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 nephronoph... See more...

Aliases for XPNPEP3 Gene

Aliases for XPNPEP3 Gene

  • X-Prolyl Aminopeptidase 3 2 3 5
  • X-Prolyl Aminopeptidase 3, Mitochondrial 2 3
  • Intermediate Cleaving Peptidase 55 2 3
  • Xaa-Pro Aminopeptidase 3 3 4
  • X-Pro Aminopeptidase 3 3 4
  • APP3 3 4
  • X-Prolyl Aminopeptidase (Aminopeptidase P) 3, Putative 2
  • Probable Xaa-Pro Aminopeptidase 3 3
  • Aminopeptidase P3 4
  • EC 3.4.11.9 4
  • NPHPL1 3
  • ICP55 3

External Ids for XPNPEP3 Gene

Previous GeneCards Identifiers for XPNPEP3 Gene

  • GC22P039583
  • GC22P041253
  • GC22P024215

Summaries for XPNPEP3 Gene

Entrez Gene Summary for XPNPEP3 Gene

  • 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]

GeneCards Summary for XPNPEP3 Gene

XPNPEP3 (X-Prolyl Aminopeptidase 3) is a Protein Coding gene. Diseases associated with XPNPEP3 include Nephronophthisis-Like Nephropathy 1 and Late-Onset Nephronophthisis. Gene Ontology (GO) annotations related to this gene include metallopeptidase activity and aminopeptidase activity. An important paralog of this gene is PEPD.

UniProtKB/Swiss-Prot Summary for XPNPEP3 Gene

  • Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889). Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889).
  • [Isoform 1]: Promotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.

Gene Wiki entry for XPNPEP3 Gene

Additional gene information for XPNPEP3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for XPNPEP3 Gene

Genomics for XPNPEP3 Gene

GeneHancer (GH) Regulatory Elements for XPNPEP3 Gene

Promoters and enhancers for XPNPEP3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around XPNPEP3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for XPNPEP3

Top Transcription factor binding sites by QIAGEN in the XPNPEP3 gene promoter:
  • C/EBPalpha
  • Elk-1
  • Evi-1
  • HNF-1
  • HNF-1A
  • Pax-3
  • POU2F1
  • POU2F1a
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for XPNPEP3 Gene

Genomic Locations for XPNPEP3 Gene
chr22:40,857,077-40,932,819
(GRCh38/hg38)
Size:
75,743 bases
Orientation:
Plus strand
chr22:41,253,081-41,363,838
(GRCh37/hg19)
Size:
110,758 bases
Orientation:
Plus strand

Genomic View for XPNPEP3 Gene

Genes around XPNPEP3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
XPNPEP3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for XPNPEP3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for XPNPEP3 Gene

Proteins for XPNPEP3 Gene

  • Protein details for XPNPEP3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NQH7-XPP3_HUMAN
    Recommended name:
    Xaa-Pro aminopeptidase 3
    Protein Accession:
    Q9NQH7
    Secondary Accessions:
    • B2R9G1
    • B7Z790
    • B7Z7B2
    • Q6I9V9
    • Q8NDA6
    • Q9BV27
    • Q9BVH0

    Protein attributes for XPNPEP3 Gene

    Size:
    507 amino acids
    Molecular mass:
    57034 Da
    Cofactor:
    Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Homodimer (PubMed:28476889). Isoform 1 interacts with TNFRSF1B/TNFR2 (activated) and TRAF2 (PubMed:25609706).

    Three dimensional structures from OCA and Proteopedia for XPNPEP3 Gene

    Alternative splice isoforms for XPNPEP3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for XPNPEP3 Gene

Post-translational modifications for XPNPEP3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for XPNPEP3 Gene

No data available for DME Specific Peptides for XPNPEP3 Gene

Domains & Families for XPNPEP3 Gene

Gene Families for XPNPEP3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for XPNPEP3 Gene

Blocks:
  • Aminopeptidase P, N-terminal
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for XPNPEP3 Gene

GenScript: Design optimal peptide antigens:
  • X-prolyl aminopeptidase (Aminopeptidase P) 3, putative (B7ZBB4_HUMAN)
  • Aminopeptidase P3 (XPP3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NQH7

UniProtKB/Swiss-Prot:

XPP3_HUMAN :
  • Belongs to the peptidase M24B family.
Family:
  • Belongs to the peptidase M24B family.
genes like me logo Genes that share domains with XPNPEP3: view

Function for XPNPEP3 Gene

Molecular function for XPNPEP3 Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the removal of a penultimate prolyl residue from the N-termini of peptides, such as Leu-Pro-Ala (PubMed:25609706, PubMed:28476889). Also shows low activity towards peptides with Ala or Ser at the P1 position (PubMed:28476889).
UniProtKB/Swiss-Prot Function:
[Isoform 1]: Promotes TNFRSF1B-mediated phosphorylation of MAPK8/JNK1 and MAPK9/JNK2, suggesting a function as an adapter protein for TNFRSF1B; the effect is independent of XPNPEP3 peptidase activity. May inhibit apoptotic cell death induced via TNF-TNFRSF1B signaling.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=Release of any N-terminal amino acid, including proline, that is linked to proline, even from a dipeptide or tripeptide.; EC=3.4.11.9; Evidence={ECO:0000269 PubMed:25609706, ECO:0000269 PubMed:28476889};.
UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=1.62 mM for Met-Pro-Ala {ECO:0000269 PubMed:28476889}; KM=2.45 mM for Leu-Pro-Ala {ECO:0000269 PubMed:28476889}; KM=3.06 mM for Phe-Pro-Ala {ECO:0000269 PubMed:28476889}; KM=0.55 mM for Tyr-Pro-Ala {ECO:0000269 PubMed:28476889}; KM=4.91 mM for Tyr-Ser-Ser {ECO:0000269 PubMed:28476889}; KM=4.20 mM for Tyr-Ala-Ala {ECO:0000269 PubMed:28476889}; KM=3.74 mM for Tyr-Ser-Ser-Ala-Ala-Ala-Ala {ECO:0000269 PubMed:28476889};

Enzyme Numbers (IUBMB) for XPNPEP3 Gene

Phenotypes From GWAS Catalog for XPNPEP3 Gene

Gene Ontology (GO) - Molecular Function for XPNPEP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004177 aminopeptidase activity IMP 20179356
GO:0005515 protein binding IPI 25609706
GO:0008233 peptidase activity IEA --
GO:0008237 metallopeptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with XPNPEP3: view
genes like me logo Genes that share phenotypes with XPNPEP3: view

Human Phenotype Ontology for XPNPEP3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for XPNPEP3

CRISPR Products

miRNA for XPNPEP3 Gene

miRTarBase miRNAs that target XPNPEP3

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for XPNPEP3

Clone Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for XPNPEP3 Gene

Localization for XPNPEP3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for XPNPEP3 Gene

[Isoform 1]: Mitochondrion. Cytoplasm. Note=Mainly mitochondrial. Translocates to the cytoplasm following TNFRSF1B activation. {ECO:0000269 PubMed:25609706}.
[Isoform 2]: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for XPNPEP3 gene
Compartment Confidence
mitochondrion 5
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for XPNPEP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 25609706
GO:0005739 mitochondrion IDA,IEA 20179356
genes like me logo Genes that share ontologies with XPNPEP3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for XPNPEP3 Gene

Pathways & Interactions for XPNPEP3 Gene

PathCards logo

SuperPathways for XPNPEP3 Gene

No Data Available

Gene Ontology (GO) - Biological Process for XPNPEP3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003094 glomerular filtration IMP 20179356
GO:0006508 proteolysis IEA,IDA 28476889
GO:0016485 protein processing IMP 20179356
genes like me logo Genes that share ontologies with XPNPEP3: view

