Q8K1R3 (PNPT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Pnpt1
Synonyms:	Pnpase

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	783 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA-binding protein implicated in numerous RNA metabolic processes. Hydrolyzes 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. Ref.7
Catalytic activity	RNA(n+1) + phosphate = RNA(n) + a nucleoside diphosphate.
Subunit structure	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 By similarity.
Subcellular location	Cytoplasm By similarity. Mitochondrion By similarity. Mitochondrion intermembrane space; Peripheral membrane protein Ref.6.
Disruption phenotype	Mice show alteration in the mechanisms of polycistronic mtRNAs processing in mitochondria, resulting in fewer mature mtRNAs and a reduction in electron transport chain (ETC) components formation. Ref.7
Sequence similarities	Belongs to the polyribonucleotide nucleotidyltransferase family. Contains 1 KH domain. Contains 1 S1 motif domain.
Sequence caution	The sequence AAO33354.1 differs from that shown. Reason: Frameshift at positions 3, 6, 20, 23, 273, 286, 300, 312, 314, 320 and 325.

Ontologies

Keywords
Biological process	Transport mRNA processing
Cellular component	Cytoplasm Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	RNA-binding
Molecular function	Exonuclease Hydrolase Nuclease Nucleotidyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to interferon-beta Inferred from electronic annotation. Source: Compara cellular response to oxidative stress Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial RNA 3'-end processing Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial RNA 5'-end processing Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial mRNA catabolic process Inferred from mutant phenotype Ref.7. Source: UniProtKB mitochondrial mRNA polyadenylation Inferred from sequence or structural similarity. Source: UniProtKB mitochondrion morphogenesis Inferred from mutant phenotype Ref.6Ref.7. Source: UniProtKB mitotic cell cycle arrest Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of growth Inferred from sequence or structural similarity. Source: UniProtKB nuclear polyadenylation-dependent mRNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mRNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of miRNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitochondrial RNA catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein homotrimerization Inferred from sequence or structural similarity. Source: UniProtKB rRNA import into mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB regulation of cellular respiration Inferred from mutant phenotype Ref.6Ref.7. Source: UniProtKB regulation of cellular senescence Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial degradosome Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial intermembrane space Inferred from direct assay Ref.6. Source: MGI plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	3'-5'-exoribonuclease activity Inferred from sequence or structural similarity. Source: UniProtKB miRNA binding Inferred from sequence or structural similarity. Source: UniProtKB poly(G) RNA binding Inferred from sequence or structural similarity. Source: UniProtKB poly(U) RNA binding Inferred from sequence or structural similarity. Source: UniProtKB polyribonucleotide nucleotidyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8K1R3-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8K1R3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     535-540: GIEDYN → ASIFPV
     541-783: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 45

45

Mitochondrion Potential

Chain

46 – 783

738

Polyribonucleotide nucleotidyltransferase 1, mitochondrial

PRO_0000024752

Regions

Domain

605 – 664

60

KH

Domain

679 – 750

72

S1 motif

Amino acid modifications

Modified residue

264

1

N6-acetyllysine By similarity

Modified residue

285

1

N6-acetyllysine By similarity

Natural variations

Alternative sequence

535 – 540

6

GIEDYN → ASIFPV in isoform 2.

VSP_013639

Alternative sequence

541 – 783

243

Missing in isoform 2.

VSP_013640

Experimental info

Sequence conflict

90

1

A → P in AAO33354. Ref.2

Sequence conflict

298

1

V → G in AAO33354. Ref.2

Sequence conflict

315

1

K → Q in AAO33354. Ref.2

Sequence conflict

415

1

I → V in AAO33354. Ref.2

Sequence conflict

431

1

P → L in BAB23374. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

783

Helix Strand Turn

Details...

