ID MCA1_YEAST Reviewed; 432 AA. AC Q08601; D6W2Q6; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 20-MAY-2008, sequence version 2. DT 27-MAR-2024, entry version 165. DE RecName: Full=Metacaspase-1; DE EC=3.4.22.- {ECO:0000269|PubMed:11983181, ECO:0000269|PubMed:22761449}; DE Contains: DE RecName: Full=Large subunit p20 {ECO:0000303|PubMed:22761449}; DE Contains: DE RecName: Full=Small subunit p10 {ECO:0000303|PubMed:22761449}; DE Flags: Precursor; GN Name=MCA1; Synonyms=YCA1; OrderedLocusNames=YOR197W; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169874; RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."; RL Nature 387:98-102(1997). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, MUTAGENESIS OF CYS-276, AND RP PROTEOLYTIC PROCESSING. RX PubMed=11983181; DOI=10.1016/s1097-2765(02)00501-4; RA Madeo F., Herker E., Maldener C., Wissing S., Laechelt S., Herlan M., RA Fehr M., Lauber K., Sigrist S.J., Wesselborg S., Froehlich K.-U.; RT "A caspase-related protease regulates apoptosis in yeast."; RL Mol. Cell 9:911-917(2002). RN [5] RP IDENTIFICATION OF PROBABLE INITIATION SITE. RX PubMed=12748633; DOI=10.1038/nature01644; RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.; RT "Sequencing and comparison of yeast species to identify genes and RT regulatory elements."; RL Nature 423:241-254(2003). RN [6] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [7] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [8] RP IDENTIFICATION OF PROBABLE INITIATION SITE. RX PubMed=12775844; DOI=10.1126/science.1084337; RA Cliften P.F., Sudarsanam P., Desikan A., Fulton L., Fulton B., Majors J., RA Waterston R., Cohen B.A., Johnston M.; RT "Finding functional features in Saccharomyces genomes by phylogenetic RT footprinting."; RL Science 301:71-76(2003). RN [9] RP FUNCTION. RX PubMed=15489197; DOI=10.1016/j.femsyr.2004.07.005; RA Bettiga M., Calzari L., Orlandi I., Alberghina L., Vai M.; RT "Involvement of the yeast metacaspase Yca1 in ubp10Delta-programmed cell RT death."; RL FEMS Yeast Res. 5:141-147(2004). RN [10] RP FUNCTION. RX PubMed=15381687; DOI=10.1083/jcb.200404138; RA Wissing S., Ludovico P., Herker E., Buettner S., Engelhardt S.M., RA Decker T., Link A., Proksch A., Rodrigues F., Corte-Real M., RA Froehlich K.-U., Manns J., Cande C., Sigrist S.J., Kroemer G., Madeo F.; RT "An AIF orthologue regulates apoptosis in yeast."; RL J. Cell Biol. 166:969-974(2004). RN [11] RP FUNCTION. RX PubMed=14970189; DOI=10.1083/jcb.200310014; RA Herker E., Jungwirth H., Lehmann K.A., Maldener C., Froehlich K.-U., RA Wissing S., Buettner S., Fehr M., Sigrist S.J., Madeo F.; RT "Chronological aging leads to apoptosis in yeast."; RL J. Cell Biol. 164:501-507(2004). RN [12] RP FUNCTION. RX PubMed=14718573; DOI=10.1091/mbc.e03-02-0114; RA Wadskog I., Maldener C., Proksch A., Madeo F., Adler L.; RT "Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show RT increased susceptibility to apoptosis-like cell death on exposure to NaCl RT stress."; RL Mol. Biol. Cell 15:1436-1444(2004). RN [13] RP FUNCTION. RX PubMed=16170310; DOI=10.1038/sj.embor.7400514; RA Mazzoni C., Herker E., Palermo V., Jungwirth H., Eisenberg T., Madeo F., RA Falcone C.; RT "Yeast caspase 1 links messenger RNA stability to apoptosis in yeast."; RL EMBO Rep. 6:1076-1081(2005). RN [14] RP FUNCTION. RX PubMed=15668299; DOI=10.1083/jcb.200408071; RA Reiter J., Herker E., Madeo F., Schmitt M.J.; RT "Viral killer toxins induce caspase-mediated apoptosis in