PEPD peptidase D [Homo sapiens (human)] - Gene

Summary

Official Symbol: PEPDprovided by HGNC
Official Full Name: peptidase Dprovided by HGNC
Primary source: HGNC:HGNC:8840
See related: Ensembl:ENSG00000124299 MIM:613230; AllianceGenome:HGNC:8840
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PROLIDASE
Summary: 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]
Expression: Broad expression in kidney (RPKM 221.6), small intestine (RPKM 95.0) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.11

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (33386950..33521791, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (35906727..36042546, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (33877856..34012697, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

KLF6 activates Sp1-mediated prolidase transcription during TGF-beta1 signaling.
Title: KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling.
Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency.
Title: Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency.
The relationship between serum prolidase activity and histone H3 protein levels and fibromyalgia.
Title: The relationship between serum prolidase activity and histone H3 protein levels and fibromyalgia.
Loss of peptidase D binding restores the tumor suppressor functions of oncogenic p53 mutants.
Title: Loss of peptidase D binding restores the tumor suppressor functions of oncogenic p53 mutants.
Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis.
Title: Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis.
Co-expression with chaperones can affect protein 3D structure as exemplified by loss-of-function variants of human prolidase.
Title: Co-expression with chaperones can affect protein 3D structure as exemplified by loss-of-function variants of human prolidase.
Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, beta1-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.
Title: Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β(1)-integrin, and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts.
Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase.
Title: Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase.
A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells.
Title: A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells.
We found that prolidase levels are significantly higher in PCOS (polycystic ovary syndrome), but that rs267606943 is not associated with prolidase levels. Moreover, no allelic frequency and genotype difference was observed between the PCOS and the control group, providing an insight that rs267606943 is also not associated with the risk of PCOS
Title: The role of rs267606943 polymorphism in the prolidase gene and plasma prolidase in polycystic ovary syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (72)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Prolidase deficiency MedGen: C0268532 OMIM: 170100 GeneReviews: Prolidase Deficiency	not available

EBI GWAS Catalog

Description
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. EBI GWAS Catalog EBI GWAS CatalogPubMed
A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S719 (e-PCR), detects polymorphism
- UniSTS:39432

GDB:374532 (e-PCR)
- UniSTS:156958

GDB:374535 (e-PCR)
- UniSTS:156959

GDB:362655 (e-PCR)
- UniSTS:156751

GDB:362661 (e-PCR)
- UniSTS:156752

GDB:362665 (e-PCR)
- UniSTS:156753

GDB:362670 (e-PCR)
- UniSTS:156754

GDB:362675 (e-PCR)
- UniSTS:156755

STS-W87536 (e-PCR)
- UniSTS:73308

SHGC-33750 (e-PCR)
- UniSTS:31581

RH11766 (e-PCR)
- UniSTS:51111

RH47236 (e-PCR)
- UniSTS:45484

PEPD__5665 (e-PCR)
- UniSTS:463790

D19S1004 (e-PCR)
- UniSTS:71145

SHGC-132252 (e-PCR)
- UniSTS:170735

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables manganese ion binding	IEA Inferred from Electronic Annotation more info
enables metalloaminopeptidase activity	IEA Inferred from Electronic Annotation more info
enables metallocarboxypeptidase activity	TAS Traceable Author Statement more info	PubMed
enables peptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables proline dipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amino acid metabolic process	TAS Traceable Author Statement more info	PubMed
involved_in collagen catabolic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of programmed cell death	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed

General protein information

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Preferred Names: xaa-Pro dipeptidase

Names: X-Pro dipeptidase; aminoacyl-L-proline hydrolase; imidodipeptidase; proline dipeptidase; testicular tissue protein Li 138

NP_000276.2

EC 3.4.13.9

NP_001159528.1

EC 3.4.13.9

NP_001159529.1

EC 3.4.13.9

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013358.2 RefSeqGene

Range

5103..139944

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000285.4 → NP_000276.2 xaa-Pro dipeptidase isoform 1

See identical proteins and their annotated locations for NP_000276.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AW512991, BC015027

Consensus CDS

CCDS42544.1

UniProtKB/Swiss-Prot

A8K3Z1, A8K416, A8K696, A8MX47, B4DDB7, B4DGJ1, E9PCE8, P12955, Q8TBN9, Q9BT75

UniProtKB/TrEMBL

A0A140VJR2, J3K000

Related

ENSP00000244137.5, ENST00000244137.12

Conserved Domains (2) summary

smart01011
Location:18 → 155

AMP_N; Aminopeptidase P, N-terminal domain

cd01087
Location:192 → 467

Prolidase; Prolidase. E.C. 3.4.13.9. Also known as Xaa-Pro dipeptidase, X-Pro dipeptidase, proline dipeptidase., imidodipeptidase, peptidase D, gamma-peptidase. Catalyses hydrolysis of Xaa-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on ...
NM_001166056.2 → NP_001159528.1 xaa-Pro dipeptidase isoform 2

See identical proteins and their annotated locations for NP_001159528.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two alternate in-frame exons in the central coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AK294619, AW512991

Consensus CDS

CCDS54245.1

UniProtKB/TrEMBL

A0A8V8TNF2

Related

ENSP00000380226.3, ENST00000397032.8

Conserved Domains (3) summary

smart01011
Location:18 → 155

AMP_N; Aminopeptidase P, N-terminal domain

COG0006
Location:60 → 435

PepP; Xaa-Pro aminopeptidase [Amino acid transport and metabolism]

cd01087
Location:160 → 426

Prolidase; Prolidase. E.C. 3.4.13.9. Also known as Xaa-Pro dipeptidase, X-Pro dipeptidase, proline dipeptidase., imidodipeptidase, peptidase D, gamma-peptidase. Catalyses hydrolysis of Xaa-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on ...
NM_001166057.2 → NP_001159529.1 xaa-Pro dipeptidase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate in-frame exons in the central coding region, compared to variant 1. The resulting isoform (3) lacks an internal segment, compared to isoform 1.

Source sequence(s)

AK293126, AW512991, BC015027, DC395475

Consensus CDS

CCDS54244.1

UniProtKB/TrEMBL

A0A8V8TLP2

Related

ENSP00000391890.2, ENST00000436370.7

Conserved Domains (2) summary

cd01087
Location:128 → 403

Prolidase; Prolidase. E.C. 3.4.13.9. Also known as Xaa-Pro dipeptidase, X-Pro dipeptidase, proline dipeptidase., imidodipeptidase, peptidase D, gamma-peptidase. Catalyses hydrolysis of Xaa-Pro dipeptides; also acts on aminoacyl-hydroxyproline analogs. No action on ...

cl23800
Location:18 → 67

Creatinase_N; Creatinase/Prolidase N-terminal domain