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Protein

Polyribonucleotide nucleotidyltransferase 1, mitochondrial

Gene

PNPT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

RNA-binding protein implicated in numerous RNA metabolic processes. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA.12 Publications

Catalytic activityi

RNA(n+1) + phosphate = RNA(n) + a nucleoside diphosphate.

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • miRNA binding Source: UniProtKB
  • poly(G) binding Source: UniProtKB
  • poly(U) RNA binding Source: UniProtKB
  • polyribonucleotide nucleotidyltransferase activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

  • cellular response to interferon-beta Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • liver regeneration Source: Ensembl
  • mitochondrial mRNA catabolic process Source: UniProtKB
  • mitochondrial mRNA polyadenylation Source: UniProtKB
  • mitochondrial RNA 3'-end processing Source: UniProtKB
  • mitochondrial RNA 5'-end processing Source: UniProtKB
  • mitochondrial RNA catabolic process Source: UniProtKB
  • mitochondrion morphogenesis Source: UniProtKB
  • mitotic cell cycle arrest Source: UniProtKB
  • mRNA catabolic process Source: UniProtKB
  • negative regulation of growth Source: UniProtKB
  • nuclear polyadenylation-dependent mRNA catabolic process Source: UniProtKB
  • positive regulation of miRNA catabolic process Source: UniProtKB
  • positive regulation of mitochondrial RNA catabolic process Source: UniProtKB
  • positive regulation of mRNA catabolic process Source: UniProtKB
  • protein homooligomerization Source: UniProtKB
  • protein homotrimerization Source: UniProtKB
  • regulation of cellular respiration Source: UniProtKB
  • regulation of cellular senescence Source: UniProtKB
  • response to cAMP Source: Ensembl
  • response to growth hormone Source: Ensembl
  • RNA catabolic process Source: UniProtKB
  • RNA import into mitochondrion Source: UniProtKB
  • RNA polyadenylation Source: UniProtKB
  • rRNA import into mitochondrion Source: UniProtKB

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, RNA-binding, Transferase
Biological processmRNA processing, Transport

Enzyme and pathway databases

BRENDAi2.7.7.8 2681

Names & Taxonomyi

Protein namesi
Recommended name:
Polyribonucleotide nucleotidyltransferase 1, mitochondrial (EC:2.7.7.8)
Alternative name(s):
3'-5' RNA exonuclease OLD35
PNPase old-35
Polynucleotide phosphorylase 1
Short name:
PNPase 1
Polynucleotide phosphorylase-like protein
Gene namesi
Name:PNPT1
Synonyms:PNPASE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000138035.14
HGNCiHGNC:23166 PNPT1
MIMi610316 gene
neXtProtiNX_Q8TCS8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Combined oxidative phosphorylation deficiency 13 (COXPD13)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA mitochondrial disorder characterized by early onset severe encephalomyopathy, dystonia, choreoathetosis, bucofacial dyskinesias and combined mitochondrial respiratory chain deficiency. Nerve conductions velocities are decreased. Levels of plasma and cerebrospinal fluid lactate are increased.
See also OMIM:614932
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069248387Q → R in COXPD13; the mutation alters multimerization of the protein. 1 PublicationCorresponds to variant dbSNP:rs397514598EnsemblClinVar.1
Deafness, autosomal recessive, 70 (DFNB70)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic deafness characterized by severe, bilateral hearing impairment with prelingual onset, resulting in inability to acquire normal speech.
See also OMIM:614934
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069249475E → G in DFNB70; results in a hypofunctional protein leading to disturbed enzyme trimerization and impaired mitochondrial RNA import. 1 PublicationCorresponds to variant dbSNP:rs397514599EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi135D → G: Inhibits poly(A) polymerase and RNA degradation activities. Inhibits the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity. 1 Publication1
Mutagenesisi445 – 446RR → EE: Stimulates in vitro poly(A) polymerase activity. Inhibits RNA degradation activity. Does not inhibit the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity. 1 Publication2
Mutagenesisi484S → A: Inhibits poly(A) polymerase and RNA degradation activities. Does not inhibit the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity. 1 Publication1
Mutagenesisi544D → A: Stimulates in vitro poly(A) polymerase activity. Inhibits RNA degradation activity. Inhibits the import or stabilization of RNase P RNA into the mitochondrial matrix. Does not inhibit homotrimerization activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness, Primary mitochondrial disease

Organism-specific databases

DisGeNETi87178
MalaCardsiPNPT1
MIMi614932 phenotype
614934 phenotype
OpenTargetsiENSG00000138035
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
319514 Combined oxidative phosphorylation defect type 13
PharmGKBiPA134915354

Polymorphism and mutation databases

DMDMi115502437

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 45MitochondrionSequence analysisAdd BLAST45
ChainiPRO_000002475146 – 783Polyribonucleotide nucleotidyltransferase 1, mitochondrialAdd BLAST738

