PNPT1_HUMAN
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 03-AUG-2022, entry version 179.
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).
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 -!- 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 (DFNB70) [MIM:614934]: A
CC form of non-syndromic deafness characterized by severe, bilateral
CC hearing impairment with prelingual onset, resulting in inability to
CC acquire normal speech. {ECO:0000269|PubMed:23084290}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the polyribonucleotide nucleotidyltransferase
CC family. {ECO:0000305}.
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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; 154.
DR DIP; DIP-50226N; -.
DR IntAct; Q8TCS8; 26.
DR MINT; Q8TCS8; -.
DR STRING; 9606.ENSP00000400646; -.
DR GlyGen; Q8TCS8; 1 site, 1 O-linked glycan (1 site).
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; Q8TCS8; -.
DR PeptideAtlas; Q8TCS8; -.
DR PRIDE; Q8TCS8; -.
DR ProteomicsDB; 74153; -.
DR Antibodypedia; 30432; 345 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 CTD; 87178; -.
DR DisGeNET; 87178; -.
DR GeneCards; PNPT1; -.
DR HGNC; HGNC:23166; PNPT1.
DR HPA; ENSG00000138035; Low tissue specificity.
DR MalaCards; PNPT1; -.
DR MIM; 610316; gene.
DR MIM; 614932; phenotype.
DR MIM; 614934; phenotype.
DR neXtProt; NX_Q8TCS8; -.
DR OpenTargets; ENSG00000138035; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 319514; Combined oxidative phosphorylation defect type 13.
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; LHILDVM; -.
DR OrthoDB; 236073at2759; -.
DR PhylomeDB; Q8TCS8; -.
DR TreeFam; TF315264; -.
DR BRENDA; 2.7.7.8; 2681.
DR PathwayCommons; Q8TCS8; -.
DR SignaLink; Q8TCS8; -.
DR SIGNOR; Q8TCS8; -.
DR BioGRID-ORCS; 87178; 660 hits in 1101 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 184 other tissues.
DR ExpressionAtlas; Q8TCS8; baseline and differential.
DR Genevisible; Q8TCS8; HS.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0042788; C:polysomal ribosome; IEA:Ensembl.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IDA:UniProtKB.
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:0070584; P:mitochondrion morphogenesis; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; IDA:UniProtKB.
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:0043631; P:RNA polyadenylation; IDA:UniProtKB.
DR GO; GO:0035928; P:rRNA import into mitochondrion; IDA:UniProtKB.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.1370.10; -; 1.
DR Gene3D; 3.30.230.70; -; 2.
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_S5_D2-typ_fold.
DR InterPro; IPR022967; S1_dom.
DR InterPro; IPR003029; S1_domain.
DR PANTHER; PTHR11252; PTHR11252; 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 PIRSF; PIRSF005499; PNPase; 1.
DR SMART; SM00322; KH; 1.
DR SMART; SM00316; S1; 1.
DR SUPFAM; SSF46915; SSF46915; 1.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF54211; SSF54211; 2.
DR SUPFAM; SSF54791; SSF54791; 1.
DR SUPFAM; SSF55666; SSF55666; 2.
DR TIGRFAMs; TIGR03591; polynuc_phos; 1.
DR PROSITE; PS50084; KH_TYPE_1; 1.
DR PROSITE; PS50126; S1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Deafness; Disease variant;
KW Exonuclease; Hydrolase; Membrane; Mitochondrion; mRNA processing;
KW Non-syndromic deafness; Nuclease; Nucleotidyltransferase; Phosphoprotein;
KW Primary mitochondrial disease; Reference proteome; RNA-binding;
KW Transferase; 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 P RNA 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 P RNA 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 P RNA 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 P RNA 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
