UniProtKB - P16444 (DPEP1_HUMAN)
Protein
Dipeptidase 1
Gene
DPEP1
Organism
Homo sapiens (Human)
Status
Functioni
Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4 (PubMed:2303490, PubMed:6334084, PubMed:31442408). Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation (By similarity). Possesses also beta lactamase activity and hydrolytically inactivates beta-lactam antibiotics (PubMed:6334084).By similarity3 Publications
Independently of its dipeptidase activity acts as an adhesion receptor for neutrophils recruitement from bloodstream into inflammed lungs and liver.By similarity
Catalytic activityi
Cofactori
Zn2+PROSITE-ProRule annotation1 PublicationNote: Binds 2 Zn2+ ion per monomer.1 Publication
Activity regulationi
Inhibited by L-penicillamine (PubMed:31442408). Beta-lactamase activity is inhibited by cilastatin (PubMed:6334084, PubMed:31442408).2 Publications
Kineticsi
- KM=10.9 µM for imipenem1 Publication
- Vmax=44.5 µmol/min/mg enzyme with imipenem as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 36 | Zinc 1; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 38 | Zinc 1; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 141 | Zinc 1; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 141 | Zinc 2; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 168 | Substrate1 Publication | 1 | |
Metal bindingi | 214 | Zinc 2; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 235 | Zinc 2; catalyticPROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 246 | Substrate1 Publication | 1 | |
Binding sitei | 304 | Substrate1 Publication | 1 |
GO - Molecular functioni
- beta-lactamase activity Source: UniProtKB
- cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
- GPI anchor binding Source: UniProtKB
- metallodipeptidase activity Source: UniProtKB
- metalloexopeptidase activity Source: UniProtKB
- modified amino acid binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- antibiotic metabolic process Source: UniProtKB
- cellular lactam catabolic process Source: UniProtKB
- cellular response to calcium ion Source: UniProtKB
- cellular response to drug Source: UniProtKB
- cellular response to nitric oxide Source: UniProtKB
- glutathione catabolic process Source: UniProtKB
- glutathione metabolic process Source: UniProtKB
- homocysteine metabolic process Source: UniProtKB
- inflammatory response Source: Ensembl
- leukotriene metabolic process Source: Reactome
- lipid metabolic process Source: UniProtKB-KW
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell migration Source: UniProtKB
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- neutrophil chemotaxis Source: Ensembl
- xenobiotic metabolic process Source: Reactome
Keywordsi
Molecular function | Dipeptidase, Hydrolase, Metalloprotease, Protease |
Biological process | Lipid metabolism |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00367-MONOMER |
BRENDAi | 3.4.13.19, 2681 |
PathwayCommonsi | P16444 |
Reactomei | R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-5423646, Aflatoxin activation and detoxification R-HSA-9664535, LTC4-CYSLTR mediated IL4 production |
SABIO-RKi | P16444 |
Protein family/group databases
MEROPSi | M19.001 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:DPEP1 Synonyms:MDP1 Publication, RDP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000015413.9 |
HGNCi | HGNC:3002, DPEP1 |
MIMi | 179780, gene |
neXtProti | NX_P16444 |
Subcellular locationi
Plasma membrane
- Apical cell membrane 1 Publication; GPI-anchor 1 Publication
