DPEP1_HUMAN
ID DPEP1_HUMAN Reviewed; 411 AA.
AC P16444; D3DX80; Q96AK2;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Dipeptidase 1;
DE EC=3.4.13.19 {ECO:0000269|PubMed:2303490, ECO:0000269|PubMed:32325220, ECO:0000269|PubMed:6334084};
DE AltName: Full=Beta-lactamase {ECO:0000305};
DE EC=3.5.2.6 {ECO:0000269|PubMed:6334084};
DE AltName: Full=Dehydropeptidase-I;
DE AltName: Full=Microsomal dipeptidase {ECO:0000303|PubMed:2303490};
DE AltName: Full=Renal dipeptidase {ECO:0000303|PubMed:8097406};
DE Short=hRDP {ECO:0000303|PubMed:8097406};
DE Flags: Precursor;
GN Name=DPEP1; Synonyms=MDP {ECO:0000303|PubMed:2303490}, RDP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8439558; DOI=10.1016/0167-4781(93)90289-p;
RA Satoh S., Kusunoki C., Konta Y., Niwa M., Kohsaka M.;
RT "Cloning and structural analysis of genomic DNA for human renal
RT dipeptidase.";
RL Biochim. Biophys. Acta 1172:181-183(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=2303490; DOI=10.1016/s0021-9258(19)39692-9;
RA Adachi H., Tawaragi Y., Inuzuka C., Kubota I., Tsujimoto M., Nishihara T.,
RA Nakazato H.;
RT "Primary structure of human microsomal dipeptidase deduced from molecular
RT cloning.";
RL J. Biol. Chem. 265:3992-3995(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=7764673; DOI=10.1021/bp00026a002;
RA Satoh S., Ohtsuka K., Keida Y., Kusunoki C., Konta Y., Niwa M., Kohsaka M.;
RT "Gene structural analysis and expression of human renal dipeptidase.";
RL Biotechnol. Prog. 10:134-140(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
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).
RN [7]
RP PROTEIN SEQUENCE OF 17-56; 111-121 AND 298-310.
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 [8]
RP PROTEIN SEQUENCE OF 17-39.
RX PubMed=2768222; DOI=10.1093/oxfordjournals.jbchem.a122787;
RA Adachi H., Kubota I., Okamura N., Iwata H., Tsujimoto M., Nakazato H.,
RA Nishihara T., Noguchi T.;
RT "Purification and characterization of human microsomal dipeptidase.";
RL J. Biochem. 105:957-961(1989).
RN [9]
RP PROTEIN SEQUENCE OF 17-31.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [10]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=6334084; DOI=10.1016/s0021-9258(17)42642-1;
RA Campbell B.J., Forrester L.J., Zahler W.L., Burks M.;
RT "Beta-lactamase activity of purified and partially characterized human
RT renal dipeptidase.";
RL J. Biol. Chem. 259:14586-14590(1984).
RN [11]
RP GPI-ANCHOR AT SER-385, PROTEIN SEQUENCE OF 379-385, AND SUBCELLULAR
RP LOCATION.
RX PubMed=2168407; DOI=10.1016/s0021-9258(18)77261-x;
RA Adachi H., Katayama T., Inuzuka C., Oikawa S., Tsujimoto M., Nakazato H.;
RT "Identification of membrane anchoring site of human renal dipeptidase and
RT construction and expression of a cDNA for its secretory form.";
RL J. Biol. Chem. 265:15341-15345(1990).
RN [12]
RP MUTAGENESIS OF GLU-141, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=8097406; DOI=10.1016/0167-4838(93)90276-w;
RA Adachi H., Katayama T., Nakazato H., Tsujimoto M.;
RT "Importance of Glu-125 in the catalytic activity of human renal
RT dipeptidase.";
RL Biochim. Biophys. Acta 1163:42-48(1993).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-279.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 17-385 IN COMPLEX WITH ZINC AND
RP CILASTATIN, SUBUNIT, COFACTOR, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-57
RP AND ASN-332.
RX PubMed=12144777; DOI=10.1016/s0022-2836(02)00632-0;
RA Nitanai Y., Satow Y., Adachi H., Tsujimoto M.;
RT "Crystal structure of human renal dipeptidase involved in beta-lactam
RT hydrolysis.";
RL J. Mol. Biol. 321:177-184(2002).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-246.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [16]
RP INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=28413640; DOI=10.3892/br.2017.870;
RA Tachibana K., Saito M., Imai J.I., Ito E., Yanagisawa Y., Honma R.,
RA Saito K., Ando J., Momma T., Ohki S., Ohtake T., Watanabe S., Waguri S.,
RA Takenoshita S.;
RT "Clinicopathological examination of dipeptidase 1 expression in colorectal
RT cancer.";
RL Biomed. Rep. 6:423-428(2017).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-141, TISSUE SPECIFICITY,
RP AND ACTIVITY REGULATION.