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei250N6-acetyllysineBy similarity1
Modified residuei264N6-acetyllysineCombined sources1
Modified residuei285N6-acetyllysineCombined sources1
Modified residuei289N6-acetyllysineCombined sources1
Modified residuei552N6-succinyllysineBy similarity1
Modified residuei754PhosphoserineCombined sources1
Modified residuei782PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8TCS8
MaxQBiQ8TCS8
PaxDbiQ8TCS8
PeptideAtlasiQ8TCS8
PRIDEiQ8TCS8
ProteomicsDBi74153

2D gel databases

REPRODUCTION-2DPAGEiIPI00291165

PTM databases

iPTMnetiQ8TCS8
PhosphoSitePlusiQ8TCS8
SwissPalmiQ8TCS8

Expressioni

Inductioni

Up-regulated in cells upon senescence and terminal differentiation. Up-regulated after treatment with IFNB1/IFN-beta.3 Publications

Gene expression databases

BgeeiENSG00000138035
CleanExiHS_PNPT1
ExpressionAtlasiQ8TCS8 baseline and differential
GenevisibleiQ8TCS8 HS

Organism-specific databases

HPAiCAB033424
HPA034602
HPA034603

Interactioni

Subunit structurei

Homotrimer; in free form. Homooligomer. Component of the mitochondrial degradosome (mtEXO) complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 copies of PNPT1. Interacts with TCL1A; the interaction has no effect on PNPT1 exonuclease activity.2 Publications

Protein-protein interaction databases

BioGridi124579, 35 interactors
DIPiDIP-50226N
IntActiQ8TCS8, 11 interactors
MINTiQ8TCS8
STRINGi9606.ENSP00000393953

Structurei

Secondary structure

1783
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi46 – 50Combined sources5
Beta strandi52 – 63Combined sources12
Beta strandi67 – 75Combined sources9
Beta strandi78 – 86Combined sources9
Beta strandi92 – 95Combined sources4
Beta strandi98 – 103Combined sources6
Beta strandi105 – 107Combined sources3
Turni108 – 111Combined sources4
Helixi125 – 138Combined sources14
Helixi139 – 141Combined sources3
Beta strandi150 – 158Combined sources9
Beta strandi161 – 163Combined sources3
Helixi165 – 179Combined sources15
Beta strandi180 – 182Combined sources3
Beta strandi189 – 196Combined sources8
Beta strandi199 – 203Combined sources5
Helixi206 – 210Combined sources5
Beta strandi212 – 221Combined sources10
Turni222 – 224Combined sources3
Beta strandi225 – 236Combined sources12
Helixi238 – 266Combined sources29
Helixi281 – 299Combined sources19
Helixi306 – 327Combined sources22
Helixi333 – 355Combined sources23
Beta strandi370 – 374Combined sources5
Beta strandi380 – 388Combined sources9
Beta strandi391 – 400Combined sources10
Helixi402 – 405Combined sources4
Helixi410 – 416Combined sources7
Helixi420 – 422Combined sources3
Beta strandi423 – 428Combined sources6
Helixi431 – 434Combined sources4
Helixi445 – 458Combined sources14
Helixi459 – 461Combined sources3
Beta strandi467 – 478Combined sources12
Helixi483 – 497Combined sources15
Beta strandi507 – 517Combined sources11
Beta strandi519 – 522Combined sources4
Beta strandi524 – 532Combined sources9
Helixi535 – 539Combined sources5
Beta strandi541 – 549Combined sources9
Beta strandi554 – 561Combined sources8
Helixi568 – 592Combined sources25
Beta strandi606 – 611Combined sources6
Helixi614 – 621Combined sources8
Helixi623 – 625Combined sources3
Helixi626 – 635Combined sources10
Beta strandi638 – 641Combined sources4
Beta strandi643 – 653Combined sources11
Helixi654 – 663Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3U1KX-ray2.13A/B/C/D46-669[»]
ProteinModelPortaliQ8TCS8
SMRiQ8TCS8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini605 – 664KHPROSITE-ProRule annotationAdd BLAST60
Domaini679 – 750S1 motifPROSITE-ProRule annotationAdd BLAST72

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1067 Eukaryota
COG1185 LUCA
GeneTreeiENSGT00390000014001
HOVERGENiHBG053625
InParanoidiQ8TCS8
KOiK00962
OMAiRYMHNYN
OrthoDBiEOG091G03MA
PhylomeDBiQ8TCS8
TreeFamiTF315264

