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Protein

Xaa-Pro dipeptidase

Gene

PEPD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.

Catalytic activityi

Hydrolysis of Xaa-|-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on Pro-|-Pro.

Cofactori

Mn2+1 PublicationNote: Binds 2 manganese ions per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi276Manganese 11
Metal bindingi287Manganese 11
Metal bindingi287Manganese 21
Metal bindingi370Manganese 21
Metal bindingi412Manganese 21
Metal bindingi452Manganese 11
Metal bindingi452Manganese 21

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDipeptidase, Hydrolase, Metalloprotease, Protease
Biological processCollagen degradation
LigandManganese, Metal-binding

Enzyme and pathway databases

BRENDAi3.4.13.9 2681

Protein family/group databases

MEROPSiM24.007

Names & Taxonomyi

Protein namesi
Recommended name:
Xaa-Pro dipeptidase (EC:3.4.13.9)
Short name:
X-Pro dipeptidase
Alternative name(s):
Imidodipeptidase
Peptidase D
Proline dipeptidase
Short name:
Prolidase
Gene namesi
Name:PEPD
Synonyms:PRD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000124299.13
HGNCiHGNC:8840 PEPD
MIMi613230 gene
neXtProtiNX_P12955

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Prolidase deficiency (PD)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA multisystem disorder associated with massive iminodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. Clinical features include skin ulcers, developmental delay, recurrent infections, and a characteristic facies.
See also OMIM:170100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011614184R → Q in PD. 1 PublicationCorresponds to variant dbSNP:rs121917722EnsemblClinVar.1
Natural variantiVAR_004404276D → N in PD. 1 PublicationCorresponds to variant dbSNP:rs121917721EnsemblClinVar.1
Natural variantiVAR_011615278G → D in PD. 1 PublicationCorresponds to variant dbSNP:rs121917723EnsemblClinVar.1
Natural variantiVAR_004405448G → R in PD. 3 PublicationsCorresponds to variant dbSNP:rs121917724EnsemblClinVar.1
Natural variantiVAR_004406452Missing in PD. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5184
MalaCardsiPEPD
MIMi170100 phenotype
OpenTargetsiENSG00000124299
Orphaneti742 Prolidase deficiency
PharmGKBiPA33181

Chemistry databases

ChEMBLiCHEMBL4185

Polymorphism and mutation databases

BioMutaiPEPD
DMDMi50403718

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001850872 – 493Xaa-Pro dipeptidaseAdd BLAST492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei167PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP12955
MaxQBiP12955
PaxDbiP12955
PeptideAtlasiP12955
PRIDEiP12955
ProteomicsDBi52886
52887 [P12955-2]

2D gel databases

REPRODUCTION-2DPAGEiIPI00257882

PTM databases

iPTMnetiP12955
PhosphoSitePlusiP12955
SwissPalmiP12955

Expressioni

Gene expression databases

BgeeiENSG00000124299 Expressed in 219 organ(s), highest expression level in nephron tubule
CleanExiHS_PEPD
ExpressionAtlasiP12955 baseline and differential
GenevisibleiP12955 HS

Organism-specific databases

HPAiHPA015599
HPA072045

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF1P542742EBI-948765,EBI-710997

Protein-protein interaction databases

BioGridi111208, 42 interactors
DIPiDIP-50038N
IntActiP12955, 14 interactors
STRINGi9606.ENSP00000244137

Chemistry databases

BindingDBiP12955

Structurei

Secondary structure

1493
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP12955
SMRiP12955
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12955

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2737 Eukaryota
COG0006 LUCA
GeneTreeiENSGT00550000074992
HOGENOMiHOG000008763
HOVERGENiHBG053562
InParanoidiP12955
KOiK14213
OMAiHALFFPH
OrthoDBiEOG091G0BAV
PhylomeDBiP12955
TreeFamiTF313396

