ID   AMPL_YEAST              Reviewed;         514 AA.
AC   P14904; D6VXI5; P22060;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 2.
DT   02-SEP-2026, entry version 218.
DE   RecName: Full=Vacuolar aminopeptidase 1 {ECO:0000303|PubMed:17329814};
DE            EC=3.4.11.22 {ECO:0000269|PubMed:19185714, ECO:0000269|PubMed:363165, ECO:0000269|PubMed:3890752, ECO:0000269|PubMed:5147, ECO:0000269|PubMed:6352682};
DE   AltName: Full=Aminopeptidase yscI {ECO:0000303|PubMed:3916861};
DE   AltName: Full=Leucine aminopeptidase IV {ECO:0000303|PubMed:6352682};
DE            Short=LAPIV {ECO:0000303|PubMed:6352682};
DE   AltName: Full=Lysosomal aminopeptidase III {ECO:0000303|PubMed:24493041};
DE   AltName: Full=Polypeptidase {ECO:0000303|Ref.6};
DE   AltName: Full=Vacuolar aminopeptidase I {ECO:0000303|PubMed:363165};
DE   Flags: Precursor;
GN   Name=APE1 {ECO:0000303|PubMed:2689224};
GN   Synonyms=API {ECO:0000303|PubMed:2651436}, LAP4
GN   {ECO:0000303|PubMed:6352682}, YSC1 {ECO:0000303|PubMed:2689224};
GN   OrderedLocusNames=YKL103C {ECO:0000312|SGD:S000001586};
GN   ORFNames=YKL455;
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=II-21;
RX   PubMed=2689224; DOI=10.1016/0014-5793(89)81510-8;
RA   Cueva R., Garcia-Alvarez N., Suarez-Rendueles P.;
RT   "Yeast vacuolar aminopeptidase yscI. Isolation and regulation of the APE1
RT   (LAP4) structural gene.";
RL   FEBS Lett. 259:125-129(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 46-63.
RX   PubMed=2651436; DOI=10.1016/s0021-9258(18)83527-x;
RA   Chang Y.-H., Smith J.A.;
RT   "Molecular cloning and sequencing of genomic DNA encoding aminopeptidase I
RT   from Saccharomyces cerevisiae.";
RL   J. Biol. Chem. 264:6979-6983(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8109175; DOI=10.1002/yea.320091113;
RA   Cheret G., Pallier C., Valens M., Daignan-Fornier B., Fukuhara H.,
RA   Bolotin-Fukuhara M., Sor F.;
RT   "The DNA sequence analysis of the HAP4-LAP4 region on chromosome XI of
RT   Saccharomyces cerevisiae suggests the presence of a second aspartate
RT   aminotransferase gene in yeast.";
RL   Yeast 9:1259-1265(1993).
RN   [4]
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   [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   IDENTIFICATION, AND COFACTOR.
RA   Johnson M.J.;
RT   "Isolation and properties of a pure yeast polypeptidase.";
RL   J. Biol. Chem. 137:575-586(1941).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=24493041; DOI=10.1007/bf00397903;
RA   Matile P., Wiemken A., Guyer W.;
RT   "A lysosomal aminopeptidase isozyme in differentiating yeast cells and
RT   protoplasts.";
RL   Planta 96:43-53(1971).
RN   [8]
RP   CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, GLYCOSYLATION,
RP   SUBUNIT, AND ACTIVITY REGULATION.
RX   PubMed=5147; DOI=10.1016/0005-2744(76)90338-7;
RA   Metz G., Roehm K.H.;
RT   "Yeast aminopeptidase I. Chemical composition and catalytic properties.";
RL   Biochim. Biophys. Acta 429:933-949(1976).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=363165; DOI=10.1016/0005-2744(78)90253-x;
RA   Frey J., Roehm K.H.;
RT   "Subcellular localization and levels of aminopeptidases and dipeptidase in
RT   Saccharomyces cerevisiae.";
RL   Biochim. Biophys. Acta 527:31-41(1978).
