DPEP1_RAT
ID DPEP1_RAT Reviewed; 410 AA.
AC P31430; Q6IN35;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Dipeptidase 1;
DE EC=3.4.13.19 {ECO:0000250|UniProtKB:P31428};
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 {ECO:0000303|PubMed:1420313};
DE Flags: Precursor;
GN Name=Dpep1; Synonyms=Rdp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=1420313; DOI=10.1016/0167-4781(92)90167-x;
RA Adachi H., Ishida N., Tsujimoto M.;
RT "Primary structure of rat renal dipeptidase and expression of its mRNA in
RT rat tissues and COS-1 cells.";
RL Biochim. Biophys. Acta 1132:311-314(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Hydrolyzes a wide range of dipeptides including the
CC conversion of leukotriene D4 to leukotriene E4. Hydrolyzes cystinyl-
CC bis-glycine (cys-bis-gly) formed during glutathione degradation.
CC Possesses also beta lactamase activity and hydrolytically inactivates
CC beta-lactam antibiotics. {ECO:0000250|UniProtKB:P31428}.
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;
CC Evidence={ECO:0000250|UniProtKB:P31428, ECO:0000255|PROSITE-
CC ProRule:PRU10073};
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:0000250|UniProtKB:P31428};
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 -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; M94056; AAA41093.1; -; mRNA.
DR EMBL; L07315; AAA41094.1; -; mRNA.
DR EMBL; L07316; AAA41095.1; -; mRNA.
DR EMBL; BC072476; AAH72476.1; -; mRNA.
DR PIR; S27204; S27204.
DR RefSeq; NP_446043.1; NM_053591.2.
DR RefSeq; XP_006255845.1; XM_006255783.3.
DR AlphaFoldDB; P31430; -.
DR SMR; P31430; -.
DR STRING; 10116.ENSRNOP00000021397; -.
DR MEROPS; M19.001; -.
DR GlyGen; P31430; 3 sites.
DR iPTMnet; P31430; -.
DR PhosphoSitePlus; P31430; -.
DR PaxDb; P31430; -.
DR PRIDE; P31430; -.
DR Ensembl; ENSRNOT00000021397; ENSRNOP00000021397; ENSRNOG00000015880.
DR GeneID; 94199; -.
DR KEGG; rno:94199; -.
DR UCSC; RGD:620324; rat.
DR CTD; 1800; -.
DR RGD; 620324; Dpep1.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000159615; -.
DR HOGENOM; CLU_031404_4_2_1; -.
DR InParanoid; P31430; -.
DR OMA; ADAHNDT; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; P31430; -.
DR TreeFam; TF324523; -.
DR Reactome; R-RNO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-RNO-5423646; Aflatoxin activation and detoxification.
DR SABIO-RK; P31430; -.
DR PRO; PR:P31430; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000015880; Expressed in pancreas and 16 other tissues.
DR Genevisible; P31430; RN.
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; IEA:Ensembl.
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; IEA:Ensembl.
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; ISS: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:0006954; P:inflammatory response; ISO:RGD.
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:0030593; P:neutrophil chemotaxis; ISO:RGD.
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 2: Evidence at transcript 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_0000018660"
FT PROPEP 385..410
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000018661"
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 121
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 409
FT /note="L -> P (in Ref. 1; AAA41093)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 410 AA; 45522 MW; 6DD618B44523862C CRC64;
MLIIWWFWSL LAICASDSFR NQAENIMRTT PVIDGHNDLP WQMLTLFNNQ LRKSEANLSA
LAETHTNIPK LRAGFVGGQF WSAYMPCDTQ NKDAVKRILE QIDVIHRMCQ LYPETFECVT
NSSDILQAFR RGKVASLIGV EGGHLIDSSL GVLRTLYHLG MRYLTLTHNC NTPWADNWLV
DKGDDEAESQ GLSPFGKLVL NEMNRLGVMI DLSHVSVATM KDALQLSKAP VIFSHSSAYS
VCPHRRNVPD DVLQLVKSTN SLVMVNFYNQ FVSCSDSATL SQVADHLDHI KKVAGAGAVG
LGGDYDGVTN LPVGLEDVSK YPDLIAELLR RNWTETEVRG LLAENLLRVF SAVELVSNIM
QVPEEETIPV EKLDGSCRTF YGHSRAPSIH LQIGALLASL ASLVFSLHLL
