DNPEP_YEAST
ID DNPEP_YEAST Reviewed; 490 AA.
AC P38821; D3DL63;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Aspartyl aminopeptidase 4;
DE EC=3.4.11.21;
GN Name=APE4; OrderedLocusNames=YHR113W;
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=8091229; DOI=10.1126/science.8091229;
RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA Waterston R., Wilson R., Vaudin M.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT VIII.";
RL Science 265:2077-2082(1994).
RN [2]
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 [3]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=11914276; DOI=10.1101/gad.970902;
RA Kumar A., Agarwal S., Heyman J.A., Matson S., Heidtman M., Piccirillo S.,
RA Umansky L., Drawid A., Jansen R., Liu Y., Cheung K.-H., Miller P.,
RA Gerstein M., Roeder G.S., Snyder M.;
RT "Subcellular localization of the yeast proteome.";
RL Genes Dev. 16:707-719(2002).
RN [4]
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 [5]
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=16367759; DOI=10.1111/j.1742-4658.2005.05057.x;
RA Yokoyama R., Kawasaki H., Hirano H.;
RT "Identification of yeast aspartyl aminopeptidase gene by purifying and
RT characterizing its product from yeast cells.";
RL FEBS J. 273:192-198(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17651441; DOI=10.1111/j.1742-4658.2007.05959.x;
RA Sarry J.E., Chen S., Collum R.P., Liang S., Peng M., Lang A., Naumann B.,
RA Dzierszinski F., Yuan C.X., Hippler M., Rea P.A.;
RT "Analysis of the vacuolar luminal proteome of Saccharomyces cerevisiae.";
RL FEBS J. 274:4287-4305(2007).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ATG19.
RX PubMed=21343297; DOI=10.1074/jbc.m110.173906;
RA Yuga M., Gomi K., Klionsky D.J., Shintani T.;
RT "Aspartyl aminopeptidase is imported from the cytoplasm to the vacuole by
RT selective autophagy in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 286:13704-13713(2011).
CC -!- FUNCTION: Aspartyl aminopeptidase that contributes to peptide
CC degradation both in the cytosol and the vacuole. Cells may respond to
CC environmental conditions by changing the distributions of the cytosolic
CC enzyme to the vacuole when cells need more active vacuolar degradation.
CC {ECO:0000269|PubMed:16367759}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal aspartate or glutamate from a
CC peptide, with a preference for aspartate.; EC=3.4.11.21;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: The metalloproteases inhibitors EDTA and 1.10-
CC phenanthroline both inhibit the activity, whereas bestatin, an
CC inhibitor of most aminopeptidases, does not affect enzyme activity.
CC {ECO:0000269|PubMed:16367759}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=64 uM for angiotensin I {ECO:0000269|PubMed:16367759};
CC pH dependence:
CC Optimum pH is 7.5-7.9. {ECO:0000269|PubMed:16367759};
CC -!- SUBUNIT: Tetrahedron-shaped homododecamer built from six homodimers.
CC {ECO:0000269|PubMed:16367759}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21343297}. Vacuole
CC lumen {ECO:0000269|PubMed:17651441, ECO:0000269|PubMed:21343297}.
CC Note=In growing conditions, a small portion localizes in the vacuole,
CC but actively transported to the vacuole under nutrient starvation
CC conditions. {ECO:0000269|PubMed:21343297}.
CC -!- MISCELLANEOUS: Present with 172 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase M18 family. {ECO:0000305}.
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DR EMBL; U00059; AAB68851.1; -; Genomic_DNA.
DR EMBL; BK006934; DAA06807.1; -; Genomic_DNA.
DR PIR; S48955; S48955.
DR RefSeq; NP_011981.1; NM_001179243.1.
DR AlphaFoldDB; P38821; -.
DR SMR; P38821; -.
DR BioGRID; 36546; 64.
DR DIP; DIP-2097N; -.
DR IntAct; P38821; 20.
DR STRING; 4932.YHR113W; -.
DR MaxQB; P38821; -.
DR PaxDb; P38821; -.
DR PRIDE; P38821; -.
DR TopDownProteomics; P38821; -.
DR DNASU; 856513; -.
DR EnsemblFungi; YHR113W_mRNA; YHR113W; YHR113W.
DR GeneID; 856513; -.
DR KEGG; sce:YHR113W; -.
DR SGD; S000001155; APE4.
DR VEuPathDB; FungiDB:YHR113W; -.
DR eggNOG; KOG2596; Eukaryota.
DR HOGENOM; CLU_019532_2_0_1; -.
DR InParanoid; P38821; -.
DR OMA; GPILKVN; -.
DR BioCyc; YEAST:G3O-31155-MON; -.
DR PRO; PR:P38821; -.
DR Proteomes; UP000002311; Chromosome VIII.
DR RNAct; P38821; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0000324; C:fungal-type vacuole; IBA:GO_Central.
DR GO; GO:0000328; C:fungal-type vacuole lumen; IDA:SGD.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:SGD.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IDA:SGD.
DR Gene3D; 2.30.250.10; -; 1.
DR InterPro; IPR001948; Peptidase_M18.
DR InterPro; IPR023358; Peptidase_M18_dom2.
DR PANTHER; PTHR28570; PTHR28570; 1.
DR Pfam; PF02127; Peptidase_M18; 1.
DR PRINTS; PR00932; AMINO1PTASE.
PE 1: Evidence at protein level;
KW Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Vacuole; Zinc.
FT CHAIN 1..490
FT /note="Aspartyl aminopeptidase 4"
FT /id="PRO_0000173455"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 308
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 362
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 362
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 397
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 456
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
SQ SEQUENCE 490 AA; 54174 MW; 511CD6EB85C4EA53 CRC64;
MFRIQLRTMS SKTCKSDYPK EFVSFLNSSH SPYHTVHNIK KHLVSNGFKE LSERDSWAGH
VAQKGKYFVT RNGSSIIAFA VGGKWEPGNP IAITGAHTDS PALRIKPISK RVSEKYLQVG
VETYGGAIWH SWFDKDLGVA GRVFVKDAKT GKSIARLVDL NRPLLKIPTL AIHLDRDVNQ
KFEFNRETQL LPIGGLQEDK TEAKTEKEIN NGEFTSIKTI VQRHHAELLG LIAKELAIDT
IEDIEDFELI LYDHNASTLG GFNDEFVFSG RLDNLTSCFT SMHGLTLAAD TEIDRESGIR
LMACFDHEEI GSSSAQGADS NFLPNILERL SILKGDGSDQ TKPLFHSAIL ETSAKSFFLS
SDVAHAVHPN YANKYESQHK PLLGGGPVIK INANQRYMTN SPGLVLVKRL AEAAKVPLQL
FVVANDSPCG STIGPILASK TGIRTLDLGN PVLSMHSIRE TGGSADLEFQ IKLFKEFFER
YTSIESEIVV