- microvillus membrane 1 Publication; GPI-anchor 1 Publication
Note: Brush border membrane.By similarity
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular space Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- apical plasma membrane Source: UniProtKB-SubCell
- microvillus membrane Source: UniProtKB-SubCell
- plasma membrane Source: UniProtKB
Other locations
- anchored component of membrane Source: UniProtKB-KW
- apical part of cell Source: UniProtKB
- cell junction Source: HPA
Keywords - Cellular componenti
Cell membrane, Cell projection, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 141 | E → C: Complete loss of activity. 1 Publication | 1 | |
Mutagenesisi | 141 | E → D: Abolished dipeptidase activity. Does not affect ability to bind neutrophils. 2 Publications | 1 | |
Mutagenesisi | 141 | E → Q: Partial loss of activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 1800 |
OpenTargetsi | ENSG00000015413 |
PharmGKBi | PA144 |
Miscellaneous databases
Pharosi | P16444, Tclin |
Chemistry databases
ChEMBLi | CHEMBL1989 |
DrugBanki | DB01597, Cilastatin DB06211, Doripenem DB01598, Imipenem |
DrugCentrali | P16444 |
Polymorphism and mutation databases
BioMutai | DPEP1 |
DMDMi | 92090943 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 16 | 3 PublicationsAdd BLAST | 16 | |
ChainiPRO_0000018652 | 17 – 385 | Dipeptidase 1Add BLAST | 369 | |
PropeptideiPRO_0000018653 | 386 – 411 | Removed in mature form1 PublicationAdd BLAST | 26 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 57 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 87 ↔ 170 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 242 ↔ 274 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 279 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 332 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 358 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 377 | InterchainPROSITE-ProRule annotation1 Publication | ||
Lipidationi | 385 | GPI-anchor amidated serine1 Publication | 1 |
Keywords - PTMi
Disulfide bond, Glycoprotein, GPI-anchor, LipoproteinProteomic databases
EPDi | P16444 |
jPOSTi | P16444 |
MassIVEi | P16444 |
MaxQBi | P16444 |
PaxDbi | P16444 |
PeptideAtlasi | P16444 |
PRIDEi | P16444 |
ProteomicsDBi | 53362 |
PTM databases
GlyConnecti | 1174, 2 N-Linked glycans (1 site) |
GlyGeni | P16444, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | P16444 |
PhosphoSitePlusi | P16444 |
Expressioni
Tissue specificityi
Expressed in lung and kidneys.2 Publications
Inductioni
Up-regulated in n colorectal cancers.1 Publication
Gene expression databases
Bgeei | ENSG00000015413, Expressed in pancreas and 130 other tissues |
ExpressionAtlasi | P16444, baseline and differential |
Genevisiblei | P16444, HS |
Organism-specific databases
HPAi | ENSG00000015413, Group enriched (intestine, kidney, pancreas) |
Interactioni
Subunit structurei
Homodimer; disulfide-linked.
PROSITE-ProRule annotation1 PublicationBinary interactionsi
Hide detailsProtein-protein interaction databases
BioGRIDi | 108134, 63 interactors |
IntActi | P16444, 55 interactors |
STRINGi | 9606.ENSP00000376807 |
Chemistry databases
BindingDBi | P16444 |
Miscellaneous databases
RNActi | P16444, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P16444 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P16444 |
Family & Domainsi
Sequence similaritiesi
Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.PROSITE-ProRule annotation
