MCA1_YEAST
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 03-AUG-2022, entry version 157.
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};
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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; 257.
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; Q08601; -.
DR PRIDE; Q08601; -.
DR EnsemblFungi; YOR197W_mRNA; YOR197W; YOR197W.
DR GeneID; 854372; -.
DR KEGG; sce:YOR197W; -.
DR SGD; S000005723; MCA1.
DR VEuPathDB; FungiDB:YOR197W; -.
DR eggNOG; KOG1546; Eukaryota.
DR HOGENOM; CLU_029389_0_1_1; -.
DR InParanoid; Q08601; -.
DR OMA; DFRTAGH; -.
DR BioCyc; YEAST:G3O-33705-MON; -.
DR PRO; PR:Q08601; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q08601; protein.
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:0006915; P:apoptotic process; IDA:SGD.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:SGD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR SUPFAM; SSF52129; SSF52129; 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
