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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
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Genomic context

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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

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Chemical Information
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