PRTB_YEAST
ID PRTB_YEAST Reviewed; 635 AA.
AC P09232; D3DLJ0;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Cerevisin;
DE EC=3.4.21.48;
DE AltName: Full=Proteinase YSCB;
DE AltName: Full=Vacuolar protease B;
DE Short=PrB;
DE Flags: Precursor;
GN Name=PRB1; OrderedLocusNames=YEL060C;
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 [GENOMIC DNA], AND PROTEIN SEQUENCE OF 281-295.
RC STRAIN=ATCC 204510 / AB320;
RX PubMed=3325823; DOI=10.1128/mcb.7.12.4390-4399.1987;
RA Moehle C.M., Tizard R., Lemmon S.K., Smart J., Jones E.W.;
RT "Protease B of the lysosomelike vacuole of the yeast Saccharomyces
RT cerevisiae is homologous to the subtilisin family of serine proteases.";
RL Mol. Cell. Biol. 7:4390-4399(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 605-635.
RC STRAIN=ATCC 204508 / S288c;
RA Saunders W.S., He L., Loo K.K., Hoyt M.;
RL Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=7021321; DOI=10.1093/genetics/97.1.45;
RA Zubenko G.S., Jones E.W.;
RT "Protein degradation, meiosis and sporulation in proteinase-deficient
RT mutants of Saccharomyces cerevisiae.";
RL Genetics 97:45-64(1981).
RN [6]
RP FUNCTION.
RX PubMed=6764902; DOI=10.1093/genetics/102.4.679;
RA Zubenko G.S., Park F.J., Jones E.W.;
RT "Genetic properties of mutations at the PEP4 locus in Saccharomyces
RT cerevisiae.";
RL Genetics 102:679-690(1982).
RN [7]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2645294; DOI=10.1083/jcb.108.2.309;
RA Moehle C.M., Dixon C.K., Jones E.W.;
RT "Processing pathway for protease B of Saccharomyces cerevisiae.";
RL J. Cell Biol. 108:309-325(1989).
RN [8]
RP INDUCTION.
RX PubMed=2407604; DOI=10.1093/genetics/124.1.39;
RA Moehle C.M., Jones E.W.;
RT "Consequences of growth media, gene copy number, and regulatory mutations
RT on the expression of the PRB1 gene of Saccharomyces cerevisiae.";
RL Genetics 124:39-55(1990).
RN [9]
RP PROTEOLYTIC PROCESSING.
RX PubMed=1744078; DOI=10.1016/s0021-9258(18)54432-x;
RA Nebes V.L., Jones E.W.;
RT "Activation of the proteinase B precursor of the yeast Saccharomyces
RT cerevisiae by autocatalysis and by an internal sequence.";
RL J. Biol. Chem. 266:22851-22857(1991).
RN [10]
RP PRION IDENTIFICATION.
RX PubMed=12923060; DOI=10.1101/gad.1115803;
RA Roberts B.T., Wickner R.B.;
RT "Heritable activity: a prion that propagates by covalent autoactivation.";
RL Genes Dev. 17:2083-2087(2003).
RN [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
CC -!- FUNCTION: Vacuolar proteinase B involved in protein degradation in the
CC vacuole. Among other substrates, acts on carboxypeptidase Y (cpY/PRC1)
CC to activate it by processing its Pro-peptide. Required for meiosis and
CC spore formation, and for optimal survival in stationary phase.
CC {ECO:0000269|PubMed:6764902, ECO:0000269|PubMed:7021321}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity, and of Bz-Arg-
CC OEt > Ac-Tyr-OEt. Does not hydrolyze peptide amides.; EC=3.4.21.48;
CC -!- SUBCELLULAR LOCATION: Vacuole.
CC -!- INDUCTION: Repressed by glucose. {ECO:0000269|PubMed:2407604}.
