U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

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

    Gene ID: 63929, updated on 5-Mar-2024

    Summary

    Go to the top of the page Help
    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
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    See XPNPEP3 in Genome Data Viewer
    Location:
    22q13.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (40857148..40932815)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (41329340..41405008)
    105.20220307 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

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. XPNPEP3 is a novel transcriptional target of canonical Wnt/β-catenin signaling. Kumar R, et al. Genes Chromosomes Cancer, 2018 Jun. PMID 29383790
    2. 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
    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. 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
    5. 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

    See all (53) 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

    Go to the top of the page Help

    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
    		Compare labs

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    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
    		  
    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

    Go to the top of the page Help
    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)

    Go to the top of the page Help

    NEW Try the new Transcript table

    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_2023_10

    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

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous