AMPL_PIG
ID AMPL_PIG Reviewed; 519 AA.
AC P28839; I3LD43;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 2.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Cytosol aminopeptidase {ECO:0000305};
DE EC=3.4.11.1 {ECO:0000250|UniProtKB:P00727};
DE AltName: Full=Cysteinylglycine-S-conjugate dipeptidase {ECO:0000250|UniProtKB:P00727};
DE EC=3.4.13.23 {ECO:0000250|UniProtKB:P00727};
DE AltName: Full=Leucine aminopeptidase 3 {ECO:0000250|UniProtKB:P28838};
DE Short=LAP-3;
DE AltName: Full=Leucyl aminopeptidase {ECO:0000250|UniProtKB:P00727};
DE AltName: Full=Proline aminopeptidase {ECO:0000305|PubMed:1908238};
DE EC=3.4.11.5 {ECO:0000305|PubMed:1908238};
DE AltName: Full=Prolyl aminopeptidase {ECO:0000250|UniProtKB:P28838};
GN Name=LAP3 {ECO:0000250|UniProtKB:P28838};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc;
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 33-68, AND CATALYTIC ACTIVITY.
RC TISSUE=Intestine, and Kidney;
RX PubMed=1908238; DOI=10.1016/0006-291x(91)91057-j;
RA Matsushima M., Takahashi T., Ichinose M., Miki K., Kurokawa K.,
RA Takahashi K.;
RT "Structural and immunological evidence for the identity of prolyl
RT aminopeptidase with leucyl aminopeptidase.";
RL Biochem. Biophys. Res. Commun. 178:1459-1464(1991).
CC -!- FUNCTION: Cytosolic metallopeptidase that catalyzes the removal of
CC unsubstituted N-terminal hydrophobic amino acids from various peptides.
CC The presence of Zn(2+) ions is essential for the peptidase activity,
CC and the association with other cofactors can modulate the substrate
CC spectificity of the enzyme. For instance, in the presence of Mn(2+), it
CC displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-
CC conjugates. Involved in the metabolism of glutathione and in the
CC degradation of glutathione S-conjugates, which may play a role in the
CC control of the cell redox status. {ECO:0000250|UniProtKB:P00727}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of an N-terminal amino acid, Xaa-|-Yaa-, in which Xaa
CC is preferably Leu, but may be other amino acids including Pro
CC although not Arg or Lys, and Yaa may be Pro. Amino acid amides and
CC methyl esters are also readily hydrolyzed, but rates on arylamides
CC are exceedingly low.; EC=3.4.11.1;
CC Evidence={ECO:0000305|PubMed:1908238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted L-cysteinylglycine + H2O = an S-substituted
CC L-cysteine + glycine; Xref=Rhea:RHEA:60444, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:58717, ChEBI:CHEBI:143103;
CC EC=3.4.13.23; Evidence={ECO:0000250|UniProtKB:P00727};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60445;
CC Evidence={ECO:0000250|UniProtKB:P00727};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-cysteinylglycine = glycine + L-cysteine;
CC Xref=Rhea:RHEA:28783, ChEBI:CHEBI:15377, ChEBI:CHEBI:35235,
CC ChEBI:CHEBI:57305, ChEBI:CHEBI:61694;
CC Evidence={ECO:0000250|UniProtKB:P00727};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28784;
CC Evidence={ECO:0000250|UniProtKB:P00727};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-benzyl-L-cysteinylglycine = glycine + S-benzyl-L-
CC cysteine; Xref=Rhea:RHEA:62568, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:145802, ChEBI:CHEBI:145803;
CC Evidence={ECO:0000250|UniProtKB:Q68FS4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62569;
CC Evidence={ECO:0000250|UniProtKB:Q68FS4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal proline from a peptide.; EC=3.4.11.5;
CC Evidence={ECO:0000305|PubMed:1908238};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P00727};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P00727};
CC Note=Binds two metal ions per subunit. Two metal binding sites with
CC different affinities are located in the enzyme active site and can be
CC occupied in vitro by different metals: site 1 is occupied by Zn(2+),
CC Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be
CC occupied by only Zn(2+) or Co(2+). One Zn(2+) ion is tightly bound to
CC site 2 and essential for enzyme activity in vivo, while site 1 can be
CC occupied by different metals to give different enzymatic activities.
CC Mn(2+) is required for Cys-Gly hydrolysis activity. A third metal
CC binding site may serve a structural role, possibly stabilizing part of
CC the interface between the N-terminal and the catalytic domain.
CC {ECO:0000250|UniProtKB:P00727};
CC -!- SUBUNIT: Homohexamer. {ECO:0000250|UniProtKB:P00727}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q68FS4}.