Family and domain databases

Gene3Di3.40.350.10, 1 hit
InterProiView protein in InterPro
IPR007865 Aminopep_P_N
IPR029149 Creatin/AminoP/Spt16_NTD
IPR036005 Creatinase/aminopeptidase-like
IPR000994 Pept_M24
IPR001131 Peptidase_M24B_aminopep-P_CS
PfamiView protein in Pfam
PF05195 AMP_N, 1 hit
PF00557 Peptidase_M24, 1 hit
SMARTiView protein in SMART
SM01011 AMP_N, 1 hit
SUPFAMiSSF53092 SSF53092, 1 hit
SSF55920 SSF55920, 1 hit
PROSITEiView protein in PROSITE
PS00491 PROLINE_PEPTIDASE, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P12955-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAAATGPSFW LGNETLKVPL ALFALNRQRL CERLRKNPAV QAGSIVVLQG
60 70 80 90 100
GEETQRYCTD TGVLFRQESF FHWAFGVTEP GCYGVIDVDT GKSTLFVPRL
110 120 130 140 150
PASHATWMGK IHSKEHFKEK YAVDDVQYVD EIASVLTSQK PSVLLTLRGV
160 170 180 190 200
NTDSGSVCRE ASFDGISKFE VNNTILHPEI VECRVFKTDM ELEVLRYTNK
210 220 230 240 250
ISSEAHREVM KAVKVGMKEY ELESLFEHYC YSRGGMRHSS YTCICGSGEN
260 270 280 290 300
SAVLHYGHAG APNDRTIQNG DMCLFDMGGE YYCFASDITC SFPANGKFTA
310 320 330 340 350
DQKAVYEAVL RSSRAVMGAM KPGVWWPDMH RLADRIHLEE LAHMGILSGS
360 370 380 390 400
VDAMVQAHLG AVFMPHGLGH FLGIDVHDVG GYPEGVERID EPGLRSLRTA
410 420 430 440 450
RHLQPGMVLT VEPGIYFIDH LLDEALADPA RASFLNREVL QRFRGFGGVR
460 470 480 490
IEEDVVVTDS GIELLTCVPR TVEEIEACMA GCDKAFTPFS GPK
Length:493
Mass (Da):54,548
Last modified:January 23, 2007 - v3
Checksum:iE8C4A2497E44BA22
GO
Isoform 2 (identifier: P12955-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     184-224: Missing.

Note: No experimental confirmation available.
Show »
Length:452
Mass (Da):49,691
Checksum:iEA1B0DFBE694A180
GO
Isoform 3 (identifier: P12955-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     68-131: Missing.

Note: No experimental confirmation available.
Show »
Length:429
Mass (Da):47,261
Checksum:i2D094B4069E39CF5
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
V9GYL0V9GYL0_HUMAN
Xaa-Pro dipeptidase
PEPD
42Annotation score:
K7ES25K7ES25_HUMAN
Xaa-Pro dipeptidase
PEPD
194Annotation score:
V9GYE4V9GYE4_HUMAN
Xaa-Pro dipeptidase
PEPD
55Annotation score:
V9GY89V9GY89_HUMAN
Xaa-Pro dipeptidase
PEPD
104Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48L → R in BAF84250 (PubMed:14702039).Curated1
Sequence conflicti66R → L in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti107W → R in BAF83470 (PubMed:14702039).Curated1
Sequence conflicti108M → I in BAF83445 (PubMed:14702039).Curated1
Sequence conflicti183C → S in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti221E → G in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti283 – 284CF → SV in AAA60064 (PubMed:2925654).Curated2
Sequence conflicti294A → R in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti311R → L in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti324V → D in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti329 – 330MH → ID in AAA60064 (PubMed:2925654).Curated2
Sequence conflicti408V → A in BAG56678 (PubMed:14702039).Curated1
Sequence conflicti458T → I in AAA60064 (PubMed:2925654).Curated1
Sequence conflicti478C → R in BAF83470 (PubMed:14702039).Curated1

