STE23_YEAST
ID STE23_YEAST Reviewed; 1027 AA.
AC Q06010; D6VZ24; E9P8R3;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=A-factor-processing enzyme;
DE EC=3.4.24.-;
DE AltName: Full=Insulin-degrading enzyme homolog;
GN Name=STE23; OrderedLocusNames=YLR389C; ORFNames=L8084.12;
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=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Hong E.L., Cherry J.M.;
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
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 943-1027, AND IDENTIFICATION OF
RP FRAMESHIFT.
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=12844361; DOI=10.1186/gb-2003-4-7-r45;
RA Brachat S., Dietrich F.S., Voegeli S., Zhang Z., Stuart L., Lerch A.,
RA Gates K., Gaffney T.D., Philippsen P.;
RT "Reinvestigation of the Saccharomyces cerevisiae genome annotation by
RT comparison to the genome of a related fungus: Ashbya gossypii.";
RL Genome Biol. 4:R45.1-R45.13(2003).
RN [5]
RP FUNCTION.
RX PubMed=7569998; DOI=10.1126/science.270.5235.464;
RA Adames N., Blundell K., Ashby M.N., Boone C.;
RT "Role of yeast insulin-degrading enzyme homologs in propheromone processing
RT and bud site selection.";
RL Science 270:464-467(1995).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15944156; DOI=10.1074/jbc.m414192200;
RA Kim S., Lapham A.N., Freedman C.G., Reed T.L., Schmidt W.K.;
RT "Yeast as a tractable genetic system for functional studies of the insulin-
RT degrading enzyme.";
RL J. Biol. Chem. 280:27481-27490(2005).
RN [7]
RP FUNCTION, INDUCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION,
RP AND IDENTIFICATION OF PROBABLE INITIATION SITE.
RX PubMed=19750477; DOI=10.1002/yea.1709;
RA Alper B.J., Rowse J.W., Schmidt W.K.;
RT "Yeast Ste23p shares functional similarities with mammalian insulin-
RT degrading enzymes.";
RL Yeast 26:595-610(2009).
CC -!- FUNCTION: Involved in the N-terminal endoproteolytic cleavage of the P2
CC precursor of the a-factor mating pheromone. Capable of proteolysing the
CC established mammalian insulin-degrading enzymes (IDEs) substrates
CC amyloid-beta peptide and insulin B-chain. {ECO:0000269|PubMed:15944156,
CC ECO:0000269|PubMed:19750477, ECO:0000269|PubMed:7569998}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by chelating agents like EDTA, TPEN and
CC 1,1-phenanthroline, as well as NEM, free cysteine and DTT.
CC {ECO:0000269|PubMed:19750477}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=215 uM for a synthetic a-factor analog
CC {ECO:0000269|PubMed:19750477};
CC Vmax=0.49 umol/min/mg enzyme towards a synthetic a-factor analog
CC {ECO:0000269|PubMed:19750477};
CC pH dependence:
CC Optimum pH is 8.1. {ECO:0000269|PubMed:19750477};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:19750477};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15944156};
CC Peripheral membrane protein {ECO:0000269|PubMed:15944156}.
CC -!- INDUCTION: Expressed in both haploid and diploid yeast cells.
CC {ECO:0000269|PubMed:19750477}.
CC -!- SIMILARITY: Belongs to the peptidase M16 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-53 is the initiator. Met-
CC 53 is probably the physiologically relevant initiator methionine, as
CC Met-1 is dispensable for the expression of functional STE23, whereas
CC Met-53 is not. {ECO:0000305}.
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DR EMBL; U19729; AAB82351.2; -; Genomic_DNA.
DR EMBL; AY260885; AAP21753.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09690.1; -; Genomic_DNA.
DR PIR; S55945; S55945.
DR RefSeq; NP_013493.2; NM_001182278.1.
DR AlphaFoldDB; Q06010; -.
DR SMR; Q06010; -.
DR BioGRID; 31648; 63.
DR DIP; DIP-1921N; -.
DR IntAct; Q06010; 7.
DR MINT; Q06010; -.
DR STRING; 4932.YLR389C; -.
DR MEROPS; M16.008; -.
DR iPTMnet; Q06010; -.
DR MaxQB; Q06010; -.
DR PaxDb; Q06010; -.
DR PRIDE; Q06010; -.
DR TopDownProteomics; Q06010; -.
