UniProtKB - P00727 (AMPL_BOVIN)
Cytosol aminopeptidase
LAP3
Functioni
Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides (PubMed:14583094, PubMed:16519517).
The presence of Zn2+ ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme (PubMed:16519517).
For instance, in the presence of Mn2+, it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates (PubMed:16519517).
Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status (PubMed:14583094).
2 PublicationsCatalytic activityi
- EC:3.4.13.231 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forwardBy similarity direction.
- Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa is preferably Leu, but may be other amino acids including Pro although not Arg or Lys, and Yaa may be Pro. Amino acid amides and methyl esters are also readily hydrolyzed, but rates on arylamides are exceedingly low.1 Publication EC:3.4.11.1
- Release of N-terminal proline from a peptide.By similarity EC:3.4.11.5
Cofactori
Activity regulationi
Kineticsi
- KM=0.42 mM for Cys-Gly (at pH 6.9 and 25 degrees Celsius)1 Publication
- KM=2.3 mM for Leu-Gly (at pH 6.9 and 25 degrees Celsius)1 Publication
- KM=2.8 mM for Met-Gly (at pH 6.9 and 25 degrees Celsius)1 Publication
- KM=0.57 mM for Cys-Gly (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=2.5 mM for Leu-Gly (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=1.5 mM for Met-Gly (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=5.2 mM for Ser-Gly (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=0.59 mM for Cys-Gly (at pH 8.3 and 25 degrees Celsius)1 Publication
- KM=1.5 mM for Leu-Gly (at pH 8.3 and 25 degrees Celsius)1 Publication
- KM=1.3 mM for Met-Gly (at pH 8.3 and 25 degrees Celsius)1 Publication
- KM=5.0 mM for Ser-Gly (at pH 8.3 and 25 degrees Celsius)1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 202 | Zinc 3; via carbonyl oxygen; structuralCombined sources1 Publication | 1 | |
Metal bindingi | 203 | Zinc 3; via carbonyl oxygen; structuralCombined sources1 Publication | 1 | |
Metal bindingi | 205 | Zinc 3; via carbonyl oxygen; structuralCombined sources1 Publication | 1 | |
Metal bindingi | 282 | Zinc 2; catalyticCombined sources2 Publications | 1 | |
Binding sitei | 282 | SubstrateCombined sources2 Publications | 1 | |
Metal bindingi | 287 | Magnesium; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 287 | Zinc 1; catalyticCombined sources3 Publications | 1 | |
Metal bindingi | 287 | Zinc 2; catalyticCombined sources2 Publications | 1 | |
Binding sitei | 287 | SubstrateCombined sources2 Publications | 1 | |
Binding sitei | 292 | SubstrateCombined sources1 Publication | 1 | |
Active sitei | 294 | 1 Publication | 1 | |
Binding sitei | 294 | SubstrateCombined sources2 Publications | 1 | |
Metal bindingi | 303 | Zinc 3; via carbonyl oxygen; structuralCombined sources1 Publication | 1 | |
Metal bindingi | 305 | Zinc 2; catalyticCombined sources2 Publications | 1 | |
Binding sitei | 305 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 364 | Magnesium; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 364 | Zinc 1; catalyticCombined sources3 Publications | 1 | |
Binding sitei | 364 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 366 | Magnesium; catalyticCombined sources1 Publication | 1 | |
Metal bindingi | 366 | Zinc 1; catalyticCombined sources3 Publications | 1 | |
Metal bindingi | 366 | Zinc 2; catalyticCombined sources3 Publications | 1 | |
Active sitei | 368 | 1 Publication | 1 |
GO - Molecular functioni
- carboxypeptidase activity Source: RHEA
- dipeptidase activity Source: UniProtKB-KW
- disordered domain specific binding Source: CAFA
- manganese ion binding Source: InterPro
- metalloaminopeptidase activity Source: InterPro
- peptidase activity Source: AgBase
Keywordsi
Molecular function | Aminopeptidase, Dipeptidase, Hydrolase, Protease |
Ligand | Cobalt, Magnesium, Manganese, Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.11.1, 908 |
SABIO-RKi | P00727 |
