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Protein

Xaa-Pro dipeptidase

Gene

PEPD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • cellular amino acid metabolic process Source: ProtInc
  • collagen catabolic process Source: UniProtKB-KW
  • proteolysis Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Dipeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Collagen degradation

Keywords - Ligandi

Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS04757-MONOMER.
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

HGNCiHGNC:8840. PEPD.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
Complete GO annotation...

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 rs121917722dbSNPEnsembl.1
Natural variantiVAR_004404276D → N in PD. 1 PublicationCorresponds to variant rs121917721dbSNPEnsembl.1
Natural variantiVAR_011615278G → D in PD. 1 PublicationCorresponds to variant rs121917723dbSNPEnsembl.1
Natural variantiVAR_004405448G → R in PD. 3 PublicationsCorresponds to variant rs121917724dbSNPEnsembl.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.

2D gel databases

REPRODUCTION-2DPAGEIPI00257882.

PTM databases

iPTMnetiP12955.
PhosphoSitePlusiP12955.
SwissPalmiP12955.

Expressioni

Gene expression databases

BgeeiENSG00000124299.
CleanExiHS_PEPD.
ExpressionAtlasiP12955. baseline and differential.
GenevisibleiP12955. HS.

Organism-specific databases

HPAiHPA015599.

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi111208. 40 interactors.
DIPiDIP-50038N.
IntActiP12955. 10 interactors.
MINTiMINT-5000488.
STRINGi9606.ENSP00000244137.

Chemistry databases

BindingDBiP12955.

Structurei

Secondary structure

1493
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi21 – 36Combined sources16
Beta strandi45 – 49Combined sources5
Beta strandi54 – 56Combined sources3
Helixi69 – 75Combined sources7
Beta strandi79 – 81Combined sources3
Beta strandi83 – 87Combined sources5
Turni88 – 90Combined sources3
Beta strandi93 – 97Combined sources5
Helixi102 – 104Combined sources3
Turni105 – 107Combined sources3
Helixi114 – 121Combined sources8
Beta strandi124 – 128Combined sources5
Helixi129 – 131Combined sources3
Helixi132 – 138Combined sources7
Turni152 – 154Combined sources3
Helixi166 – 168Combined sources3
Helixi176 – 185Combined sources10
Helixi189 – 212Combined sources24
Helixi219 – 234Combined sources16
Beta strandi238 – 241Combined sources4
Beta strandi244 – 247Combined sources4
Helixi248 – 252Combined sources5
Beta strandi272 – 277Combined sources6
Beta strandi279 – 281Combined sources3
Beta strandi288 – 293Combined sources6
Helixi300 – 319Combined sources20
Helixi326 – 343Combined sources18
Helixi351 – 356Combined sources6
Turni357 – 359Combined sources3
Helixi360 – 363Combined sources4
Beta strandi373 – 377Combined sources5
Helixi394 – 396Combined sources3
Beta strandi408 – 411Combined sources4
Beta strandi414 – 416Combined sources3
Helixi419 – 427Combined sources9
Helixi429 – 432Combined sources4
Helixi437 – 443Combined sources7
Beta strandi448 – 450Combined sources3
Beta strandi452 – 457Combined sources6
Beta strandi459 – 464Combined sources6
Helixi472 – 479Combined sources8

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[»]
ProteinModelPortaliP12955.
SMRiP12955.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12955.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.350.10. 1 hit.
3.90.230.10. 1 hit.
InterProiIPR007865. Aminopep_P_N.
IPR029149. Creatin/AminoP/Spt16_NTD.
IPR028980. Creatinase/Aminopeptidase_P_N.
IPR000994. Pept_M24.
IPR001131. Peptidase_M24B_aminopep-P_CS.
[Graphical view]
PfamiPF05195. AMP_N. 1 hit.
PF00557. Peptidase_M24. 1 hit.
[Graphical view]
SMARTiSM01011. AMP_N. 1 hit.
[Graphical view]
SUPFAMiSSF53092. SSF53092. 1 hit.
SSF55920. SSF55920. 1 hit.
PROSITEiPS00491. PROLINE_PEPTIDASE. 1 hit.
[Graphical view]

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

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

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 rs121917722dbSNPEnsembl.1
Natural variantiVAR_004404276D → N in PD. 1 PublicationCorresponds to variant rs121917721dbSNPEnsembl.1
Natural variantiVAR_011615278G → D in PD. 1 PublicationCorresponds to variant rs121917723dbSNPEnsembl.1
Natural variantiVAR_051574388R → H.Corresponds to variant rs2230062dbSNPEnsembl.1
Natural variantiVAR_014723435L → F.2 PublicationsCorresponds to variant rs17570dbSNPEnsembl.1
Natural variantiVAR_004405448G → R in PD. 3 PublicationsCorresponds to variant rs121917724dbSNPEnsembl.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

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[»]
ProteinModelPortaliP12955.
SMRiP12955.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111208. 40 interactors.
DIPiDIP-50038N.
IntActiP12955. 10 interactors.
MINTiMINT-5000488.
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-2DPAGEIPI00257882.

Proteomic databases

EPDiP12955.
MaxQBiP12955.
PaxDbiP12955.
PeptideAtlasiP12955.
PRIDEiP12955.

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.
GeneCardsiPEPD.
HGNCiHGNC:8840. PEPD.
HPAiHPA015599.
MalaCardsiPEPD.
MIMi170100. phenotype.
613230. gene.
neXtProtiNX_P12955.
OpenTargetsiENSG00000124299.
Orphaneti742. Prolidase deficiency.
PharmGKBiPA33181.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS04757-MONOMER.
BRENDAi3.4.13.9. 2681.

Miscellaneous databases

ChiTaRSiPEPD. human.
EvolutionaryTraceiP12955.
GeneWikiiPEPD.
GenomeRNAii5184.
PROiP12955.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124299.
CleanExiHS_PEPD.
ExpressionAtlasiP12955. baseline and differential.
GenevisibleiP12955. HS.

Family and domain databases

Gene3Di3.40.350.10. 1 hit.
3.90.230.10. 1 hit.
InterProiIPR007865. Aminopep_P_N.
IPR029149. Creatin/AminoP/Spt16_NTD.
IPR028980. Creatinase/Aminopeptidase_P_N.
IPR000994. Pept_M24.
IPR001131. Peptidase_M24B_aminopep-P_CS.
[Graphical view]
PfamiPF05195. AMP_N. 1 hit.
PF00557. Peptidase_M24. 1 hit.
[Graphical view]
SMARTiSM01011. AMP_N. 1 hit.
[Graphical view]
SUPFAMiSSF53092. SSF53092. 1 hit.
SSF55920. SSF55920. 1 hit.
PROSITEiPS00491. PROLINE_PEPTIDASE. 1 hit.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 194 of the entry and version 3 of the sequence. [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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.