Mass spectrometryi

Molecular mass is 54251.73 Da from positions 2 - 493. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_011614184R → Q in PD. 1 PublicationCorresponds to variant dbSNP:rs121917722EnsemblClinVar.1
Natural variantiVAR_004404276D → N in PD. 1 PublicationCorresponds to variant dbSNP:rs121917721EnsemblClinVar.1
Natural variantiVAR_011615278G → D in PD. 1 PublicationCorresponds to variant dbSNP:rs121917723EnsemblClinVar.1
Natural variantiVAR_051574388R → H. Corresponds to variant dbSNP:rs2230062EnsemblClinVar.1
Natural variantiVAR_014723435L → F2 PublicationsCorresponds to variant dbSNP:rs17570EnsemblClinVar.1
Natural variantiVAR_004405448G → R in PD. 3 PublicationsCorresponds to variant dbSNP:rs121917724EnsemblClinVar.1
Natural variantiVAR_004406452Missing in PD. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04537068 – 131Missing in isoform 3. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_042629184 – 224Missing in isoform 2. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04605 mRNA Translation: AAA60064.1
BT006692 mRNA Translation: AAP35338.1
AK290756 mRNA Translation: BAF83445.1
AK290781 mRNA Translation: BAF83470.1
AK291561 mRNA Translation: BAF84250.1
AK293126 mRNA Translation: BAG56678.1
AK294619 mRNA Translation: BAG57802.1
AC008744 Genomic DNA No translation available.
AC010485 Genomic DNA No translation available.
BC004305 mRNA Translation: AAH04305.1
BC015027 mRNA Translation: AAH15027.1
BC028295 mRNA Translation: AAH28295.1
CCDSiCCDS42544.1 [P12955-1]
CCDS54244.1 [P12955-3]
CCDS54245.1 [P12955-2]
PIRiA32454
RefSeqiNP_000276.2, NM_000285.3 [P12955-1]
NP_001159528.1, NM_001166056.1 [P12955-2]
NP_001159529.1, NM_001166057.1 [P12955-3]
UniGeneiHs.36473

Genome annotation databases

EnsembliENST00000244137; ENSP00000244137; ENSG00000124299 [P12955-1]
ENST00000397032; ENSP00000380226; ENSG00000124299 [P12955-2]
ENST00000436370; ENSP00000391890; ENSG00000124299 [P12955-3]
GeneIDi5184
KEGGihsa:5184
UCSCiuc002nur.5 human [P12955-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04605 mRNA Translation: AAA60064.1
BT006692 mRNA Translation: AAP35338.1
AK290756 mRNA Translation: BAF83445.1
AK290781 mRNA Translation: BAF83470.1
AK291561 mRNA Translation: BAF84250.1
AK293126 mRNA Translation: BAG56678.1
AK294619 mRNA Translation: BAG57802.1
AC008744 Genomic DNA No translation available.
AC010485 Genomic DNA No translation available.
BC004305 mRNA Translation: AAH04305.1
BC015027 mRNA Translation: AAH15027.1
BC028295 mRNA Translation: AAH28295.1
CCDSiCCDS42544.1 [P12955-1]
CCDS54244.1 [P12955-3]
CCDS54245.1 [P12955-2]
PIRiA32454
RefSeqiNP_000276.2, NM_000285.3 [P12955-1]
NP_001159528.1, NM_001166056.1 [P12955-2]
NP_001159529.1, NM_001166057.1 [P12955-3]
UniGeneiHs.36473