CC -!- PTM: Activated by N- and C-terminal proteolytic cleavage. Protease B
CC (PrB/PRB1) processing requires at least 4 cleavages. First, the signal
CC peptide is removed from the 76 kDa preproprotease B by signal peptidase
CC in the ER. Then, PrB removes its own Pro-region (in trans) at the N-
CC terminus, producing a 39 kDa form before exiting the ER. In the Golgi
CC complex, the C-terminal Post-region of the 40 kDa proprotease B
CC undergoes protease A (PrA/PEP4)-mediated processing to a 37 kDa
CC intermediate, which in turn is quickly processed again by PrB in trans
CC to yield the 31 kDa mature PrB.
CC -!- PTM: Glycosylated. Preproprotease B is a 76 kDa unglycosylated
CC precursor that enters the endoplasmic reticulum (ER), where it receives
CC one Asn-linked and an undetermined number of non-Asn-linked
CC carbohydrate side chains. In the Golgi complex, the 39 kDa form becomes
CC 40 kDa, due to elaboration of the Asn-linked side chain. The ultimate
CC processing step removes a peptide containing the Asn-linked chain.
CC Mature PrB has only non-Asn-linked carbohydrates.
CC -!- MISCELLANEOUS: [beta] is the prion form of PrB. In contrast to other
CC prions, [beta] is not the result of a conformational change of the
CC cellular PrB, but distinguishes itself by autoactivation in trans.
CC Usually, PrB is already involved in its own maturatiuon, but PrA plays
CC a critical role. PrpA mutants lack PrB. However, in growth conditions
CC that favor PRB1 expression, PrB activity persists in PrA mutants due to
CC autocleavage of PrB in trans. This condition is stably transmitted to
CC daughter cells in mitosis. [beta] can be cured by growing in PRB1-
CC repressing conditions. Once a cell has lost PrB activity, it remains
CC stably inactive. Thus, there are 2 alternative states, that are
CC chromosomally identical, but phenotypically distinct. Since PrA is able
CC to activate PrB, normal cells always carry the [beta] prion. Its
CC absence and transmission are only observable in the absence of PrA.
CC {ECO:0000305|PubMed:12923060}.
CC -!- MISCELLANEOUS: Present with 1600 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. {ECO:0000305}.
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DR EMBL; M18097; AAA34901.1; -; Genomic_DNA.
DR EMBL; U18795; AAB65027.1; -; Genomic_DNA.
DR EMBL; Z11859; CAA77886.1; -; Genomic_DNA.
DR EMBL; M90522; AAA34495.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07594.1; -; Genomic_DNA.
DR PIR; A29358; A29358.
DR RefSeq; NP_010854.1; NM_001178875.1.
DR AlphaFoldDB; P09232; -.
DR SMR; P09232; -.
DR BioGRID; 36669; 136.
DR DIP; DIP-2544N; -.
DR IntAct; P09232; 23.
DR MINT; P09232; -.
DR STRING; 4932.YEL060C; -.
DR MEROPS; S08.052; -.
DR iPTMnet; P09232; -.
DR UCD-2DPAGE; P09232; -.
DR MaxQB; P09232; -.
DR PaxDb; P09232; -.
DR PRIDE; P09232; -.
DR TopDownProteomics; P09232; -.
DR EnsemblFungi; YEL060C_mRNA; YEL060C; YEL060C.
DR GeneID; 856649; -.
DR KEGG; sce:YEL060C; -.
DR SGD; S000000786; PRB1.
DR VEuPathDB; FungiDB:YEL060C; -.
DR eggNOG; KOG1153; Eukaryota.
DR GeneTree; ENSGT00940000176425; -.
DR HOGENOM; CLU_011263_3_0_1; -.
DR InParanoid; P09232; -.
DR OMA; SNYGKCN; -.
DR BioCyc; YEAST:YEL060C-MON; -.
DR Reactome; R-SCE-8866427; VLDLR internalisation and degradation.
DR Reactome; R-SCE-8964038; LDL clearance.
DR PRO; PR:P09232; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P09232; protein.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0000324; C:fungal-type vacuole; TAS:SGD.