Family and domain databases

Gene3Di3.30.1370.10, 1 hit
3.30.230.70, 2 hits
InterProiView protein in InterPro
IPR001247 ExoRNase_PH_dom1
IPR015847 ExoRNase_PH_dom2
IPR036345 ExoRNase_PH_dom2_sf
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR012340 NA-bd_OB-fold
IPR012162 PNPase
IPR027408 PNPase/RNase_PH_dom_sf
IPR015848 PNPase_PH_RNA-bd_bac/org-type
IPR036456 PNPase_PH_RNA-bd_sf
IPR020568 Ribosomal_S5_D2-typ_fold
IPR022967 S1_dom
IPR003029 S1_domain
PANTHERiPTHR11252 PTHR11252, 1 hit
PfamiView protein in Pfam
PF00013 KH_1, 1 hit
PF03726 PNPase, 1 hit
PF01138 RNase_PH, 2 hits
PF03725 RNase_PH_C, 1 hit
PF00575 S1, 1 hit
PIRSFiPIRSF005499 PNPase, 1 hit
SMARTiView protein in SMART
SM00322 KH, 1 hit
SM00316 S1, 1 hit
SUPFAMiSSF46915 SSF46915, 1 hit
SSF50249 SSF50249, 1 hit
SSF54211 SSF54211, 2 hits
SSF54791 SSF54791, 1 hit
SSF55666 SSF55666, 2 hits
TIGRFAMsiTIGR03591 polynuc_phos, 1 hit
PROSITEiView protein in PROSITE
PS50084 KH_TYPE_1, 1 hit
PS50126 S1, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8TCS8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAACRYCCSC LRLRPLSDGP FLLPRRDRAL TQLQVRALWS SAGSRAVAVD
60 70 80 90 100
LGNRKLEISS GKLARFADGS AVVQSGDTAV MVTAVSKTKP SPSQFMPLVV
110 120 130 140 150
DYRQKAAAAG RIPTNYLRRE IGTSDKEILT SRIIDRSIRP LFPAGYFYDT
160 170 180 190 200
QVLCNLLAVD GVNEPDVLAI NGASVALSLS DIPWNGPVGA VRIGIIDGEY
210 220 230 240 250
VVNPTRKEMS SSTLNLVVAG APKSQIVMLE ASAENILQQD FCHAIKVGVK
260 270 280 290 300
YTQQIIQGIQ QLVKETGVTK RTPQKLFTPS PEIVKYTHKL AMERLYAVFT
310 320 330 340 350
DYEHDKVSRD EAVNKIRLDT EEQLKEKFPE ADPYEIIESF NVVAKEVFRS
360 370 380 390 400
IVLNEYKRCD GRDLTSLRNV SCEVDMFKTL HGSALFQRGQ TQVLCTVTFD
410 420 430 440 450
SLESGIKSDQ VITAINGIKD KNFMLHYEFP PYATNEIGKV TGLNRRELGH
460 470 480 490 500
GALAEKALYP VIPRDFPFTI RVTSEVLESN GSSSMASACG GSLALMDSGV
510 520 530 540 550
PISSAVAGVA IGLVTKTDPE KGEIEDYRLL TDILGIEDYN GDMDFKIAGT
560 570 580 590 600
NKGITALQAD IKLPGIPIKI VMEAIQQASV AKKEILQIMN KTISKPRASR
610 620 630 640 650
KENGPVVETV QVPLSKRAKF VGPGGYNLKK LQAETGVTIS QVDEETFSVF
660 670 680 690 700
APTPSAMHEA RDFITEICKD DQEQQLEFGA VYTATITEIR DTGVMVKLYP
710 720 730 740 750
NMTAVLLHNT QLDQRKIKHP TALGLEVGQE IQVKYFGRDP ADGRMRLSRK
760 770 780
VLQSPATTVV RTLNDRSSIV MGEPISQSSS NSQ
Length:783
Mass (Da):85,951
Last modified:October 3, 2006 - v2
Checksum:i52DBC2119F7234E9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti656A → V in AAK13047 (PubMed:12473748).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027787121I → V3 PublicationsCorresponds to variant dbSNP:rs782572EnsemblClinVar.1
Natural variantiVAR_050610230E → Q. Corresponds to variant dbSNP:rs34928857EnsemblClinVar.1
Natural variantiVAR_069248387Q → R in COXPD13; the mutation alters multimerization of the protein. 1 PublicationCorresponds to variant dbSNP:rs397514598EnsemblClinVar.1
Natural variantiVAR_069249475E → G in DFNB70; results in a hypofunctional protein leading to disturbed enzyme trimerization and impaired mitochondrial RNA import. 1 PublicationCorresponds to variant dbSNP:rs397514599EnsemblClinVar.1
Natural variantiVAR_027788590N → D. Corresponds to variant dbSNP:rs7594497EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ458465 mRNA Translation: CAD30289.1
AY027528 mRNA Translation: AAK13047.1
AC015982 Genomic DNA Translation: AAY24271.1
BC000862 mRNA Translation: AAH00862.2
BC005986 mRNA Translation: AAH05986.1
BC053660 mRNA Translation: AAH53660.1
AY290863 mRNA Translation: AAP44472.1
CR749867 mRNA Translation: CAH18709.1
CCDSiCCDS1856.1
PIRiT50626
RefSeqiNP_149100.2, NM_033109.4
UniGeneiHs.388733

Genome annotation databases

EnsembliENST00000415374; ENSP00000393953; ENSG00000138035
ENST00000447944; ENSP00000400646; ENSG00000138035
GeneIDi87178
KEGGihsa:87178
UCSCiuc002rzf.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPNPT1_HUMAN
AccessioniPrimary (citable) accession number: Q8TCS8
Secondary accession number(s): Q53SU0
, Q68CN1, Q7Z7D1, Q8IWX1, Q96T05, Q9BRU3, Q9BVX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2005
Last sequence update: October 3, 2006
Last modified: June 20, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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