DPEP1_MOUSE
ID DPEP1_MOUSE Reviewed; 410 AA.
AC P31428; G5E824;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Dipeptidase 1;
DE Short=DPEP-1;
DE EC=3.4.13.19 {ECO:0000269|PubMed:12738806, ECO:0000269|PubMed:31442408};
DE AltName: Full=Beta-lactamase {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000269|PubMed:12738806};
DE AltName: Full=Membrane-bound dipeptidase 1 {ECO:0000303|PubMed:12738806};
DE Short=MBD-1 {ECO:0000303|PubMed:12738806};
DE AltName: Full=Microsomal dipeptidase;
DE AltName: Full=Renal dipeptidase {ECO:0000303|PubMed:8507661};
DE Flags: Precursor;
GN Name=Dpep1; Synonyms=Mbd1, Rdp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8507661; DOI=10.1016/0167-4838(93)90157-m;
RA Satoh S., Keida Y., Konta Y., Maeda M., Matsumoto Y., Niwa M., Kohsaka M.;
RT "Purification and molecular cloning of mouse renal dipeptidase.";
RL Biochim. Biophys. Acta 1163:234-242(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9560193; DOI=10.1073/pnas.95.9.4859;
RA Habib G.M., Shi Z.Z., Cuevas A.A., Guo Q., Matzuk M.M., Lieberman M.W.;
RT "Leukotriene D4 and cystinyl-bis-glycine metabolism in membrane-bound
RT dipeptidase-deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:4859-4863(1998).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RX PubMed=12738806; DOI=10.1096/fj.02-0899fje;
RA Habib G.M., Shi Z.-Z., Cuevas A.A., Lieberman M.W.;
RT "Identification of two additional members of the membrane-bound dipeptidase
RT family.";
RL FASEB J. 17:1313-1315(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Lung, Pancreas, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=31442408; DOI=10.1016/j.cell.2019.07.017;
RA Choudhury S.R., Babes L., Rahn J.J., Ahn B.Y., Goring K.R., King J.C.,
RA Lau A., Petri B., Hao X., Chojnacki A.K., Thanabalasuriar A., McAvoy E.F.,
RA Tabaries S., Schraeder C., Patel K.D., Siegel P.M., Kopciuk K.A.,
RA Schriemer D.C., Muruve D.A., Kelly M.M., Yipp B.G., Kubes P., Robbins S.M.,
RA Senger D.L.;
RT "Dipeptidase-1 is an adhesion receptor for neutrophil recruitment in lungs
RT and liver.";
RL Cell 178:1205-1221(2019).
CC -!- FUNCTION: Hydrolyzes a wide range of dipeptides including the
CC conversion of leukotriene D4 to leukotriene E4 (PubMed:12738806,
CC PubMed:31442408, PubMed:9560193). Hydrolyzes cystinyl-bis-glycine (cys-
CC bis-gly) formed during glutathione degradation (PubMed:12738806,
CC PubMed:9560193). Possesses also beta lactamase activity and
CC hydrolytically inactivates beta-lactam antibiotics (PubMed:12738806).
CC {ECO:0000269|PubMed:12738806, ECO:0000269|PubMed:31442408,
CC ECO:0000269|PubMed:9560193}.
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:0000269|PubMed:31442408}.
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:12738806,
CC ECO:0000269|PubMed:31442408};
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:0000269|PubMed:12738806};
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:0000269|PubMed:12738806};
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:0000269|PubMed:12738806};
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:31442408};
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. Inhibited by
CC cilastatin. {ECO:0000250|UniProtKB:P16444}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for leukotriene D4 {ECO:0000269|PubMed:12738806};
CC KM=0.45 mM for cystinyl-bis-glycine {ECO:0000269|PubMed:12738806};
CC KM=111 uM for beta-lactam {ECO:0000269|PubMed:12738806};
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 heart, lung, skeletal muscle, kidney,
CC liver, and testis. Not detected in brain and spleen.
CC {ECO:0000269|PubMed:12738806, ECO:0000269|PubMed:31442408}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are phenotypically normal. However
CC deficient mice display a partial loss in the conversion of leukotriene
CC D4 to leukotrience E4 and in the conversion of cys-bis-gly to cysteine
CC and glycine (PubMed:9560193). Deficient mice display reduces mortality
CC in models of sepsis (PubMed:31442408). {ECO:0000269|PubMed:31442408,
CC ECO:0000269|PubMed:9560193}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; D13139; BAA02432.1; -; mRNA.
