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P16444 (DPEP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dipeptidase 1

EC=3.4.13.19
Alternative name(s):
Dehydropeptidase-I
Microsomal dipeptidase
Renal dipeptidase
Short name=hRDP
Gene names
Name:DPEP1
Synonyms:MDP, RDP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length411 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. Converts leukotriene D4 to leukotriene E4; it may play an important role in the regulation of leukotriene activity.

Catalytic activity

Hydrolysis of dipeptides.

Cofactor

Zinc. Ref.13

Enzyme regulation

Inhibited by L-penicillamine By similarity.

Subunit structure

Homodimer; disulfide-linked. Ref.13

Subcellular location

Apical cell membrane; Lipid-anchorGPI-anchor. Cell projectionmicrovillus membrane; Lipid-anchorGPI-anchor. Note: Brush border membrane.

Sequence similarities

Belongs to the peptidase M19 family.

Ontologies

Keywords
   Cellular componentCell membrane
Cell projection
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionDipeptidase
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
GPI-anchor
Lipoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantibiotic metabolic process

Inferred from direct assay PubMed 8737157. Source: UniProtKB

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

cellular lactam catabolic process

Traceable author statement Ref.13. Source: UniProtKB

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to drug

Inferred from direct assay PubMed 20435919. Source: UniProtKB

cellular response to nitric oxide

Inferred from sequence or structural similarity. Source: UniProtKB

glutathione metabolic process

Traceable author statement PubMed 20031578. Source: UniProtKB

homocysteine metabolic process

Inferred from direct assay PubMed 20031578. Source: UniProtKB

leukotriene metabolic process

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 20435919. Source: UniProtKB

negative regulation of cell migration

Inferred from mutant phenotype PubMed 20824289. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from mutant phenotype PubMed 20435919. Source: UniProtKB

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentanchored component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

apical part of cell

Inferred from direct assay PubMed 20824289. Source: UniProtKB

apical plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 11487543. Source: UniProtKB

microvillus membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay Ref.13. Source: UniProtKB

   Molecular_functionGPI anchor binding

Inferred from sequence or structural similarity. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from mutant phenotype PubMed 20435919. Source: UniProtKB

dipeptidyl-peptidase activity

Inferred from electronic annotation. Source: InterPro

metallodipeptidase activity

Inferred from direct assay Ref.13PubMed 19879002. Source: UniProtKB

metalloexopeptidase activity

Traceable author statement Ref.2. Source: UniProtKB

modified amino acid binding

Inferred from direct assay PubMed 20031578. Source: UniProtKB

zinc ion binding

Inferred from direct assay PubMed 19879002. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KIAA1279Q96EK52EBI-749514,EBI-744150

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Ref.7 Ref.8 Ref.9
Chain17 – 385369Dipeptidase 1
PRO_0000018652
Propeptide386 – 41126Removed in mature form
PRO_0000018653

Sites

Metal binding361Zinc 1; catalytic
Metal binding381Zinc 1; catalytic
Metal binding1411Zinc 1; catalytic
Metal binding1411Zinc 2; catalytic
Metal binding2141Zinc 2; catalytic
Metal binding2351Zinc 2; catalytic
Binding site1681Substrate
Binding site2461Substrate
Binding site3041Substrate

Amino acid modifications

Lipidation3851GPI-anchor amidated serine Ref.10
Glycosylation571N-linked (GlcNAc...) Ref.12 Ref.13
Glycosylation2791N-linked (GlcNAc...) Ref.12
Glycosylation3321N-linked (GlcNAc...) Ref.13
Glycosylation3581N-linked (GlcNAc...) Potential
Disulfide bond87 ↔ 170 Ref.13
Disulfide bond242 ↔ 274 Ref.13
Disulfide bond377Interchain Ref.13

Natural variations

Natural variant2461R → H in a colorectal cancer sample; somatic mutation. Ref.14
VAR_036496
Natural variant3511E → K.
Corresponds to variant rs1126464 [ dbSNP | Ensembl ].
VAR_061375
Natural variant3511E → Q.
Corresponds to variant rs1126464 [ dbSNP | Ensembl ].
VAR_061376

Experimental info

Mutagenesis1411E → D or C: Complete loss of activity.
Mutagenesis1411E → Q: Partial loss of activity.
Sequence conflict91P → S Ref.1
Sequence conflict91P → S Ref.3
Sequence conflict1021M → R Ref.2
Sequence conflict1251I → R Ref.2

Secondary structure

.................................................................................. 411
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16444 [UniParc].

Last modified March 7, 2006. Version 3.
Checksum: C8C6474C3479D20D

FASTA41145,674
        10         20         30         40         50         60 
MWSGWWLWPL VAVCTADFFR DEAERIMRDS PVIDGHNDLP WQLLDMFNNR LQDERANLTT 

        70         80         90        100        110        120 
LAGTHTNIPK LRAGFVGGQF WSVYTPCDTQ NKDAVRRTLE QMDVVHRMCR MYPETFLYVT 

       130        140        150        160        170        180 
SSAGIRQAFR EGKVASLIGV EGGHSIDSSL GVLRALYQLG MRYLTLTHSC NTPWADNWLV 

       190        200        210        220        230        240 
DTGDSEPQSQ GLSPFGQRVV KELNRLGVLI DLAHVSVATM KATLQLSRAP VIFSHSSAYS 

       250        260        270        280        290        300 
VCASRRNVPD DVLRLVKQTD SLVMVNFYNN YISCTNKANL SQVADHLDHI KEVAGARAVG 