Helix

281 – 299

19

Helix

307 – 324

18

Turn

325 – 327

3

Beta strand

329 – 331

3

Helix

333 – 352

20

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: F35F6BE91AAB5626	FASTA	783	85,683
	10 20 30 40 50 60 MAACRLCCLC PCLRPLGCGP LGRPGRNRAL SYLQMRALWS STGSRAVTVD LGHRKLEISS 70 80 90 100 110 120 GKLARFADGC AVIQSGDTAV MVTAVSKTKA SPSQFMPLVV DYRQKAAAAG RIPTNYLRRE 130 140 150 160 170 180 IGSSDREVLT SRVIDRSIRP LFPAGYFYDT QVLCNLLAVD GINEPDILAV NGASVALSLS 190 200 210 220 230 240 DIPWNGPVGA VRIGMIDGEC VVNPTRREMS SSTLNLVVAG APKSQIVMLE ASAENILQQD 250 260 270 280 290 300 FCHAIKVGVK YTQQIIQGIQ QLVKEIGVAK RTPQKIFTPS AEIVKYTKII AMEKLYAVFT 310 320 330 340 350 360 DYEHDKVSRD EAVNKIRLDT EEHLKEKFPE VDQFEIIESF NIVAKEVFRS IILNEYKRCD 370 380 390 400 410 420 GRDLTSLRNI SCEVDMFKTL HGSALFQRGQ TQVLCTVTFD SLESSIKSDQ IITAINGVKD 430 440 450 460 470 480 KNFMLHYEFP PYATNETGKV TGVNRRELGH GALAEKALCP VIPKDFPFTI RVTSEVLESN 490 500 510 520 530 540 GSSSMASACG GSLALMDAGV PISSAVAGVA VGLVTKTNPE KGEIEDYRLL TDILGIEDYN 550 560 570 580 590 600 GDMDFKIAGT NKGITALQAD IKLPGVPIKI IMEAIQQASV AKKEILQIMN KTISKPRASR 610 620 630 640 650 660 KENGPVVETV KVPLSKRAKF VGPGGYHLKK LQAETGVTIS QVDEETFSIF APTPTAMHEA 670 680 690 700 710 720 RDFITEICRD DQEQQLEFGA VYTATITEIR DTGVMVKLYP NMTAVLLHNS QLDQRKIKHP 730 740 750 760 770 780 TALGLEVGQE IQVKYFGRDP ADGRMRLSRK VLQSPATTAL KTLNDRSSIV MGEPVSQSSN SNP
	Isoform 2 [UniParc]. Checksum: E57BFA2B602361C4	FASTA	540	58,923
	10 20 30 40 50 60 MAACRLCCLC PCLRPLGCGP LGRPGRNRAL SYLQMRALWS STGSRAVTVD LGHRKLEISS 70 80 90 100 110 120 GKLARFADGC AVIQSGDTAV MVTAVSKTKA SPSQFMPLVV DYRQKAAAAG RIPTNYLRRE 130 140 150 160 170 180 IGSSDREVLT SRVIDRSIRP LFPAGYFYDT QVLCNLLAVD GINEPDILAV NGASVALSLS 190 200 210 220 230 240 DIPWNGPVGA VRIGMIDGEC VVNPTRREMS SSTLNLVVAG APKSQIVMLE ASAENILQQD 250 260 270 280 290 300 FCHAIKVGVK YTQQIIQGIQ QLVKEIGVAK RTPQKIFTPS AEIVKYTKII AMEKLYAVFT 310 320 330 340 350 360 DYEHDKVSRD EAVNKIRLDT EEHLKEKFPE VDQFEIIESF NIVAKEVFRS IILNEYKRCD 370 380 390 400 410 420 GRDLTSLRNI SCEVDMFKTL HGSALFQRGQ TQVLCTVTFD SLESSIKSDQ IITAINGVKD 430 440 450 460 470 480 KNFMLHYEFP PYATNETGKV TGVNRRELGH GALAEKALCP VIPKDFPFTI RVTSEVLESN 490 500 510 520 530 540 GSSSMASACG GSLALMDAGV PISSAVAGVA VGLVTKTNPE KGEIEDYRLL TDILASIFPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring." Raijmakers R., Vree Egberts W., van Venrooij W.J., Pruijn G.J.M. J. Mol. Biol. 323:653-663(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning of mouse homolog of old-35." Leszczyniecka M., Fisher P.B. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Liver and Lung.
[4]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N. Tissue: Mammary gland and Mammary tumor.
[6]	"Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis." Chen H.W., Rainey R.N., Balatoni C.E., Dawson D.W., Troke J.J., Wasiak S., Hong J.S., McBride H.M., Koehler C.M., Teitell M.A., French S.W. Mol. Cell. Biol. 26:8475-8487(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[7]	"PNPASE regulates RNA import into mitochondria." Wang G., Chen H.W., Oktay Y., Zhang J., Allen E.L., Smith G.M., Fan K.C., Hong J.S., French S.W., McCaffery J.M., Lightowlers R.N., Morse H.C. III, Koehler C.M., Teitell M.A. Cell 142:456-467(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]	"Solution structure of the alpha-helical domain from mouse hypothetical PNPase." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 273-363.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ507387 mRNA. Translation: CAD45436.1.
AF465249 mRNA. Translation: AAO33354.1. Frameshift.
AK004563 mRNA. Translation: BAB23374.1.
AK149419 mRNA. Translation: BAE28862.1.
BX000351 Genomic DNA. Translation: CAI25081.1.
BC027228 mRNA. Translation: AAH27228.2.
BC049283 mRNA. Translation: AAH49283.1.
BC055826 mRNA. Translation: AAH55826.1.

