KEX2_YEAST
ID KEX2_YEAST Reviewed; 814 AA.
AC P13134; D6W0V5;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Kexin;
DE EC=3.4.21.61;
DE AltName: Full=Protease KEX2;
DE AltName: Full=Proteinase YSCF;
DE Flags: Precursor;
GN Name=KEX2; Synonyms=QDS1; OrderedLocusNames=YNL238W; ORFNames=N1122;
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].
RX PubMed=2845974; DOI=10.1016/s0006-291x(88)80832-5;
RA Mizuno K., Nakamura T., Ohshima T., Tanaka S., Matsuo H.;
RT "Yeast KEX2 genes encodes an endopeptidase homologous to subtilisin-like
RT serine proteases.";
RL Biochem. Biophys. Res. Commun. 156:246-254(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2646633; DOI=10.1073/pnas.86.5.1434;
RA Fuller R.S., Brake A., Thorner J.;
RT "Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent
RT serine protease.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:1434-1438(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8896273;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1071::aid-yea4>3.0.co;2-s;
RA Pandolfo D., de Antoni A., Lanfranchi G., Valle G.;
RT "The DNA sequence of cosmid 14-5 from chromosome XIV reveals 21 open
RT reading frames including a novel gene encoding a globin-like domain.";
RL Yeast 12:1071-1076(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169873;
RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT evolutionary implications.";
RL Nature 387:93-98(1997).
RN [5]
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 [6]
RP PROTEOLYTIC PROCESSING, AND CHARACTERIZATION.
RX PubMed=1736307; DOI=10.1073/pnas.89.3.922;
RA Brenner C., Fuller R.S.;
RT "Structural and enzymatic characterization of a purified prohormone-
RT processing enzyme: secreted, soluble Kex2 protease.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:922-926(1992).
RN [7]
RP PROTEOLYTIC PROCESSING.
RX PubMed=1544507; DOI=10.1016/0014-5793(92)80132-z;
RA Germain D., Dumas F., Vernet T., Bourbonnais Y., Thomas D.Y., Boileau G.;
RT "The pro-region of the Kex2 endoprotease of Saccharomyces cerevisiae is
RT removed by self-processing.";
RL FEBS Lett. 299:283-286(1992).
RN [8]
RP POST-TRANSLATIONAL MODIFICATIONS.
RX PubMed=1918142; DOI=10.1083/jcb.115.2.297;
RA Wilcox C.A., Fuller R.S.;
RT "Posttranslational processing of the prohormone-cleaving Kex2 protease in
RT the Saccharomyces cerevisiae secretory pathway.";
RL J. Cell Biol. 115:297-307(1991).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 123-599 IN COMPLEX WITH INHIBITOR.
RX PubMed=12779325; DOI=10.1021/bi034434t;
RA Holyoak T., Wilson M.A., Fenn T.D., Kettner C.A., Petsko G.A., Fuller R.S.,
RA Ringe D.;
RT "2.4 A resolution crystal structure of the prototypical hormone-processing
RT protease Kex2 in complex with an Ala-Lys-Arg boronic acid inhibitor.";
RL Biochemistry 42:6709-6718(2003).
CC -!- FUNCTION: Processing of precursors of alpha-factors and killer toxin.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of -Lys-Arg-|-Xaa- and -Arg-Arg-|-Xaa- bonds to
CC process yeast alpha-factor pheromone and killer toxin precursors.;
CC EC=3.4.21.61;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 3 Ca(2+) ions per subunit.;
CC -!- INTERACTION:
CC P13134; P32790: SLA1; NbExp=16; IntAct=EBI-9658, EBI-17313;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane;
CC Single-pass type I membrane protein.
CC -!- PTM: O-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase S8 family. Furin subfamily.
CC {ECO:0000305}.
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DR EMBL; M22870; AAA34719.1; -; Genomic_DNA.
DR EMBL; M24201; AAA34718.1; -; Genomic_DNA.
DR EMBL; Z69381; CAA93360.1; -; Genomic_DNA.
DR EMBL; Z71514; CAA96143.1; -; Genomic_DNA.
DR EMBL; BK006947; DAA10321.1; -; Genomic_DNA.
DR PIR; A28931; KXBY.
DR RefSeq; NP_014161.1; NM_001183076.1.
DR PDB; 1OT5; X-ray; 2.40 A; A/B=123-599.
DR PDB; 1R64; X-ray; 2.20 A; A/B=121-601.
DR PDB; 2ID4; X-ray; 1.90 A; A/B=114-613.
DR PDBsum; 1OT5; -.
DR PDBsum; 1R64; -.
DR PDBsum; 2ID4; -.
DR AlphaFoldDB; P13134; -.
DR SMR; P13134; -.
DR BioGRID; 35601; 239.
DR DIP; DIP-6287N; -.
DR IntAct; P13134; 15.
DR MINT; P13134; -.
DR STRING; 4932.YNL238W; -.
DR MEROPS; S08.070; -.
DR iPTMnet; P13134; -.
DR MaxQB; P13134; -.
DR PaxDb; P13134; -.
DR PRIDE; P13134; -.