DR EnsemblFungi; YLR389C_mRNA; YLR389C; YLR389C.
DR GeneID; 851105; -.
DR KEGG; sce:YLR389C; -.
DR SGD; S000004381; STE23.
DR VEuPathDB; FungiDB:YLR389C; -.
DR eggNOG; KOG0959; Eukaryota.
DR GeneTree; ENSGT00940000155780; -.
DR HOGENOM; CLU_004639_1_1_1; -.
DR InParanoid; Q06010; -.
DR OMA; WIFDEMK; -.
DR BioCyc; YEAST:G3O-32455-MON; -.
DR Reactome; R-SCE-9033241; Peroxisomal protein import.
DR PRO; PR:Q06010; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q06010; protein.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:SGD.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR GO; GO:0071432; P:peptide mating pheromone maturation involved in positive regulation of conjugation with cellular fusion; IGI:SGD.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0019236; P:response to pheromone; IEA:UniProtKB-KW.
DR InterPro; IPR011249; Metalloenz_LuxS/M16.
DR InterPro; IPR011765; Pept_M16_N.
DR InterPro; IPR001431; Pept_M16_Zn_BS.
DR InterPro; IPR007863; Peptidase_M16_C.
DR InterPro; IPR032632; Peptidase_M16_M.
DR Pfam; PF00675; Peptidase_M16; 1.
DR Pfam; PF05193; Peptidase_M16_C; 2.
DR Pfam; PF16187; Peptidase_M16_M; 1.
DR SUPFAM; SSF63411; SSF63411; 4.
DR PROSITE; PS00143; INSULINASE; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Pheromone response;
KW Protease; Reference proteome; Zinc.
FT CHAIN 1..1027
FT /note="A-factor-processing enzyme"
FT /id="PRO_0000074418"
FT ACT_SITE 121
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10096"
SQ SEQUENCE 1027 AA; 117579 MW; C07B7F7EDA5785F3 CRC64;
MGVSLLASSS AFVTKPLLTQ LVHLSPISLN FTVRRFKPFT CLSRYYTTNP YNMTSNFKTF
NLDFLKPDLD ERSYRFIELP NKLKALLIQD PKADKAAASL DVNIGAFEDP KNLPGLAHFC
EHLLFMGSEK FPDENEYSSY LSKHGGSSNA YTASQNTNYF FEVNHQHLFG ALDRFSGFFS
CPLFNKDSTD KEINAVNSEN KKNLQNDIWR IYQLDKSLTN TKHPYHKFST GNIETLGTLP
KENGLNVRDE LLKFHKNFYS ANLMKLCILG REDLDTLSDW TYDLFKDVAN NGREVPLYAE
PIMQPEHLQK IIQVRPVKDL KKLEISFTVP DMEEHWESKP PRILSHLIGH EGSGSLLAHL
KKLGWANELS AGGHTVSKGN AFFAVDIDLT DNGLTHYRDV IVLIFQYIEM LKNSLPQKWI
FNELQDISNA TFKFKQAGSP SSTVSSLAKC LEKDYIPVSR ILAMGLLTKY EPDLLTQYTD
ALVPENSRVT LISRSLETDS AEKWYGTAYK VVDYPADLIK NMKSPGLNPA LTLPRPNEFV
STNFKVDKID GIKPLDEPVL LLSDDVSKLW YKKDDRFWQP RGYIYLSFKL PHTHASIINS
MLSTLYTQLA NDALKDVQYD AACADLRISF NKTNQGLAIT ASGFNEKLII LLTRFLQGVN
SFEPKKDRFE ILKDKTIRHL KNLLYEVPYS QMSNYYNAII NERSWSTAEK LQVFEKLTFE
QLINFIPTIY EGVYFETLIH GNIKHEEALE VDSLIKSLIP NNIHNLQVSN NRLRSYLLPK
GKTFRYETAL KDSQNVNSCI QHVTQLDVYS EDLSALSGLF AQLIHEPCFD TLRTKEQLGY
VVFSSSLNNH GTANIRILIQ SEHTTPYLEW RINNFYETFG QVLRDMPEED FEKHKEALCN
SLLQKFKNMA EESARYTAAI YLGDYNFTHR QKKAKLVANI TKQQMIDFYE NYIMSENASK
LILHLKSQVE NKELNENELD TAKYPTGQLI EDVGAFKSTL FVAPVRQPMK DFEISAPPKL
NNSSESE
