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Database: UniProt
Entry: AMPL_XENTR
LinkDB: AMPL_XENTR
Original site: AMPL_XENTR 
ID   AMPL_XENTR              Reviewed;         520 AA.
AC   Q5XGB9;
DT   23-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   27-MAR-2024, entry version 104.
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:0000250|UniProtKB:P28839};
DE            EC=3.4.11.5 {ECO:0000250|UniProtKB:P28839};
DE   AltName: Full=Prolyl aminopeptidase {ECO:0000250|UniProtKB:P28838};
GN   Name=lap3;
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
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:0000250|UniProtKB:P00727};
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:0000250|UniProtKB:P28839};
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}.
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DR   EMBL; BC084523; AAH84523.1; -; mRNA.
DR   RefSeq; NP_001011124.1; NM_001011124.2.
DR   AlphaFoldDB; Q5XGB9; -.
DR   SMR; Q5XGB9; -.
DR   STRING; 8364.ENSXETP00000008235; -.
DR   MEROPS; M17.001; -.
DR   PaxDb; 8364-ENSXETP00000043882; -.
DR   Ensembl; ENSXETT00000043882; ENSXETP00000043882; ENSXETG00000020343.
DR   GeneID; 496537; -.
DR   KEGG; xtr:496537; -.
DR   AGR; Xenbase:XB-GENE-1006711; -.
DR   CTD; 51056; -.
DR   Xenbase; XB-GENE-1006711; lap3.
DR   eggNOG; KOG2597; Eukaryota.
DR   HOGENOM; CLU_013734_1_2_1; -.
DR   InParanoid; Q5XGB9; -.
DR   OMA; MVTMKAD; -.
DR   OrthoDB; 2899215at2759; -.
DR   PhylomeDB; Q5XGB9; -.
DR   Proteomes; UP000008143; Chromosome 1.
DR   Bgee; ENSXETG00000020343; Expressed in heart and 13 other cell types or tissues.
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; Leucine Aminopeptidase, subunit E, domain 1; 1.
DR   Gene3D; 3.40.630.10; Zn peptidases; 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:SF52; CYTOSOL AMINOPEPTIDASE; 1.
DR   PANTHER; PTHR11963; LEUCINE AMINOPEPTIDASE-RELATED; 1.
DR   Pfam; PF00883; Peptidase_M17; 1.
DR   Pfam; PF02789; Peptidase_M17_N; 1.
DR   PRINTS; PR00481; LAMNOPPTDASE.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
DR   PROSITE; PS00631; CYTOSOL_AP; 1.
PE   2: Evidence at transcript level;
KW   Aminopeptidase; Cytoplasm; Hydrolase; Magnesium; Manganese; Metal-binding;
KW   Protease; Reference proteome; Zinc.
FT   CHAIN           1..520
FT                   /note="Cytosol aminopeptidase"
FT                   /id="PRO_0000274147"
FT   ACT_SITE        292
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   ACT_SITE        366
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         200
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         201
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         280
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         280
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         285
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         285
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         285
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         285
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         290
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         292
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         301
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         303
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="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         362
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         362
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         362
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         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="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
FT   BINDING         364
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:P00727"
SQ   SEQUENCE   520 AA;  56333 MW;  33ADD5840F6E7837 CRC64;
     MLPFRTLLKW SVNRNCCRGF AVSQQNYNSV KKGLVLGVYE KEKEEESLTL TNAGDAVDNA
     VLGKLRDQLA RSGPSLKKGK SRIFYGLHED FPSIVVVGLG KKSAGVNQHE LWNEAKENIR
     AAVSVGCRQM QDMEIVQVEV DPCGDAQAAA EGAVLGLFEY NEMKKKKKKA VTTHLHGSSE
     ITAWEKGVLY AEGQNLARHL MEAPANYITP TKFAETFEQR LANMGSNVKV FTRSKQWIEE
     QQMGAFLSVA KGSEEPPVFL EIHYSGSSDA SQPPLVFVGK GVTFDSGGIS LKPSSGMDAM
     RGDMGGAATV CSAITTAAKL KLPINIISLA PLCENMPNGR ANKPGDVVKA KNGKTIQVDN
     TDAEGRLLLA DALCYAHSFN PRAIVNAATL TGAMDVALGS AAAGVFTNSS WLWTHLQEAS
     VVTGDRVWRM PLFEHYSKQV TESALADLNN IGKYSRSGGA CTAAAFLKEF VTAPHWAHLD
     IAGVMSNKDE VPYLRKGMSG RPTRTLIEFA ARLSEDKQTI
//
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