No data available for Pathways by source and SIGNOR curated interactions for XPNPEP3 Gene

Drugs & Compounds for XPNPEP3 Gene

(2) Drugs for XPNPEP3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cobalt Approved, Experimental Pharma 198
Manganese Approved Nutra 51
genes like me logo Genes that share compounds with XPNPEP3: view

Transcripts for XPNPEP3 Gene

mRNA/cDNA for XPNPEP3 Gene

2 REFSEQ mRNAs :
22 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for XPNPEP3

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for XPNPEP3 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15
SP1: - - - -
SP2: - - - - -
SP3: - - - -
SP4: - - -
SP5: - -
SP6: -
SP7: - - -

Relevant External Links for XPNPEP3 Gene

GeneLoc Exon Structure for
XPNPEP3

Expression for XPNPEP3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for XPNPEP3 Gene

Protein differential expression in normal tissues from HIPED for XPNPEP3 Gene

This gene is overexpressed in Adrenal (11.0), Heart (7.9), and Testis (6.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for XPNPEP3 Gene



Protein tissue co-expression partners for XPNPEP3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for XPNPEP3

SOURCE GeneReport for Unigene cluster for XPNPEP3 Gene:

Hs.529163

mRNA Expression by UniProt/SwissProt for XPNPEP3 Gene:

Q9NQH7-XPP3_HUMAN
Tissue specificity: Isoform 1 and isoform 2 are widely expressed, with isoform 1 being more abundant.

Evidence on tissue expression from TISSUES for XPNPEP3 Gene

  • Lung(4.3)
  • Nervous system(3.8)

Phenotype-based relationships between genes and organs from Gene ORGANizer for XPNPEP3 Gene

Germ Layers:
  • mesoderm
Systems:
  • urinary
Regions:
Abdomen:
  • kidney
genes like me logo Genes that share expression patterns with XPNPEP3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for XPNPEP3 Gene

Orthologs for XPNPEP3 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for XPNPEP3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia XPNPEP3 31 30
  • 99.61 (n)
OneToOne
dog
(Canis familiaris)
Mammalia XPNPEP3 31 30
  • 90.6 (n)
OneToOne
cow
(Bos Taurus)
Mammalia XPNPEP3 31 30
  • 88.03 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Xpnpep3 30
  • 87.81 (n)
mouse
(Mus musculus)
Mammalia Xpnpep3 31
  • 85 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia XPNPEP3 31
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia XPNPEP3 31
  • 81 (a)
OneToOne
chicken
(Gallus gallus)
Aves XPNPEP3 31 30
  • 74.48 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia XPNPEP3 31
  • 73 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia xpnpep3 30
  • 68.1 (n)
Str.10537 30
zebrafish
(Danio rerio)
Actinopterygii xpnpep3 31 30
  • 61.82 (n)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta CG9581 31 30
  • 50.71 (n)
OneToMany
CG32454 31
  • 22 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000887 30
  • 50.51 (n)
worm
(Caenorhabditis elegans)
Secernentea R119.2 31
  • 35 (a)
OneToOne
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ACL028W 30
  • 47.77 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ICP55 33 31 30
  • 47.63 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C07645g 30
  • 44.94 (n)
thale cress
(Arabidopsis thaliana)
eudicotyledons AT1G09300 30
  • 50.07 (n)
rice
(Oryza sativa)
Liliopsida Os12g0563500 30
  • 48.42 (n)
bread mold
(Neurospora crassa)
Ascomycetes NCU05971 30
  • 47.48 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes icp55 30
  • 47.37 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 37 (a)
OneToOne
Species where no ortholog for XPNPEP3 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for XPNPEP3 Gene

ENSEMBL:
Gene Tree for XPNPEP3 (if available)
TreeFam:
Gene Tree for XPNPEP3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for XPNPEP3: view image