Protein family/group databases
MEROPSi | M17.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytosol aminopeptidaseCurated (EC:3.4.11.11 Publication)Alternative name(s): Cysteinylglycine-S-conjugate dipeptidase1 Publication (EC:3.4.13.231 Publication) Leucine aminopeptidase 3By similarity Short name: LAP-3 Leucyl aminopeptidase1 Publication Short name: LAP1 Publication Peptidase SBy similarity Proline aminopeptidaseBy similarity (EC:3.4.11.5By similarity) Prolyl aminopeptidaseBy similarity |
Gene namesi | Name:LAP3By similarity |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | HostDB:ENSBTAG00000005989 |
VGNCi | VGNC:30786, LAP3 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytosol
- cytosol Source: Ensembl
Mitochondrion
- mitochondrion Source: AgBase
Nucleus
- nucleoplasm Source: Ensembl
Other locations
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
---|---|---|---|---|---|
ChainiPRO_0000165824 | 1 – 519 | Cytosol aminopeptidaseAdd BLAST | 519 | ||
Isoform 3 (identifier: P00727-3) | |||||
Initiator methioninei | Removed5 Publications |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 42 | PhosphoserineBy similarity | 1 | |
Modified residuei | 45 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 54 | PhosphoserineBy similarity | 1 | |
Modified residuei | 61 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 103 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 180 | PhosphoserineBy similarity | 1 | |
Modified residuei | 194 | PhosphoserineBy similarity | 1 | |
Modified residuei | 238 | PhosphoserineBy similarity | 1 | |
Modified residuei | 455 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 455 | N6-succinyllysine; alternateBy similarity | 1 | |
Modified residuei | 476 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 489 | N6-acetyllysine; alternateBy similarity | 1 | |
Modified residuei | 489 | N6-succinyllysine; alternateBy similarity | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
PaxDbi | P00727 |
PeptideAtlasi | P00727 |
PRIDEi | P00727 |
Expressioni
Gene expression databases
Bgeei | ENSBTAG00000005989, Expressed in caput epididymis and 97 other tissues |
Interactioni
Subunit structurei
Homohexamer.
1 PublicationGO - Molecular functioni
- disordered domain specific binding Source: CAFA
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000007860 |
Chemistry databases
BindingDBi | P00727 |
Structurei
Secondary structure
3D structure databases
SMRi | P00727 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P00727 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2597, Eukaryota |
GeneTreei | ENSGT00530000063255 |
InParanoidi | P00727 |
OMAi | MKNTGPR |
OrthoDBi | 562530at2759 |
TreeFami | TF314954 |
Family and domain databases
CDDi | cd00433, Peptidase_M17, 1 hit |
Gene3Di | 3.40.220.10, 1 hit |
HAMAPi | MF_00181, Cytosol_peptidase_M17, 1 hit |
InterProi | View protein in InterPro IPR011356, Leucine_aapep/pepB IPR043472, Macro_dom-like IPR000819, Peptidase_M17_C IPR023042, Peptidase_M17_leu_NH2_pept IPR008283, Peptidase_M17_N |
PANTHERi | PTHR11963, PTHR11963, 1 hit |
Pfami | View protein in Pfam PF00883, Peptidase_M17, 1 hit PF02789, Peptidase_M17_N, 1 hit |
PRINTSi | PR00481, LAMNOPPTDASE |
SUPFAMi | SSF52949, SSF52949, 1 hit |
PROSITEi | View protein in PROSITE PS00631, CYTOSOL_AP, 1 hit |
s (3)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative initiation. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MFLLPLPAAA RVAVRHLSVK RLWAPGPAAA DMTKGLVLGI YSKEKEEDEP
60 70 80 90 100
QFTSAGENFN KLVSGKLREI LNISGPPLKA GKTRTFYGLH EDFPSVVVVG
110 120 130 140 150
LGKKTAGIDE QENWHEGKEN IRAAVAAGCR QIQDLEIPSV EVDPCGDAQA
160 170 180 190 200
AAEGAVLGLY EYDDLKQKRK VVVSAKLHGS EDQEAWQRGV LFASGQNLAR
210 220 230 240 250
RLMETPANEM TPTKFAEIVE ENLKSASIKT DVFIRPKSWI EEQEMGSFLS
260 270 280 290 300
VAKGSEEPPV FLEIHYKGSP NASEPPLVFV GKGITFDSGG ISIKAAANMD
310 320 330 340 350
LMRADMGGAA TICSAIVSAA KLDLPINIVG LAPLCENMPS GKANKPGDVV
360 370 380 390 400
