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 03-AUG-2022, entry version 98.
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 MEROPS; M17.001; -.
DR PaxDb; Q5XGB9; -.
DR GeneID; 496537; -.
DR KEGG; xtr:496537; -.
DR CTD; 51056; -.
DR Xenbase; XB-GENE-1006711; lap3.
DR eggNOG; KOG2597; Eukaryota.
DR HOGENOM; CLU_013734_1_2_1; -.
DR InParanoid; Q5XGB9; -.
DR OrthoDB; 562530at2759; -.
DR PhylomeDB; Q5XGB9; -.
DR Proteomes; UP000008143; Chromosome 1.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000020343; Expressed in heart and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0008233; F:peptidase activity; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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.
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