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IW2X-ray1.82A/B2-493[»]
2OKNX-ray2.45A/B2-493[»]
5M4GX-ray1.48A/B6-488[»]
5M4JX-ray1.55A/B6-489[»]
5M4LX-ray1.49A/B6-489[»]
5M4QX-ray1.73A/B6-489[»]
5MBYX-ray1.55A/B6-490[»]
5MBZX-ray1.50A/B6-489[»]
5MC0X-ray1.56A/B6-486[»]
5MC1X-ray1.43A/B6-490[»]
5MC2X-ray1.70A/B6-488[»]
5MC3X-ray1.52A/B6-489[»]
5MC4X-ray1.80A/B6-487[»]
5MC5X-ray1.90A/B6-484[»]
6H2PX-ray1.48A/B1-493[»]
6H2QX-ray1.78A/B1-493[»]
ProteinModelPortaliP12955
SMRiP12955
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111208, 42 interactors
DIPiDIP-50038N
IntActiP12955, 14 interactors
STRINGi9606.ENSP00000244137

Chemistry databases

BindingDBiP12955
ChEMBLiCHEMBL4185

Protein family/group databases

MEROPSiM24.007

PTM databases

iPTMnetiP12955
PhosphoSitePlusiP12955
SwissPalmiP12955

Polymorphism and mutation databases

BioMutaiPEPD
DMDMi50403718

2D gel databases

REPRODUCTION-2DPAGEiIPI00257882

Proteomic databases

EPDiP12955
MaxQBiP12955
PaxDbiP12955
PeptideAtlasiP12955
PRIDEiP12955
ProteomicsDBi52886
52887 [P12955-2]

Protocols and materials databases

DNASUi5184
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244137; ENSP00000244137; ENSG00000124299 [P12955-1]
ENST00000397032; ENSP00000380226; ENSG00000124299 [P12955-2]
ENST00000436370; ENSP00000391890; ENSG00000124299 [P12955-3]
GeneIDi5184
KEGGihsa:5184
UCSCiuc002nur.5 human [P12955-1]

Organism-specific databases

CTDi5184
DisGeNETi5184
EuPathDBiHostDB:ENSG00000124299.13
GeneCardsiPEPD
HGNCiHGNC:8840 PEPD
HPAiHPA015599
HPA072045
MalaCardsiPEPD
MIMi170100 phenotype
613230 gene
neXtProtiNX_P12955
OpenTargetsiENSG00000124299
Orphaneti742 Prolidase deficiency
PharmGKBiPA33181
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2737 Eukaryota
COG0006 LUCA
GeneTreeiENSGT00550000074992
HOGENOMiHOG000008763
HOVERGENiHBG053562
InParanoidiP12955
KOiK14213
OMAiHALFFPH
OrthoDBiEOG091G0BAV
PhylomeDBiP12955
TreeFamiTF313396

Enzyme and pathway databases

BRENDAi3.4.13.9 2681

Miscellaneous databases

ChiTaRSiPEPD human
EvolutionaryTraceiP12955
GeneWikiiPEPD
GenomeRNAii5184
PROiPR:P12955
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124299 Expressed in 219 organ(s), highest expression level in nephron tubule
CleanExiHS_PEPD
ExpressionAtlasiP12955 baseline and differential
GenevisibleiP12955 HS

Family and domain databases

Gene3Di3.40.350.10, 1 hit
InterProiView protein in InterPro
IPR007865 Aminopep_P_N
IPR029149 Creatin/AminoP/Spt16_NTD
IPR036005 Creatinase/aminopeptidase-like
IPR000994 Pept_M24
IPR001131 Peptidase_M24B_aminopep-P_CS
PfamiView protein in Pfam
PF05195 AMP_N, 1 hit
PF00557 Peptidase_M24, 1 hit
SMARTiView protein in SMART
SM01011 AMP_N, 1 hit
SUPFAMiSSF53092 SSF53092, 1 hit
SSF55920 SSF55920, 1 hit
PROSITEiView protein in PROSITE
PS00491 PROLINE_PEPTIDASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPEPD_HUMAN
AccessioniPrimary (citable) accession number: P12955
Secondary accession number(s): A8K3Z1
, A8K416, A8K696, A8MX47, B4DDB7, B4DGJ1, E9PCE8, Q8TBN9, Q9BT75
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 209 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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