       310        320        330        340        350        360 
FGGDFDGVPR VPEGLEDVSK YPDLIAELLR RNWTEAEVKG ALADNLLRVF EAVEQASNLT 

       370        380        390        400        410 
QAPEEEPIPL DQLGGSCRTH YGYSSGASSL HRHWGLLLAS LAPLVLCLSL L 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and structural analysis of genomic DNA for human renal dipeptidase."
Satoh S., Kusunoki C., Konta Y., Niwa M., Kohsaka M.
Biochim. Biophys. Acta 1172:181-183(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver.
[2]"Primary structure of human microsomal dipeptidase deduced from molecular cloning."
Adachi H., Tawaragi Y., Inuzuka C., Kubota I., Tsujimoto M., Nishihara T., Nakazato H.
J. Biol. Chem. 265:3992-3995(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Gene structural analysis and expression of human renal dipeptidase."
Satoh S., Ohtsuka K., Keida Y., Kusunoki C., Konta Y., Niwa M., Kohsaka M.
Biotechnol. Prog. 10:134-140(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon.
[7]"Characterization of the glycosyl-phosphatidylinositol-anchored human renal dipeptidase reveals that it is more extensively glycosylated than the pig enzyme."
Hooper N.M., Keen J.N., Turner A.J.
Biochem. J. 265:429-433(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-56; 111-121 AND 298-310.
[8]"Purification and characterization of human microsomal dipeptidase."
Adachi H., Kubota I., Okamura N., Iwata H., Tsujimoto M., Nakazato H., Nishihara T., Noguchi T.
J. Biochem. 105:957-961(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-39.
[9]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 17-31.
[10]"Identification of membrane anchoring site of human renal dipeptidase and construction and expression of a cDNA for its secretory form."
Adachi H., Katayama T., Inuzuka C., Oikawa S., Tsujimoto M., Nakazato H.
J. Biol. Chem. 265:15341-15345(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: GPI-ANCHOR AT SER-385.
[11]"Importance of Glu-125 in the catalytic activity of human renal dipeptidase."
Adachi H., Katayama T., Nakazato H., Tsujimoto M.
Biochim. Biophys. Acta 1163:42-48(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY CHEMICAL MODIFICATION.
[12]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-57 AND ASN-279.
Tissue: Liver.
[13]"Crystal structure of human renal dipeptidase involved in beta-lactam hydrolysis."
Nitanai Y., Satow Y., Adachi H., Tsujimoto M.
J. Mol. Biol. 321:177-184(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 17-385 IN COMPLEX WITH ZINC AND CILASTATIN, SUBUNIT, COFACTOR, DISULFIDE BONDS, GLYCOSYLATION AT ASN-57 AND ASN-332.
[14]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-246.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS29848.
RefSeqNP_001121613.1. NM_001128141.2.
NP_004404.1. NM_004413.3.
XP_005256342.1. XM_005256285.2.
XP_005256343.1. XM_005256286.1.
UniGeneHs.109.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ITQX-ray2.30A/B17-385[»]
1ITUX-ray2.00A/B17-385[»]
ProteinModelPortalP16444.
SMRP16444. Positions 17-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108134. 2 interactions.
IntActP16444. 1 interaction.
MINTMINT-5000950.
STRING9606.ENSP00000261615.

Chemistry

BindingDBP16444.
ChEMBLCHEMBL1989.
DrugBankDB01597. Cilastatin.

Protein family/group databases

MEROPSM19.001.

PTM databases

PhosphoSiteP16444.

Polymorphism databases

DMDM92090943.

Proteomic databases

PaxDbP16444.
PRIDEP16444.

Protocols and materials databases

DNASU1800.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261615; ENSP00000261615; ENSG00000015413.
ENST00000393092; ENSP00000376807; ENSG00000015413.
ENST00000421184; ENSP00000397313; ENSG00000015413.
GeneID1800.
KEGGhsa:1800.
UCSCuc002fnr.4. human.

Organism-specific databases

CTD1800.
GeneCardsGC16P089679.
HGNCHGNC:3002. DPEP1.
HPAHPA009426.
HPA012783.
MIM179780. gene.
neXtProtNX_P16444.
PharmGKBPA144.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2355.
HOGENOMHOG000072016.
HOVERGENHBG002339.
InParanoidP16444.
KOK01273.
OMAKPLVATH.
PhylomeDBP16444.
TreeFamTF324523.

Enzyme and pathway databases

BioCycMetaCyc:HS00367-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP16444.

Gene expression databases

ArrayExpressP16444.
BgeeP16444.
CleanExHS_DPEP1.
GenevestigatorP16444.

Family and domain databases

InterProIPR028536. Dpep1-like.
IPR000180. Renal_dipep_AS.
IPR008257. Renal_dipep_fam.
[Graphical view]
PANTHERPTHR10443. PTHR10443. 1 hit.
PTHR10443:SF12. PTHR10443:SF12. 1 hit.
PfamPF01244. Peptidase_M19. 1 hit.
[Graphical view]
PROSITEPS00869. RENAL_DIPEPTIDASE_1. 1 hit.
PS51365. RENAL_DIPEPTIDASE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP16444.
GeneWikiDipeptidase_1.
GenomeRNAi1800.
NextBio7331.
PROP16444.
SOURCESearch...

Entry information

Entry nameDPEP1_HUMAN
AccessionPrimary (citable) accession number: P16444
Secondary accession number(s): D3DX80, Q96AK2
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 156 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM