ID PNPT1_HUMAN Reviewed; 783 AA. AC Q8TCS8; Q53SU0; Q68CN1; Q7Z7D1; Q8IWX1; Q96T05; Q9BRU3; Q9BVX0; DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 188. DE RecName: Full=Polyribonucleotide nucleotidyltransferase 1, mitochondrial {ECO:0000305}; DE EC=2.7.7.8 {ECO:0000269|PubMed:18083836}; DE AltName: Full=3'-5' RNA exonuclease OLD35; DE AltName: Full=PNPase old-35; DE AltName: Full=Polynucleotide phosphorylase 1; DE Short=PNPase 1; DE AltName: Full=Polynucleotide phosphorylase-like protein; DE Flags: Precursor; GN Name=PNPT1 {ECO:0000312|HGNC:HGNC:23166}; Synonyms=PNPASE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-121. RC TISSUE=Teratocarcinoma; RX PubMed=12419256; DOI=10.1016/s0022-2836(02)00947-6; RA Raijmakers R., Vree Egberts W., van Venrooij W.J., Pruijn G.J.M.; RT "Protein-protein interactions between human exosome components support the RT assembly of RNase PH-type subunits into a six-membered PNPase-like ring."; RL J. Mol. Biol. 323:653-663(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-121, FUNCTION, AND INDUCTION. RC TISSUE=Melanoma; RX PubMed=12473748; DOI=10.1073/pnas.252643699; RA Leszczyniecka M., Kang D.-C., Sarkar D., Su Z.-Z., Holmes M., Valerie K., RA Fisher P.B.; RT "Identification and cloning of human polynucleotide phosphorylase, hPNPase RT (old-35), in the context of terminal differentiation and cellular RT senescence."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16636-16641(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-121. RC TISSUE=Cervix, Skin, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 509-783. RA Takahashi H., Furukawa T., Yano T., Takizawa J., Abe T., Narita M., RA Fuse I., Koyama S., Takahashi M., Aizawa Y.; RT "Immunogenic antigens eliciting humoral immune response identified in RT leukemia cells by SEREX method."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 538-783. RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [7] RP FUNCTION. RX PubMed=12721301; DOI=10.1074/jbc.m302421200; RA Sarkar D., Leszczyniecka M., Kang D.C., Lebedeva I.V., Valerie K., Dhar S., RA Pandita T.K., Fisher P.B.; RT "Down-regulation of Myc as a potential target for growth arrest induced by RT human polynucleotide phosphorylase (hPNPaseold-35) in human melanoma RT cells."; RL J. Biol. Chem. 278:24542-24551(2003). RN [8] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12798676; DOI=10.1016/s0022-2836(03)00528-x; RA Piwowarski J., Grzechnik P., Dziembowski A., Dmochowska A., Minczuk M., RA Stepien P.P.; RT "Human polynucleotide phosphorylase, hPNPase, is localized in RT mitochondria."; RL J. Mol. Biol. 329:853-857(2003). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16055741; DOI=10.1128/mcb.25.16.7333-7343.2005; RA Sarkar D., Park E.S., Emdad L., Randolph A., Valerie K., Fisher P.B.; RT "Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) RT mediating cellular senescence."; RL Mol. Cell. Biol. 25:7333-7343(2005). RN [10] RP FUNCTION, AND INDUCTION. RX PubMed=16410805; DOI=10.1038/sj.cdd.4401829; RA Sarkar D., Park E.S., Fisher P.B.; RT "Defining the mechanism by which IFN-beta dowregulates c-myc expression in RT human melanoma cells: pivotal role for human polynucleotide phosphorylase RT (hPNPaseold-35)."; RL Cell Death Differ. 13:1541-1553(2006). RN [11] RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=16966381; DOI=10.1128/mcb.01002-06; RA Chen H.W., Rainey R.N., Balatoni C.E., Dawson D.W., Troke J.J., Wasiak S., RA Hong J.S., McBride H.M., Koehler C.M., Teitell M.A., French S.W.; RT "Mammalian polynucleotide phosphorylase is an intermembrane space RNase RT that maintains mitochondrial homeostasis."; RL Mol. Cell. Biol. 26:8475-8487(2006). RN [12] RP FUNCTION, INTERACTION WITH TCL1A, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16934922; DOI=10.1016/j.canlet.2006.07.006; RA French S.W., Dawson D.W., Chen H.-W., Rainey R.N., Sievers S.A., RA Balatoni C.E., Wong L., Troke J.J., Nguyen M.T.N., Koehler C.M., RA Teitell M.A.; RT "The TCL1 oncoprotein binds the RNase PH domains of the PNPase RT exoribonuclease without affecting its RNA degrading activity."; RL Cancer Lett. 248:198-210(2007). RN [13] RP FUNCTION. RX PubMed=18501193; DOI=10.1016/j.bbrc.2008.05.058; RA Wu J., Li Z.; RT "Human polynucleotide phosphorylase reduces oxidative RNA damage and RT protects HeLa cell against oxidative stress."; RL Biochem. Biophys. Res. Commun. 372:288-292(2008). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, AND RNA-BINDING. RX PubMed=18083836; DOI=10.1261/rna.698108; RA Portnoy V., Palnizky G., Yehudai-Resheff S., Glaser F., Schuster G.; RT "Analysis of the human polynucleotide phosphorylase (PNPase) reveals RT differences in RNA binding and response to phosphate compared to its RT bacterial and chloroplast counterparts."; RL RNA 14:297-309(2008). RN [15] RP FUNCTION. RX PubMed=18083837; DOI=10.1261/rna.697308; RA Slomovic S., Schuster G.; RT "Stable PNPase RNAi silencing: its effect on the processing and adenylation RT of human mitochondrial RNA."; RL RNA 14:310-323(2008). RN [16] RP FUNCTION, IDENTIFICATION IN THE MITOCHONDRIAL DEGRADOSOME COMPLEX, AND RP HOMOTRIMERIZATION. RX PubMed=19509288; DOI=10.1074/jbc.m109.009605; RA Wang D.D., Shu Z., Lieser S.A., Chen P.L., Lee W.H.; RT "Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa RT heteropentamer to cooperatively degrade double-stranded RNA with a 3'-to-5' RT directionality."; RL J. Biol. Chem. 284:20812-20821(2009). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-264; LYS-285 AND LYS-289, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [18] RP FUNCTION, HOMOTRIMERIZATION, HOMOOLIGOMERIZATION, AND MUTAGENESIS OF RP ASP-135; 445-ARG-ARG-446; SER-484 AND ASP-544. RX PubMed=20691904; DOI=10.1016/j.cell.2010.06.035; RA Wang G., Chen H.W., Oktay Y., Zhang J., Allen E.L., Smith G.M., Fan K.C., RA Hong J.S., French S.W., McCaffery J.M., Lightowlers R.N., Morse H.C. III, RA Koehler C.M., Teitell M.A.; RT "PNPASE regulates RNA import into mitochondria."; RL Cell 142:456-467(2010). RN [19] RP FUNCTION. RX PubMed=20547861; DOI=10.1073/pnas.0914143107; RA Das S.K., Sokhi U.K., Bhutia S.K., Azab B., Su Z.Z., Sarkar D., RA Fisher P.B.; RT "Human polynucleotide phosphorylase selectively and preferentially degrades RT microRNA-221 in human melanoma cells."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11948-11953(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-782, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-754, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [24] RP FUNCTION, IDENTIFICATION IN THE MITOCHONDRIAL DEGRADOSOME COMPLEX, AND RP INTERACTION WITH GRSF1. RX PubMed=29967381; DOI=10.1038/s41467-018-05007-9; RA Pietras Z., Wojcik M.A., Borowski L.S., Szewczyk M., Kulinski T.M., RA Cysewski D., Stepien P.P., Dziembowski A., Szczesny R.J.; RT "Dedicated surveillance mechanism controls G-quadruplex forming non-coding RT RNAs in human mitochondria."; RL Nat. Commun. 9:2558-2558(2018). RN [25] RP VARIANT COXPD13 ARG-387, AND CHARACTERIZATION OF VARIANT COXPD13 ARG-387. RX PubMed=23084291; DOI=10.1016/j.ajhg.2012.09.001; RA Vedrenne V., Gowher A., De Lonlay P., Nitschke P., Serre V., Boddaert N., RA Altuzarra C., Mager-Heckel A.M., Chretien F., Entelis N., Munnich A., RA Tarassov I., Rotig A.; RT "Mutation in PNPT1, which encodes a polyribonucleotide RT nucleotidyltransferase, impairs RNA import into mitochondria and causes RT respiratory-chain deficiency."; RL Am. J. Hum. Genet. 91:912-918(2012). RN [26] RP VARIANT DFNB70 GLY-475, AND CHARACTERIZATION OF VARIANT DFNB70 GLY-475. RX PubMed=23084290; DOI=10.1016/j.ajhg.2012.09.002; RA von Ameln S., Wang G., Boulouiz R., Rutherford M.A., Smith G.M., Li Y., RA Pogoda H.M., Nurnberg G., Stiller B., Volk A.E., Borck G., Hong J.S., RA Goodyear R.J., Abidi O., Nurnberg P., Hofmann K., Richardson G.P., RA Hammerschmidt M., Moser T., Wollnik B., Koehler C.M., Teitell M.A., RA Barakat A., Kubisch C.; RT "A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, RT causes hereditary hearing loss."; RL Am. J. Hum. Genet. 91:919-927(2012). RN [27] RP INVOLVEMENT IN SCA25. RX PubMed=35411967; DOI=10.1002/ana.26366; RA Barbier M., Bahlo M., Pennisi A., Jacoupy M., Tankard R.M., Ewenczyk C., RA Davies K.C., Lino-Coulon P., Colace C., Rafehi H., Auger N., Ansell B.R.E., RA van der Stelt I., Howell K.B., Coutelier M., Amor D.J., Mundwiller E., RA Guillot-Noel L., Storey E., Gardner R.J.M., Wallis M.J., Brusco A., RA Corti O., Roetig A., Leventer R.J., Brice A., Delatycki M.B., Stevanin G., RA Lockhart P.J., Durr A.; RT "Heterozygous PNPT1 Variants Cause Spinocerebellar Ataxia Type 25."; RL Ann. Neurol. 92:122-137(2022). CC -!- FUNCTION: RNA-binding protein implicated in numerous RNA metabolic CC processes. Catalyzes the phosphorolysis of single-stranded CC polyribonucleotides processively in the 3'-to-5' direction. CC Mitochondrial intermembrane factor with RNA-processing exoribonulease CC activity. Component of the mitochondrial degradosome (mtEXO) complex, CC that degrades 3' overhang double-stranded RNA with a 3'-to-5' CC directionality in an ATP-dependent manner. Involved in the degradation CC of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like CC molecules (PubMed:29967381). Required for correct processing and CC polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic CC RNA import factor that mediates the translocation of small RNA CC components, like the 5S RNA, the RNA subunit of ribonuclease P and the CC mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. CC Plays a role in mitochondrial morphogenesis and respiration; regulates CC the expression of the electron transport chain (ETC) components at the CC mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' CC exoribonuclease mediating mRNA degradation activity; degrades c-myc CC mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest CC in melanoma cells. Regulates the stability of specific mature miRNAs in CC melanoma cells; specifically and selectively degrades miR-221, CC preferentially. Also plays a role in RNA cell surveillance by cleaning CC up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA CC and miR-221 microRNA. {ECO:0000269|PubMed:12473748, CC ECO:0000269|PubMed:12721301, ECO:0000269|PubMed:12798676, CC ECO:0000269|PubMed:16055741, ECO:0000269|PubMed:16410805, CC ECO:0000269|PubMed:16934922, ECO:0000269|PubMed:18083836, CC ECO:0000269|PubMed:18083837, ECO:0000269|PubMed:18501193, CC ECO:0000269|PubMed:19509288, ECO:0000269|PubMed:20547861, CC ECO:0000269|PubMed:20691904, ECO:0000269|PubMed:29967381}. CC -!- CATALYTIC ACTIVITY: CC Reaction=phosphate + RNA(n+1) = a ribonucleoside 5'-diphosphate + CC RNA(n); Xref=Rhea:RHEA:22096, Rhea:RHEA-COMP:14527, Rhea:RHEA- CC COMP:17342, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:140395; CC EC=2.7.7.8; Evidence={ECO:0000269|PubMed:18083836}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22097; CC Evidence={ECO:0000305|PubMed:18083836}; CC -!- SUBUNIT: Homotrimer; in free form (PubMed:19509288). Homooligomer CC (PubMed:19509288). Component of the mitochondrial degradosome (mtEXO) CC complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 CC copies of PNPT1 (PubMed:19509288, PubMed:29967381). As part of the CC mitochondrial degradosome complex, interacts with GRSF1 in an RNA- CC dependent manner; the interaction enhances the activity of the complex CC (PubMed:29967381). Interacts with TCL1A; the interaction has no effect CC on PNPT1 exonuclease activity (PubMed:16934922). CC {ECO:0000269|PubMed:16934922, ECO:0000269|PubMed:19509288, CC ECO:0000269|PubMed:29967381}. CC -!- INTERACTION: CC Q8TCS8; P78563-4: ADARB1; NbExp=3; IntAct=EBI-1052020, EBI-12002366; CC Q8TCS8; Q8TCS8: PNPT1; NbExp=2; IntAct=EBI-1052020, EBI-1052020; CC Q8TCS8; Q8IYB8: SUPV3L1; NbExp=6; IntAct=EBI-1052020, EBI-2876787; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16055741}. CC Mitochondrion matrix {ECO:0000269|PubMed:12798676, CC ECO:0000269|PubMed:16055741}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:16966381}; Peripheral membrane protein CC {ECO:0000269|PubMed:16966381}. CC -!- INDUCTION: Up-regulated in cells upon senescence and terminal CC differentiation. Up-regulated after treatment with IFNB1/IFN-beta. CC {ECO:0000269|PubMed:12473748, ECO:0000269|PubMed:16410805, CC ECO:0000269|PubMed:16966381}. CC -!- DISEASE: Combined oxidative phosphorylation deficiency 13 (COXPD13) CC [MIM:614932]: A mitochondrial disorder characterized by early onset CC severe encephalomyopathy, dystonia, choreoathetosis, bucofacial CC dyskinesias and combined mitochondrial respiratory chain deficiency. CC Nerve conductions velocities are decreased. Levels of plasma and CC cerebrospinal fluid lactate are increased. CC {ECO:0000269|PubMed:23084291}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Deafness, autosomal recessive, 70, with or without adult-onset CC neurodegeneration (DFNB70) [MIM:614934]: A form of non-syndromic CC deafness characterized by severe, bilateral hearing impairment with CC prelingual onset, resulting in inability to acquire normal speech. CC Affected individuals may develop a neurodegenerative disease in CC adulthood, including ataxia with loss of ambulation, optic atrophy, CC dystonia or spasticity, and cognitive decline with psychiatric CC features. {ECO:0000269|PubMed:23084290}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Spinocerebellar ataxia 25 (SCA25) [MIM:608703]: An autosomal CC dominant form of spinocerebellar ataxia, a clinically and genetically CC heterogeneous group of cerebellar disorders. Patients show progressive CC incoordination of gait and often poor coordination of hands, speech and CC eye movements, due to degeneration of the cerebellum with variable CC involvement of the brainstem and spinal cord. SCA25 is characterized by CC the onset of lower limb ataxia and gait difficulties in the first few CC decades of life, although later onset has been reported. There is CC incomplete penetrance and variable expressivity, even within families. CC {ECO:0000269|PubMed:35411967}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Both genetic variants CC associated so far with this disease are affecting splicing. CC {ECO:0000269|PubMed:35411967}. CC -!