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).
RN [18]
RP FUNCTION, TRANSPORTER ACTIVITY, MUTAGENESIS OF GLU-141 AND ASP-304, AND
RP ZINC-BINDING.
RX PubMed=32325220; DOI=10.1016/j.jsb.2020.107512;
RA Hayashi K., Longenecker K.L., Koenig P., Prashar A., Hampl J., Stoll V.,
RA Vivona S.;
RT "Structure of human DPEP3 in complex with the SC-003 antibody Fab fragment
RT reveals basis for lack of dipeptidase activity.";
RL J. Struct. Biol. 211:107512-107512(2020).
CC -!- FUNCTION: Hydrolyzes a wide range of dipeptides including the
CC conversion of leukotriene D4 to leukotriene E4 (PubMed:2303490,
CC PubMed:6334084, PubMed:31442408, PubMed:32325220). Hydrolyzes cystinyl-
CC bis-glycine (cys-bis-gly) formed during glutathione degradation
CC (PubMed:32325220). Possesses also beta lactamase activity and can
CC hydrolyze the beta-lactam antibiotic imipenem (PubMed:6334084,
CC PubMed:32325220). {ECO:0000250|UniProtKB:P31428,
CC ECO:0000269|PubMed:2303490, ECO:0000269|PubMed:31442408,
CC ECO:0000269|PubMed:32325220, ECO:0000269|PubMed:6334084}.
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:2303490,
CC ECO:0000269|PubMed:32325220};
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:2303490, ECO:0000269|PubMed:32325220};
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:32325220, ECO:0000269|PubMed:6334084};
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:32325220};
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:2303490, ECO:0000269|PubMed:31442408,
CC ECO:0000269|PubMed:6334084};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10073,
CC ECO:0000269|PubMed:12144777};
CC Note=Binds 2 Zn(2+) ion per monomer. {ECO:0000269|PubMed:12144777};
CC -!- ACTIVITY REGULATION: Inhibited by L-penicillamine (PubMed:31442408).
CC Beta-lactamase activity is inhibited by cilastatin (PubMed:6334084,
CC PubMed:31442408). {ECO:0000269|PubMed:31442408,
CC ECO:0000269|PubMed:6334084}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.9 uM for imipenem {ECO:0000269|PubMed:6334084};
CC Vmax=44.5 umol/min/mg enzyme with imipenem as substrate
CC {ECO:0000269|PubMed:6334084};
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000255|PROSITE-
CC ProRule:PRU10073, ECO:0000269|PubMed:12144777}.
CC -!- INTERACTION:
CC P16444; Q92624: APPBP2; NbExp=3; IntAct=EBI-749514, EBI-743771;
CC P16444; Q96EK5: KIFBP; NbExp=2; IntAct=EBI-749514, EBI-744150;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:28413640}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:2168407}. Cell projection, microvillus membrane
CC {ECO:0000269|PubMed:2168407}; Lipid-anchor, GPI-anchor
CC {ECO:0000269|PubMed:2168407}. Note=Brush border membrane.
CC {ECO:0000250|UniProtKB:P31429}.
CC -!- TISSUE SPECIFICITY: Expressed in lung and kidneys.
CC {ECO:0000269|PubMed:31442408, ECO:0000269|PubMed:8439558}.
CC -!- INDUCTION: Up-regulated in n colorectal cancers.
CC {ECO:0000269|PubMed:28413640}.
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Peptidase M19 family. {ECO:0000255|PROSITE-ProRule:PRU10073}.
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DR EMBL; D13137; BAA02430.1; -; Genomic_DNA.
DR EMBL; J05257; AAB59410.1; -; mRNA.
DR EMBL; D13138; BAA02431.1; -; mRNA.
DR EMBL; S70330; AAC60630.2; -; Genomic_DNA.
DR EMBL; S70329; AAC60630.2; JOINED; Genomic_DNA.
DR EMBL; CH471184; EAW66719.1; -; Genomic_DNA.
DR EMBL; CH471184; EAW66720.1; -; Genomic_DNA.
DR EMBL; BC017023; AAH17023.1; -; mRNA.
DR EMBL; BT006664; AAP35310.1; -; mRNA.
