FT /note="M -> MDCVGWPPGRKWHLEKNTSCGGSSGICASYVTQM (in isoform
FT Alpha')"
FT /evidence="ECO:0000303|PubMed:19054851,
FT ECO:0000303|PubMed:8521391, ECO:0000303|PubMed:9070923"
FT /id="VSP_000806"
FT VAR_SEQ 149..303
FT /note="VIYGKDGVTPIKDLTAHFRGDRCKTLLEKPKLFFIQACRGTELDDGIQADSG
FT PINDTDANPRYKIPVEADFLFAYSTVPGYYSWRSPGRGSWFVQALCSILEEHGKDLEIM
FT QILTRVNDRVARHFESQSDDPHFHEKKQIPCVVSMLTKELYFSQ -> MESCSVTQAGV
FT QRRDLGRLQPPPPRLAEGPSLMMASRPTRGPSMTQMLILDTRSQWKLTSSSPIPRFQAI
FT TRGGAQEEAPGLCKPSAPSWRSTEKTWKSCRSSPG (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:8521391"
FT /id="VSP_000807"
FT VARIANT 4
FT /note="D -> E (in dbSNP:rs11555408)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_048617"
FT VARIANT 255
FT /note="D -> E (in dbSNP:rs2227310)"
FT /id="VAR_048618"
FT MUTAGEN 23
FT /note="D->A: Abolished cleavage at the N-terminus, leading
FT to impaired activation and thiol protease activity. In P7-
FT D2A mutant; abolished cleavage and activation, leading to
FT decreased but mesureable activity; when associated with A-
FT 198."
FT /evidence="ECO:0000269|PubMed:12824163,
FT ECO:0000269|PubMed:22451931, ECO:0000269|PubMed:23650375,
FT ECO:0000269|PubMed:34156061"
FT MUTAGEN 30
FT /note="S->A: Abolished phosphorylation by PAK2; when
FT associated with A-173 and A-239."
FT /evidence="ECO:0000269|PubMed:21555521"
FT MUTAGEN 30
FT /note="S->E: Mimics phosphorylation; does not affect thiol
FT protease activity."
FT /evidence="ECO:0000269|PubMed:27889207"
FT MUTAGEN 38..41
FT /note="KKKK->AAAA: Decreased ability to cleave PARP1 and
FT PTGES3."
FT /evidence="ECO:0000269|PubMed:22451931,
FT ECO:0000269|PubMed:28863261"
FT MUTAGEN 38..41
FT /note="KKKK->AKKA: Decreased ability to cleave PARP1."
FT /evidence="ECO:0000269|PubMed:31586028"
FT MUTAGEN 39..40
FT /note="KK->AA: Does not affect ability to cleave PARP1."
FT /evidence="ECO:0000269|PubMed:22451931,
FT ECO:0000269|PubMed:31586028"
FT MUTAGEN 39..40
FT /note="KK->EE: Decreased ability to cleave PARP1. Decreased
FT RNA-binding."
FT /evidence="ECO:0000269|PubMed:22451931,
FT ECO:0000269|PubMed:31586028, ECO:0000269|PubMed:34156061"
FT MUTAGEN 39
FT /note="K->E: Decreased ability to cleave PARP1."
FT /evidence="ECO:0000269|PubMed:22451931"
FT MUTAGEN 173
FT /note="T->A: Abolished phosphorylation by PAK2; when
FT associated with A-30 and A-239."
FT /evidence="ECO:0000269|PubMed:21555521"
FT MUTAGEN 186
FT /note="C->A: Abolished thiol protease activity."
FT /evidence="ECO:0000269|PubMed:11701129,
FT ECO:0000269|PubMed:11752425, ECO:0000269|PubMed:12824163,
FT ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:27889207,
FT ECO:0000269|PubMed:8576161"
FT MUTAGEN 187
FT /note="R->K: Does not significantly affect thiol protease
FT catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:19581639"
FT MUTAGEN 187
FT /note="R->M,A,G: Reduced thiol protease catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:19581639"
FT MUTAGEN 187
FT /note="R->W,N: Strongly reduced thiol protease catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:19581639"
FT MUTAGEN 192
FT /note="D->A: Strongly reduced thiol protease activity."
FT /evidence="ECO:0000269|PubMed:16916640"
FT MUTAGEN 195..206
FT /note="IQADSGPINDTD->LVPRGS: In mutant II; prevents
FT cleavage of loop L2 region; retains significant thiol
FT protease activity."
FT /evidence="ECO:0000269|PubMed:23897474"
FT MUTAGEN 195..200
FT /note="IQADSG->LVPRGS: In mutant III; prevents cleavage of
FT loop L2 region; abolished thiol protease activity."
FT /evidence="ECO:0000269|PubMed:23897474"
FT MUTAGEN 198..204
FT /note="DSGPIND->ASGPINDLVPRGS: In mutant IV; prevents
FT cleavage of loop L2 region; retains significant thiol
FT protease activity."
