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 24-JAN-2024, entry version 226. 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10073, 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}. 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; 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; 74. 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 DrugBank; DB00760; Meropenem. DR DrugBank; DB03424; Ubenimex. DR DrugCentral; P16444; -. DR MEROPS; M19.001; -. DR GlyConnect; 1174; 2 N-Linked glycans (1 site). DR GlyCosmos; P16444; 5 sites, 3 glycans. DR GlyGen; P16444; 6 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (2 sites). DR iPTMnet; P16444; -. DR PhosphoSitePlus; P16444; -. DR SwissPalm; P16444; -. DR BioMuta; DPEP1; -. DR DMDM; 92090943; -. DR EPD; P16444; -. DR jPOST; P16444; -. DR MassIVE; P16444; -. DR MaxQB; P16444; -. DR PaxDb; 9606-ENSP00000376807; -. DR PeptideAtlas; P16444; -. DR ProteomicsDB; 53362; -. DR Antibodypedia; 1973; 248 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 AGR; HGNC:3002; -. 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; 5476406at2759; -. DR PhylomeDB; P16444; -. DR TreeFam; TF324523; -. DR BioCyc; MetaCyc:HS00367-MONOMER; -. 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; 11 hits in 1162 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 125 other cell types or tissues. DR ExpressionAtlas; P16444; baseline and differential. 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:0098552; C:side of membrane; IEA:UniProtKB-KW. 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: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:0006954; P:inflammatory response; IEA:Ensembl. DR GO; GO:0072340; P:lactam catabolic process; TAS:UniProtKB. DR GO; GO:1901749; P:leukotriene D4 catabolic process; IDA:UniProtKB. 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:0030593; P:neutrophil chemotaxis; IEA:Ensembl. 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. DR Genevisible; P16444; HS. 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 FT cystinyl-bis-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 //