DPEP1_RABIT
ID DPEP1_RABIT Reviewed; 410 AA.
AC P31429;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Dipeptidase 1;
DE EC=3.4.13.19 {ECO:0000250|UniProtKB:P31428};
DE AltName: Full=43 kDa renal band 3-related protein {ECO:0000303|PubMed:1741759};
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 Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-40, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Kidney;
RX PubMed=1741759; DOI=10.1042/bj2800071;
RA Igarashi P., Karniski L.P.;
RT "Cloning of cDNAs encoding a rabbit renal brush border membrane protein
RT immunologically related to band 3. Sequence similarity with microsomal
RT dipeptidase.";
RL Biochem. J. 280:71-78(1991).
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:0000269|PubMed:1741759}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; X61503; CAA43720.1; -; mRNA.
DR PIR; S18442; S18442.
DR RefSeq; NP_001095167.1; NM_001101697.1.
DR AlphaFoldDB; P31429; -.
DR SMR; P31429; -.
DR STRING; 9986.ENSOCUP00000008950; -.
DR MEROPS; M19.001; -.
DR PRIDE; P31429; -.
DR GeneID; 100009273; -.
DR KEGG; ocu:100009273; -.
DR CTD; 1800; -.
DR eggNOG; KOG4127; Eukaryota.
DR InParanoid; P31429; -.
DR OrthoDB; 1272387at2759; -.
DR Proteomes; UP000001811; 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; 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; 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:0030593; P:neutrophil chemotaxis; 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:1741759"
FT CHAIN 17..384
FT /note="Dipeptidase 1"
FT /id="PRO_0000018658"
FT PROPEP 385..410
FT /note="Removed in mature form"
FT /evidence="ECO:0000250|UniProtKB:P16444"
FT /id="PRO_0000018659"
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 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"
SQ SEQUENCE 410 AA; 45305 MW; 2033F7BFBBF2CC72 CRC64;
MWTSWWLWPL VAVCTADSFL DQAVQILRVT PVIDGHNDLP WQLLNKFNNR LQDSRANLTV
LADTHTNIPK LRAGFVGGQF WSAYTPCDTQ NKDTVRRTLE QMDVVHRMCQ LYPETFLCVT
DSAGIQQAFR EGKVASLIGV EGGHSIDSSL GVLRALYRLG MRYLTLTHNC NTPWADNWLV
DRGDDEAQSG GLSVFGQRVV REMNRLGVMI DLAHVSVATM KAALQLSTAP VIFSHSSAFT
VCAHKRNVPD DVLQLVKETG SLVMVNFYND YVSCASEATL SQVADHLDYI KNVAGAAAVR
FGGDFDGVTR LPVGLEDVSK YPDLVAELLR RGWTEAEVRG ALAENLLRVF REVEQVSNQA
QVPEEEPISL EQLGGSCRTQ YGYSEAPSLH RRPGALLASL SLLLLSLGLL