RN   [10]
RP   CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=6352682; DOI=10.1128/jb.156.1.36-48.1983;
RA   Trumbly R.J., Bradley G.;
RT   "Isolation and characterization of aminopeptidase mutants of Saccharomyces
RT   cerevisiae.";
RL   J. Bacteriol. 156:36-48(1983).
RN   [11]
RP   CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
RX   PubMed=3890752; DOI=10.1016/0003-9861(85)90829-x;
RA   Roehm K.H.;
RT   "Chloride as allosteric effector of yeast aminopeptidase I.";
RL   Arch. Biochem. Biophys. 239:216-225(1985).
RN   [12]
RP   COFACTOR, AND ACTIVITY REGULATION.
RX   PubMed=3882418; DOI=10.1111/j.1432-1033.1985.tb08698.x;
RA   Roehm K.H.;
RT   "Metal binding to yeast aminopeptidase I.";
RL   Eur. J. Biochem. 146:633-639(1985).
RN   [13]
RP   NOMENCLATURE.
RX   PubMed=3916861; DOI=10.1002/yea.320010203;
RA   Achstetter T., Wolf D.H.;
RT   "Proteinases, proteolysis and biological control in the yeast Saccharomyces
RT   cerevisiae.";
RL   Yeast 1:139-157(1985).
RN   [14]
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=1400574; DOI=10.1083/jcb.119.2.287;
RA   Klionsky D.J., Cueva R., Yaver D.S.;
RT   "Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole
RT   independent of the secretory pathway.";
RL   J. Cell Biol. 119:287-299(1992).
RN   [15]
RP   PROTEOLYTIC PROCESSING.
RX   PubMed=8521804; DOI=10.1002/j.1460-2075.1995.tb00234.x;
RA   Segui-Real B., Martinez M., Sandoval I.V.;
RT   "Yeast aminopeptidase I is post-translationally sorted from the cytosol to
RT   the vacuole by a mechanism mediated by its bipartite N-terminal
RT   extension.";
RL   EMBO J. 14:5476-5484(1995).
RN   [16]
RP   SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX   PubMed=8601598; DOI=10.1083/jcb.132.6.999;
RA   Oda M.N., Scott S.V., Hefner-Gravink A., Caffarelli A.D., Klionsky D.J.;
RT   "Identification of a cytoplasm to vacuole targeting determinant in
RT   aminopeptidase I.";
RL   J. Cell Biol. 132:999-1010(1996).
RN   [17]
RP   FUNCTION, AND PROTEOLYTIC PROCESSING.
RX   PubMed=8901576; DOI=10.1073/pnas.93.22.12304;
RA   Scott S.V., Hefner-Gravink A., Morano K.A., Noda T., Ohsumi Y.,
RA   Klionsky D.J.;
RT   "Cytoplasm-to-vacuole targeting and autophagy employ the same machinery to
RT   deliver proteins to the yeast vacuole.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:12304-12308(1996).
RN   [18]
RP   SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=9151668; DOI=10.1083/jcb.137.3.609;
RA   Kim J., Scott S.V., Oda M.N., Klionsky D.J.;
RT   "Transport of a large oligomeric protein by the cytoplasm to vacuole
RT   protein targeting pathway.";
RL   J. Cell Biol. 137:609-618(1997).
RN   [19]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9214379; DOI=10.1083/jcb.138.1.37;
RA   Scott S.V., Baba M., Ohsumi Y., Klionsky D.J.;
RT   "Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular
RT   mechanism.";
RL   J. Cell Biol. 138:37-44(1997).
RN   [20]
RP   FUNCTION.
RX   PubMed=9412464; DOI=10.1083/jcb.139.7.1687;
RA   Baba M., Osumi M., Scott S.V., Klionsky D.J., Ohsumi Y.;
RT   "Two distinct pathways for targeting proteins from the cytoplasm to the
RT   vacuole/lysosome.";
RL   J. Cell Biol. 139:1687-1695(1997).
