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Protein

Vacuolar aminopeptidase 1

Gene

APE1

Organism
Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Resident vacuolar enzyme that catalyzes the removal of amino acids from the N-terminus of peptides and proteins. Also acts as the major cargo protein of the cytoplasm-to-vacuole targeting (Cvt) pathway. The precursor form of aminopeptidase 1 (prApe1) assembles into dodecamers and the propeptide mediates the aggregation of dodecamers into higher multimers. The multimers are then recognized via the propeptide by their receptor ATG19, and ATG19 further interacts with ATG11, which tethers the APE1-ATG19 complex to the pre-autophagosomal structure (PAS). The cargo-receptor complex (also Cvt complex) is selectively enwrapped by a double-membrane structure termed the Cvt vesicle under vegetative growth conditions and by a similar but larger double-membrane structure termed the autophagosome under nitrogen starvation conditions. The Cvt vesicle or the autophagosome fuses with the vacuolar membrane and release its content in the vacuolar lumen. In the vacuole, prApe1 is processed into mature aminopeptidase 1 (mApe1).8 Publications

Catalytic activityi

Release of an N-terminal amino acid, preferably a neutral or hydrophobic one, from a polypeptide. Aminoacyl-arylamides are poor substrates.5 Publications

Cofactori

Zn2+By similarity5 PublicationsNote: Binds 2 Zn2+ ions per subunit. The average amount of Zn2+ bound at physiological metal concentrations will be lower than stoichiometric.By similarity5 Publications

Enzyme regulationi

Strongly and specifically activated by Cl- and Br-, which act as positive allosteric effectors. Inactivated by metal-chelating agents.3 Publications

pH dependencei

Optimum pH is 7-8.5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi132Zinc 1By similarity1
Binding sitei210SubstrateBy similarity1
Metal bindingi303Zinc 1By similarity1
Metal bindingi303Zinc 2By similarity1
Binding sitei339SubstrateBy similarity1
Metal bindingi340Zinc 2By similarity1
Metal bindingi385Zinc 1By similarity1
Binding sitei385SubstrateBy similarity1
Binding sitei388SubstrateBy similarity1
Metal bindingi479Zinc 2By similarity1

GO - Molecular functioni

  • metalloaminopeptidase activity Source: SGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • peptide metabolic process Source: GO_Central
  • protein catabolic process in the vacuole Source: SGD
  • protein transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Aminopeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciYEAST:YKL103C-MONOMER.
BRENDAi3.4.11.22. 984.

Protein family/group databases

MEROPSiM18.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Vacuolar aminopeptidase 11 Publication (EC:3.4.11.225 Publications)
Alternative name(s):
Aminopeptidase yscI1 Publication
Leucine aminopeptidase IV1 Publication
Short name:
LAPIV1 Publication
Lysosomal aminopeptidase III1 Publication
Polypeptidase1 Publication
Vacuolar aminopeptidase I1 Publication
Gene namesi
Name:APE11 Publication
Synonyms:API1 Publication, LAP41 Publication, YSC11 Publication
Ordered Locus Names:YKL103CImported
ORF Names:YKL455
OrganismiSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Taxonomic identifieri559292 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces
Proteomesi
  • UP000002311 Componenti: Chromosome XI

Organism-specific databases

EuPathDBiFungiDB:YKL103C.
SGDiS000001586. APE1.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: GO_Central
  • fungal-type vacuole Source: SGD
Complete GO annotation...

Keywords - Cellular componenti

Vacuole

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1741175.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000268061 – 45Required for vacuolar localization. Mediates aggregation and vesicle formation in Cvt pathway3 PublicationsAdd BLAST45
ChainiPRO_000002680746 – 514Vacuolar aminopeptidase 1Add BLAST469

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi107N-linked (GlcNAc...)PROSITE-ProRule annotation1
Glycosylationi110N-linked (GlcNAc...)PROSITE-ProRule annotation1
Modified residuei356PhosphoserineCombined sources1
Glycosylationi448N-linked (GlcNAc...)PROSITE-ProRule annotation1

Post-translational modificationi

Synthesized in a precursor form (prApe1) that has an amino-terminal propeptide. The N-terminal extension of the 61 kDa precursor is proteolytically processed in two sequential steps. The first step involves proteinase A (PrA/PEP4) and produces a 55 kDa unstable intermediate (iAPI). The second step involves proteinase B (PrB/PRB1) and converts iAPI into the 50 kDa stable, mature enzyme (mApe1).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei45 – 46Cleavage; by protease B (PrB/PRB1)1 Publication2

Keywords - PTMi

Glycoprotein, Phosphoprotein, Zymogen

Proteomic databases

MaxQBiP14904.
PRIDEiP14904.

PTM databases

iPTMnetiP14904.