DR EMBL; AC163617; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466525; EDL11712.1; -; Genomic_DNA.
DR CCDS; CCDS22750.1; -.
DR PIR; S33757; S33757.
DR RefSeq; NP_031902.2; NM_007876.2.
DR RefSeq; XP_017168047.1; XM_017312558.1.
DR AlphaFoldDB; P31428; -.
DR SMR; P31428; -.
DR IntAct; P31428; 1.
DR STRING; 10090.ENSMUSP00000019422; -.
DR SwissLipids; SLP:000001461; -.
DR MEROPS; M19.001; -.
DR GlyGen; P31428; 3 sites.
DR PhosphoSitePlus; P31428; -.
DR jPOST; P31428; -.
DR MaxQB; P31428; -.
DR PaxDb; P31428; -.
DR PeptideAtlas; P31428; -.
DR PRIDE; P31428; -.
DR ProteomicsDB; 279563; -.
DR Antibodypedia; 1973; 219 antibodies from 28 providers.
DR DNASU; 13479; -.
DR Ensembl; ENSMUST00000019422; ENSMUSP00000019422; ENSMUSG00000019278.
DR GeneID; 13479; -.
DR KEGG; mmu:13479; -.
DR UCSC; uc009nui.2; mouse.
DR CTD; 1800; -.
DR MGI; MGI:94917; Dpep1.
DR VEuPathDB; HostDB:ENSMUSG00000019278; -.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000159615; -.
DR HOGENOM; CLU_031404_4_2_1; -.
DR InParanoid; P31428; -.
DR OMA; CDHPRNI; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; P31428; -.
DR TreeFam; TF324523; -.
DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-MMU-5423646; Aflatoxin activation and detoxification.
DR BioGRID-ORCS; 13479; 2 hits in 79 CRISPR screens.
DR ChiTaRS; Dpep1; mouse.
DR PRO; PR:P31428; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P31428; protein.
DR Bgee; ENSMUSG00000019278; Expressed in aorta tunica adventitia and 154 other tissues.
DR ExpressionAtlas; P31428; baseline and differential.
DR Genevisible; P31428; MM.
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:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0008800; F:beta-lactamase activity; IDA: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; IDA: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; IMP:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB.
DR GO; GO:1901749; P:leukotriene D4 catabolic process; ISS:UniProtKB.
DR GO; GO:0006691; P:leukotriene metabolic process; IDA: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:0030593; P:neutrophil chemotaxis; IMP: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; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipid metabolism; Lipoprotein; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..16
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT CHAIN 17..384
FT /note="Dipeptidase 1"
FT /id="PRO_0000018654"
FT PROPEP 385..410
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000018655"
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 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
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 204
FT /note="N -> T (in Ref. 1; BAA02432)"
FT /evidence="ECO:0000305"
FT CONFLICT 358
FT /note="N -> S (in Ref. 1; BAA02432)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 45722 MW; 46A454B51CA57BB5 CRC64;
MVIIWWFWSL LAICASDSFR DQAVAIMRTT PVIDGHNDLP WQLLNLFNNQ LLRPDADLNK
LAQTHTNIPK LKAGFVGGQF WSAYMPCDTQ NKDAVKRILE QMDVIHRMCQ LYPETFMCVT
NSSDILQAFR RGKVASLIGV EGGHLIDSSL GVLRTLYHLG MRYLTLTHNC NTPWADNWLV
DRGDDEAESH GLSPFGKRLL NEMNRLGVMI DLSHVSVATM KDALQISRAP VIFSHSSAYS
LCPHRRNVPD DVLQLVKNTS SLVMVNFFSN FVSCSDSATL PQVADHLDHI KKVAGAGAVG
LGGDYDGVTM LPVGLEDVSK YPDLIAELLR RNWTETEVRG LLADNLIRVF SEVELVSNNM
QSPEEVPITL KELDGSCRTY YGYSQAHSIH LQTGALVASL ASLLFRLHLL
