DPEP1_PIG
ID DPEP1_PIG Reviewed; 409 AA.
AC P22412;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Dipeptidase 1;
DE EC=3.4.13.19 {ECO:0000269|PubMed:8045301, ECO:0000269|PubMed:8823187};
DE AltName: Full=Beta-lactamase {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000250|UniProtKB:P31428};
DE AltName: Full=Microsomal dipeptidase;
DE AltName: Full=Renal dipeptidase;
DE Flags: Precursor;
GN Name=DPEP1; Synonyms=RDP;
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 [MRNA], PARTIAL PROTEIN SEQUENCE, AND GLYCOSYLATION AT
RP ASN-57.
RC TISSUE=Kidney cortex;
RX PubMed=2173907; DOI=10.1042/bj2710755;
RA Rached E., Hooper N.M., James P., Semenza G., Turner A.J., Mantei N.;
RT "cDNA cloning and expression in Xenopus laevis oocytes of pig renal
RT dipeptidase, a glycosyl-phosphatidylinositol-anchored ectoenzyme.";
RL Biochem. J. 271:755-760(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Satoh S., Koyama S., Ohtuka K., Keida Y., Niwa M., Kohsaka M.;
RT "Purification and cDNA cloning for porcine renal dipeptidase.";
RL Submitted (SEP-1992) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PROTEIN SEQUENCE OF 17-39.
RX PubMed=2137335; DOI=10.1042/bj2650429;
RA Hooper N.M., Keen J.N., Turner A.J.;
RT "Characterization of the glycosyl-phosphatidylinositol-anchored human renal
RT dipeptidase reveals that it is more extensively glycosylated than the pig
RT enzyme.";
RL Biochem. J. 265:429-433(1990).
RN [4]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-235; ASP-285; HIS-286; ASP-288 AND
RP HIS-289, SUBCELLULAR LOCATION, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=8045301; DOI=10.1016/0014-5793(94)00637-7;
RA Keynan S., Hooper N.M., Turner A.J.;
RT "Directed mutagenesis of pig renal membrane dipeptidase. His219 is critical
RT but the DHXXH motif is not essential for zinc binding or catalytic
RT activity.";
RL FEBS Lett. 349:50-54(1994).
RN [5]
RP INTERCHAIN DISULFIDE BOND, MUTAGENESIS OF CYS-87; CYS-109; CYS-170;
RP CYS-242; CYS-274 AND CYS-377, CATALYTIC ACTIVITY, SUBUNIT, AND ACTIVITY
RP REGULATION.
RX PubMed=8823187; DOI=10.1021/bi961193z;
RA Keynan S., Habgood N.T., Hooper N.M., Turner A.J.;
RT "Site-directed mutagenesis of conserved cysteine residues in porcine
RT membrane dipeptidase. Cys-361 alone is involved in disulfide-linked
RT dimerization.";
RL Biochemistry 35:12511-12517(1996).
RN [6]
RP GPI-ANCHOR AT SER-384, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16689534; DOI=10.1021/ac0517949;
RA Omaetxebarria M.J., Hagglund P., Elortza F., Hooper N.M., Arizmendi J.M.,
RA Jensen O.N.;
RT "Isolation and characterization of glycosylphosphatidylinositol-anchored
RT peptides by hydrophilic interaction chromatography and MALDI tandem mass
RT spectrometry.";
RL Anal. Chem. 78:3335-3341(2006).
CC -!- FUNCTION: Hydrolyzes a wide range of dipeptides (PubMed:8045301,
CC PubMed:8823187). Hydrolyzes the conversion of leukotriene D4 to
CC leukotriene E4. 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:8045301,
CC ECO:0000269|PubMed:8823187}.
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:8045301,
CC ECO:0000269|PubMed:8823187};
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:8045301, ECO:0000269|PubMed:8823187};
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 (By similarity).
CC Inhibited by cilastatin (PubMed:8823187, PubMed:8045301).
CC {ECO:0000250|UniProtKB:P16444, ECO:0000269|PubMed:8045301,
CC ECO:0000269|PubMed:8823187}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000269|PubMed:8823187}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:16689534}. Cell projection, microvillus membrane;
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:16689534}. Cell membrane
CC {ECO:0000269|PubMed:8045301}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:8045301}. Note=Brush border membrane.