Miscellaneous databases

PMAP-CutDBP14904.

Interactioni

Subunit structurei

Homododecamer. The precursor form of aminopeptidase 1 (prApe1) assembles into dodecamers and further aggregates into higher multimers (the Ape1 complex) in the cytoplasm. The Ape1 complex is disaggregated in the vacuolar lumen, but mature aminopeptidase 1 (mApe1) retains its dodecameric form. Dodecamer assembly in the cytoplasm is essential for formation of an enzymatically active complex. If cytoplasmic homododecamerization of prApe1 is disturbed in mutants, homododecamers of mApe1 will form in the vacuole, but they are enzymatically inactive. Interacts with ATG19.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-2571,EBI-2571

Protein-protein interaction databases

BioGridi34031. 58 interactors.
DIPiDIP-1409N.
IntActiP14904. 31 interactors.
MINTiMINT-387783.

Chemistry databases

BindingDBiP14904.

Structurei

Secondary structure

1514
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1 – 17Combined sources17
Helixi34 – 43Combined sources10
Beta strandi45 – 47Combined sources3
Helixi48 – 62Combined sources15
Helixi66 – 79Combined sources14
Turni92 – 94Combined sources3
Beta strandi100 – 106Combined sources7
Turni107 – 109Combined sources3
Beta strandi110 – 116Combined sources7
Helixi122 – 124Combined sources3
Beta strandi127 – 132Combined sources6
Beta strandi136 – 140Combined sources5
Beta strandi152 – 154Combined sources3
Beta strandi157 – 162Combined sources6
Helixi166 – 168Combined sources3
Beta strandi173 – 181Combined sources9
Beta strandi190 – 195Combined sources6
Helixi209 – 211Combined sources3
Helixi213 – 215Combined sources3
Turni221 – 224Combined sources4
Beta strandi228 – 230Combined sources3
Helixi246 – 248Combined sources3
Turni250 – 254Combined sources5
Helixi257 – 267Combined sources11
Helixi271 – 273Combined sources3
Beta strandi274 – 283Combined sources10
Beta strandi288 – 291Combined sources4
Beta strandi296 – 300Combined sources5
Helixi302 – 319Combined sources18
Turni324 – 326Combined sources3
Beta strandi330 – 337Combined sources8
Helixi339 – 341Combined sources3
Helixi349 – 351Combined sources3
Helixi353 – 365Combined sources13
Helixi372 – 377Combined sources6
Beta strandi380 – 384Combined sources5
Helixi395 – 397Combined sources3
Beta strandi411 – 413Combined sources3
Beta strandi418 – 420Combined sources3
Helixi424 – 437Combined sources14
Beta strandi442 – 444Combined sources3
Helixi457 – 464Combined sources8
Beta strandi467 – 472Combined sources6
Beta strandi474 – 477Combined sources4
Beta strandi480 – 486Combined sources7
Helixi489 – 508Combined sources20
Helixi509 – 511Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R8FX-ray2.50A/B/C/D46-514[»]
5JGEX-ray1.91C/F1-20[»]
5JGFX-ray1.83A/B/C/D46-514[»]
5JH9X-ray2.10A/B/C/D1-514[»]
5JHCX-ray3.40A/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/d1-22[»]
5JM9electron microscopy24.00A1-514[»]
ProteinModelPortaliP14904.
SMRiP14904.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase M18 family.Curated

Phylogenomic databases

HOGENOMiHOG000253244.
InParanoidiP14904.
KOiK01268.
OMAiKETQAVP.
OrthoDBiEOG092C3JCE.