RN   [21]
RP   SUBUNIT.
RX   PubMed=11152450; DOI=10.1074/jbc.m003846200;
RA   Andrei-Selmer C., Knuppel A., Satyanarayana C., Heese C., Schu P.V.;
RT   "A new class of mutants deficient in dodecamerization of aminopeptidase 1
RT   and vacuolar transport.";
RL   J. Biol. Chem. 276:11606-11614(2001).
RN   [22]
RP   FUNCTION, AND INTERACTION WITH ATG19.
RX   PubMed=11382752; DOI=10.1074/jbc.m101438200;
RA   Leber R., Silles E., Sandoval I.V., Mazon M.J.;
RT   "Yol082p, a novel CVT protein involved in the selective targeting of
RT   aminopeptidase I to the yeast vacuole.";
RL   J. Biol. Chem. 276:29210-29217(2001).
RN   [23]
RP   FUNCTION, AND INTERACTION WITH ATG19.
RX   PubMed=11430817; DOI=10.1016/s1097-2765(01)00263-5;
RA   Scott S.V., Guan J., Hutchins M.U., Kim J., Klionsky D.J.;
RT   "Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway.";
RL   Mol. Cell 7:1131-1141(2001).
RN   [24]
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   [25]
RP   FUNCTION.
RX   PubMed=15138258; DOI=10.1074/jbc.m404399200;
RA   Shintani T., Klionsky D.J.;
RT   "Cargo proteins facilitate the formation of transport vesicles in the
RT   cytoplasm to vacuole targeting pathway.";
RL   J. Biol. Chem. 279:29889-29894(2004).
RN   [26]
RP   CRYSTALLIZATION.
RX   PubMed=17329814; DOI=10.1107/s1744309107005441;
RA   Adachi W., Suzuki N.N., Fujioka Y., Suzuki K., Ohsumi Y., Inagaki F.;
RT   "Crystallization of Saccharomyces cerevisiae aminopeptidase 1, the major
RT   cargo protein of the Cvt pathway.";
RL   Acta Crystallogr. F 63:200-203(2007).
RN   [27]
RP   CATALYTIC ACTIVITY.
RX   PubMed=19185714; DOI=10.1016/s0076-6879(08)03206-0;
RA   Schu P.;
RT   "Aminopeptidase I enzymatic activity.";
RL   Methods Enzymol. 451:67-78(2008).
RN   [28]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356, AND IDENTIFICATION BY
RP   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).
RN   [29]
RP   FUNCTION.
RX   PubMed=22123825; DOI=10.1074/jbc.m111.311696;
RA   Morales Quinones M., Winston J.T., Stromhaug P.E.;
RT   "Propeptide of aminopeptidase 1 protein mediates aggregation and vesicle
RT   formation in cytoplasm-to-vacuole targeting pathway.";
RL   J. Biol. Chem. 287:10121-10133(2012).
RN   [30] {ECO:0007744|PDB:4R8F}
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 46-514.
RX   PubMed=26208681; DOI=10.1080/15548627.2015.1067363;
RA   Su M.Y., Peng W.H., Ho M.R., Su S.C., Chang Y.C., Chen G.C., Chang C.I.;
RT   "Structure of yeast Ape1 and its role in autophagic vesicle formation.";
RL   Autophagy 11:1580-1593(2015).
RN   [31] {ECO:0007744|PDB:5JGE, ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9, ECO:0007744|PDB:5JHC}
RP   X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 46-514 IN COMPLEX WITH ZN(2+).
RX   PubMed=27320913; DOI=10.1016/j.celrep.2016.05.066;
RA   Yamasaki A., Watanabe Y., Adachi W., Suzuki K., Matoba K., Kirisako H.,
RA   Kumeta H., Nakatogawa H., Ohsumi Y., Inagaki F., Noda N.N.;
RT   "Structural basis for receptor-mediated selective autophagy of
RT   aminopeptidase I aggregates.";
RL   Cell Rep. 16:19-27(2016).