IPI

IPI00321923.
IPI00556889.

RefSeq

NP_082145.1. NM_027869.1.
XP_003689309.1. XM_003689261.1.

UniGene

Mm.211131.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WHU	NMR	-	A	273-363	[»]

ProteinModelPortal

Q8K1R3.

SMR

Q8K1R3. Positions 44-666.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1853678.

PTM databases

PhosphoSite

Q8K1R3.

Proteomic databases

PaxDb

Q8K1R3.

PRIDE

Q8K1R3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000020756; ENSMUSP00000020756; ENSMUSG00000020464.

GeneID

71701.

KEGG

mmu:71701.

UCSC

uc007igp.1. mouse.

Organism-specific databases

CTD

87178.

MGI

MGI:1918951. Pnpt1.

Phylogenomic databases

eggNOG

COG1185.

GeneTree

ENSGT00390000014001.

HOGENOM

HOG000218327.

HOVERGEN

HBG053625.

InParanoid

Q8K1R3.

KO

K00962.

OMA

RDKTLMI.

OrthoDB

EOG4T4CTT.

Gene expression databases

Bgee

Q8K1R3.

Genevestigator

Q8K1R3.

GermOnline

ENSMUSG00000020464. Mus musculus.

Family and domain databases

Gene3D

1.10.10.400. 1 hit.
2.40.50.140. 1 hit.
3.30.230.70. 2 hits.

InterPro

IPR001247. ExoRNase_PH_dom1.
IPR015847. ExoRNase_PH_dom2.
IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR012340. NA-bd_OB-fold.
IPR012162. PNPase.
IPR027408. PNPase/RNase_PH_dom.
IPR015848. PNPase_PH_RNA-bd_bac/org-type.
IPR003029. Rbsml_prot_S1_RNA-bd_dom.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR022967. RNA-binding_domain_S1.
[Graphical view]

PANTHER

PTHR11252. PTHR11252. 1 hit.

Pfam

PF00013. KH_1. 1 hit.
PF03726. PNPase. 1 hit.
PF01138. RNase_PH. 2 hits.
PF03725. RNase_PH_C. 2 hits.
PF00575. S1. 1 hit.
[Graphical view]

PIRSF

PIRSF005499. PNPase. 1 hit.

SMART

SM00322. KH. 1 hit.
SM00316. S1. 1 hit.
[Graphical view]

SUPFAM

SSF46915. 3_ExoRNase. 1 hit.
SSF55666. 3_ExoRNase. 2 hits.
SSF50249. Nucleic_acid_OB. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 2 hits.

TIGRFAMs

TIGR03591. polynuc_phos. 1 hit.

PROSITE

PS50084. KH_TYPE_1. 1 hit.
PS50126. S1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8K1R3.

NextBio

334263.

SOURCE

Search...

Entry information

Entry name

PNPT1_MOUSE

Accession

Primary (citable) accession number: Q8K1R3
Secondary accession number(s): Q3UEP9 , Q810U7, Q812B3, Q8R2U3, Q9DC52

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	October 1, 2002
Last modified:	May 29, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program