FT /evidence="ECO:0000269|PubMed:23897474"
FT MUTAGEN 198
FT /note="D->A: Strongly reduced cleavage and activation by
FT initiator caspases. Abolished cleavage and activation by
FT initiator caspases; when associated with A-206. In P7-D2A
FT mutant; abolished cleavage and activation, leading to
FT decreased but mesureable activity; when associated with A-
FT 23."
FT /evidence="ECO:0000269|PubMed:12824163,
FT ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:23650375"
FT MUTAGEN 206
FT /note="D->A: Reduced cleavage and activation by initiator
FT caspases. Abolished cleavage and activation by initiator
FT caspases; when associated with A-198."
FT /evidence="ECO:0000269|PubMed:12824163,
FT ECO:0000269|PubMed:16916640"
FT MUTAGEN 223
FT /note="Y->A,F,W,D,E: Does not significantly affect thiol
FT protease catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:19581639"
FT MUTAGEN 229
FT /note="Y->W: Strongly reduced thiol protease catalytic
FT efficiency."
FT /evidence="ECO:0000269|PubMed:19581639"
FT MUTAGEN 230..234
FT /note="YSWRS->VSYRV: In esCasp-7 V3 mutant; promotes
FT specificity toward alternate peptides with VEID, YVAD,
FT WEHD, LETD or LEHD sequence; when associated with C-276. In
FT esCasp-7 V4 mutant; promotes specificity toward alternate
FT peptides with VEID, YVAD, WEHD, LETD or LEHD sequence; when
FT associated with D-276."
FT /evidence="ECO:0000269|PubMed:27032039"
FT MUTAGEN 232..234
FT /note="WRS->HRE: In dsCasp-7 mutant; unable to cleave DEVD
FT and VEID peptides; when associated with F-276."
FT /evidence="ECO:0000269|PubMed:27032039"
FT MUTAGEN 233
FT /note="R->A: Abolished ADP-riboxanation by C.violaceum
FT CopC."
FT /evidence="ECO:0000269|PubMed:35446120"
FT MUTAGEN 239
FT /note="S->A: Abolished phosphorylation by PAK2; when
FT associated with A-30 and A-173."
FT /evidence="ECO:0000269|PubMed:21555521"
FT MUTAGEN 239
FT /note="S->E: Mimics phosphorylation; leading to inactivate
FT thiol protease activity."
FT /evidence="ECO:0000269|PubMed:27889207"
FT MUTAGEN 276
FT /note="Q->C: In esCasp-7 V3 mutant; promotes specificity
FT toward alternate peptides with VEID, YVAD, WEHD, LETD or
FT LEHD sequence; when associated with 230-V--V-234."
FT /evidence="ECO:0000269|PubMed:27032039"
FT MUTAGEN 276
FT /note="Q->D: In esCasp-7 V4 mutant; promotes specificity
FT toward alternate peptides with VEID, YVAD, WEHD, LETD or
FT LEHD sequence; when associated with 230-V--V-234."
FT /evidence="ECO:0000269|PubMed:27032039"
FT MUTAGEN 276
FT /note="Q->F: In dsCasp-7 mutant; unable to cleave DEVD sand
FT VEID peptides; when associated with 232-H--E-234."
FT /evidence="ECO:0000269|PubMed:27032039"
FT MUTAGEN 290
FT /note="C->S: Decreased phosphorylation by PAK2."
FT /evidence="ECO:0000269|PubMed:27889207"
FT MUTAGEN 290
FT /note="C->T,N: Does not significantly affect thiol protease
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:19581639"
FT CONFLICT 194
FT /note="G -> A (in Ref. 2; AAC50346)"
FT /evidence="ECO:0000305"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:4JB8"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 90..104
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 116..127
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:1F1J"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 159..163
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:4JR2"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4JB8"
FT TURN 209..211
FT /evidence="ECO:0007829|PDB:4JR1"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:4HQ0"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4JR2"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 240..252
FT /evidence="ECO:0007829|PDB:4JR2"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:4JR2"
FT HELIX 258..272
FT /evidence="ECO:0007829|PDB:4JR2"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:4ZVO"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:4JR2"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:4JR2"
SQ SEQUENCE 303 AA; 34277 MW; CD373EE54A232CA4 CRC64;
MADDQGCIEE QGVEDSANED SVDAKPDRSS FVPSLFSKKK KNVTMRSIKT TRDRVPTYQY
NMNFEKLGKC IIINNKNFDK VTGMGVRNGT DKDAEALFKC FRSLGFDVIV YNDCSCAKMQ
DLLKKASEED HTNAACFACI LLSHGEENVI YGKDGVTPIK DLTAHFRGDR CKTLLEKPKL
FFIQACRGTE LDDGIQADSG PINDTDANPR YKIPVEADFL FAYSTVPGYY SWRSPGRGSW
FVQALCSILE EHGKDLEIMQ ILTRVNDRVA RHFESQSDDP HFHEKKQIPC VVSMLTKELY
FSQ
//
