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XPNPEP3 X-prolyl aminopeptidase 3 [ Homo sapiens (human) ]

Gene ID: 63929, updated on 2-Nov-2024

Summary

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Official Symbol
XPNPEP3provided by HGNC
Official Full Name
X-prolyl aminopeptidase 3provided by HGNC
Primary source
HGNC:HGNC:28052
See related
Ensembl:ENSG00000196236 MIM:613553; AllianceGenome:HGNC:28052
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
APP3; ICP55; NPHPL1
Summary
The protein encoded by this gene belongs to the family of X-pro-aminopeptidases that utilize a metal cofactor, and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. This protein has been shown to localize to the mitochondria of renal cells, and have a role in ciliary function. Mutations in this gene are associated with nephronophthisis-like nephropathy-1. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene, however, expression of some of these isoforms in vivo is not known.[provided by RefSeq, Mar 2011]
Expression
Broad expression in testis (RPKM 4.3), kidney (RPKM 2.0) and 25 other tissues See more
Orthologs
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Genomic context

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See XPNPEP3 in Genome Data Viewer
Location:
22q13.2
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (40857148..40932815)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (41329340..41405008)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (41253152..41328819)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene solute carrier family 25 member 17 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19100 Neighboring gene microRNA 4766 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:41252371-41253140 Neighboring gene ST13 Hsp70 interacting protein Neighboring gene uncharacterized LOC124905124 Neighboring gene DnaJ heat shock protein family (Hsp40) member B7 Neighboring gene small nucleolar RNA U13 Neighboring gene RNA, U6 small nuclear 379, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:41346344-41346934 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19103 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:41348114-41348702 Neighboring gene ring-box 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:41387857-41388358 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:41388359-41388858 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:41416645-41417222 Neighboring gene H3K27ac hESC enhancer GRCh37_chr22:41418377-41418953 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:41444536-41445346 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:41445347-41446155 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:41460351-41460851 Neighboring gene ribosomal protein S9 pseudogene 2

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 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. Aminopeptidase P isozyme expression in human tissues and peripheral blood mononuclear cell fractions. Erşahin C, et al. Arch Biochem Biophys, 2005 Mar 15. PMID 15708373
  2. XPNPEP3 is a novel transcriptional target of canonical Wnt/β-catenin signaling. Kumar R, et al. Genes Chromosomes Cancer, 2018 Jun. PMID 29383790
  3. Structure of the human aminopeptidase XPNPEP3 and comparison of its in vitro activity with Icp55 orthologs: Insights into diverse cellular processes. Singh R, et al. J Biol Chem, 2017 Jun 16. PMID 28476889, Free PMC Article
  4. Mitochondrial aminopeptidase deletion increases chronological lifespan and oxidative stress resistance while decreasing respiratory metabolism in S. cerevisiae. Stames EM, et al. PLoS One, 2013. PMID 24116217, Free PMC Article
  5. Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex, induces phosphorylation of JNK1 and JNK2. Inoue M, et al. J Cell Sci, 2015 Feb 15. PMID 25609706

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. results therefore suggest XPNPEP3 to be a transcriptional target of Wnt/beta-catenin pathway with particular significance for CRC
    Title: XPNPEP3 is a novel transcriptional target of canonical Wnt/β-catenin signaling.
  2. Data suggest that human XPNPEP3, Ashbya gossypii Icp55, and Fusarium graminearum Icp55 exhibit structural and functional properties of genuine Xaa-Pro specific aminopeptidases; these enzymes appear to function in the previously observed mitochondrial role of Icp55 in processing of Nfs1 (mitochondrial cysteine desulfurase) substrate. [Icp55 = intermediate-cleavage metalloexopeptidases 55]
    Title: Structure of the human aminopeptidase XPNPEP3 and comparison of its in vitro activity with Icp55 orthologs: Insights into diverse cellular processes.
  3. The findings reveal that APP3m is a new member of the TNF-TNFR2 signaling complex and characterize an APP3-mediated TNFR2 signal transduction mechanism that induces activation of JNK1 and JNK2.
    Title: Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex, induces phosphorylation of JNK1 and JNK2.
  4. Observational study of gene-disease association. (HuGE Navigator)
    Title: Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy.
  5. Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.
    Title: Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.
Submit: New GeneRIF Correction

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
Nephronophthisis-like nephropathy 1
MedGen: C3150419 OMIM: 613159 GeneReviews: Nephronophthisis-Related Ciliopathies
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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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: RBX1

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables aminopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables aminopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables manganese ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables metalloaminopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
acts_upstream_of_or_within glomerular filtration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
acts_upstream_of_or_within protein processing IMP
Inferred from Mutant Phenotype
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 cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
xaa-Pro aminopeptidase 3
Names
Intermediate Cleaving Peptidase 55
X-Pro aminopeptidase 3
X-prolyl aminopeptidase 3, mitochondrial
probable Xaa-Pro aminopeptidase 3
NP_001191756.1
NP_071381.1

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_028221.1 RefSeqGene

    Range
    5068..80735
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001204827.2 → NP_001191756.1  xaa-Pro aminopeptidase 3 isoform 2

    See identical proteins and their annotated locations for NP_001191756.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) shares the first exon in common with variant 1 and contains two alternate exons at the 3' end. This results in a frame-shift and a very short isoform (2) with a distinct C-terminus compared to isoform 1. This variant is supported by transcript evidence, but the encoded isoform lacks experimental support.
    Source sequence(s)
    BC053556, BM980889, BP346902
    Consensus CDS
    CCDS74869.1
    UniProtKB/TrEMBL
    A0A087X0Z2
    Related
    ENSP00000483752.1, ENST00000614001.1
    Conserved Domains (1) summary
    pfam13900
    Location:26 → 48
    GVQW; Putative domain of unknown function

  2. NM_022098.4 → NP_071381.1  xaa-Pro aminopeptidase 3 isoform 1

    See identical proteins and their annotated locations for NP_071381.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1, also known as APP3m). This isoform has been shown to be localized to the mitochondria (PMID:20179356).
    Source sequence(s)
    AI446638, AL035450, AL080242, AL365514, BC004989, BP346902, BX648018
    Consensus CDS
    CCDS14007.1
    UniProtKB/Swiss-Prot
    B2R9G1, B7Z790, B7Z7B2, Q6I9V9, Q8NDA6, Q9BV27, Q9BVH0, Q9NQH7
    Related
    ENSP00000349658.4, ENST00000357137.9
    Conserved Domains (3) summary
    PRK10879
    Location:67 → 506
    PRK10879; proline aminopeptidase P II; Provisional
    cd01087
    Location:252 → 490
    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 ...
    pfam05195
    Location:72 → 205
    AMP_N; Aminopeptidase P, N-terminal domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    40857148..40932815
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    41329340..41405008
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NQH7.1 GenPept UniProtKB/Swiss-Prot:Q9NQH7

Gene LinkOut

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