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    PGPEP1 pyroglutamyl-peptidase I [ Homo sapiens (human) ]

    Gene ID: 54858, updated on 5-Mar-2024

    Summary

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    Official Symbol
    PGPEP1provided by HGNC
    Official Full Name
    pyroglutamyl-peptidase Iprovided by HGNC
    Primary source
    HGNC:HGNC:13568
    See related
    Ensembl:ENSG00000130517 MIM:610694; AllianceGenome:HGNC:13568
    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
    PGI; PGP; Pcp; PGPI; PAP-I; PGP-I
    Summary
    The gene encodes a cysteine protease and member of the peptidase C15 family of proteins. The encoded protein cleaves amino terminal pyroglutamate residues from protein substrates including thyrotropin-releasing hormone and other neuropeptides. Expression of this gene may be downregulated in colorectal cancer, while activity of the encoded protein may be negatively correlated with cancer progression in colorectal cancer patients. Activity of the encoded protease may also be altered in other disease states including in liver cirrhosis, which is associated with reduced protease activity, and in necrozoospermia, which is associated with elevated protease activity. [provided by RefSeq, Jul 2016]
    Expression
    Ubiquitous expression in kidney (RPKM 13.0), duodenum (RPKM 6.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PGPEP1 in Genome Data Viewer
    Location:
    19p13.11
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (18340598..18369950)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (18474715..18504090)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (18451408..18480760)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105372300 Neighboring gene LSM4 homolog, U6 small nuclear RNA and mRNA degradation associated Neighboring gene Sharpr-MPRA regulatory region 14103 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18429424-18430170 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10389 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14313 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:18434425-18435027 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14314 Neighboring gene uncharacterized LOC124904654 Neighboring gene RNA, 7SL, cytoplasmic 513, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18451278-18451965 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:18454745-18455584 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:18455585-18456422 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr19:18456925-18457507 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:18460464-18460672 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:18472794-18473579 Neighboring gene Sharpr-MPRA regulatory region 798 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr19:18484262-18485461 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:18486310-18486537 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:18491252-18491819 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:18496512-18497334 Neighboring gene microRNA 3189 Neighboring gene growth differentiation factor 15 Neighboring gene leucine rich repeat containing 25

    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. Two-photon fluorogenic probe for visualizing PGP-1 activity in inflammatory tissues and serum from patients. Bai H, et al. Chem Commun (Camb), 2021 Dec 7. PMID 34816269
    2. Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis. Megias MJ, et al. Endocr Regul, 2015 Jan. PMID 25687677
    3. Regional and subcellular distribution of soluble aminopeptidase in the human and the rat brain: a comparative study. Gil J, et al. Neuropeptides, 2001 Oct-Dec. PMID 12030812
    4. Pyroglutamyl peptidase: an overview of the three known enzymatic forms. Cummins PM, et al. Biochim Biophys Acta, 1998 Dec 8. PMID 9920379
    5. Pyroglutamyl peptidase II inhibition specifically increases recovery of TRH released from rat brain slices. Charli JL, et al. Neuropeptides, 1989 Oct. PMID 2575716

    See all (25) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Circ-PGPEP1 augments renal cell carcinoma proliferation, Warburg effect, and distant metastasis.
      Title: Circ-PGPEP1 augments renal cell carcinoma proliferation, Warburg effect, and distant metastasis.
    2. Two-photon fluorogenic probe for visualizing PGP-1 activity in inflammatory tissues and serum from patients.
      Title: Two-photon fluorogenic probe for visualizing PGP-1 activity in inflammatory tissues and serum from patients.
    3. cytosolic peptidases(puromycin-sensitive aminopeptidase (PSA), aminopeptidase B (APB) and pyroglutamyl-peptidase I (PGI) ) may be involved in colorectal carcinogenesis
      Title: Altered Activity and Expression of Cytosolic Peptidases in Colorectal Cancer.
    4. The specific reduction of the levels of pyroglutamyl-aminopeptidase activity in serum of liver cirrhosis patients might be considered as a potential candidate to be included in a combination of markers for the diagnosis of this disease.
      Title: Serum pyroglutamyl aminopeptidase activity: a promising novel biomarker candidate for liver cirrhosis.
    5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    6. The activities of pyroglutamyl peptidase I and prolyl endopeptidase in necrozoospermia were found to be higher in the corresponding soluble and particulate sperm fractions, respectively, with respect to those measured in normozoospermic semen
      Title: Pyroglutamyl peptidase I and prolyl endopeptidase in human semen: increased activity in necrozoospermia.
    7. cloning and sequencing of the human (AJ278828) pyroglutamyl-peptidase I
      Title: Pyroglutamyl-peptidase I: cloning, sequencing, and characterisation of the recombinant human enzyme.
    8. VX-710 modulates Pgp, MRP-1, and BCRP(R482), and has potential as a clinical broad-spectrum multidrug resistance modulator in malignancies.
      Title: VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein.
    Submit: New GeneRIF Correction