DR CCDS; CCDS10982.1; -.
DR PIR; S29848; S29848.
DR RefSeq; NP_001121613.1; NM_001128141.2.
DR RefSeq; NP_004404.1; NM_004413.3.
DR RefSeq; XP_005256342.1; XM_005256285.4.
DR RefSeq; XP_005256343.1; XM_005256286.3.
DR RefSeq; XP_011521227.1; XM_011522925.2.
DR PDB; 1ITQ; X-ray; 2.30 A; A/B=17-385.
DR PDB; 1ITU; X-ray; 2.00 A; A/B=17-385.
DR PDBsum; 1ITQ; -.
DR PDBsum; 1ITU; -.
DR AlphaFoldDB; P16444; -.
DR SMR; P16444; -.
DR BioGRID; 108134; 73.
DR IntAct; P16444; 55.
DR STRING; 9606.ENSP00000376807; -.
DR BindingDB; P16444; -.
DR ChEMBL; CHEMBL1989; -.
DR DrugBank; DB01597; Cilastatin.
DR DrugBank; DB06211; Doripenem.
DR DrugBank; DB01598; Imipenem.
DR DrugCentral; P16444; -.
DR MEROPS; M19.001; -.
DR GlyConnect; 1174; 2 N-Linked glycans (1 site).
DR GlyGen; P16444; 6 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (2 sites).
DR iPTMnet; P16444; -.
DR PhosphoSitePlus; P16444; -.
DR BioMuta; DPEP1; -.
DR DMDM; 92090943; -.
DR EPD; P16444; -.
DR jPOST; P16444; -.
DR MassIVE; P16444; -.
DR MaxQB; P16444; -.
DR PaxDb; P16444; -.
DR PeptideAtlas; P16444; -.
DR PRIDE; P16444; -.
DR ProteomicsDB; 53362; -.
DR Antibodypedia; 1973; 219 antibodies from 28 providers.
DR DNASU; 1800; -.
DR Ensembl; ENST00000261615.5; ENSP00000261615.4; ENSG00000015413.10.
DR Ensembl; ENST00000393092.7; ENSP00000376807.3; ENSG00000015413.10.
DR Ensembl; ENST00000421184.5; ENSP00000397313.1; ENSG00000015413.10.
DR Ensembl; ENST00000690203.1; ENSP00000508584.1; ENSG00000015413.10.
DR GeneID; 1800; -.
DR KEGG; hsa:1800; -.
DR MANE-Select; ENST00000690203.1; ENSP00000508584.1; NM_001389466.1; NP_001376395.1.
DR UCSC; uc002fnr.5; human.
DR CTD; 1800; -.
DR DisGeNET; 1800; -.
DR GeneCards; DPEP1; -.
DR HGNC; HGNC:3002; DPEP1.
DR HPA; ENSG00000015413; Group enriched (intestine, kidney, pancreas).
DR MIM; 179780; gene.
DR neXtProt; NX_P16444; -.
DR OpenTargets; ENSG00000015413; -.
DR PharmGKB; PA144; -.
DR VEuPathDB; HostDB:ENSG00000015413; -.
DR eggNOG; KOG4127; Eukaryota.
DR GeneTree; ENSGT00940000159615; -.
DR HOGENOM; CLU_031404_4_2_1; -.
DR InParanoid; P16444; -.
DR OMA; CDHPRNI; -.
DR OrthoDB; 1272387at2759; -.
DR PhylomeDB; P16444; -.
DR TreeFam; TF324523; -.
DR BioCyc; MetaCyc:HS00367-MON; -.
DR BRENDA; 3.4.13.19; 2681.
DR PathwayCommons; P16444; -.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-5423646; Aflatoxin activation and detoxification.
DR Reactome; R-HSA-9664535; LTC4-CYSLTR mediated IL4 production.
DR SABIO-RK; P16444; -.
DR SignaLink; P16444; -.
DR BioGRID-ORCS; 1800; 10 hits in 1071 CRISPR screens.
DR ChiTaRS; DPEP1; human.
DR EvolutionaryTrace; P16444; -.
DR GeneWiki; Dipeptidase_1; -.
DR GenomeRNAi; 1800; -.
DR Pharos; P16444; Tclin.
DR PRO; PR:P16444; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P16444; protein.
DR Bgee; ENSG00000015413; Expressed in ileal mucosa and 123 other tissues.
DR ExpressionAtlas; P16444; baseline and differential.
DR Genevisible; P16444; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA: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; IMP: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; IDA:UniProtKB.
DR GO; GO:0008235; F:metalloexopeptidase activity; TAS:UniProtKB.