yeast."; RL J. Cell Biol. 168:353-358(2005). RN [15] RP FUNCTION. RX PubMed=15939758; DOI=10.1083/jcb.200410064; RA Vachova L., Palkova Z.; RT "Physiological regulation of yeast cell death in multicellular colonies is RT triggered by ammonia."; RL J. Cell Biol. 169:711-717(2005). RN [16] RP FUNCTION. RX PubMed=16079294; DOI=10.1242/jcs.02477; RA Weinberger M., Ramachandran L., Feng L., Sharma K., Sun X., Marchetti M., RA Huberman J.A., Burhans W.C.; RT "Apoptosis in budding yeast caused by defects in initiation of DNA RT replication."; RL J. Cell Sci. 118:3543-3553(2005). RN [17] RP FUNCTION. RX PubMed=16301538; DOI=10.1073/pnas.0508120102; RA Khan M.A., Chock P.B., Stadtman E.R.; RT "Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates RT oxidized proteins in Saccharomyces cerevisiae."; RL Proc. Natl. Acad. Sci. U.S.A. 102:17326-17331(2005). RN [18] RP RETRACTED PAPER. RX PubMed=19174511; DOI=10.1073/pnas.0812470106; RA Nemecek J., Nakayashiki T., Wickner R.B.; RT "A prion of yeast metacaspase homolog (Mca1p) detected by a genetic RT screen."; RL Proc. Natl. Acad. Sci. U.S.A. 106:1892-1896(2009). RN [19] RP RETRACTION NOTICE OF PUBMED:19174511. RX PubMed=21628591; DOI=10.1073/pnas.1107490108; RA Nemecek J., Nakayashiki T., Wickner R.B.; RL Proc. Natl. Acad. Sci. U.S.A. 108:10022-10022(2011). RN [20] RP FUNCTION, AND DOMAIN PRION. RX PubMed=20624963; DOI=10.1073/pnas.1006610107; RA Lee R.E., Brunette S., Puente L.G., Megeney L.A.; RT "Metacaspase Yca1 is required for clearance of insoluble protein RT aggregates."; RL Proc. Natl. Acad. Sci. U.S.A. 107:13348-13353(2010). RN [21] {ECO:0007744|PDB:4F6O} RP X-RAY CRYSTALLOGRAPHY (1.68 ANGSTROMS) OF 83-432, PROTEIN SEQUENCE OF RP 332-336 AND 335-339, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, RP SUBUNIT, PROTEOLYTIC CLEAVAGE, ACTIVE SITE, AND MUTAGENESIS OF RP 2-TYR--LYS-86; ARG-72; LYS-86; HIS-220; CYS-276 AND HIS-277. RX PubMed=22761449; DOI=10.1074/jbc.m112.381806; RA Wong A.H., Yan C., Shi Y.; RT "Crystal structure of the yeast metacaspase Yca1."; RL J. Biol. Chem. 287:29251-29259(2012). RN [22] {ECO:0007744|PDB:4F6P} RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 83-432 OF MUTANT ALA-276. RA Wong A.H., Yan C.Y., Shi Y.G.; RT "Crystal structure of the metacaspase Yca1."; RL Submitted (MAY-2012) to the PDB data bank. CC -!- FUNCTION: Cysteine protease that cleaves specifically after arginine or CC lysine residues (PubMed:22761449). Mediates cell death (apoptosis) CC triggered by oxygen stress, salt stress or chronological aging. CC Regulated cell death can prevent a release of toxic cellular CC components, thus avoiding necrotic collapse of the colony, and can also CC provide nutrients for healthy cells. Therefore, regulated cell death in CC yeast colonies can be as important for their development as are CC apoptosis and related processes that occur within metazoa. Promotes the CC removal of insoluble protein aggregates during normal growth. CC {ECO:0000269|PubMed:11983181, ECO:0000269|PubMed:14718573, CC ECO:0000269|PubMed:14970189, ECO:0000269|PubMed:15381687, CC ECO:0000269|PubMed:15489197, ECO:0000269|PubMed:15668299, CC ECO:0000269|PubMed:15939758, ECO:0000269|PubMed:16079294, CC ECO:0000269|PubMed:16170310, ECO:0000269|PubMed:16301538, CC ECO:0000269|PubMed:20624963, ECO:0000269|PubMed:22761449}. CC -!- ACTIVITY REGULATION: Activated by Ca(2+) which induces self-processing CC and is required for the activity of the mature enzyme. CC {ECO:0000269|PubMed:22761449}. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:22761449}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus CC {ECO:0000269|PubMed:14562095}. CC -!- DOMAIN: The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain. It CC targets the protein to insoluble protein aggregates. CC {ECO:0000269|PubMed:20624963}. CC -!- PTM: Proteolytic cleavage of the propeptide appears to occur after Arg- CC 72 and/or Lys-86; it is not clear how the processing takes place CC (PubMed:11983181, PubMed:22761449). Proteolytic cleavage after Lys-331 CC generates a large (p20) and a small (p10) subunits (PubMed:22761449). CC The small subunit may be further cleaved to give rise to a shorter CC product starting at Gly-335 (PubMed:22761449). CC {ECO:0000269|PubMed:11983181, ECO:0000269|PubMed:22761449}. CC -!- MISCELLANEOUS: Present with 1400 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the peptidase C14B family. {ECO:0000305}. CC -!- CAUTION: PubMed:19174511 reported that MCA1 may have a prion form, CC dubbed [MCA]. However, the same authors have later not been able to CC reproduce these results and retracted the paper. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAT92851.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAA99410.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z75105; CAA99410.1; ALT_INIT; Genomic_DNA. DR EMBL; AY692832; AAT92851.1; ALT_INIT; Genomic_DNA. DR EMBL; BK006948; DAA10972.1; -; Genomic_DNA. DR PIR; S67089; S67089. DR RefSeq; NP_014840.4; NM_001183616.3. DR PDB; 4F6O; X-ray; 1.68 A; A=83-432. DR PDB; 4F6P; X-ray; 1.62 A; A=83-432. DR PDBsum; 4F6O; -. DR PDBsum; 4F6P; -. DR AlphaFoldDB; Q08601; -. DR SMR; Q08601; -. DR BioGRID; 34595; 267. DR DIP; DIP-2802N; -. DR IntAct; Q08601; 27. DR MINT; Q08601; -. DR STRING; 4932.YOR197W; -. DR MEROPS; C14.035; -. DR iPTMnet; Q08601; -. DR MaxQB; Q08601; -. DR PaxDb; 4932-YOR197W; -. DR PeptideAtlas; Q08601; -. DR EnsemblFungi; YOR197W_mRNA; YOR197W; YOR197W. DR GeneID; 854372; -. DR KEGG; sce:YOR197W; -. DR AGR; SGD:S000005723; -. DR SGD; S000005723; MCA1. DR VEuPathDB; FungiDB:YOR197W; -. DR eggNOG; KOG1546; Eukaryota. DR HOGENOM; CLU_029389_0_1_1; -. DR InParanoid; Q08601; -. DR OMA; MHRIMVT; -. DR OrthoDB; 1077459at2759; -. DR BioCyc; YEAST:G3O-33705-MONOMER; -. DR BioGRID-ORCS; 854372; 3 hits in 10 CRISPR screens. DR PRO; PR:Q08601; -. DR Proteomes; UP000002311; Chromosome XV. DR RNAct; Q08601; Protein. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:SGD. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IDA:SGD. DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:SGD. DR GO; GO:0006508; P:proteolysis; IBA:GO_Central. DR Gene3D; 3.40.50.12660; -; 2. DR InterPro; IPR029030; Caspase-like_dom_sf. DR InterPro; IPR011600; Pept_C14_caspase. DR PANTHER; PTHR48104:SF30; METACASPASE-1; 1. DR PANTHER; PTHR48104; METACASPASE-4; 1. DR Pfam; PF00656; Peptidase_C14; 1. DR SUPFAM; SSF52129; Caspase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Apoptosis; Cytoplasm; Direct protein sequencing; Hydrolase; KW Nucleus; Protease; Reference proteome; Thiol protease; Zymogen. FT PROPEP 1..? FT /evidence="ECO:0000269|PubMed:22761449" FT /id="PRO_0000268683" FT CHAIN 87..331 FT /note="Large subunit p20" FT /evidence="ECO:0000269|PubMed:22761449" FT /id="PRO_0000451182" FT CHAIN 332..432 FT /note="Small subunit p10" FT /evidence="ECO:0000269|PubMed:22761449" FT /id="PRO_0000451183" FT CHAIN ?..432 FT /note="Metacaspase-1" FT /id="PRO_0000268684" FT REGION 1..70 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 29..131 FT /note="Prion domain (PrD)" FT COMPBIAS 9..58 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 220 FT /evidence="ECO:0000305|PubMed:22761449" FT ACT_SITE 276 FT /evidence="ECO:0000305|PubMed:11983181, FT ECO:0000305|PubMed:22761449" FT SITE 72..73 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:22761449" FT SITE 86..87 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:22761449" FT SITE 331..332 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:22761449" FT SITE 334..335 FT /note="Cleavage; by autolysis" FT /evidence="ECO:0000269|PubMed:22761449" FT MUTAGEN 2..86 FT /note="Missing: Does not affect catalytic activity." FT /evidence="ECO:0000269|PubMed:22761449" FT MUTAGEN 72 FT /note="R->A: Prevents auto-cleavage at Arg-72 but not at FT Lys-86. Does not affect catalytic activity; when associated FT with A-86." FT /evidence="ECO:0000269|PubMed:22761449" FT MUTAGEN 86 FT /note="K->A: Prevents auto-cleavage at Lys-86 but not at FT Arg-72. Does not affect catalytic activity; when associated FT with A-72." FT /evidence="ECO:0000269|PubMed:22761449" FT MUTAGEN 220 FT /note="H->A: Blocks Ca(2+)-stimulated auto-processing and FT its catalytic activity towards substrates." FT /evidence="ECO:0000269|PubMed:11983181, FT ECO:0000269|PubMed:22761449" FT MUTAGEN 276 FT /note="C->A: Blocks Ca(2+)-stimulated auto-processing and FT its catalytic activity towards substrates." FT /evidence="ECO:0000269|PubMed:11983181, FT ECO:0000269|PubMed:22761449" FT MUTAGEN 277 FT /note="H->A: No effect on auto-processing and catalytic FT activity towards substrates." FT /evidence="ECO:0000269|PubMed:22761449" FT TURN 92..94 FT /evidence="ECO:0007829|PDB:4F6O" FT STRAND 102..104 FT /evidence="ECO:0007829|PDB:4F6O" FT STRAND 136..142 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 155..167 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 174..176 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 177..181 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 187..189 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 193..204 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 212..219 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 244..247 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 252..259 FT /evidence="ECO:0007829|PDB:4F6P" FT TURN 260..262 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 268..273 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 275..277 FT /evidence="ECO:0007829|PDB:4F6P" FT TURN 279..282 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 285..289 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 354..362 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 380..391 FT /evidence="ECO:0007829|PDB:4F6P" FT HELIX 397..408 FT /evidence="ECO:0007829|PDB:4F6P" FT TURN 409..411 FT /evidence="ECO:0007829|PDB:4F6P" FT STRAND 415..422 FT /evidence="ECO:0007829|PDB:4F6P" SQ SEQUENCE 432 AA; 47982 MW; 547D186E3EB481B7 CRC64; MYPGSGRYTY NNAGGNNGYQ RPMAPPPNQQ YGQQYGQQYE QQYGQQYGQQ NDQQFSQQYA PPPGPPPMAY NRPVYPPPQF QQEQAKAQLS NGYNNPNVNA SNMYGPPQNM SLPPPQTQTI QGTDQPYQYS QCTGRRKALI IGINYIGSKN QLRGCINDAH NIFNFLTNGY GYSSDDIVIL TDDQNDLVRV PTRANMIRAM QWLVKDAQPN DSLFLHYSGH GGQTEDLDGD EEDGMDDVIY PVDFETQGPI IDDEMHDIMV KPLQQGVRLT ALFDSCHSGT VLDLPYTYST KGIIKEPNIW KDVGQDGLQA AISYATGNRA ALIGSLGSIF KTVKGGMGNN VDRERVRQIK FSAADVVMLS GSKDNQTSAD AVEDGQNTGA MSHAFIKVMT LQPQQSYLSL LQNMRKELAG KYSQKPQLSS SHPIDVNLQF IM //