RN   [32] {ECO:0007744|PDB:5JM9}
RP   STRUCTURE BY ELECTRON MICROSCOPY (24.00 ANGSTROMS).
RX   PubMed=27266708; DOI=10.15252/embr.201541960;
RA   Bertipaglia C., Schneider S., Jakobi A.J., Tarafder A.K., Bykov Y.S.,
RA   Picco A., Kukulski W., Kosinski J., Hagen W.J., Ravichandran A.C.,
RA   Wilmanns M., Wilmanns M., Kaksonen M., Briggs J.A., Sachse C.;
RT   "Higher-order assemblies of oligomeric cargo receptor complexes form the
RT   membrane scaffold of the Cvt vesicle.";
RL   EMBO Rep. 17:1044-1060(2016).
CC   -!- FUNCTION: Resident vacuolar enzyme that catalyzes the removal of amino
CC       acids from the N-terminus of peptides and proteins. Also acts as the
CC       major cargo protein of the cytoplasm-to-vacuole targeting (Cvt)
CC       pathway. The precursor form of aminopeptidase 1 (prApe1) assembles into
CC       dodecamers and the propeptide mediates the aggregation of dodecamers
CC       into higher multimers. The multimers are then recognized via the
CC       propeptide by their receptor ATG19, and ATG19 further interacts with
CC       ATG11, which tethers the APE1-ATG19 complex to the pre-autophagosomal
CC       structure (PAS). The cargo-receptor complex (also Cvt complex) is
CC       selectively enwrapped by a double-membrane structure termed the Cvt
CC       vesicle under vegetative growth conditions and by a similar but larger
CC       double-membrane structure termed the autophagosome under nitrogen
CC       starvation conditions. The Cvt vesicle or the autophagosome fuses with
CC       the vacuolar membrane and release its content in the vacuolar lumen. In
CC       the vacuole, prApe1 is processed into mature aminopeptidase 1 (mApe1).
CC       {ECO:0000269|PubMed:11382752, ECO:0000269|PubMed:11430817,
CC       ECO:0000269|PubMed:15138258, ECO:0000269|PubMed:22123825,
CC       ECO:0000269|PubMed:363165, ECO:0000269|PubMed:8901576,
CC       ECO:0000269|PubMed:9214379, ECO:0000269|PubMed:9412464}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal amino acid, preferably a neutral or
CC         hydrophobic one, from a polypeptide. Aminoacyl-arylamides are poor
CC         substrates.; EC=3.4.11.22; Evidence={ECO:0000269|PubMed:19185714,
CC         ECO:0000269|PubMed:363165, ECO:0000269|PubMed:3890752,
CC         ECO:0000269|PubMed:5147, ECO:0000269|PubMed:6352682};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:Q9ULA0, ECO:0000269|PubMed:3882418,
CC         ECO:0000269|PubMed:3890752, ECO:0000269|PubMed:5147,
CC         ECO:0000269|PubMed:6352682, ECO:0000269|Ref.6};
CC       Note=Binds 2 Zn(2+) ions per subunit. The average amount of Zn(2+)
CC       bound at physiological metal concentrations will be lower than
CC       stoichiometric. {ECO:0000250|UniProtKB:Q9ULA0,
CC       ECO:0000269|PubMed:3882418, ECO:0000269|PubMed:3890752,
CC       ECO:0000269|PubMed:5147, ECO:0000269|PubMed:6352682,
CC       ECO:0000269|Ref.6};
CC   -!- ACTIVITY REGULATION: Strongly and specifically activated by Cl(-) and
CC       Br(-), which act as positive allosteric effectors. Inactivated by
CC       metal-chelating agents. {ECO:0000269|PubMed:3882418,
CC       ECO:0000269|PubMed:3890752, ECO:0000269|PubMed:5147}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 7-8.5. {ECO:0000269|PubMed:5147};
CC   -!- SUBUNIT: Homododecamer. The precursor form of aminopeptidase 1 (prApe1)
CC       assembles into dodecamers and further aggregates into higher multimers
CC       (the Ape1 complex) in the cytoplasm. The Ape1 complex is disaggregated
CC       in the vacuolar lumen, but mature aminopeptidase 1 (mApe1) retains its
CC       dodecameric form. Dodecamer assembly in the cytoplasm is essential for
CC       formation of an enzymatically active complex. If cytoplasmic
CC       homododecamerization of prApe1 is disturbed in mutants, homododecamers
CC       of mApe1 will form in the vacuole, but they are enzymatically inactive.