- SIMILARITY: Belongs to the polyribonucleotide nucleotidyltransferase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ458465; CAD30289.1; -; mRNA. DR EMBL; AY027528; AAK13047.1; -; mRNA. DR EMBL; AC015982; AAY24271.1; -; Genomic_DNA. DR EMBL; BC000862; AAH00862.2; -; mRNA. DR EMBL; BC005986; AAH05986.1; -; mRNA. DR EMBL; BC053660; AAH53660.1; -; mRNA. DR EMBL; AY290863; AAP44472.1; -; mRNA. DR EMBL; CR749867; CAH18709.1; -; mRNA. DR CCDS; CCDS1856.1; -. DR PIR; T50626; T50626. DR RefSeq; NP_149100.2; NM_033109.4. DR PDB; 3U1K; X-ray; 2.13 A; A/B/C/D=46-669. DR PDB; 5ZF6; X-ray; 2.80 A; A/B=46-669. DR PDBsum; 3U1K; -. DR PDBsum; 5ZF6; -. DR AlphaFoldDB; Q8TCS8; -. DR SMR; Q8TCS8; -. DR BioGRID; 124579; 173. DR ComplexPortal; CPX-2842; Mitochondrial degradosome complex. DR DIP; DIP-50226N; -. DR IntAct; Q8TCS8; 27. DR MINT; Q8TCS8; -. DR STRING; 9606.ENSP00000400646; -. DR GlyGen; Q8TCS8; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q8TCS8; -. DR MetOSite; Q8TCS8; -. DR PhosphoSitePlus; Q8TCS8; -. DR SwissPalm; Q8TCS8; -. DR BioMuta; PNPT1; -. DR DMDM; 115502437; -. DR REPRODUCTION-2DPAGE; IPI00291165; -. DR EPD; Q8TCS8; -. DR jPOST; Q8TCS8; -. DR MassIVE; Q8TCS8; -. DR MaxQB; Q8TCS8; -. DR PaxDb; 9606-ENSP00000400646; -. DR PeptideAtlas; Q8TCS8; -. DR ProteomicsDB; 74153; -. DR Pumba; Q8TCS8; -. DR Antibodypedia; 30432; 364 antibodies from 31 providers. DR DNASU; 87178; -. DR Ensembl; ENST00000415374.5; ENSP00000393953.1; ENSG00000138035.15. DR Ensembl; ENST00000447944.7; ENSP00000400646.2; ENSG00000138035.15. DR GeneID; 87178; -. DR KEGG; hsa:87178; -. DR MANE-Select; ENST00000447944.7; ENSP00000400646.2; NM_033109.5; NP_149100.2. DR UCSC; uc002rzf.4; human. DR AGR; HGNC:23166; -. DR CTD; 87178; -. DR DisGeNET; 87178; -. DR GeneCards; PNPT1; -. DR HGNC; HGNC:23166; PNPT1. DR HPA; ENSG00000138035; Low tissue specificity. DR MalaCards; PNPT1; -. DR MIM; 608703; phenotype. DR MIM; 610316; gene. DR MIM; 614932; phenotype. DR MIM; 614934; phenotype. DR neXtProt; NX_Q8TCS8; -. DR OpenTargets; ENSG00000138035; -. DR Orphanet; 319514; Combined oxidative phosphorylation defect type 13. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR Orphanet; 101111; Spinocerebellar ataxia type 25. DR PharmGKB; PA134915354; -. DR VEuPathDB; HostDB:ENSG00000138035; -. DR eggNOG; KOG1067; Eukaryota. DR GeneTree; ENSGT00390000014001; -. DR HOGENOM; CLU_004217_2_2_1; -. DR InParanoid; Q8TCS8; -. DR OMA; RFMFHYN; -. DR OrthoDB; 937144at2759; -. DR PhylomeDB; Q8TCS8; -. DR TreeFam; TF315264; -. DR BRENDA; 2.7.7.8; 2681. DR PathwayCommons; Q8TCS8; -. DR Reactome; R-HSA-9836573; Mitochondrial RNA degradation. DR SignaLink; Q8TCS8; -. DR SIGNOR; Q8TCS8; -. DR BioGRID-ORCS; 87178; 692 hits in 1180 CRISPR screens. DR ChiTaRS; PNPT1; human. DR GenomeRNAi; 87178; -. DR Pharos; Q8TCS8; Tbio. DR PRO; PR:Q8TCS8; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q8TCS8; Protein. DR Bgee; ENSG00000138035; Expressed in left ventricle myocardium and 186 other cell types or tissues. DR ExpressionAtlas; Q8TCS8; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:Ensembl. DR GO; GO:0045025; C:mitochondrial degradosome; IDA:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005840; C:ribosome; IEA:Ensembl. DR GO; GO:0000175; F:3'-5'-RNA exonuclease activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035198; F:miRNA binding; IDA:UniProtKB. DR GO; GO:0034046; F:poly(G) binding; IDA:UniProtKB. DR GO; GO:0008266; F:poly(U) RNA binding; IDA:UniProtKB. DR GO; GO:0004654; F:polyribonucleotide nucleotidyltransferase activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProtKB. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0000958; P:mitochondrial mRNA catabolic process; IDA:UniProtKB. DR GO; GO:0097222; P:mitochondrial mRNA polyadenylation; IMP:UniProtKB. DR GO; GO:0000965; P:mitochondrial RNA 3'-end processing; IMP:UniProtKB. DR GO; GO:0000964; P:mitochondrial RNA 5'-end processing; IMP:UniProtKB. DR GO; GO:0000957; P:mitochondrial RNA catabolic process; IDA:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; ISS:UniProtKB. DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0045926; P:negative regulation of growth; IDA:UniProtKB. DR GO; GO:0071042; P:nuclear polyadenylation-dependent mRNA catabolic process; IDA:UniProtKB. DR GO; GO:2000627; P:positive regulation of miRNA catabolic process; IDA:UniProtKB. DR GO; GO:0000962; P:positive regulation of mitochondrial RNA catabolic process; IDA:UniProtKB. DR GO; GO:0061014; P:positive regulation of mRNA catabolic process; IMP:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0043457; P:regulation of cellular respiration; ISS:UniProtKB. DR GO; GO:2000772; P:regulation of cellular senescence; IDA:UniProtKB. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0060416; P:response to growth hormone; IEA:Ensembl. DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB. DR GO; GO:0035927; P:RNA import into mitochondrion; IDA:UniProtKB. DR GO; GO:0035928; P:rRNA import into mitochondrion; IDA:UniProtKB. DR CDD; cd09033; KH-I_PNPT1; 1. DR CDD; cd11363; RNase_PH_PNPase_1; 1. DR CDD; cd11364; RNase_PH_PNPase_2; 1. DR Gene3D; 3.30.230.70; GHMP Kinase, N-terminal domain; 2. DR Gene3D; 3.30.1370.10; K Homology domain, type 1; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 1. DR Gene3D; 1.10.10.400; Polyribonucleotide nucleotidyltransferase, RNA-binding domain; 1. DR InterPro; IPR001247; ExoRNase_PH_dom1. DR InterPro; IPR015847; ExoRNase_PH_dom2. DR InterPro; IPR036345; ExoRNase_PH_dom2_sf. DR InterPro; IPR004087; KH_dom. DR InterPro; IPR004088; KH_dom_type_1. DR InterPro; IPR036612; KH_dom_type_1_sf. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR012162; PNPase. DR InterPro; IPR027408; PNPase/RNase_PH_dom_sf. DR InterPro; IPR015848; PNPase_PH_RNA-bd_bac/org-type. DR InterPro; IPR036456; PNPase_PH_RNA-bd_sf. DR InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF. DR InterPro; IPR003029; S1_domain. DR NCBIfam; TIGR03591; polynuc_phos; 1. DR PANTHER; PTHR11252; POLYRIBONUCLEOTIDE NUCLEOTIDYLTRANSFERASE; 1. DR PANTHER; PTHR11252:SF9; POLYRIBONUCLEOTIDE NUCLEOTIDYLTRANSFERASE 1, MITOCHONDRIAL; 1. DR Pfam; PF00013; KH_1; 1. DR Pfam; PF03726; PNPase; 1. DR Pfam; PF01138; RNase_PH; 2. DR Pfam; PF03725; RNase_PH_C; 1. DR Pfam; PF00575; S1; 1. DR PIRSF; PIRSF005499; PNPase; 1. DR SMART; SM00322; KH; 1. DR SMART; SM00316; S1; 1. DR SUPFAM; SSF54791; Eukaryotic type KH-domain (KH-domain type I); 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 1. DR SUPFAM; SSF46915; Polynucleotide phosphorylase/guanosine pentaphosphate synthase (PNPase/GPSI), domain 3; 1. DR SUPFAM; SSF55666; Ribonuclease PH domain 2-like; 2. DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 2. DR PROSITE; PS50084; KH_TYPE_1; 1. DR PROSITE; PS50126; S1; 1. DR Genevisible; Q8TCS8; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Deafness; Disease variant; KW Exonuclease; Hydrolase; Membrane; Mitochondrion; mRNA processing; KW Neurodegeneration; Non-syndromic deafness; Nuclease; KW Nucleotidyltransferase; Phosphoprotein; Primary mitochondrial disease; KW Reference proteome; RNA-binding; Spinocerebellar ataxia; Transferase; KW Transit peptide; Transport. FT TRANSIT 1..45 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 46..783 FT /note="Polyribonucleotide nucleotidyltransferase 1, FT mitochondrial" FT /id="PRO_0000024751" FT DOMAIN 605..664 FT /note="KH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117" FT DOMAIN 679..750 FT /note="S1 motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00180" FT MOD_RES 250 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K1R3" FT MOD_RES 264 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 285 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 289 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 552 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K1R3" FT MOD_RES 754 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 782 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT VARIANT 121 FT /note="I -> V (in dbSNP:rs782572)" FT /evidence="ECO:0000269|PubMed:12419256, FT ECO:0000269|PubMed:12473748, ECO:0000269|PubMed:15489334" FT /id="VAR_027787" FT VARIANT 230 FT /note="E -> Q (in dbSNP:rs34928857)" FT /id="VAR_050610" FT VARIANT 387 FT /note="Q -> R (in COXPD13; the mutation alters FT multimerization of the protein; dbSNP:rs397514598)" FT /evidence="ECO:0000269|PubMed:23084291" FT /id="VAR_069248" FT VARIANT 475 FT /note="E -> G (in DFNB70; results in a hypofunctional FT protein leading to disturbed enzyme trimerization and FT impaired mitochondrial RNA import; dbSNP:rs397514599)" FT /evidence="ECO:0000269|PubMed:23084290" FT /id="VAR_069249" FT VARIANT 590 FT /note="N -> D (in dbSNP:rs7594497)" FT /id="VAR_027788" FT MUTAGEN 135 FT /note="D->G: Inhibits poly(A) polymerase and RNA FT degradation activities. Inhibits the import or FT stabilization of RNase PRNA into the mitochondrial matrix. FT Does not inhibit homotrimerization activity." FT /evidence="ECO:0000269|PubMed:20691904" FT MUTAGEN 445..446 FT /note="RR->EE: Stimulates in vitro poly(A) polymerase FT activity. Inhibits RNA degradation activity. Does not FT inhibit the import or stabilization of RNase PRNA into the FT mitochondrial matrix. Does not inhibit homotrimerization FT activity." FT /evidence="ECO:0000269|PubMed:20691904" FT MUTAGEN 484 FT /note="S->A: Inhibits poly(A) polymerase and RNA FT degradation activities. Does not inhibit the import or FT stabilization of RNase PRNA into the mitochondrial matrix. FT Does not inhibit homotrimerization activity." FT /evidence="ECO:0000269|PubMed:20691904" FT MUTAGEN 544 FT /note="D->A: Stimulates in vitro poly(A) polymerase FT activity. Inhibits RNA degradation activity. Inhibits the FT import or stabilization of RNase PRNA into the FT mitochondrial matrix. Does not inhibit homotrimerization FT activity." FT /evidence="ECO:0000269|PubMed:20691904" FT CONFLICT 656 FT /note="A -> V (in Ref. 2; AAK13047)" FT /evidence="ECO:0000305" FT STRAND 46..50 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 52..63 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 67..75 