DR GO; GO:0072341; F:modified amino acid binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0016999; P:antibiotic metabolic process; IDA:UniProtKB.
DR GO; GO:0072340; P:cellular lactam catabolic process; TAS: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; IDA:UniProtKB.
DR GO; GO:0006751; P:glutathione catabolic process; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; TAS:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; IDA:UniProtKB.
DR GO; GO:1901749; P:leukotriene D4 catabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; 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 3D-structure; Cell membrane; Cell projection; Dipeptidase;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; GPI-anchor;
KW Hydrolase; Lipid metabolism; Lipoprotein; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal; Zinc.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:15340161,
FT ECO:0000269|PubMed:2137335, ECO:0000269|PubMed:2768222"
FT CHAIN 17..385
FT /note="Dipeptidase 1"
FT /id="PRO_0000018652"
FT PROPEP 386..411
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:2168407"
FT /id="PRO_0000018653"
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 ECO:0000269|PubMed:12144777"
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 ECO:0000269|PubMed:12144777"
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 ECO:0000269|PubMed:12144777, ECO:0000269|PubMed:32325220"
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 ECO:0000269|PubMed:12144777, ECO:0000269|PubMed:32325220"
FT BINDING 168
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12144777"
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 ECO:0000269|PubMed:12144777"
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 ECO:0000269|PubMed:12144777"
FT BINDING 246
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12144777"
FT BINDING 304
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12144777"
FT LIPID 385
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000269|PubMed:2168407"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12144777,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12144777"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073,
FT ECO:0000269|PubMed:12144777"
FT DISULFID 242..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073,
FT ECO:0000269|PubMed:12144777"
FT DISULFID 377
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10073,
FT ECO:0000269|PubMed:12144777"
FT VARIANT 246
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1043397364)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036496"
FT VARIANT 351
FT /note="E -> K (in dbSNP:rs1126464)"
FT /id="VAR_061375"
FT VARIANT 351
FT /note="E -> Q (in dbSNP:rs1126464)"
FT /id="VAR_061376"
FT MUTAGEN 141
FT /note="E->A: Loss of zinc binding."
FT /evidence="ECO:0000269|PubMed:32325220"
FT MUTAGEN 141
FT /note="E->C: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:8097406"
FT MUTAGEN 141
FT /note="E->D: Abolished dipeptidase activity. Does not
FT affect ability to bind neutrophils."
FT /evidence="ECO:0000269|PubMed:31442408,
FT ECO:0000269|PubMed:8097406"
FT MUTAGEN 141
FT /note="E->Q: Partial loss of activity."
FT /evidence="ECO:0000269|PubMed:8097406"
FT MUTAGEN 304
FT /note="D->L: Loss of ability to hydrolyze cystinyl-bis-
FT glycine."
FT /evidence="ECO:0000269|PubMed:32325220"
FT CONFLICT 9
FT /note="P -> S (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="M -> R (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="I -> R (in Ref. 2)"
FT /evidence="ECO:0000305"
FT HELIX 18..27
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 32..37
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 39..47
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 68..73
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 90..93
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 94..111
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 134..141
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 161..166
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 188..192
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 194..206
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 217..226
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 280..294
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:1ITQ"
FT HELIX 321..330
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 335..342
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 344..356
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:1ITU"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:1ITU"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:1ITU"
FT TURN 381..383
FT /evidence="ECO:0007829|PDB:1ITU"
SQ SEQUENCE 411 AA; 45674 MW; C8C6474C3479D20D CRC64;
MWSGWWLWPL VAVCTADFFR DEAERIMRDS PVIDGHNDLP WQLLDMFNNR LQDERANLTT
LAGTHTNIPK LRAGFVGGQF WSVYTPCDTQ NKDAVRRTLE QMDVVHRMCR MYPETFLYVT
SSAGIRQAFR EGKVASLIGV EGGHSIDSSL GVLRALYQLG MRYLTLTHSC NTPWADNWLV
DTGDSEPQSQ GLSPFGQRVV KELNRLGVLI DLAHVSVATM KATLQLSRAP VIFSHSSAYS
VCASRRNVPD DVLRLVKQTD SLVMVNFYNN YISCTNKANL SQVADHLDHI KEVAGARAVG
FGGDFDGVPR VPEGLEDVSK YPDLIAELLR RNWTEAEVKG ALADNLLRVF EAVEQASNLT
QAPEEEPIPL DQLGGSCRTH YGYSSGASSL HRHWGLLLAS LAPLVLCLSL L
