ID   APE2_YEAST              Reviewed;         952 AA.
AC   P32454; D6VX41; P36055;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   21-SEP-2011, sequence version 4.
DT   27-MAR-2024, entry version 207.
DE   RecName: Full=Aminopeptidase 2, mitochondrial;
DE            Short=AP-II;
DE            Short=Aminopeptidase II;
DE            EC=3.4.11.-;
DE   AltName: Full=YscII;
DE   Flags: Precursor;
GN   Name=APE2; Synonyms=LAP1; OrderedLocusNames=YKL157W;
GN   ORFNames=YKL158W, YKL611, YKL612;
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].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8091859; DOI=10.1002/yea.320100005;
RA   Vandenbol M., Bolle P.-A., Dion C., Portetelle D., Hilger F.;
RT   "DNA sequencing of a 36.2 kb fragment located between the FAS1 and LAP loci
RT   of chromosome XI of Saccharomyces cerevisiae.";
RL   Yeast 10:S35-S40(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8196765; DOI=10.1038/369371a0;
RA   Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA   Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA   Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA   Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA   Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA   Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA   Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA   Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA   Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA   Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA   Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA   Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA   Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA   Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA   Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA   Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA   Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA   Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA   Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA   van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA   von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA   Becker I., Mewes H.-W.;
RT   "Complete DNA sequence of yeast chromosome XI.";
RL   Nature 369:371-378(1994).
RN   [3]
RP   GENOME REANNOTATION, AND SEQUENCE REVISION TO 935.
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 1-93.
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   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-952.
RC   STRAIN=ATCC 204510 / AB320;
RX   PubMed=1765107; DOI=10.1111/j.1432-1033.1991.tb16461.x;
RA   Garcia-Alvarez N., Cueva R., Suarez-Rendueles P.;
RT   "Molecular cloning of soluble aminopeptidases from Saccharomyces
RT   cerevisiae. Sequence analysis of aminopeptidase yscII, a putative zinc-
RT   metallopeptidase.";
RL   Eur. J. Biochem. 202:993-1002(1991).
RN   [6]
RP   SUBCELLULAR LOCATION.
RX   PubMed=383482; DOI=10.1111/j.1432-1033.1979.tb13099.x;
RA   Frey J., Roehm K.-H.;
RT   "External and internal forms of yeast aminopeptidase II.";
RL   Eur. J. Biochem. 97:169-173(1979).
RN   [7]
RP   IDENTIFICATION OF INTRON.
RX   PubMed=10734188; DOI=10.1093/nar/28.8.1700;
RA   Davis C.A., Grate L., Spingola M., Ares M. Jr.;
RT   "Test of intron predictions reveals novel splice sites, alternatively
RT   spliced mRNAs and new introns in meiotically regulated genes of yeast.";
RL   Nucleic Acids Res. 28:1700-1706(2000).
RN   [8]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 76625 / YPH499;
RX   PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA   Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA   Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA   Pfanner N., Meisinger C.;
RT   "The proteome of Saccharomyces cerevisiae mitochondria.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN   [9]
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   [10]
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   [11]
RP   SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=14597615; DOI=10.1074/jbc.m310160200;
RA   Ohlmeier S., Kastaniotis A.J., Hiltunen J.K., Bergmann U.;
RT   "The yeast mitochondrial proteome, a study of fermentative and respiratory
RT   growth.";
RL   J. Biol. Chem. 279:3956-3979(2004).
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: Involved in the cellular supply of leucine from externally
CC       offered leucine-containing dipeptide substrates.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Periplasm. Cytoplasm. Mitochondrion.
CC   -!- MISCELLANEOUS: Present with 2910 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAS56682.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA45403.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA81496.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA81497.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA81497.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAA81999.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA81999.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=CAA82000.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; Z26877; CAA81496.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; Z26877; CAA81497.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; Z28157; CAA81999.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; Z28158; CAA82000.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AY558356; AAS56682.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; X63998; CAA45403.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; BK006944; DAA09007.2; -; Genomic_DNA.
DR   PIR; S37793; S37793.
DR   PIR; S37794; S37794.
DR   RefSeq; NP_012765.3; NM_001179723.2.
DR   AlphaFoldDB; P32454; -.
DR   SMR; P32454; -.
DR   BioGRID; 33980; 168.
DR   DIP; DIP-4391N; -.
DR   IntAct; P32454; 53.
DR   MINT; P32454; -.
DR   STRING; 4932.YKL157W; -.
DR   MEROPS; M01.006; -.
DR   GlyCosmos; P32454; 2 sites, No reported glycans.
DR   GlyGen; P32454; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P32454; -.
DR   MaxQB; P32454; -.
DR   PaxDb; 4932-YKL157W; -.
DR   PeptideAtlas; P32454; -.
DR   EnsemblFungi; YKL157W_mRNA; YKL157W; YKL157W.
DR   GeneID; 853699; -.
DR   KEGG; sce:YKL157W; -.
DR   AGR; SGD:S000001640; -.
DR   SGD; S000001640; APE2.
DR   VEuPathDB; FungiDB:YKL157W; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   GeneTree; ENSGT00940000155246; -.
DR   HOGENOM; CLU_003705_0_1_1; -.
DR   InParanoid; P32454; -.
DR   OMA; MMEYVAI; -.
DR   OrthoDB; 3085317at2759; -.
DR   BioCyc; YEAST:YKL157W-MONOMER; -.
DR   Reactome; R-SCE-6798695; Neutrophil degranulation.
DR   Reactome; R-SCE-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   Reactome; R-SCE-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR   BioGRID-ORCS; 853699; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P32454; -.
DR   Proteomes; UP000002311; Chromosome XI.
DR   RNAct; P32454; Protein.
DR   GO; GO:0030287; C:cell wall-bounded periplasmic space; IDA:SGD.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IDA:SGD.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0043171; P:peptide catabolic process; IDA:SGD.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   CDD; cd09601; M1_APN-Q_like; 1.
DR   Gene3D; 1.25.50.20; -; 1.
DR   Gene3D; 2.60.40.1910; -; 1.
DR   Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1.
DR   Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 1.
DR   InterPro; IPR045357; Aminopeptidase_N-like_N.
DR   InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR   InterPro; IPR024571; ERAP1-like_C_dom.
DR   InterPro; IPR034016; M1_APN-typ.
DR   InterPro; IPR001930; Peptidase_M1.
DR   InterPro; IPR014782; Peptidase_M1_dom.
DR   InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR   PANTHER; PTHR11533; PROTEASE M1 ZINC METALLOPROTEASE; 1.
DR   PANTHER; PTHR11533:SF174; PUROMYCIN-SENSITIVE AMINOPEPTIDASE-RELATED; 1.
DR   Pfam; PF11838; ERAP1_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   Pfam; PF17900; Peptidase_M1_N; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SUPFAM; SSF63737; Leukotriene A4 hydrolase N-terminal domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   Aminopeptidase; Cytoplasm; Glycoprotein; Hydrolase; Metal-binding;
KW   Metalloprotease; Mitochondrion; Periplasm; Protease; Reference proteome;
KW   Transit peptide; Zinc.
FT   TRANSIT         1..52
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           53..952
FT                   /note="Aminopeptidase 2, mitochondrial"
FT                   /id="PRO_0000095104"
FT   ACT_SITE        397
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         228
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         360..364
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         396
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         400
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         419
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            482
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        381
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        713
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        73
FT                   /note="R -> A (in Ref. 5; CAA45403)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        92..93
FT                   /note="LL -> FI (in Ref. 5; CAA45403)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        255
FT                   /note="D -> V (in Ref. 5; CAA45403)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        533
FT                   /note="D -> E (in Ref. 5; CAA45403)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   952 AA;  107755 MW;  391C068DF4A18C2D CRC64;
     MPIVRWLLLK SAVRGSSLIG KAHPCLRSIA AHPRYLSNVY SPPAGVSRSL RINVMWKQSK
     LTPPRFVKIM NRRPLFTETS HACAKCQKTS QLLNKTPNRE ILPDNVVPLH YDLTVEPDFK
     TFKFEGSVKI ELKINNPAID TVTLNTVDTD IHSAKIGDVT SSEIISEEEQ QVTTFAFPKG
     TMSSFKGNAF LDIKFTGILN DNMAGFYRAK YEDKLTGETK YMATTQMEPT DARRAFPCFD
     EPNLKASFAI TLVSDPSLTH LSNMDVKNEY VKDGKKVTLF NTTPKMSTYL VAFIVAELKY
     VESKNFRIPV RVYATPGNEK HGQFAADLTA KTLAFFEKTF GIQYPLPKMD NVAVHEFSAG
     AMENWGLVTY RVVDLLLDKD NSTLDRIQRV AEVVQHELAH QWFGNLVTMD WWEGLWLNEG
     FATWMSWYSC NEFQPEWKVW EQYVTDTLQH ALSLDSLRSS HPIEVPVKKA DEINQIFDAI
     SYSKGASLLR MISKWLGEET FIKGVSQYLN KFKYGNAKTE DLWDALADAS GKDVRSVMNI
     WTKKVGFPVI SVSEDGNGKI TFRQNRYLST ADVKPDEDKT IYPVFLALKT KNGVDSSVVL
     SERSKTIELE DPTFFKVNSE QSGIYITSYT DERWAKLGQQ ADLLSVEDRV GLVADVKTLS
     ASGYTSTTNF LNLVSKWNNE KSFVVWDQII NSISSMKSTW LFEPKETQDA LDNFTKQLIS
     GMTHHLGWEF KSSDSFSTQR LKVTMFGAAC AARDADVEKA ALKMFTDYCS GNKEAIPALI
     KPIVFNTVAR VGGAENYEKV YKIYLDPISN DEKLAALRSL GRFKEPKLLE RTLGYLFDGT
     VLNQDIYIPM QGMRAHQEGV EALWNWVKKN WDELVKRLPP GLSMLGSVVT LGTSGFTSMQ
     KIDEIKKFFA TKSTKGFDQS LAQSLDTITS KAQWVNRDRD VVNKYLKENG YY
//