Q08601 (MCA1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metacaspase-1
EC=3.4.22.-

Gene names

Name:	MCA1
Synonyms:	YCA1
Ordered Locus Names:	YOR197W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	432 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Mediates cell death (apoptosis) triggered by oxygen stress, salt stress or chronological aging. Regulated cell death can prevent a release of toxic cellular components, thus avoiding necrotic collapse of the colony, and can also provide nutrients for healthy cells. Therefore, regulated cell death in yeast colonies can be as important for their development as are apoptosis and related processes that occur within metazoa. Promotes the removal of insoluble protein aggregates during normal growth. Ref.4 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.20
Subcellular location	Cytoplasm. Nucleus Ref.6.
Domain	The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain. It targets the protein to insoluble protein aggregates. Ref.20
Miscellaneous	Present with 1400 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the peptidase C14B family.
Caution	Ref.18 reported that MCA1 may have a prion form, dubbed [MCA]. However, the same authors have later not been able to reproduce these results and retracted the paper.
Sequence caution	The sequence AAT92851.1 differs from that shown. Reason: Erroneous initiation. The sequence CAA99410.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Molecular function	Hydrolase Protease Thiol protease
PTM	Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from direct assay Ref.4. Source: SGD misfolded or incompletely synthesized protein catabolic process Inferred from mutant phenotype Ref.20. Source: SGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 12062425. Source: SGD
Molecular_function	calcium-dependent cysteine-type endopeptidase activity Inferred from direct assay PubMed 22761449. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Propeptide

1 – ?

Potential

PRO_0000268683

Chain

? – 432

Metacaspase-1

PRO_0000268684

Regions

Region

29 – 131

103

Prion domain (PrD)

Sites

Active site

220

1

By similarity

Active site

276

1

Experimental info

Mutagenesis

276

1

C → A: Blocks the processing and reduces caspase activity. Ref.4

Secondary structure

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432

Helix Strand Turn

Details...