CC       Interacts with ATG19. {ECO:0000269|PubMed:11152450,
CC       ECO:0000269|PubMed:11382752, ECO:0000269|PubMed:11430817,
CC       ECO:0000269|PubMed:5147, ECO:0000269|PubMed:9151668}.
CC   -!- INTERACTION:
CC       P14904; P22855: AMS1; NbExp=3; IntAct=EBI-2571, EBI-10398;
CC       P14904; P14904: APE1; NbExp=3; IntAct=EBI-2571, EBI-2571;
CC       P14904; P35193: ATG19; NbExp=4; IntAct=EBI-2571, EBI-29291;
CC   -!- SUBCELLULAR LOCATION: Vacuole {ECO:0000269|PubMed:24493041,
CC       ECO:0000269|PubMed:363165, ECO:0000269|PubMed:8601598}.
CC       Note=Transported to the vacuole by the cytosol-to-vacuole targeting
CC       (Cvt) pathway. {ECO:0000269|PubMed:9151668, ECO:0000269|PubMed:9214379,
CC       ECO:0000269|PubMed:9412464}.
CC   -!- PTM: Synthesized in a precursor form (prApe1) that has an amino-
CC       terminal propeptide. The N-terminal extension of the 61 kDa precursor
CC       is proteolytically processed in two sequential steps. The first step
CC       involves proteinase A (PrA/PEP4) and produces a 55 kDa unstable
CC       intermediate (iAPI). The second step involves proteinase B (PrB/PRB1)
CC       and converts iAPI into the 50 kDa stable, mature enzyme (mApe1).
CC       {ECO:0000269|PubMed:8521804}.
CC   -!- MISCELLANEOUS: Present with 5730 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the peptidase M18 family. {ECO:0000305}.
CC   -!- CAUTION: It is unsure whether this protein is glycosylated or not.
CC       PubMed:5147 has shown that a preparation of aminopeptidase 1 contains
CC       about 12% of conjugated carbohydrate, while PubMed:1400574 could not
CC       identify any glycosylation, which is in agreement with the fact that
CC       aminopeptidase 1 does not transit through the secretory pathway.
CC       {ECO:0000305|PubMed:1400574, ECO:0000305|PubMed:5147}.
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DR   EMBL; Y07522; CAA68815.1; -; Genomic_DNA.
DR   EMBL; M25548; AAA34738.1; -; Genomic_DNA.
DR   EMBL; X71133; CAA50454.1; -; Genomic_DNA.
DR   EMBL; Z28103; CAA81943.1; -; Genomic_DNA.
DR   EMBL; BK006944; DAA09055.1; -; Genomic_DNA.
DR   PIR; A33879; A33879.
DR   RefSeq; NP_012819.1; NM_001179669.1.
DR   PDB; 4R8F; X-ray; 2.50 A; A/B/C/D=46-514.
DR   PDB; 5JGE; X-ray; 1.91 A; C/F=1-20.
DR   PDB; 5JGF; X-ray; 1.83 A; A/B/C/D=46-514.
DR   PDB; 5JH9; X-ray; 2.10 A; A/B/C/D=1-514.
DR   PDB; 5JHC; X-ray; 3.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=1-22.
DR   PDB; 5JM9; EM; 24.00 A; A=1-514.
DR   AlphaFoldDB; P14904; -.
DR   EMDB; EMD-8167; -.
DR   SMR; P14904; -.
DR   BioGRID; 34031; 93.
DR   DIP; DIP-1409N; -.
DR   FunCoup; P14904; 312.
DR   IntAct; P14904; 79.
DR   MINT; P14904; -.
DR   STRING; 4932.YKL103C; -.
DR   BindingDB; P14904; -.
DR   ChEMBL; CHEMBL1741175; -.
DR   MEROPS; M18.001; -.
DR   CarbonylDB; P14904; -.
DR   GlyCosmos; P14904; 3 sites, No reported glycans.
DR   GlyGen; P14904; 3 sites.
DR   iPTMnet; P14904; -.
DR   PaxDb; 4932-YKL103C; -.
DR   PeptideAtlas; P14904; -.
DR   EnsemblFungi; YKL103C_mRNA; YKL103C; YKL103C.
DR   GeneID; 853758; -.
DR   KEGG; sce:YKL103C; -.
DR   AGR; SGD:S000001586; -.
DR   SGD; S000001586; APE1.
DR   VEuPathDB; FungiDB:YKL103C; -.
DR   eggNOG; KOG2596; Eukaryota.
DR   HOGENOM; CLU_019532_3_0_1; -.
DR   InParanoid; P14904; -.
DR   OMA; DWPIAKI; -.
DR   OrthoDB; 9880441at2759; -.
DR   BioCyc; YEAST:YKL103C-MONOMER; -.
DR   BRENDA; 3.4.11.22; 984.
DR   BioGRID-ORCS; 853758; 0 hits in 10 CRISPR screens.
DR   CD-CODE; 00C0C35B; Synthetic Condensate 000282.
DR   CD-CODE; 35D5A3ED; Synthetic Condensate 000344.
DR   CD-CODE; 6697AF75; Synthetic Condensate 000332.
DR   CD-CODE; 67785C55; Hypersomatic shock foci.
DR   EvolutionaryTrace; P14904; -.
DR   PRO; PR:P14904; -.
DR   Proteomes; UP000002311; Chromosome XI.
DR   RNAct; P14904; protein.
DR   GO; GO:0034270; C:Cvt complex; IDA:SGD.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0000324; C:fungal-type vacuole; IDA:SGD.
DR   GO; GO:0005773; C:vacuole; EXP:UniProtKB.
DR   GO; GO:0004177; F:aminopeptidase activity; EXP:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IDA:SGD.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0032258; P:cytoplasm to vacuole targeting by the Cvt pathway; IMP:SGD.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   CDD; cd05639; M18; 1.
DR   FunFam; 2.30.250.10:FF:000001; Aspartyl aminopeptidase 1; 1.
DR   Gene3D; 2.30.250.10; Aminopeptidase i, Domain 2; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 1.
DR   InterPro; IPR001948; Peptidase_M18.
DR   InterPro; IPR023358; Peptidase_M18_dom2.
DR   PANTHER; PTHR28570; ASPARTYL AMINOPEPTIDASE; 1.
DR   PANTHER; PTHR28570:SF4; VACUOLAR AMINOPEPTIDASE 1; 1.
DR   Pfam; PF02127; Peptidase_M18; 1.
DR   PRINTS; PR00932; AMINO1PTASE.
DR   SUPFAM; SSF101821; Aminopeptidase/glucanase lid domain; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PDBsum; 4R8F; -.
DR   PDBsum; 5JGE; -.
DR   PDBsum; 5JGF; -.
DR   PDBsum; 5JH9; -.
DR   PDBsum; 5JHC; -.
DR   PDBsum; 5JM9; -.
PE   1: Evidence at protein level;
KW   3D-structure; Aminopeptidase; Direct protein sequencing; Glycoprotein;
KW   Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW   Protein transport; Reference proteome; Transport; Vacuole; Zinc; Zymogen.
