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    PEPD peptidase D [ Homo sapiens (human) ]

    Gene ID: 5184, updated on 5-Mar-2024

    Summary

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    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

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    See PEPD in Genome Data Viewer
    Location:
    19q13.11
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (33386950..33521791, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (35906727..36042546, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (33877856..34012697, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene aldo-keto reductase family 1 member B1 pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10497 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33868709-33869402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33880343-33881245 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33883417-33884181 Neighboring gene CCAAT enhancer binding protein gamma Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:33886169-33886998 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:33886999-33887828 Neighboring gene uncharacterized LOC124904692 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:33897606-33898163 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14446 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33909297-33910182 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33976998-33977858 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33977859-33978718 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:33978719-33979578 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr19:33994022-33994738 Neighboring gene OCT4-H3K4me1 hESC enhancer GRCh37_chr19:34001184-34001982 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:34011998-34012961 Neighboring gene uncharacterized LOC105372370 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:34012962-34013924 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:34024395-34024912 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:34024913-34025429 Neighboring gene uncharacterized LOC100996681

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. The relationship between serum prolidase activity and histone H3 protein levels and fibromyalgia. Ozturk A, et al. Eur Rev Med Pharmacol Sci, 2022 Dec. PMID 36591822
    2. Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency. Erol Koc EM, et al. Eur J Obstet Gynecol Reprod Biol, 2023 Feb. PMID 36521400
    3. Co-expression with chaperones can affect protein 3D structure as exemplified by loss-of-function variants of human prolidase. Wątor E, et al. FEBS Lett, 2020 Sep. PMID 32598484
    4. A Novel Role of Prolidase in Cocaine-Mediated Breach in the Barrier of Brain Microvascular Endothelial Cells. Ysrayl BB, et al. Sci Rep, 2019 Feb 22. PMID 30796241, Free PMC Article
    5. Plasma prolidase levels as a biomarker for polycystic ovary syndrome. Bhatnager R, et al. Biomark Med, 2018 Jun. PMID 29873502

    See all (123) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. KLF6 activates Sp1-mediated prolidase transcription during TGF-beta1 signaling.
      Title: KLF6 activates Sp1-mediated prolidase transcription during TGF-β(1) signaling.
    2. Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency.
      Title: Prolidase as a marker of fibrogenesis in idiopathic primary ovarian insufficiency.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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
    		Compare labs

    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
    A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
    EBI GWAS Catalog
    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC10905

    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 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
    NP_001159528.1
    NP_001159529.1

    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

    1. NG_013358.2 RefSeqGene

      Range
      5103..139944
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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 ...

    2. 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 ...

    3. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      33386950..33521791 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      35906727..36042546 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P12955.3 GenPept UniProtKB/Swiss-Prot:P12955

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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