CC -!- SIMILARITY: Belongs to the peptidase M17 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/LAPC/";
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DR EMBL; AEMK02000064; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; PT0430; PT0430.
DR RefSeq; XP_005666604.2; XM_005666547.2.
DR AlphaFoldDB; P28839; -.
DR SMR; P28839; -.
DR IntAct; P28839; 1.
DR MINT; P28839; -.
DR STRING; 9823.ENSSSCP00000021972; -.
DR ChEMBL; CHEMBL5624; -.
DR DrugCentral; P28839; -.
DR MEROPS; M17.001; -.
DR PaxDb; P28839; -.
DR PeptideAtlas; P28839; -.
DR Ensembl; ENSSSCT00000027356; ENSSSCP00000021972; ENSSSCG00000023604.
DR Ensembl; ENSSSCT00025106731; ENSSSCP00025047982; ENSSSCG00025076934.
DR Ensembl; ENSSSCT00035091598; ENSSSCP00035038416; ENSSSCG00035067851.
DR Ensembl; ENSSSCT00040035908; ENSSSCP00040014877; ENSSSCG00040026831.
DR Ensembl; ENSSSCT00055060655; ENSSSCP00055048599; ENSSSCG00055030467.
DR Ensembl; ENSSSCT00060016457; ENSSSCP00060006509; ENSSSCG00060012541.
DR Ensembl; ENSSSCT00065043816; ENSSSCP00065018655; ENSSSCG00065032265.
DR VGNC; VGNC:89635; LAP3.
DR eggNOG; KOG2597; Eukaryota.
DR GeneTree; ENSGT00530000063255; -.
DR HOGENOM; CLU_013734_1_1_1; -.
DR OMA; MKNTGPR; -.
DR SABIO-RK; P28839; -.
DR Proteomes; UP000008227; Chromosome 8.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000023604; Expressed in adult mammalian kidney and 45 other tissues.
DR ExpressionAtlas; P28839; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:RHEA.
DR GO; GO:0030145; F:manganese ion binding; IEA:InterPro.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00433; Peptidase_M17; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR HAMAP; MF_00181; Cytosol_peptidase_M17; 1.
DR InterPro; IPR011356; Leucine_aapep/pepB.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR000819; Peptidase_M17_C.
DR InterPro; IPR023042; Peptidase_M17_leu_NH2_pept.
DR InterPro; IPR008283; Peptidase_M17_N.
DR PANTHER; PTHR11963; PTHR11963; 1.
DR Pfam; PF00883; Peptidase_M17; 1.
DR Pfam; PF02789; Peptidase_M17_N; 1.
DR PRINTS; PR00481; LAMNOPPTDASE.
DR SUPFAM; SSF52949; SSF52949; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminopeptidase; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Manganese; Metal-binding; Phosphoprotein; Protease;
KW Reference proteome; Zinc.
FT CHAIN 1..519
FT /note="Cytosol aminopeptidase"
FT /id="PRO_0000165827"
FT ACT_SITE 294
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT ACT_SITE 368
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 205
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 282
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 287
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 287
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 292
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 294
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 303
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /ligand_note="structural"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 305
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 305
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 364
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 364
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 364
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 366
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00727"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FS4"
FT MOD_RES 45
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FS4"
FT MOD_RES 61
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 103
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P28838"
FT MOD_RES 221
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 221
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 455
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 455
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 476
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 489
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT MOD_RES 489
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9CPY7"
FT CONFLICT 62
FT /note="L -> W (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 56047 MW; A24F2494E4246FD1 CRC64;
MFLLPLPAAA RVAVRQLSVR RFWGPGPDAA NMTKGLVLGI YSKEKEDDAP QFTSAGENFD
KLVSGKLREI LNISGPPLKA GKTRTFYGLH EDFSSVVVVG LGKKGAGVDD QENWHEGKEN
IRAAVAAGCR QIQDLEIPSV EVDPCGDAQA AAEGAVLGLY EYDELKQKKK VVVSAKLHGS
GDQEAWQRGV LFASGQNLAR HLMETPANEM TPTRFAEVIE KNLKSASSKT DVHIRPKSWI
EEQEMGSFLS VAKGSEEPPV FLEIHYKGSP DASDPPLVFV GKGITFDSGG ISIKASANMD
LMRADMGGAA TICSTIVSAA KLDLPINLVG LAPLCENMPS GKANKPGDVV RAKNGKTIQV
DNTDAEGRLI LADALCYAHT FNPKVIINAA TLTGAMDIAL GSGATGVFTN SSWLWNKLFE
ASIETGDRVW RMPLFEHYTK QIVDCQLADV NNIGKYRSAG ACTAAAFLKE FVTHPKWAHL
DIAGVMTNKD EVPYLRKGMA GRPTRTLIEF LLRFSQDSA
