ID   DPEP1_SHEEP             Reviewed;         410 AA.
AC   P43477;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   08-NOV-2023, entry version 128.
DE   RecName: Full=Dipeptidase 1;
DE            EC=3.4.13.19 {ECO:0000250|UniProtKB:P31428, ECO:0000269|PubMed:8054366};
DE   AltName: Full=Beta-lactamase {ECO:0000305};
DE            EC=3.5.2.6 {ECO:0000250|UniProtKB:P31428};
DE   AltName: Full=Microsomal dipeptidase;
DE   Flags: Precursor;
GN   Name=DPEP1;
OS   Ovis aries (Sheep).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Caprinae; Ovis.
OX   NCBI_TaxID=9940;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-56, FUNCTION, TISSUE
RP   SPECIFICITY, AND CATALYTIC ACTIVITY.
RC   TISSUE=Lung;
RX   PubMed=8054366; DOI=10.1016/0925-4439(94)90046-9;
RA   An S., Schmidt F.J., Campbell B.J.;
RT   "Molecular cloning of sheep lung dipeptidase: a glycosyl
RT   phosphatidylinositol-anchored ectoenzyme that converts leukotriene D4 to
RT   leukotriene E4.";
RL   Biochim. Biophys. Acta 1226:337-340(1994).
CC   -!- FUNCTION: Hydrolyzes a wide range of dipeptides (PubMed:8054366).
CC       Hydrolyzes the conversion of leukotriene D4 to leukotriene E4 (By
CC       similarity). Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed
CC       during glutathione degradation. Possesses also beta lactamase activity
CC       and hydrolytically inactivates beta-lactam antibiotics (By similarity).
CC       {ECO:0000250|UniProtKB:P31428, ECO:0000269|PubMed:8054366}.
CC   -!- FUNCTION: Independently of its dipeptidase activity, acts as an
CC       adhesion receptor for neutrophil recruitment from bloodstream into
CC       inflamed lungs and liver. {ECO:0000250|UniProtKB:P31428}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=an L-aminoacyl-L-amino acid + H2O = 2 an L-alpha-amino acid;
CC         Xref=Rhea:RHEA:48940, ChEBI:CHEBI:15377, ChEBI:CHEBI:59869,
CC         ChEBI:CHEBI:77460; EC=3.4.13.19; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10073, ECO:0000269|PubMed:8054366};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + leukotriene D4 = glycine + leukotriene E4;
CC         Xref=Rhea:RHEA:48616, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305,
CC         ChEBI:CHEBI:57462, ChEBI:CHEBI:63166;
CC         Evidence={ECO:0000250|UniProtKB:P31428};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H2O + L-cystine-bis-glycine = 2 glycine + L-cystine;
CC         Xref=Rhea:RHEA:60520, ChEBI:CHEBI:15377, ChEBI:CHEBI:35491,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:143812;
CC         Evidence={ECO:0000250|UniProtKB:P31428};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a beta-lactam + H2O = a substituted beta-amino acid;
CC         Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627,
CC         ChEBI:CHEBI:140347; EC=3.5.2.6;
CC         Evidence={ECO:0000250|UniProtKB:P31428};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=glycyldehydrophenylalanine + H2O = 2,3-didehydrophenylalanine
CC         + glycine; Xref=Rhea:RHEA:62704, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:57305, ChEBI:CHEBI:145925, ChEBI:CHEBI:145926;
CC         Evidence={ECO:0000269|PubMed:8054366};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P16444, ECO:0000255|PROSITE-
CC         ProRule:PRU10073};
CC   -!- ACTIVITY REGULATION: Inhibited by L-penicillamine. Beta-lactamase
CC       activity is inhibited by cilastatin. {ECO:0000250|UniProtKB:P16444}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P16444}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000250|UniProtKB:P16444}; Lipid-anchor, GPI-anchor
CC       {ECO:0000250|UniProtKB:P16444}. Cell projection, microvillus membrane
CC       {ECO:0000250|UniProtKB:P16444}; Lipid-anchor, GPI-anchor
CC       {ECO:0000250|UniProtKB:P16444}. Note=Brush border membrane.
CC       {ECO:0000250|UniProtKB:P31429}.
CC   -!- TISSUE SPECIFICITY: Expressed in lung, kidney and intestinal tissues.
CC       {ECO:0000269|PubMed:8054366}.
CC   -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC       Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; L27113; AAA21725.1; -; mRNA.
