P16444 (DPEP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	411 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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-anchor › GPI-anchor. Cell projection › microvillus membrane; Lipid-anchor › GPI-anchor. Note: Brush border membrane.
Sequence similarities	Belongs to the peptidase M19 family.

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Membrane
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Dipeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antibiotic metabolic process Inferred from direct assay PubMed 8737157. Source: UniProtKB 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 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 proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	anchored to 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 microvillus membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.13. Source: UniProtKB
Molecular_function	GPI 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 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
KIAA1279	Q96EK5	2	EBI-749514,EBI-744150

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.7 Ref.8 Ref.9

Chain

17 – 385

369

Dipeptidase 1

PRO_0000018652

Propeptide

386 – 411

26

Removed in mature form

PRO_0000018653

Sites

Metal binding

36

1

Zinc 1; catalytic

Metal binding

38

1

Zinc 1; catalytic

Metal binding

141

1

Zinc 1; catalytic

Metal binding

141

1

Zinc 2; catalytic

Metal binding

214

1

Zinc 2; catalytic

Metal binding

235

1

Zinc 2; catalytic

Binding site

168

1

Substrate

Binding site

246

1

Substrate

Binding site

304

1

Substrate

Amino acid modifications

Lipidation

385

1

GPI-anchor amidated serine Ref.10

Glycosylation

57

1

N-linked (GlcNAc...) Ref.12 Ref.13

Glycosylation

279

1

N-linked (GlcNAc...) Ref.12

Glycosylation

332

1

N-linked (GlcNAc...) Ref.13

Glycosylation

358

1

N-linked (GlcNAc...) Potential

Disulfide bond

87 ↔ 170

Ref.13

Disulfide bond

242 ↔ 274

Ref.13

Disulfide bond

377

Interchain Ref.13

Natural variations

Natural variant

246

1

R → H in a colorectal cancer sample; somatic mutation. Ref.14

VAR_036496

Natural variant

351

1

E → K.
Corresponds to variant rs1126464 [ dbSNP | Ensembl ].

VAR_061375

Natural variant

351

1

E → Q.
Corresponds to variant rs1126464 [ dbSNP | Ensembl ].

VAR_061376

Experimental info

Mutagenesis

141

1

E → D or C: Complete loss of activity.

Mutagenesis

141

1

E → Q: Partial loss of activity.

Sequence conflict

9

1

P → S Ref.1

Sequence conflict

9

1

P → S Ref.3

Sequence conflict

102

1

M → R Ref.2

Sequence conflict

125

1

I → R Ref.2

Secondary structure

1

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411

Helix Strand Turn

Details...

Helix

18 – 27

10

Beta strand

32 – 37

6

Helix

39 – 47

9

Helix

54 – 56

3

Turn

58 – 60

3

Beta strand

63 – 65

3

Helix

68 – 73

6

Beta strand

76 – 83

8

Helix

87 – 89

3

Turn

90 – 93

4

Helix

94 – 111

18

Turn

113 – 115

3

Beta strand

116 – 118

3

Helix

122 – 131

10

Beta strand

134 – 141

8

Helix

143 – 146

4

Helix

150 – 158

9

Beta strand

161 – 166

6

Beta strand

168 – 170

3

Beta strand

173 – 175

3

Helix

178 – 180

3

Turn

181 – 183

3

Beta strand

188 – 192

5

Helix

194 – 206

13

Beta strand

209 – 211

3

Helix

217 – 226

10

Beta strand

232 – 235

4

Turn

239 – 241

3

Helix

250 – 259

10

Beta strand

262 – 265

4

Helix

269 – 272

4

Beta strand

274 – 276

3

Helix

280 – 294

15

Helix

296 – 298

3

Beta strand

299 – 301

3

Turn

305 – 307

3

Helix

321 – 330

10

Helix

335 – 342

8

Helix

344 – 356

13

Beta strand

359 – 361

3

Helix

370 – 372

3

Beta strand

375 – 377

3

Turn

381 – 383

3

Sequences

	Sequence		Length	Mass (Da)
	P16444 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: C8C6474C3479D20D	FASTA	411	45,674
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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. , 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.

IPI

IPI00059476.

PIR

S29848.

RefSeq

NP_001121613.1. NM_001128141.2.
NP_004404.1. NM_004413.3.

UniGene

Hs.109.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P16444.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16444. 1 interaction.

MINT

MINT-5000950.

STRING

9606.ENSP00000261615.

Protein family/group databases

MEROPS

M19.001.

PTM databases

PhosphoSite

P16444.

Polymorphism databases

DMDM

92090943.

Proteomic databases

PaxDb

P16444.

PRIDE

P16444.

Protocols and materials databases

DNASU

1800.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261615; ENSP00000261615; ENSG00000015413.
ENST00000393092; ENSP00000376807; ENSG00000015413.
ENST00000421184; ENSP00000397313; ENSG00000015413.

GeneID

1800.

KEGG

hsa:1800.

UCSC

uc002fnr.4. human.

Organism-specific databases

CTD

1800.

GeneCards

GC16P089679.

HGNC

HGNC:3002. DPEP1.

HPA

HPA009426.
HPA012783.

MIM

179780. gene.

neXtProt

NX_P16444.

PharmGKB

PA144.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2355.

HOGENOM

HOG000072016.

HOVERGEN

HBG002339.

InParanoid

P16444.

KO

K01273.

OMA

FDGVPRV.

OrthoDB

EOG4CVG74.

PhylomeDB

P16444.

Enzyme and pathway databases

BioCyc

MetaCyc:HS00367-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P16444.

Gene expression databases

ArrayExpress

P16444.

Bgee

P16444.

CleanEx

HS_DPEP1.

Genevestigator

P16444.

GermOnline

ENSG00000015413. Homo sapiens.

Family and domain databases

InterPro

IPR000180. Pept_M19_AS.
IPR008257. Peptidase_M19.
[Graphical view]

PANTHER

PTHR10443. PTHR10443. 1 hit.

Pfam

PF01244. Peptidase_M19. 1 hit.
[Graphical view]

PROSITE

PS00869. RENAL_DIPEPTIDASE_1. 1 hit.
PS51365. RENAL_DIPEPTIDASE_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P16444.

ChEMBL

CHEMBL1989.

DrugBank

DB01597. Cilastatin.

EvolutionaryTrace

P16444.

GenomeRNAi

1800.

NextBio

7331.

SOURCE

Search...

Entry information

Entry name

DPEP1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 146 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.