Turn

92 – 94

3

Beta strand

102 – 104

3

Beta strand

136 – 142

7

Helix

155 – 169

15

Helix

174 – 176

3

Beta strand

177 – 181

5

Helix

187 – 189

3

Helix

193 – 204

12

Beta strand

212 – 219

8

Beta strand

221 – 223

3

Beta strand

237 – 239

3

Helix

244 – 247

4

Helix

252 – 259

8

Turn

260 – 262

3

Beta strand

268 – 273

6

Beta strand

275 – 277

3

Turn

279 – 282

4

Beta strand

285 – 289

5

Beta strand

292 – 295

4

Beta strand

354 – 362

9

Helix

380 – 391

12

Helix

397 – 408

12

Turn

409 – 411

3

Beta strand

415 – 422

8

Sequences

	Sequence		Length	Mass (Da)
	Q08601 [UniParc]. Last modified May 20, 2008. Version 2. Checksum: 547D186E3EB481B7	FASTA	432	47,982
	10 20 30 40 50 60 MYPGSGRYTY NNAGGNNGYQ RPMAPPPNQQ YGQQYGQQYE QQYGQQYGQQ NDQQFSQQYA 70 80 90 100 110 120 PPPGPPPMAY NRPVYPPPQF QQEQAKAQLS NGYNNPNVNA SNMYGPPQNM SLPPPQTQTI 130 140 150 160 170 180 QGTDQPYQYS QCTGRRKALI IGINYIGSKN QLRGCINDAH NIFNFLTNGY GYSSDDIVIL 190 200 210 220 230 240 TDDQNDLVRV PTRANMIRAM QWLVKDAQPN DSLFLHYSGH GGQTEDLDGD EEDGMDDVIY 250 260 270 280 290 300 PVDFETQGPI IDDEMHDIMV KPLQQGVRLT ALFDSCHSGT VLDLPYTYST KGIIKEPNIW 310 320 330 340 350 360 KDVGQDGLQA AISYATGNRA ALIGSLGSIF KTVKGGMGNN VDRERVRQIK FSAADVVMLS 370 380 390 400 410 420 GSKDNQTSAD AVEDGQNTGA MSHAFIKVMT LQPQQSYLSL LQNMRKELAG KYSQKPQLSS 430 SHPIDVNLQF IM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K. Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"A caspase-related protease regulates apoptosis in yeast." Madeo F., Herker E., Maldener C., Wissing S., Laechelt S., Herlan M., Fehr M., Lauber K., Sigrist S.J., Wesselborg S., Froehlich K.-U. Mol. Cell 9:911-917(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF CYS-276, PROTEOLYTIC PROCESSING.
[5]	"Sequencing and comparison of yeast species to identify genes and regulatory elements." Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S. Nature 423:241-254(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF PROBABLE INITIATION SITE.
[6]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[7]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[8]	"Finding functional features in Saccharomyces genomes by phylogenetic footprinting." Cliften P.F., Sudarsanam P., Desikan A., Fulton L., Fulton B., Majors J., Waterston R., Cohen B.A., Johnston M. Science 301:71-76(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF PROBABLE INITIATION SITE.
[9]	"Involvement of the yeast metacaspase Yca1 in ubp10Delta-programmed cell death." Bettiga M., Calzari L., Orlandi I., Alberghina L., Vai M. FEMS Yeast Res. 5:141-147(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"An AIF orthologue regulates apoptosis in yeast." Wissing S., Ludovico P., Herker E., Buettner S., Engelhardt S.M., Decker T., Link A., Proksch A., Rodrigues F., Corte-Real M., Froehlich K.-U., Manns J., Cande C., Sigrist S.J., Kroemer G., Madeo F. J. Cell Biol. 166:969-974(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Chronological aging leads to apoptosis in yeast." Herker E., Jungwirth H., Lehmann K.A., Maldener C., Froehlich K.-U., Wissing S., Buettner S., Fehr M., Sigrist S.J., Madeo F. J. Cell Biol. 164:501-507(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Yeast lacking the SRO7/SOP1-encoded tumor suppressor homologue show increased susceptibility to apoptosis-like cell death on exposure to NaCl stress." Wadskog I., Maldener C., Proksch A., Madeo F., Adler L. Mol. Biol. Cell 15:1436-1444(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Yeast caspase 1 links messenger RNA stability to apoptosis in yeast." Mazzoni C., Herker E., Palermo V., Jungwirth H., Eisenberg T., Madeo F., Falcone C. EMBO Rep. 6:1076-1081(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[14]	"Viral killer toxins induce caspase-mediated apoptosis in yeast." Reiter J., Herker E., Madeo F., Schmitt M.J. J. Cell Biol. 168:353-358(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Physiological regulation of yeast cell death in multicellular colonies is triggered by ammonia." Vachova L., Palkova Z. J. Cell Biol. 169:711-717(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Apoptosis in budding yeast caused by defects in initiation of DNA replication." Weinberger M., Ramachandran L., Feng L., Sharma K., Sun X., Marchetti M., Huberman J.A., Burhans W.C. J. Cell Sci. 118:3543-3553(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae." Khan M.A., Chock P.B., Stadtman E.R. Proc. Natl. Acad. Sci. U.S.A. 102:17326-17331(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"A prion of yeast metacaspase homolog (Mca1p) detected by a genetic screen." Nemecek J., Nakayashiki T., Wickner R.B. Proc. Natl. Acad. Sci. U.S.A. 106:1892-1896(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION.
[19]	Erratum Nemecek J., Nakayashiki T., Wickner R.B. Proc. Natl. Acad. Sci. U.S.A. 108:10022-10022(2011) [PubMed] [Europe PMC] [Abstract] Cited for: RETRACTION.
[20]	"Metacaspase Yca1 is required for clearance of insoluble protein aggregates." Lee R.E., Brunette S., Puente L.G., Megeney L.A. Proc. Natl. Acad. Sci. U.S.A. 107:13348-13353(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DOMAIN PRION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z75105 Genomic DNA. Translation: CAA99410.1. Different initiation.
AY692832 Genomic DNA. Translation: AAT92851.1. Different initiation.
BK006948 Genomic DNA. Translation: DAA10972.1.

PIR

S67089.

RefSeq

NP_014840.4. NM_001183616.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F6O	X-ray	1.68	A	83-432	[»]

ProteinModelPortal

Q08601.

SMR

Q08601. Positions 90-432.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2802N.

IntAct

Q08601. 6 interactions.

MINT

MINT-533648.

STRING

4932.YOR197W.

Protein family/group databases

MEROPS

C14.035.

Proteomic databases

PaxDb

Q08601.

PeptideAtlas

Q08601.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YOR197W; YOR197W; YOR197W.

GeneID

854372.

KEGG

sce:YOR197W.
sce:YOR201C.

Organism-specific databases

CYGD

YOR197w.

SGD

S000005723. MCA1.

Phylogenomic databases

eggNOG

NOG68179.

HOGENOM

HOG000240109.

KO

K15507.

OMA

CKDSQTS.

OrthoDB

EOG45HW6F.

Gene expression databases

Genevestigator

Q08601.

GermOnline

YOR197W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR011600. Pept_C14_cat.
[Graphical view]

Pfam

PF00656. Peptidase_C14. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

976502.

Entry information

Entry name

MCA1_YEAST

Accession

Primary (citable) accession number: Q08601
Secondary accession number(s): D6W2Q6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 12, 2006
Last sequence update:	May 20, 2008
Last modified:	April 3, 2013
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program