Family and domain databases

CDDicd05639. M18. 1 hit.
Gene3Di2.30.250.10. 1 hit.
InterProiIPR033818. Aminopeptidase_I.
IPR001948. Peptidase_M18.
IPR023358. Peptidase_M18_dom2.
[Graphical view]
PfamiPF02127. Peptidase_M18. 1 hit.
[Graphical view]
PRINTSiPR00932. AMINO1PTASE.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P14904-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEEQREILEQ LKKTLQMLTV EPSKNNQIAN EEKEKKENEN SWCILEHNYE
60 70 80 90 100
DIAQEFIDFI YKNPTTYHVV SFFAELLDKH NFKYLSEKSN WQDSIGEDGG
110 120 130 140 150
KFYTIRNGTN LSAFILGKNW RAEKGVGVIG SHVDALTVKL KPVSFKDTAE
160 170 180 190 200
GYGRIAVAPY GGTLNELWLD RDLGIGGRLL YKKKGTNEIK SALVDSTPLP
210 220 230 240 250
VCRIPSLAPH FGKPAEGPFD KEDQTIPVIG FPTPDEEGNE PPTDDEKKSP
260 270 280 290 300
LFGKHCIHLL RYVAKLAGVE VSELIQMDLD LFDVQKGTIG GIGKHFLFAP
310 320 330 340 350
RLDDRLCSFA AMIALICYAK DVNTEESDLF STVTLYDNEE IGSLTRQGAK
360 370 380 390 400
GGLLESVVER SSSAFTKKPV DLHTVWANSI ILSADVNHLY NPNFPEVYLK
410 420 430 440 450
NHFPVPNVGI TLSLDPNGHM ATDVVGTALV EELARRNGDK VQYFQIKNNS
460 470 480 490 500
RSGGTIGPSL ASQTGARTID LGIAQLSMHS IRAATGSKDV GLGVKFFNGF
510
FKHWRSVYDE FGEL
Length:514
Mass (Da):57,093
Last modified:February 1, 1994 - v2
Checksum:i702A8C88A2124C24
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti233T → S in CAA68815 (PubMed:2689224).Curated1
Sequence conflicti323N → D in CAA68815 (PubMed:2689224).Curated1
Sequence conflicti328D → E in CAA68815 (PubMed:2689224).Curated1
Sequence conflicti369P → A in CAA68815 (PubMed:2689224).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07522 Genomic DNA. Translation: CAA68815.1.
M25548 Genomic DNA. Translation: AAA34738.1.
X71133 Genomic DNA. Translation: CAA50454.1.
Z28103 Genomic DNA. Translation: CAA81943.1.
BK006944 Genomic DNA. Translation: DAA09055.1.
PIRiA33879.
RefSeqiNP_012819.1. NM_001179669.1.

Genome annotation databases

EnsemblFungiiYKL103C; YKL103C; YKL103C.
GeneIDi853758.
KEGGisce:YKL103C.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y07522 Genomic DNA. Translation: CAA68815.1.
M25548 Genomic DNA. Translation: AAA34738.1.
X71133 Genomic DNA. Translation: CAA50454.1.
Z28103 Genomic DNA. Translation: CAA81943.1.
BK006944 Genomic DNA. Translation: DAA09055.1.
PIRiA33879.
RefSeqiNP_012819.1. NM_001179669.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R8FX-ray2.50A/B/C/D46-514[»]
5JGEX-ray1.91C/F1-20[»]
5JGFX-ray1.83A/B/C/D46-514[»]
5JH9X-ray2.10A/B/C/D1-514[»]
5JHCX-ray3.40A/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/d1-22[»]
5JM9electron microscopy24.00A1-514[»]
ProteinModelPortaliP14904.
SMRiP14904.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi34031. 58 interactors.
DIPiDIP-1409N.
IntActiP14904. 31 interactors.
MINTiMINT-387783.

Chemistry databases

BindingDBiP14904.
ChEMBLiCHEMBL1741175.

Protein family/group databases

MEROPSiM18.001.

PTM databases

iPTMnetiP14904.

Proteomic databases

MaxQBiP14904.
PRIDEiP14904.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiYKL103C; YKL103C; YKL103C.
GeneIDi853758.
KEGGisce:YKL103C.

Organism-specific databases

EuPathDBiFungiDB:YKL103C.
SGDiS000001586. APE1.

Phylogenomic databases

HOGENOMiHOG000253244.
InParanoidiP14904.
KOiK01268.
OMAiKETQAVP.
OrthoDBiEOG092C3JCE.

Enzyme and pathway databases

BioCyciYEAST:YKL103C-MONOMER.
BRENDAi3.4.11.22. 984.

Miscellaneous databases

PMAP-CutDBP14904.
PROiP14904.

Family and domain databases

CDDicd05639. M18. 1 hit.
Gene3Di2.30.250.10. 1 hit.
InterProiIPR033818. Aminopeptidase_I.
IPR001948. Peptidase_M18.
IPR023358. Peptidase_M18_dom2.
[Graphical view]
PfamiPF02127. Peptidase_M18. 1 hit.
[Graphical view]
PRINTSiPR00932. AMINO1PTASE.
ProtoNetiSearch...

Entry informationi

Entry nameiAMPL_YEAST
AccessioniPrimary (citable) accession number: P14904
Secondary accession number(s): D6VXI5, P22060
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: February 1, 1994
Last modified: November 30, 2016
This is version 160 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Miscellaneous

Present with 5730 molecules/cell in log phase SD medium.1 Publication

Caution

It is unsure whether this protein is glycosylated or not. PubMed:5147 has shown that a preparation of aminopeptidase 1 contains about 12% of conjugated carbohydrate, while PubMed:1400574 could not identify any glycosylation, which is in agreement with the fact that aminopeptidase 1 does not transit through the secretory pathway.2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families
  4. Yeast
    Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD
  5. Yeast chromosome XI
    Yeast (Saccharomyces cerevisiae) chromosome XI: entries and gene names

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.