PEPD

Protein identityUniProt · HPA

UniProt accession

P12955

Gene

PEPD

Ensembl

ENSG00000124299

Chromosome

19

Canonical length

493 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the peptidase family. The protein forms a homodimer that hydrolyzes dipeptides or tripeptides with C-terminal proline or hydroxyproline residues. The enzyme serves an important role in the recycling of proline, and may be rate limiting for the production of collagen. Mutations in this gene result in prolidase deficiency, which is characterized by the excretion of large amount of di- and tri-peptides containing proline. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

493 residues, UniProt reviewed canonical sequence.

>P12955|PEPD
     1  MAAATGPSFW LGNETLKVPL ALFALNRQRL CERLRKNPAV QAGSIVVLQG GEETQRYCTD
    61  TGVLFRQESF FHWAFGVTEP GCYGVIDVDT GKSTLFVPRL PASHATWMGK IHSKEHFKEK
   121  YAVDDVQYVD EIASVLTSQK PSVLLTLRGV NTDSGSVCRE ASFDGISKFE VNNTILHPEI
   181  VECRVFKTDM ELEVLRYTNK ISSEAHREVM KAVKVGMKEY ELESLFEHYC YSRGGMRHSS
   241  YTCICGSGEN SAVLHYGHAG APNDRTIQNG DMCLFDMGGE YYCFASDITC SFPANGKFTA
   301  DQKAVYEAVL RSSRAVMGAM KPGVWWPDMH RLADRIHLEE LAHMGILSGS VDAMVQAHLG
   361  AVFMPHGLGH FLGIDVHDVG GYPEGVERID EPGLRSLRTA RHLQPGMVLT VEPGIYFIDH
   421  LLDEALADPA RASFLNREVL QRFRGFGGVR IEEDVVVTDS GIELLTCVPR TVEEIEACMA
   481  GCDKAFTPFS GPK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PEPD can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Unknown

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

310 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PEPD.

Disease | AllUniProt

Conditions PEPD is implicated in, by any mechanism.

• Prolidase deficiency (PD) MIM:170100

Disease | GeneticClinVar

79 pathogenic / likely-pathogenic of 816 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Prolidase deficiency
• Thyroid cancer, nonmedullary, 1
• PEPD-related disorder
• Melanoma
• Nonpapillary renal cell carcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.26

gnomAD pLI

0

gnomAD missense Z

-0.18

DepMap mean gene effect

0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amino acid metabolic process
• collagen catabolic process
• negative regulation of programmed cell death
• proteolysis

Molecular functions

• manganese ion binding
• metalloaminopeptidase activity
• metallocarboxypeptidase activity
• peptidase activity
• proline dipeptidase activity

Cellular components

• extracellular exosome

Protein domainsUniProt · Pfam · InterPro

• Peptidase M24
• Peptidase M24B, X-Pro dipeptidase/aminopeptidase P, conserved site
• Aminopeptidase P, N-terminal
• Creatinase/Aminopeptidase P/Spt16, N-terminal
• Creatinase/aminopeptidase-like
• Xaa-Pro dipeptidase-like
• Metallopeptidase family M24
• Aminopeptidase P, N-terminal domain

KeywordsUniProt

• Acetylation
• Collagen degradation
• Dipeptidase
• Hydrolase
• Manganese
• Metal-binding
• Metalloprotease
• Phosphoprotein
• Protease