PNPT1

Protein identityUniProt · HPA

UniProt accession

Q8TCS8

Gene

PNPT1

Ensembl

ENSG00000138035

Chromosome

2

Canonical length

783 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria,Cytosol

Quaternary structure

Homotrimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the evolutionary conserved polynucleotide phosphorylase family comprised of phosphate dependent 3'-to-5' exoribonucleases implicated in RNA processing and degradation. This enzyme is predominantly localized in the mitochondrial intermembrane space and is involved in import of RNA to mitochondria. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency-13 and autosomal recessive nonsyndromic deafness-70. Related pseudogenes are found on chromosomes 3 and 7. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

783 residues, UniProt reviewed canonical sequence.

>Q8TCS8|PNPT1
     1  MAACRYCCSC LRLRPLSDGP FLLPRRDRAL TQLQVRALWS SAGSRAVAVD LGNRKLEISS
    61  GKLARFADGS AVVQSGDTAV MVTAVSKTKP SPSQFMPLVV DYRQKAAAAG RIPTNYLRRE
   121  IGTSDKEILT SRIIDRSIRP LFPAGYFYDT QVLCNLLAVD GVNEPDVLAI NGASVALSLS
   181  DIPWNGPVGA VRIGIIDGEY VVNPTRKEMS SSTLNLVVAG APKSQIVMLE ASAENILQQD
   241  FCHAIKVGVK YTQQIIQGIQ QLVKETGVTK RTPQKLFTPS PEIVKYTHKL AMERLYAVFT
   301  DYEHDKVSRD EAVNKIRLDT EEQLKEKFPE ADPYEIIESF NVVAKEVFRS IVLNEYKRCD
   361  GRDLTSLRNV SCEVDMFKTL HGSALFQRGQ TQVLCTVTFD SLESGIKSDQ VITAINGIKD
   421  KNFMLHYEFP PYATNEIGKV TGLNRRELGH GALAEKALYP VIPRDFPFTI RVTSEVLESN
   481  GSSSMASACG GSLALMDSGV PISSAVAGVA IGLVTKTDPE KGEIEDYRLL TDILGIEDYN
   541  GDMDFKIAGT NKGITALQAD IKLPGIPIKI VMEAIQQASV AKKEILQIMN KTISKPRASR
   601  KENGPVVETV QVPLSKRAKF VGPGGYNLKK LQAETGVTIS QVDEETFSVF APTPSAMHEA
   661  RDFITEICKD DQEQQLEFGA VYTATITEIR DTGVMVKLYP NMTAVLLHNT QLDQRKIKHP
   721  TALGLEVGQE IQVKYFGRDP ADGRMRLSRK VLQSPATTVV RTLNDRSSIV MGEPISQSSS
   781  NSQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PNPT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

11 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PNPT1.

Disease | AllUniProt

Conditions PNPT1 is implicated in, by any mechanism.

• Combined oxidative phosphorylation deficiency 13 (COXPD13) MIM:614932
• Deafness, autosomal recessive, 70, with or without adult-onset neurodegeneration (DFNB70) MIM:614934
• Spinocerebellar ataxia 25 (SCA25) MIM:608703

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 1,001 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined oxidative phosphorylation defect type 13
• Autosomal recessive nonsyndromic hearing loss 70
• Spinocerebellar ataxia type 25
• PNPT1-related disorder
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.48

gnomAD pLI

0

gnomAD missense Z

0.42

DepMap mean gene effect

-0.83

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to interferon-beta
• cellular response to oxidative stress
• liver regeneration
• mitochondrial mRNA catabolic process
• mitochondrial mRNA polyadenylation
• mitochondrial RNA 3'-end processing
• mitochondrial RNA 5'-end processing
• mitochondrial RNA catabolic process
• mitochondrion organization
• mRNA catabolic process
• mRNA processing
• positive regulation of miRNA catabolic process
• positive regulation of mitochondrial RNA catabolic process
• positive regulation of mRNA catabolic process
• protein homooligomerization
• protein homotrimerization
• regulation of cellular respiration
• regulation of cellular senescence
• response to cAMP
• response to growth hormone
• RNA catabolic process
• rRNA import into mitochondrion
• nuclear polyadenylation-dependent mRNA catabolic process
• RNA import into mitochondrion

Molecular functions

• 3'-5'-RNA exonuclease activity
• identical protein binding
• miRNA binding
• poly(G) binding
• poly(U) RNA binding
• RNA binding
• polyribonucleotide nucleotidyltransferase activity

Cellular components

• cytoplasm
• cytosol
• endoplasmic reticulum membrane
• mitochondrial degradosome
• mitochondrial intermembrane space
• mitochondrial matrix
• mitochondrion
• ribosome

Protein domainsUniProt · Pfam · InterPro

• Exoribonuclease, phosphorolytic domain 1
• S1 domain
• K Homology domain
• K Homology domain, type 1
• Nucleic acid-binding, OB-fold
• Exoribonuclease, phosphorolytic domain 2
• Ribosomal protein uS5 domain 2-type superfamily
• PNPase/RNase PH domain superfamily
• Exoribonuclease, PH domain 2 superfamily
• K Homology domain, type 1 superfamily
• KH domain
• S1 RNA binding domain
• 3' exoribonuclease family, domain 1
• 3' exoribonuclease family, domain 2
• Polyribonucleotide nucleotidyltransferase
• Polyribonucleotide nucleotidyltransferase, RNA-binding domain
• Polyribonucleotide nucleotidyltransferase, RNA-binding domain superfamily
• Polyribonucleotide nucleotidyltransferase, RNA binding domain

KeywordsUniProt

• Acetylation
• Cytoplasm
• Deafness
• Exonuclease
• Hydrolase
• Membrane
• Mitochondrion
• mRNA processing
• Neurodegeneration
• Non-syndromic deafness
• Nuclease
• Nucleotidyltransferase
• Phosphoprotein
• Primary mitochondrial disease
• RNA-binding
• Spinocerebellar ataxia
• Transferase
• Transit peptide
• Transport

InteractionsUniProt · HPA

Protein binding partners of PNPT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GRSF1
• TCL1A
• HSCB
• MTG2