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 24-JAN-2024, entry version 145. 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, ECO:0000255|PROSITE- CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSOCUP00000041294; -. DR MEROPS; M19.001; -. DR GlyCosmos; P31429; 1 site, No reported glycans. DR PaxDb; 9986-ENSOCUP00000008950; -. DR GeneID; 100009273; -. DR KEGG; ocu:100009273; -. DR CTD; 1800; -. DR eggNOG; KOG4127; Eukaryota. DR InParanoid; P31429; -. DR OrthoDB; 5476406at2759; -. DR Proteomes; UP000001811; Unplaced. 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:0098552; C:side of membrane; IEA:UniProtKB-KW. 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: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 Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1. DR InterPro; IPR000180; Dipep_AS. DR InterPro; IPR032466; Metal_Hydrolase. DR InterPro; IPR008257; Pept_M19. DR PANTHER; PTHR10443:SF38; DIPEPTIDASE 1; 1. DR PANTHER; PTHR10443; MICROSOMAL DIPEPTIDASE; 1. DR Pfam; PF01244; Peptidase_M19; 1. DR SUPFAM; SSF51556; Metallo-dependent hydrolases; 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 //