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder.
    EBI GWAS Catalog
    Genome-wide association study of chronic periodontitis in a general German population.
    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

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of pyroglutamyl-peptidase I (PGPEP1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20208, MGC10812

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables pyroglutamyl-peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    pyroglutamyl-peptidase 1
    Names
    5-oxoprolyl-peptidase
    pGlu-peptidase I
    pyroglutamyl aminopeptidase I
    pyrrolidone-carboxylate peptidase
    NP_001287856.1
    NP_001295295.1
    NP_001316400.1
    NP_001316405.1
    NP_001316406.1
    NP_001316407.1
    NP_060182.1

    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_051188.1 RefSeqGene

      Range
      5026..34378
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001300927.2 → NP_001287856.1  pyroglutamyl-peptidase 1 isoform 2

      See identical proteins and their annotated locations for NP_001287856.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate exon in the coding region, resulting in a frameshift and an early stop codon, compared to variant 1. It encodes isoform 2, which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC008397, AK000215, AK289968, DB276426
      Consensus CDS
      CCDS74314.1
      UniProtKB/TrEMBL
      U3KQ24
      Related
      ENSP00000475477.2, ENST00000597431.2
      Conserved Domains (1) summary
      cl00237
      Location:6 → 71
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    2. NM_001308366.2 → NP_001295295.1  pyroglutamyl-peptidase 1 isoform 3

      See identical proteins and their annotated locations for NP_001295295.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region that results in a frame-shift and a novel 3' coding region compared to variant 1. It encodes isoform 3, which is shorter than and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC008397, AI635563, AK289968, BC004942, DA738481
      Consensus CDS
      CCDS77264.1
      UniProtKB/TrEMBL
      S4R2Y9, U3KQG9
      Related
      ENSP00000473772.3, ENST00000604499.6
      Conserved Domains (1) summary
      cd00501
      Location:6 → 146
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    3. NM_001329471.2 → NP_001316400.1  pyroglutamyl-peptidase 1 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (4) is the same length but contains a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AI635563, AK289968, CF129240
      UniProtKB/Swiss-Prot
      Q9NXJ5
      Conserved Domains (1) summary
      cd00501
      Location:6 → 146
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    4. NM_001329476.2 → NP_001316405.1  pyroglutamyl-peptidase 1 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (6) is shorter and contains a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AI635563, AK289968, BX473633
      UniProtKB/Swiss-Prot
      Q9NXJ5
      Conserved Domains (1) summary
      cl00237
      Location:6 → 68
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    5. NM_001329477.2 → NP_001316406.1  pyroglutamyl-peptidase 1 isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR, lacks a portion of the 5' coding region and uses a downstream translation start site compared to variant 1. The encoded isoform (7) has a shorter N-terminus than isoform 1. Both variants 7 and 8 encode the same isoform (7).
      Source sequence(s)
      AC008397, AK289968, AK294497, BC004942
      Consensus CDS
      CCDS82319.1
      UniProtKB/Swiss-Prot
      Q9NXJ5
      Related
      ENSP00000252813.5, ENST00000252813.5
      Conserved Domains (1) summary
      cl00237
      Location:1 → 122
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    6. NM_001329478.2 → NP_001316407.1  pyroglutamyl-peptidase 1 isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR and uses a downstream translation start site compared to variant 1. The encoded isoform (7) has a shorter N-terminus than isoform 1. Both variants 7 and 8 encode the same isoform (7).
      Source sequence(s)
      AC008397, AK289968, BC004942, BC042138
      Consensus CDS
      CCDS82319.1
      UniProtKB/Swiss-Prot
      Q9NXJ5
      Conserved Domains (1) summary
      cl00237
      Location:1 → 122
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    7. NM_017712.4 → NP_060182.1  pyroglutamyl-peptidase 1 isoform 1

      See identical proteins and their annotated locations for NP_060182.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC008397, AK000215, DA315740
      Consensus CDS
      CCDS12375.1
      UniProtKB/Swiss-Prot
      A8K1Q3, Q8IVT1, Q9NXJ5
      Related
      ENSP00000269919.3, ENST00000269919.11
      Conserved Domains (1) summary
      cd00501
      Location:6 → 199
      Peptidase_C15; Pyroglutamyl peptidase (PGP) type I, also known as pyrrolidone carboxyl peptidase (pcp) type I: Enzymes responsible for cleaving pyroglutamate (pGlu) from the N-terminal end of specialized proteins. The N-terminal pGlu protects these proteins from ...

    RNA

    1. NR_138029.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC008397, AK289968, BC004942, BC028063

    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
      18340598..18369950
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      18474715..18504090
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NXJ5.1 GenPept UniProtKB/Swiss-Prot:Q9NXJ5

    Gene LinkOut

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

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