DR   AlphaFoldDB; P43477; -.
DR   SMR; P43477; -.
DR   STRING; 9940.ENSOARP00000015196; -.
DR   MEROPS; M19.001; -.
DR   GlyCosmos; P43477; 3 sites, No reported glycans.
DR   PaxDb; 9940-ENSOARP00000015196; -.
DR   eggNOG; KOG4127; Eukaryota.
DR   Proteomes; UP000002356; Unplaced.
DR   GO; GO:0045177; C:apical part of cell; ISS:UniProtKB.
DR   GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0008800; F:beta-lactamase activity; ISS:UniProtKB.
DR   GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISS:UniProtKB.
DR   GO; GO:0016805; F:dipeptidase activity; IDA:UniProtKB.
DR   GO; GO:0034235; F:GPI anchor binding; ISS:UniProtKB.
DR   GO; GO:0070573; F:metallodipeptidase activity; ISS:UniProtKB.
DR   GO; GO:0072341; F:modified amino acid binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR   GO; GO:0016999; P:antibiotic metabolic process; ISS:UniProtKB.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR   GO; GO:0071732; P:cellular response to nitric oxide; ISS:UniProtKB.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISS:UniProtKB.
DR   GO; GO:0006751; P:glutathione catabolic process; ISS:UniProtKB.
DR   GO; GO:0050667; P:homocysteine metabolic process; ISS:UniProtKB.
DR   GO; GO:1901749; P:leukotriene D4 catabolic process; ISS:UniProtKB.
DR   GO; GO:0006691; P:leukotriene metabolic process; ISS:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR   GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd01301; rDP_like; 1.
DR   Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1.
DR   InterPro; IPR000180; Dipep_AS.
DR   InterPro; IPR032466; Metal_Hydrolase.
DR   InterPro; IPR008257; Pept_M19.
DR   PANTHER; PTHR10443:SF38; DIPEPTIDASE 1; 1.
DR   PANTHER; PTHR10443; MICROSOMAL DIPEPTIDASE; 1.
DR   Pfam; PF01244; Peptidase_M19; 1.
DR   SUPFAM; SSF51556; Metallo-dependent hydrolases; 1.
DR   PROSITE; PS00869; RENAL_DIPEPTIDASE_1; 1.
DR   PROSITE; PS51365; RENAL_DIPEPTIDASE_2; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Dipeptidase; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipid metabolism;
KW   Lipoprotein; Membrane; Metal-binding; Metalloprotease; Protease;
KW   Reference proteome; Signal; Zinc.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000250"
FT   CHAIN           17..384
FT                   /note="Dipeptidase 1"
FT                   /id="PRO_0000018662"
FT   PROPEP          385..410
FT                   /note="Removed in mature form"
FT                   /evidence="ECO:0000250|UniProtKB:P16444"
FT                   /id="PRO_0000018663"
FT   BINDING         36
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         38
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         168
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         214
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         235
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         246
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   BINDING         304
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   LIPID           384
FT                   /note="GPI-anchor amidated serine"
FT                   /evidence="ECO:0000250|UniProtKB:P22412"
FT   CARBOHYD        57
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        62
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        87..170
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   DISULFID        242..274
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   DISULFID        377
FT                   /note="Interchain"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10073"
FT   CONFLICT        42
FT                   /note="A -> Q (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   410 AA;  45096 MW;  AA818C8B8BB91F31 CRC64;
     MWTGWWLWPL VAVCTADQFR DNAVRLMQST PVIDGHNDLP WALLKKFNNQ LQDPRANLTS
     LNSTHTNIPK LKAGFVGAQF WSAYTPCDTQ NKDSVKRTVE QIDVIQRMCQ LYPETFLCVT
     DSAGIQQAFQ EGKVASLVGV EGGHSIDSSL GVLRALYHLG MRYLTLTHSC NTPWADNWLV
     DTGEDKAQSQ GLSSFGQSVV KEMNRLGIII DLAHVSVATM EAALQLSKAP VIFSHSSAYS
     LCHHRRNVPD HVLQLVKQTG SLVMVNFYND YVSCKAEANL SQVADHLDYI KKVAGAGAVG
     FGGDYDGVSR LPSGLEDVSK YPDLVAELLR RQWTEEEVRG ALAENLLRVF KAVEQASDHK
     QAPGEEPIPL GQLEASCRTK YGYSGTPSLH LQPGSLLASL VTLLLSLCLL
//