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 78..86 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:3U1K" FT TURN 108..111 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 125..138 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 150..158 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 165..179 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 189..196 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 199..203 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 206..210 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 212..221 FT /evidence="ECO:0007829|PDB:3U1K" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 225..236 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 238..266 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 281..299 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 306..327 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 333..355 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 370..374 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 380..388 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 391..400 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 402..405 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 410..416 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 420..422 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 423..428 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 431..434 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 445..458 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 459..461 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 467..478 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 483..497 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 507..517 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 519..522 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 524..532 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 535..539 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 541..549 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 554..561 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 568..592 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 606..611 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 614..621 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 623..625 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 626..635 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 638..641 FT /evidence="ECO:0007829|PDB:3U1K" FT STRAND 643..653 FT /evidence="ECO:0007829|PDB:3U1K" FT HELIX 654..663 FT /evidence="ECO:0007829|PDB:3U1K" SQ SEQUENCE 783 AA; 85951 MW; 52DBC2119F7234E9 CRC64; MAACRYCCSC LRLRPLSDGP FLLPRRDRAL TQLQVRALWS SAGSRAVAVD LGNRKLEISS GKLARFADGS AVVQSGDTAV MVTAVSKTKP SPSQFMPLVV DYRQKAAAAG RIPTNYLRRE IGTSDKEILT SRIIDRSIRP LFPAGYFYDT QVLCNLLAVD GVNEPDVLAI NGASVALSLS DIPWNGPVGA VRIGIIDGEY VVNPTRKEMS SSTLNLVVAG APKSQIVMLE ASAENILQQD FCHAIKVGVK YTQQIIQGIQ QLVKETGVTK RTPQKLFTPS PEIVKYTHKL AMERLYAVFT DYEHDKVSRD EAVNKIRLDT EEQLKEKFPE ADPYEIIESF NVVAKEVFRS IVLNEYKRCD GRDLTSLRNV SCEVDMFKTL HGSALFQRGQ TQVLCTVTFD SLESGIKSDQ VITAINGIKD KNFMLHYEFP PYATNEIGKV TGLNRRELGH GALAEKALYP VIPRDFPFTI RVTSEVLESN GSSSMASACG GSLALMDSGV PISSAVAGVA IGLVTKTDPE KGEIEDYRLL TDILGIEDYN GDMDFKIAGT NKGITALQAD IKLPGIPIKI VMEAIQQASV AKKEILQIMN KTISKPRASR KENGPVVETV QVPLSKRAKF VGPGGYNLKK LQAETGVTIS QVDEETFSVF APTPSAMHEA RDFITEICKD DQEQQLEFGA VYTATITEIR DTGVMVKLYP NMTAVLLHNT QLDQRKIKHP TALGLEVGQE IQVKYFGRDP ADGRMRLSRK VLQSPATTVV RTLNDRSSIV MGEPISQSSS NSQ //