RARNGKTIQV DNTDAEGRLI LADALCYAHT FNPKVIINAA TLTGAMDIAL
410 420 430 440 450
GSGATGVFTN SSWLWNKLFE ASIETGDRVW RMPLFEHYTR QVIDCQLADV
460 470 480 490 500
NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL DIAGVMTNKD EVPYLRKGMA
510
GRPTRTLIEF LFRFSQDSA
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 77 | P → S in AAB28170 (PubMed:8369298).Curated | 1 | |
Sequence conflicti | 414 – 415 | LW → M AA sequence (PubMed:7085616).Curated | 2 | |
Sequence conflicti | 414 – 415 | LW → M AA sequence (PubMed:7085617).Curated | 2 | |
Sequence conflicti | 506 – 513 | Missing AA sequence (PubMed:7085616).Curated | 8 | |
Sequence conflicti | 506 – 513 | Missing AA sequence (PubMed:7085617).Curated | 8 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_058150 | 1 – 31 | Missing in isoform 3. CuratedAdd BLAST | 31 | |
Alternative sequenceiVSP_022634 | 11 – 31 | Missing in isoform 2. 1 PublicationAdd BLAST | 21 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S65367 mRNA Translation: AAB28170.1 Different initiation. BC105385 mRNA Translation: AAI05386.1 AJ871963 Genomic DNA Translation: CAI44744.1 |
PIRi | A54338, APBOL |
RefSeqi | NP_776523.2, NM_174098.3 [P00727-1] |
Genome annotation databases
Ensembli | ENSBTAT00000007860; ENSBTAP00000007860; ENSBTAG00000005989 [P00727-1] |
GeneIDi | 781648 |
KEGGi | bta:781648 |
Keywords - Coding sequence diversityi
Alternative initiationSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S65367 mRNA Translation: AAB28170.1 Different initiation. BC105385 mRNA Translation: AAI05386.1 AJ871963 Genomic DNA Translation: CAI44744.1 |
PIRi | A54338, APBOL |
RefSeqi | NP_776523.2, NM_174098.3 [P00727-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BLL | X-ray | 2.40 | E | 33-519 | [»] | |
1BPM | X-ray | 2.90 | A | 33-519 | [»] | |
1BPN | X-ray | 2.90 | A | 33-519 | [»] | |
1LAM | X-ray | 1.60 | A | 33-516 | [»] | |
1LAN | X-ray | 1.90 | A | 33-516 | [»] | |
1LAP | X-ray | 2.70 | A | 33-519 | [»] | |
1LCP | X-ray | 1.65 | A/B | 33-516 | [»] | |
2EWB | X-ray | 1.85 | A | 33-518 | [»] | |
2J9A | X-ray | 1.73 | A | 33-519 | [»] | |
SMRi | P00727 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000007860 |
Chemistry databases
BindingDBi | P00727 |
ChEMBLi | CHEMBL1671610 |
DrugCentrali | P00727 |
Protein family/group databases
MEROPSi | M17.001 |
Proteomic databases
PaxDbi | P00727 |
PeptideAtlasi | P00727 |
PRIDEi | P00727 |
Genome annotation databases
Ensembli | ENSBTAT00000007860; ENSBTAP00000007860; ENSBTAG00000005989 [P00727-1] |
GeneIDi | 781648 |
KEGGi | bta:781648 |
Organism-specific databases
CTDi | 51056 |
VEuPathDBi | HostDB:ENSBTAG00000005989 |
VGNCi | VGNC:30786, LAP3 |
Phylogenomic databases
eggNOGi | KOG2597, Eukaryota |
GeneTreei | ENSGT00530000063255 |
InParanoidi | P00727 |
OMAi | MKNTGPR |
OrthoDBi | 562530at2759 |
TreeFami | TF314954 |
Enzyme and pathway databases
BRENDAi | 3.4.11.1, 908 |
SABIO-RKi | P00727 |
Miscellaneous databases
EvolutionaryTracei | P00727 |
Gene expression databases
Bgeei | ENSBTAG00000005989, Expressed in caput epididymis and 97 other tissues |
Family and domain databases
CDDi | cd00433, Peptidase_M17, 1 hit |
Gene3Di | 3.40.220.10, 1 hit |
HAMAPi | MF_00181, Cytosol_peptidase_M17, 1 hit |
InterProi | View protein in InterPro IPR011356, Leucine_aapep/pepB IPR043472, Macro_dom-like IPR000819, Peptidase_M17_C IPR023042, Peptidase_M17_leu_NH2_pept IPR008283, Peptidase_M17_N |
PANTHERi | PTHR11963, PTHR11963, 1 hit |
Pfami | View protein in Pfam PF00883, Peptidase_M17, 1 hit PF02789, Peptidase_M17_N, 1 hit |
PRINTSi | PR00481, LAMNOPPTDASE |
SUPFAMi | SSF52949, SSF52949, 1 hit |
PROSITEi | View protein in PROSITE PS00631, CYTOSOL_AP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AMPL_BOVIN | |
Accessioni | P00727Primary (citable) accession number: P00727 Secondary accession number(s): Q2HJH5, Q2PC24 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 23, 2022 | |
This is version 179 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families