Paralogs for XPNPEP3 Gene

genes like me logo Genes that share paralogs with XPNPEP3: view

Variants for XPNPEP3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for XPNPEP3 Gene

SNP ID Clinical significance and condition Chr 22 pos Variation AA Info Type
641596 Uncertain Significance: Nephronophthisis-like nephropathy 1 40,869,053(+) G/A MISSENSE_VARIANT
695160 Likely Benign: not provided 40,907,611(+) A/G MISSENSE_VARIANT
695441 Benign: not provided 40,886,304(+) C/T INTRON_VARIANT
696213 Benign: not provided 40,922,324(+) C/T INTRON_VARIANT
700347 Likely Benign: not provided 40,886,320(+) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for XPNPEP3 Gene

Structural Variations from Database of Genomic Variants (DGV) for XPNPEP3 Gene

Variant ID Type Subtype PubMed ID
esv2667574 CNV deletion 23128226
esv3647784 CNV loss 21293372
nsv1058653 CNV gain 25217958
nsv1109471 CNV deletion 24896259
nsv1109472 CNV deletion 24896259
nsv1114323 CNV deletion 24896259
nsv1124863 CNV duplication 24896259
nsv3635 CNV insertion 18451855
nsv428389 CNV loss 18775914

Variation tolerance for XPNPEP3 Gene

Residual Variation Intolerance Score: 9.05% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.87; 18.15% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for XPNPEP3 Gene

Human Gene Mutation Database (HGMD)
XPNPEP3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
XPNPEP3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for XPNPEP3 Gene

Disorders for XPNPEP3 Gene

MalaCards: The human disease database

(11) MalaCards diseases for XPNPEP3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
nephronophthisis-like nephropathy 1
  • nphpl1
late-onset nephronophthisis
nephronophthisis
  • medullary cystic disease
cystic kidney disease
  • renal cyst
nephronophthisis 19
  • nphp19
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

XPP3_HUMAN
  • Nephronophthisis-like nephropathy 1 (NPHPL1) [MIM:613159]: A disorder with features of nephronophthisis, a cystic kidney disease leading to end-stage renal failure. Nephronophthisis is histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical manifestation are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms are frequent. In NPHPL1 patients, extrarenal symptoms include hypertension, essential tremor, sensorineural hearing loss and gout. Severely affected individuals can manifest a mitochondrial disorder with isolated complex I deficiency activity in muscle, seizures, mental retardation and hypertrophic dilated cardiomyopathy. {ECO:0000269 PubMed:20179356}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for XPNPEP3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with XPNPEP3: view

No data available for Genatlas for XPNPEP3 Gene

Publications for XPNPEP3 Gene

  1. Structure of the human aminopeptidase XPNPEP3 and comparison of its in vitro activity with Icp55 orthologs: Insights into diverse cellular processes. (PMID: 28476889) Singh R … Makde RD (The Journal of biological chemistry 2017) 2 3 4 54
  2. Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy. (PMID: 20179356) O'Toole JF … Hildebrandt F (The Journal of clinical investigation 2010) 2 3 4 54
  3. Aminopeptidase P isozyme expression in human tissues and peripheral blood mononuclear cell fractions. (PMID: 15708373) Erşahin C … Simmons WH (Archives of biochemistry and biophysics 2005) 2 3 4 54
  4. Aminopeptidase P3, a new member of the TNF-TNFR2 signaling complex, induces phosphorylation of JNK1 and JNK2. (PMID: 25609706) Inoue M … Tsunoda S (Journal of cell science 2015) 3 4 54
  5. Mitochondrial aminopeptidase deletion increases chronological lifespan and oxidative stress resistance while decreasing respiratory metabolism in S. cerevisiae. (PMID: 24116217) Stames EM … O'Toole JF (PloS one 2013) 2 3 54

Products for XPNPEP3 Gene

Sources for XPNPEP3 Gene