CC {ECO:0000250|UniProtKB:P31429}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; X53730; CAA37762.1; -; mRNA.
DR EMBL; D13142; BAA02433.1; -; mRNA.
DR PIR; JS0759; JS0759.
DR RefSeq; NP_999273.1; NM_214108.1.
DR AlphaFoldDB; P22412; -.
DR SMR; P22412; -.
DR STRING; 9823.ENSSSCP00000019823; -.
DR BindingDB; P22412; -.
DR ChEMBL; CHEMBL2626; -.
DR DrugCentral; P22412; -.
DR MEROPS; M19.001; -.
DR iPTMnet; P22412; -.
DR PaxDb; P22412; -.
DR PeptideAtlas; P22412; -.
DR Ensembl; ENSSSCT00025034816; ENSSSCP00025014499; ENSSSCG00025025766.
DR Ensembl; ENSSSCT00035005011; ENSSSCP00035001713; ENSSSCG00035004024.
DR Ensembl; ENSSSCT00045014623; ENSSSCP00045010144; ENSSSCG00045008656.
DR Ensembl; ENSSSCT00065097843; ENSSSCP00065042890; ENSSSCG00065071207.
DR GeneID; 397196; -.
DR KEGG; ssc:397196; -.
DR CTD; 1800; -.
DR eggNOG; KOG4127; Eukaryota.
DR InParanoid; P22412; -.
DR BioCyc; MetaCyc:MON-9981; -.
DR PRO; PR:P22412; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA: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; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0071732; P:cellular response to nitric oxide; IDA: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:0006507; P:GPI anchor release; IDA: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 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:0000269|PubMed:2137335"
FT CHAIN 17..384
FT /note="Dipeptidase 1"
FT /id="PRO_0000018656"
FT PROPEP 385..409
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000018657"
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:0000269|PubMed:16689534"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:2173907"
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:0000269|PubMed:8823187"
FT MUTAGEN 87
FT /note="C->G: Does not affect dimerization. Does not affect
FT dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
FT MUTAGEN 109
FT /note="C->A: Does not affect dimerization. Does not affect
FT dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
FT MUTAGEN 170
FT /note="C->G: Does not affect dimerization. Does not affect
FT dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
FT MUTAGEN 235
FT /note="H->R,K,L: Complete abolition of dipeptidase
FT activity. Does not affect cell membrane localization."
FT /evidence="ECO:0000269|PubMed:8045301"
FT MUTAGEN 242
FT /note="C->A: Does not affect dimerization. Does not affect
FT dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
FT MUTAGEN 274
FT /note="C->G: Does not affect dimerization. Does not affect
FT dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
FT MUTAGEN 285
FT /note="D->A: Does not affect dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8045301"
FT MUTAGEN 286
FT /note="H->L,Q,K: Does not affect dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8045301"
FT MUTAGEN 288
FT /note="D->A: Does not affect dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8045301"
FT MUTAGEN 289
FT /note="H->R: Does not affect dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8045301"
FT MUTAGEN 377
FT /note="C->G: Abolished disulfide-linked dimerization. Does
FT not affect dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:8823187"
SQ SEQUENCE 409 AA; 44700 MW; 926B7F0044FA055F CRC64;
MWTSWWLWPL VAVCAADQFR DLAVRIMQDT PVIDGHNDLP WQLLNLFNNQ LQDPGANLSS
LAHTHTNIPK LKAGFVGGQF WSAYVPCDTQ NRDAVKRTLE QIDVIQRMCQ AYPETFACVT
SSTGIRQAFR EGKVASLVGV EGGHSIDSSL GVLRALYHLG MRYMTLTHSC NTPWADNWLV
DTGDDKAQSQ GLSHFGQSVV KEMNRLGVMI DLAHVSVATM RAALKLSQAP VIFSHSSAYS
LCPHRRNVPD DVLQLVKETG SLVMVNFYND YVSCSAKANL SQVADHLDHI KKVAGAAAVG
FGGDYDGVSR VPSGLEDVSK YPDLVAELLR RQWTEAEVRG ALADNLLRVF EAVEQASNHA
QVPGEEPIPL GQLEASCRTN YGYSAAPSLH LPPGSLLASL VPLLLLSLP
