DPEP1_SHEEP
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 03-AUG-2022, entry version 123.
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,
CC ECO:0000255|PROSITE-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}.
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DR EMBL; L27113; AAA21725.1; -; mRNA.
DR AlphaFoldDB; P43477; -.
DR SMR; P43477; -.
DR STRING; 9940.ENSOARP00000015196; -.
DR MEROPS; M19.001; -.
DR eggNOG; KOG4127; Eukaryota.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
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: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:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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 InterPro; IPR000180; Dipep_AS.
DR InterPro; IPR028536; Dpep1.
DR InterPro; IPR032466; Metal_Hydrolase.
DR InterPro; IPR008257; Pept_M19.
DR PANTHER; PTHR10443; PTHR10443; 1.
DR PANTHER; PTHR10443:SF38; PTHR10443:SF38; 1.
DR Pfam; PF01244; Peptidase_M19; 1.
DR SUPFAM; SSF51556; SSF51556; 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