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4127, Eukaryota |
GeneTreei | ENSGT00940000159615 |
HOGENOMi | CLU_031404_4_2_1 |
InParanoidi | P16444 |
OMAi | HLDHMRE |
OrthoDBi | 1272387at2759 |
PhylomeDBi | P16444 |
TreeFami | TF324523 |
Family and domain databases
CDDi | cd01301, rDP_like, 1 hit |
InterProi | View protein in InterPro IPR000180, Dipep_AS IPR028536, Dpep1 IPR032466, Metal_Hydrolase IPR008257, Pept_M19 |
PANTHERi | PTHR10443, PTHR10443, 1 hit PTHR10443:SF38, PTHR10443:SF38, 1 hit |
Pfami | View protein in Pfam PF01244, Peptidase_M19, 1 hit |
SUPFAMi | SSF51556, SSF51556, 1 hit |
PROSITEi | View protein in PROSITE PS00869, RENAL_DIPEPTIDASE_1, 1 hit PS51365, RENAL_DIPEPTIDASE_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P16444-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MWSGWWLWPL VAVCTADFFR DEAERIMRDS PVIDGHNDLP WQLLDMFNNR
60 70 80 90 100
LQDERANLTT LAGTHTNIPK LRAGFVGGQF WSVYTPCDTQ NKDAVRRTLE
110 120 130 140 150
QMDVVHRMCR MYPETFLYVT SSAGIRQAFR EGKVASLIGV EGGHSIDSSL
160 170 180 190 200
GVLRALYQLG MRYLTLTHSC NTPWADNWLV DTGDSEPQSQ GLSPFGQRVV
210 220 230 240 250
KELNRLGVLI DLAHVSVATM KATLQLSRAP VIFSHSSAYS VCASRRNVPD
260 270 280 290 300
DVLRLVKQTD SLVMVNFYNN YISCTNKANL SQVADHLDHI KEVAGARAVG
310 320 330 340 350
FGGDFDGVPR VPEGLEDVSK YPDLIAELLR RNWTEAEVKG ALADNLLRVF
360 370 380 390 400
EAVEQASNLT QAPEEEPIPL DQLGGSCRTH YGYSSGASSL HRHWGLLLAS
410
LAPLVLCLSL L
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BP43 | H3BP43_HUMAN | Dipeptidase | DPEP1 | 111 | Annotation score: | ||
H3BQS5 | H3BQS5_HUMAN | Dipeptidase | DPEP1 | 107 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 9 | P → S (PubMed:8439558).Curated | 1 | |
Sequence conflicti | 9 | P → S (PubMed:7764673).Curated | 1 | |
Sequence conflicti | 102 | M → R (PubMed:2303490).Curated | 1 | |
Sequence conflicti | 125 | I → R (PubMed:2303490).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036496 | 246 | R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1043397364Ensembl. | 1 | |
Natural variantiVAR_061375 | 351 | E → K. Corresponds to variant dbSNP:rs1126464Ensembl. | 1 | |
Natural variantiVAR_061376 | 351 | E → Q. Corresponds to variant dbSNP:rs1126464Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D13137 Genomic DNA Translation: BAA02430.1 J05257 mRNA Translation: AAB59410.1 D13138 mRNA Translation: BAA02431.1 S70330, S70329 Genomic DNA Translation: AAC60630.2 CH471184 Genomic DNA Translation: EAW66719.1 CH471184 Genomic DNA Translation: EAW66720.1 BC017023 mRNA Translation: AAH17023.1 BT006664 mRNA Translation: AAP35310.1 |
CCDSi | CCDS10982.1 |
PIRi | S29848 |
RefSeqi | NP_001121613.1, NM_001128141.2 NP_004404.1, NM_004413.3 XP_005256342.1, XM_005256285.4 XP_005256343.1, XM_005256286.3 XP_011521227.1, XM_011522925.2 |
Genome annotation databases
Ensembli | ENST00000261615; ENSP00000261615; ENSG00000015413 ENST00000393092; ENSP00000376807; ENSG00000015413 ENST00000421184; ENSP00000397313; ENSG00000015413 |
GeneIDi | 1800 |
KEGGi | hsa:1800 |
UCSCi | uc002fnr.5, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D13137 Genomic DNA Translation: BAA02430.1 J05257 mRNA Translation: AAB59410.1 D13138 mRNA Translation: BAA02431.1 S70330, S70329 Genomic DNA Translation: AAC60630.2 CH471184 Genomic DNA Translation: EAW66719.1 CH471184 Genomic DNA Translation: EAW66720.1 BC017023 mRNA Translation: AAH17023.1 BT006664 mRNA Translation: AAP35310.1 |
CCDSi | CCDS10982.1 |
PIRi | S29848 |