DR GO; GO:0000328; C:fungal-type vacuole lumen; TAS:SGD.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IMP:SGD.
DR GO; GO:0009267; P:cellular response to starvation; IMP:SGD.
DR GO; GO:0000425; P:pexophagy; IMP:SGD.
DR GO; GO:0007039; P:protein catabolic process in the vacuole; IMP:SGD.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IMP:SGD.
DR CDD; cd04077; Peptidases_S8_PCSK9_ProteinaseK_like; 1.
DR Gene3D; 3.30.70.80; -; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR034193; PCSK9_ProteinaseK-like.
DR InterPro; IPR000209; Peptidase_S8/S53_dom.
DR InterPro; IPR036852; Peptidase_S8/S53_dom_sf.
DR InterPro; IPR023827; Peptidase_S8_Asp-AS.
DR InterPro; IPR022398; Peptidase_S8_His-AS.
DR InterPro; IPR023828; Peptidase_S8_Ser-AS.
DR InterPro; IPR015500; Peptidase_S8_subtilisin-rel.
DR InterPro; IPR010259; S8pro/Inhibitor_I9.
DR InterPro; IPR037045; S8pro/Inhibitor_I9_sf.
DR Pfam; PF05922; Inhibitor_I9; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51892; SUBTILASE; 1.
DR PROSITE; PS00136; SUBTILASE_ASP; 1.
DR PROSITE; PS00137; SUBTILASE_HIS; 1.
DR PROSITE; PS00138; SUBTILASE_SER; 1.
PE 1: Evidence at protein level;
KW Amyloid; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Prion; Protease; Reference proteome; Serine protease; Signal;
KW Vacuole; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..280
FT /evidence="ECO:0000269|PubMed:3325823"
FT /id="PRO_0000027136"
FT CHAIN 281..?574
FT /note="Cerevisin"
FT /id="PRO_0000027137"
FT PROPEP ?575..635
FT /id="PRO_0000417567"
FT DOMAIN 182..278
FT /note="Inhibitor I9"
FT /evidence="ECO:0000255"
FT DOMAIN 289..614
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT REGION 35..155
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..53
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 60..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..137
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 138..154
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 325
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 357
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 519
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT CARBOHYD 594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 460..491
FT /evidence="ECO:0000255"
FT CONFLICT 622
FT /note="F -> K (in Ref. 4; CAA77886/AAA34495)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 635 AA; 69621 MW; C346C2B1C7DDDC48 CRC64;
MKLENTLFTL GALGSISAAL VIPNLENAAD HHELINKEDH HERPRKVEFT KDDDEEPSDS
EDKEHGKFHK KGRKGQDKES PEFNGKRASG SHGSAHEGGK GMKPKHESSN DDDNDDKKKK
PHHKGGCHEN KVEEKKMKGK KVKGKKHHEK TLEKGRHHNR LAPLVSTAQF NPDAISKIIP
NRYIIVFKRG APQEEIDFHK ENVQQAQLQS VENLSAEDAF FISTKDTSLS TSEAGGIQDS
FNIDNLFSGY IGYFTQEIVD LIRQNPLVDF VERDSIVEAT EFDTQNSAPW GLARISHRER
LNLGSFNKYL YDDDAGRGVT SYVIDTGVNI NHKDFEKRAI WGKTIPLNDE DLDGNGHGTH
CAGTIASKHY GVAKNANVVA VKVLRSNGSG TMSDVVKGVE YAAKAHQKEA QEKKKGFKGS
TANMSLGGGK SPALDLAVNA AVEVGIHFAV AAGNENQDAC NTSPASADKA ITVGASTLSD
DRAYFSNWGK CVDVFAPGLN ILSTYIGSDD ATATLSGTSM ASPHVAGLLT YFLSLQPGSD
SEFFELGQDS LTPQQLKKKL IHYSTKDILF DIPEDTPNVL IYNGGGQDLS AFWNDTKKSH
SSGFKQELNM DEFIGSKTDL IFDQVRDILD KLNII