DR EnsemblFungi; YNL238W_mRNA; YNL238W; YNL238W.
DR GeneID; 855483; -.
DR KEGG; sce:YNL238W; -.
DR SGD; S000005182; KEX2.
DR VEuPathDB; FungiDB:YNL238W; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000167869; -.
DR HOGENOM; CLU_002976_2_1_1; -.
DR InParanoid; P13134; -.
DR OMA; AYEFDII; -.
DR BioCyc; YEAST:YNL238W-MON; -.
DR BRENDA; 3.4.21.61; 984.
DR EvolutionaryTrace; P13134; -.
DR PRO; PR:P13134; -.
DR Proteomes; UP000002311; Chromosome XIV.
DR RNAct; P13134; protein.
DR GO; GO:0000324; C:fungal-type vacuole; HDA:SGD.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:SGD.
DR GO; GO:0007323; P:peptide pheromone maturation; IMP:SGD.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR CDD; cd04059; Peptidases_S8_Protein_convertases_Kexins_Furin-like; 1.
DR Gene3D; 3.40.50.200; -; 1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR034182; Kexin/furin.
DR InterPro; IPR002884; P_dom.
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 Pfam; PF01483; P_proprotein; 1.
DR Pfam; PF00082; Peptidase_S8; 1.
DR PRINTS; PR00723; SUBTILISIN.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF52743; SSF52743; 1.
DR PROSITE; PS51829; P_HOMO_B; 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 3D-structure; Calcium; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Hydrolase; Membrane; Metal-binding;
KW Protease; Reference proteome; Serine protease; Signal; Transmembrane;
KW Transmembrane helix; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..109
FT /id="PRO_0000027043"
FT PROPEP 110..113
FT /note="Removed by dipeptidylpeptidase STE13"
FT /id="PRO_0000027044"
FT CHAIN 114..814
FT /note="Kexin"
FT /id="PRO_0000027045"
FT TOPO_DOM 114..678
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 679..699
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 700..814
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 141..453
FT /note="Peptidase S8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT DOMAIN 462..596
FT /note="P/Homo B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01173"
FT REGION 651..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 756..814
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 756..782
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 790..814
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 213
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT ACT_SITE 385
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01240"
FT BINDING 135
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 227
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 277
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 320
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 350
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 404
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 230..377
FT DISULFID 322..352
FT HELIX 123..130
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 157..161
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 183..188
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 209..212
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 213..222
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 225..230
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 234..237
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 238..244
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:1R64"
FT HELIX 252..258
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 259..265
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 287..303
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 333..339
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 355..360
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 384..401
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 407..417
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 425..427
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 433..439
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 440..442
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 449..456
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 465..469
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 486..492
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 494..499
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 502..518
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 522..527
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 533..537
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 549..557
FT /evidence="ECO:0007829|PDB:2ID4"
FT TURN 558..561
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 566..576
FT /evidence="ECO:0007829|PDB:2ID4"
FT STRAND 581..595
FT /evidence="ECO:0007829|PDB:2ID4"
FT HELIX 597..599
FT /evidence="ECO:0007829|PDB:2ID4"
SQ SEQUENCE 814 AA; 90003 MW; 5DCEEDADCF439C78 CRC64;
MKVRKYITLC FWWAFSTSAL VSSQQIPLKD HTSRQYFAVE SNETLSRLEE MHPNWKYEHD
VRGLPNHYVF SKELLKLGKR SSLEELQGDN NDHILSVHDL FPRNDLFKRL PVPAPPMDSS
LLPVKEAEDK LSINDPLFER QWHLVNPSFP GSDINVLDLW YNNITGAGVV AAIVDDGLDY
ENEDLKDNFC AEGSWDFNDN TNLPKPRLSD DYHGTRCAGE IAAKKGNNFC GVGVGYNAKI
SGIRILSGDI TTEDEAASLI YGLDVNDIYS CSWGPADDGR HLQGPSDLVK KALVKGVTEG
RDSKGAIYVF ASGNGGTRGD NCNYDGYTNS IYSITIGAID HKDLHPPYSE GCSAVMAVTY
SSGSGEYIHS SDINGRCSNS HGGTSAAAPL AAGVYTLLLE ANPNLTWRDV QYLSILSAVG
LEKNADGDWR DSAMGKKYSH RYGFGKIDAH KLIEMSKTWE NVNAQTWFYL PTLYVSQSTN
STEETLESVI TISEKSLQDA NFKRIEHVTV TVDIDTEIRG TTTVDLISPA GIISNLGVVR
PRDVSSEGFK DWTFMSVAHW GENGVGDWKI KVKTTENGHR IDFHSWRLKL FGESIDSSKT
ETFVFGNDKE EVEPAATEST VSQYSASSTS ISISATSTSS ISIGVETSAI PQTTTASTDP
DSDPNTPKKL SSPRQAMHYF LTIFLIGATF LVLYFMFFMK SRRRIRRSRA ETYEFDIIDT
DSEYDSTLDN GTSGITEPEE VEDFDFDLSD EDHLASLSSS ENGDAEHTID SVLTNENPFS
DPIKQKFPND ANAESASNKL QELQPDVPPS SGRS
