P22412 (DPEP1_PIG) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dipeptidase 1
EC=3.4.13.19

Alternative name(s):
Microsomal dipeptidase
Renal dipeptidase

Gene names

Name:	DPEP1
Synonyms:	RDP

Organism

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	409 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.
Enzyme regulation	Inhibited by L-penicillamine By similarity.
Subunit structure	Homodimer; disulfide-linked. Ref.4
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
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Dipeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	GPI anchor release Inferred from direct assay PubMed 17615681. Source: UniProtKB antibiotic metabolic process Inferred from sequence or structural similarity. Source: UniProtKB cellular response to calcium ion Inferred from direct assay PubMed 11139399PubMed 17615681. Source: UniProtKB cellular response to drug Inferred from sequence or structural similarity. Source: UniProtKB cellular response to insulin stimulus Inferred from direct assay PubMed 17615681. Source: UniProtKB cellular response to nitric oxide Inferred from direct assay PubMed 11988094. Source: UniProtKB homocysteine metabolic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell migration Inferred from sequence or structural similarity. 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 sequence or structural similarity. Source: UniProtKB apical plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from direct assay PubMed 17615681. Source: UniProtKB extracellular space Inferred from direct assay PubMed 11139399. Source: UniProtKB microvillus membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay PubMed 11139399PubMed 11988094PubMed 17615681. Source: UniProtKB
Molecular_function	GPI anchor binding Inferred from direct assay PubMed 11139399PubMed 11988094. Source: UniProtKB cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB dipeptidyl-peptidase activity Inferred from electronic annotation. Source: InterPro metallodipeptidase activity Inferred from sequence or structural similarity. Source: UniProtKB modified amino acid binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Ref.3
	Chain	17 – 384	368	Dipeptidase 1		PRO_0000018656
	Propeptide	385 – 409	25	Removed in mature form By similarity		PRO_0000018657
Sites
	Metal binding	36	1	Zinc 1; catalytic By similarity
	Metal binding	38	1	Zinc 1; catalytic By similarity
	Metal binding	141	1	Zinc 1; catalytic By similarity
	Metal binding	141	1	Zinc 2; catalytic By similarity
	Metal binding	214	1	Zinc 2; catalytic By similarity
	Metal binding	235	1	Zinc 2; catalytic By similarity
	Binding site	168	1	Substrate By similarity
	Binding site	246	1	Substrate By similarity
	Binding site	304	1	Substrate By similarity
Amino acid modifications
	Lipidation	384	1	GPI-anchor amidated serine Ref.5
	Glycosylation	57	1	N-linked (GlcNAc...) Ref.1
	Glycosylation	279	1	N-linked (GlcNAc...) Potential
	Disulfide bond	87 ↔ 170		By similarity
	Disulfide bond	242 ↔ 274		By similarity
	Disulfide bond	377		Interchain Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P22412 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 926B7F0044FA055F	FASTA	409	44,700
	10 20 30 40 50 60 MWTSWWLWPL VAVCAADQFR DLAVRIMQDT PVIDGHNDLP WQLLNLFNNQ LQDPGANLSS 70 80 90 100 110 120 LAHTHTNIPK LKAGFVGGQF WSAYVPCDTQ NRDAVKRTLE QIDVIQRMCQ AYPETFACVT 130 140 150 160 170 180 SSTGIRQAFR EGKVASLVGV EGGHSIDSSL GVLRALYHLG MRYMTLTHSC NTPWADNWLV 190 200 210 220 230 240 DTGDDKAQSQ GLSHFGQSVV KEMNRLGVMI DLAHVSVATM RAALKLSQAP VIFSHSSAYS 250 260 270 280 290 300 LCPHRRNVPD DVLQLVKETG SLVMVNFYND YVSCSAKANL SQVADHLDHI KKVAGAAAVG 310 320 330 340 350 360 FGGDYDGVSR VPSGLEDVSK YPDLVAELLR RQWTEAEVRG ALADNLLRVF EAVEQASNHA 370 380 390 400 QVPGEEPIPL GQLEASCRTN YGYSAAPSLH LPPGSLLASL VPLLLLSLP

References

[1]	"cDNA cloning and expression in Xenopus laevis oocytes of pig renal dipeptidase, a glycosyl-phosphatidylinositol-anchored ectoenzyme." Rached E., Hooper N.M., James P., Semenza G., Turner A.J., Mantei N. Biochem. J. 271:755-760(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-57. Tissue: Kidney cortex.
[2]	"Purification and cDNA cloning for porcine renal dipeptidase." Satoh S., Koyama S., Ohtuka K., Keida Y., Niwa M., Kohsaka M. Submitted (SEP-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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 17-39.
[4]	"Site-directed mutagenesis of conserved cysteine residues in porcine membrane dipeptidase. Cys-361 alone is involved in disulfide-linked dimerization." Keynan S., Habgood N.T., Hooper N.M., Turner A.J. Biochemistry 35:12511-12517(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERCHAIN DISULFIDE BOND.
[5]	"Isolation and characterization of glycosylphosphatidylinositol-anchored peptides by hydrophilic interaction chromatography and MALDI tandem mass spectrometry." Omaetxebarria M.J., Hagglund P., Elortza F., Hooper N.M., Arizmendi J.M., Jensen O.N. Anal. Chem. 78:3335-3341(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR AT SER-384, MASS SPECTROMETRY.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X53730 mRNA. Translation: CAA37762.1. D13142 mRNA. Translation: BAA02433.1.
PIR	JS0759.
RefSeq	NP_999273.1. NM_214108.1.
UniGene	Ssc.315.
3D structure databases
ProteinModelPortal	P22412.
SMR	P22412. Positions 17-385.
ModBase	Search...
Protein family/group databases
MEROPS	M19.001.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	397196.
KEGG	ssc:397196.
Organism-specific databases
CTD	1800.
Phylogenomic databases
HOVERGEN	HBG002339.
KO	K01273.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-9981.
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	P22412.
ChEMBL	CHEMBL2626.

Entry information

Entry name

DPEP1_PIG

Accession

Primary (citable) accession number: P22412

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	April 3, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program