FT   PROPEP          1..45
FT                   /note="Required for vacuolar localization. Mediates
FT                   aggregation and vesicle formation in Cvt pathway"
FT                   /evidence="ECO:0000269|PubMed:2651436,
FT                   ECO:0000269|PubMed:8521804, ECO:0000269|PubMed:8601598"
FT                   /id="PRO_0000026806"
FT   CHAIN           46..514
FT                   /note="Vacuolar aminopeptidase 1"
FT                   /id="PRO_0000026807"
FT   BINDING         132
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         210
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ULA0"
FT   BINDING         303
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         303
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         339
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ULA0"
FT   BINDING         339
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         339
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:5JGF"
FT   BINDING         340
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5JGF"
FT   BINDING         340
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         385
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ULA0"
FT   BINDING         385
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   BINDING         388
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ULA0"
FT   BINDING         479
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0007744|PDB:5JGF, ECO:0007744|PDB:5JH9"
FT   SITE            45..46
FT                   /note="Cleavage; by protease B (PrB/PRB1)"
FT                   /evidence="ECO:0000269|PubMed:1400574"
FT   MOD_RES         356
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   CARBOHYD        107
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        110
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CONFLICT        233
FT                   /note="T -> S (in Ref. 1; CAA68815)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        323
FT                   /note="N -> D (in Ref. 1; CAA68815)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        328
FT                   /note="D -> E (in Ref. 1; CAA68815)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        369
FT                   /note="P -> A (in Ref. 1; CAA68815)"
FT                   /evidence="ECO:0000305"
FT   HELIX           1..17
FT                   /evidence="ECO:0007829|PDB:5JGE"
FT   HELIX           34..43
FT                   /evidence="ECO:0007829|PDB:5JH9"
FT   STRAND          45..47
FT                   /evidence="ECO:0007829|PDB:5JH9"
FT   HELIX           48..62
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           66..79
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   TURN            92..94
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          100..106
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   TURN            107..109
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          110..116
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           122..124
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          127..132
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          136..140
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          157..162
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           166..168
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          173..181
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          190..195
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           205..208
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           209..211
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           213..215
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   TURN            221..224
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          228..230
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           241..243
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           246..248
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   TURN            250..254
FT                   /evidence="ECO:0007829|PDB:4R8F"
FT   HELIX           257..267
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           271..273
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          274..283
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           285..287
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          288..291
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          296..300
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           302..319
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   TURN            324..326
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          330..337
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           339..341
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           349..351
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           353..365
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           372..377
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          380..384
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           395..397
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          411..413
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          418..420
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           424..437
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          442..444
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           457..464
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          467..472
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          474..477
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   STRAND          480..486
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           489..508
FT                   /evidence="ECO:0007829|PDB:5JGF"
FT   HELIX           509..511
FT                   /evidence="ECO:0007829|PDB:5JH9"
SQ   SEQUENCE   514 AA;  57093 MW;  702A8C88A2124C24 CRC64;
     MEEQREILEQ LKKTLQMLTV EPSKNNQIAN EEKEKKENEN SWCILEHNYE DIAQEFIDFI
     YKNPTTYHVV SFFAELLDKH NFKYLSEKSN WQDSIGEDGG KFYTIRNGTN LSAFILGKNW
     RAEKGVGVIG SHVDALTVKL KPVSFKDTAE GYGRIAVAPY GGTLNELWLD RDLGIGGRLL
     YKKKGTNEIK SALVDSTPLP VCRIPSLAPH FGKPAEGPFD KEDQTIPVIG FPTPDEEGNE
     PPTDDEKKSP LFGKHCIHLL RYVAKLAGVE VSELIQMDLD LFDVQKGTIG GIGKHFLFAP
     RLDDRLCSFA AMIALICYAK DVNTEESDLF STVTLYDNEE IGSLTRQGAK GGLLESVVER
     SSSAFTKKPV DLHTVWANSI ILSADVNHLY NPNFPEVYLK NHFPVPNVGI TLSLDPNGHM
     ATDVVGTALV EELARRNGDK VQYFQIKNNS RSGGTIGPSL ASQTGARTID LGIAQLSMHS
     IRAATGSKDV GLGVKFFNGF FKHWRSVYDE FGEL
//