RefSeqi | NP_001121613.1, NM_001128141.2 NP_004404.1, NM_004413.3 XP_005256342.1, XM_005256285.4 XP_005256343.1, XM_005256286.3 XP_011521227.1, XM_011522925.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1ITQ | X-ray | 2.30 | A/B | 17-385 | [»] | |
1ITU | X-ray | 2.00 | A/B | 17-385 | [»] | |
SMRi | P16444 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108134, 63 interactors |
IntActi | P16444, 55 interactors |
STRINGi | 9606.ENSP00000376807 |
Chemistry databases
BindingDBi | P16444 |
ChEMBLi | CHEMBL1989 |
DrugBanki | DB01597, Cilastatin DB06211, Doripenem DB01598, Imipenem |
DrugCentrali | P16444 |
Protein family/group databases
MEROPSi | M19.001 |
PTM databases
GlyConnecti | 1174, 2 N-Linked glycans (1 site) |
GlyGeni | P16444, 5 sites, 1 O-linked glycan (1 site) |
iPTMneti | P16444 |
PhosphoSitePlusi | P16444 |
Polymorphism and mutation databases
BioMutai | DPEP1 |
DMDMi | 92090943 |
Proteomic databases
EPDi | P16444 |
jPOSTi | P16444 |
MassIVEi | P16444 |
MaxQBi | P16444 |
PaxDbi | P16444 |
PeptideAtlasi | P16444 |
PRIDEi | P16444 |
ProteomicsDBi | 53362 |
Protocols and materials databases
Antibodypediai | 1973, 208 antibodies |
DNASUi | 1800 |
Genome annotation databases
Ensembli | ENST00000261615; ENSP00000261615; ENSG00000015413 ENST00000393092; ENSP00000376807; ENSG00000015413 ENST00000421184; ENSP00000397313; ENSG00000015413 |
GeneIDi | 1800 |
KEGGi | hsa:1800 |
UCSCi | uc002fnr.5, human |
Organism-specific databases
CTDi | 1800 |
DisGeNETi | 1800 |
EuPathDBi | HostDB:ENSG00000015413.9 |
GeneCardsi | DPEP1 |
HGNCi | HGNC:3002, DPEP1 |
HPAi | ENSG00000015413, Group enriched (intestine, kidney, pancreas) |
MIMi | 179780, gene |
neXtProti | NX_P16444 |
OpenTargetsi | ENSG00000015413 |
PharmGKBi | PA144 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4127, Eukaryota |
GeneTreei | ENSGT00940000159615 |
HOGENOMi | CLU_031404_4_2_1 |
InParanoidi | P16444 |
OMAi | HLDHMRE |
OrthoDBi | 1272387at2759 |
PhylomeDBi | P16444 |
TreeFami | TF324523 |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00367-MONOMER |
BRENDAi | 3.4.13.19, 2681 |
PathwayCommonsi | P16444 |
Reactomei | R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-5423646, Aflatoxin activation and detoxification R-HSA-9664535, LTC4-CYSLTR mediated IL4 production |
SABIO-RKi | P16444 |
Miscellaneous databases
BioGRID-ORCSi | 1800, 3 hits in 843 CRISPR screens |
ChiTaRSi | DPEP1, human |
EvolutionaryTracei | P16444 |
GeneWikii | Dipeptidase_1 |
GenomeRNAii | 1800 |
Pharosi | P16444, Tclin |
PROi | PR:P16444 |
RNActi | P16444, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000015413, Expressed in pancreas and 130 other tissues |
ExpressionAtlasi | P16444, baseline and differential |
Genevisiblei | P16444, HS |
Family and domain databases
CDDi | cd01301, rDP_like, 1 hit |
InterProi | View protein in InterPro IPR000180, Dipep_AS IPR028536, Dpep1 IPR032466, Metal_Hydrolase IPR008257, Pept_M19 |
PANTHERi | PTHR10443, PTHR10443, 1 hit PTHR10443:SF38, PTHR10443:SF38, 1 hit |
Pfami | View protein in Pfam PF01244, Peptidase_M19, 1 hit |
SUPFAMi | SSF51556, SSF51556, 1 hit |
PROSITEi | View protein in PROSITE PS00869, RENAL_DIPEPTIDASE_1, 1 hit PS51365, RENAL_DIPEPTIDASE_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DPEP1_HUMAN | |
Accessioni | P16444Primary (citable) accession number: P16444 Secondary accession number(s): D3DX80, Q96AK2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | March 7, 2006 | |
Last modified: | December 2, 2020 | |
This is version 211 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations