Full text data of PARN
PARN
(DAN)
[Confidence: low (only semi-automatic identification from reviews)]
Poly(A)-specific ribonuclease PARN; 3.1.13.4 (Deadenylating nuclease; Deadenylation nuclease; Polyadenylate-specific ribonuclease)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Poly(A)-specific ribonuclease PARN; 3.1.13.4 (Deadenylating nuclease; Deadenylation nuclease; Polyadenylate-specific ribonuclease)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O95453
ID PARN_HUMAN Reviewed; 639 AA.
AC O95453; B2RCB3; B4DDG8; B4DWR4; B4E1H6;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Poly(A)-specific ribonuclease PARN;
DE EC=3.1.13.4;
DE AltName: Full=Deadenylating nuclease;
DE AltName: Full=Deadenylation nuclease;
DE AltName: Full=Polyadenylate-specific ribonuclease;
GN Name=PARN; Synonyms=DAN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9736620; DOI=10.1093/emboj/17.18.5427;
RA Koerner C.G., Wormington M., Muckenthaler M., Schneider S., Dehlin E.,
RA Wahle E.;
RT "The deadenylating nuclease (DAN) is involved in poly(A) tail removal
RT during the meiotic maturation of Xenopus oocytes.";
RL EMBO J. 17:5427-5437(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Adrenal gland, Esophagus, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10640832;
RA Buiting K., Koerner C., Ulrich B., Wahle E., Horsthemke B.;
RT "The human gene for the poly(A)-specific ribonuclease (PARN) maps to
RT 16p13 and has a truncated copy in the Prader-Willi/Angelman syndrome
RT region on 15q11-->q13.";
RL Cytogenet. Cell Genet. 87:125-131(1999).
RN [7]
RP ENZYME ACTIVITY, SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10801819; DOI=10.1074/jbc.M001705200;
RA Martinez J., Ren Y.-G., Thuresson A.-C., Hellman U., Aastroem J.,
RA Virtanen A.;
RT "A 54-kDa fragment of the Poly(A)-specific ribonuclease is an
RT oligomeric, processive, and cap-interacting Poly(A)-specific 3'
RT exonuclease.";
RL J. Biol. Chem. 275:24222-24230(2000).
RN [8]
RP FUNCTION.
RX PubMed=10882133; DOI=10.1016/S1097-2765(00)80442-6;
RA Gao M., Fritz D.T., Ford L.P., Wilusz J.;
RT "Interaction between a poly(A)-specific ribonuclease and the 5' cap
RT influences mRNA deadenylation rates in vitro.";
RL Mol. Cell 5:479-488(2000).
RN [9]
RP FUNCTION, AND COFACTOR.
RX PubMed=11359775; DOI=10.1074/jbc.M102270200;
RA Martinez J., Ren Y.-G., Nilsson P., Ehrenberg M., Virtanen A.;
RT "The mRNA cap structure stimulates rate of poly(A) removal and
RT amplifies processivity of degradation.";
RL J. Biol. Chem. 276:27923-27929(2001).
RN [10]
RP MUTAGENESIS OF ASP-28; GLU-30; ASP-292 AND ASP-382.
RX PubMed=11742007; DOI=10.1074/jbc.M111515200;
RA Ren Y.-G., Martinez J., Virtanen A.;
RT "Identification of the active site of poly(A)-specific ribonuclease by
RT site-directed mutagenesis and Fe(2+)-mediated cleavage.";
RL J. Biol. Chem. 277:5982-5987(2002).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.E02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [12]
RP IDENTIFICATION IN A MRNA DECAY COMPLEX WITH RENT1; RENT2 AND RENT3B.
RX PubMed=14527413; DOI=10.1016/S1097-2765(03)00349-6;
RA Lejeune F., Li X., Maquat L.E.;
RT "Nonsense-mediated mRNA decay in mammalian cells involves decapping,
RT deadenylating, and exonucleolytic activities.";
RL Mol. Cell 12:675-687(2003).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ASP-28; GLU-30 AND ASP-382.
RX PubMed=12748283; DOI=10.1128/MCB.23.11.3798-3812.2003;
RA Lai W.S., Kennington E.A., Blackshear P.J.;
RT "Tristetraprolin and its family members can promote the cell-free
RT deadenylation of AU-rich element-containing mRNAs by poly(A)
RT ribonuclease.";
RL Mol. Cell. Biol. 23:3798-3812(2003).
RN [14]
RP FUNCTION, AND INTERACTION WITH KHSRP.
RX PubMed=15175153; DOI=10.1016/j.molcel.2004.05.002;
RA Gherzi R., Lee K.-Y., Briata P., Wegmueller D., Moroni C., Karin M.,
RA Chen C.-Y.;
RT "A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA
RT turnover by recruiting the degradation machinery.";
RL Mol. Cell 14:571-583(2004).
RN [15]
RP COFACTOR, AND MUTAGENESIS OF ASP-28; GLU-30; ASP-292 AND ASP-382.
RX PubMed=15358788; DOI=10.1074/jbc.M403858200;
RA Ren Y.-G., Kirsebom L.A., Virtanen A.;
RT "Coordination of divalent metal ions in the active site of poly(A)-
RT specific ribonuclease.";
RL J. Biol. Chem. 279:48702-48706(2004).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163 AND SER-557, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP INTERACTION WITH CELF1.
RX PubMed=16601207; DOI=10.1261/rna.59606;
RA Moraes K.C., Wilusz C.J., Wilusz J.;
RT "CUG-BP binds to RNA substrates and recruits PARN deadenylase.";
RL RNA 12:1084-1091(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220 AND LYS-499, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619; SER-628
RP AND THR-631, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP INTERACTION WITH ZC3HAV1.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L.,
RA Zheng Y.T., Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619 AND
RP SER-623, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-430 IN COMPLEX WITH DNA,
RP MUTAGENESIS OF PHE-31; ILE-34; ILE-113; PHE-123 AND HIS-377, AND
RP SUBUNIT.
RX PubMed=16281054; DOI=10.1038/sj.emboj.7600869;
RA Wu M., Reuter M., Lilie H., Liu Y., Wahle E., Song H.;
RT "Structural insight into poly(A) binding and catalytic mechanism of
RT human PARN.";
RL EMBO J. 24:4082-4093(2005).
RN [27]
RP PHOSPHORYLATION AT SER-557 BY MAPKAPK2, AND PHOSPHORYLATION AT
RP SER-557.
RX PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018;
RA Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S.,
RA van Vugt M.A., Wang X., Linding R., Ong S.E., Weaver D., Carr S.A.,
RA Yaffe M.B.;
RT "DNA damage activates a spatially distinct late cytoplasmic cell-cycle
RT checkpoint network controlled by MK2-mediated RNA stabilization.";
RL Mol. Cell 40:34-49(2010).
CC -!- FUNCTION: 3'-exoribonuclease that has a preference for poly(A)
CC tails of mRNAs, thereby efficiently degrading poly(A) tails.
CC Exonucleolytic degradation of the poly(A) tail is often the first
CC step in the decay of eukaryotic mRNAs and is also used to silence
CC certain maternal mRNAs translationally during oocyte maturation
CC and early embryonic development. Interacts with both the 3'-end
CC poly(A) tail and the 5'-end cap structure during degradation, the
CC interaction with the cap structure being required for an efficient
CC degradation of poly(A) tails. Involved in nonsense-mediated mRNA
CC decay, a critical process of selective degradation of mRNAs that
CC contain premature stop codons. Also involved in degradation of
CC inherently unstable mRNAs that contain AU-rich elements (AREs) in
CC their 3'-UTR, possibly via its interaction with KHSRP. Probably
CC mediates the removal of poly(A) tails of AREs mRNAs, which
CC constitutes the first step of destabilization.
CC -!- CATALYTIC ACTIVITY: Exonucleolytic cleavage of poly(A) to 5'-AMP.
CC -!- COFACTOR: Divalent metal cations. Mg(2+) is the most probable.
CC -!- SUBUNIT: Homodimer. Interacts with KHSRP and CELF1/CUGBP1. Found
CC in a mRNA decay complex with RENT1, RENT2 and RENT3B. Interacts
CC with ZC3HAV1 in an RNA-independent manner.
CC -!- INTERACTION:
CC Q99728:BARD1; NbExp=4; IntAct=EBI-372832, EBI-473181;
CC P33240:CSTF2; NbExp=5; IntAct=EBI-372832, EBI-711360;
CC Q09161:NCBP1; NbExp=2; IntAct=EBI-372832, EBI-464743;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus, nucleolus.
CC Note=Some nuclear fraction is nucleolar.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95453-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95453-2; Sequence=VSP_042846;
CC Note=No experimental confirmation available. Non canonical
CC splice junctions;
CC Name=3;
CC IsoId=O95453-3; Sequence=VSP_042847;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylation by MAPKAPK2, preventing GADD45A mRNA
CC degradation after genotoxic stress.
CC -!- SIMILARITY: Belongs to the CAF1 family.
CC -!- SIMILARITY: Contains 1 R3H domain.
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DR EMBL; AJ005698; CAA06683.1; -; mRNA.
DR EMBL; AK293189; BAG56729.1; -; mRNA.
DR EMBL; AK301648; BAG63126.1; -; mRNA.
DR EMBL; AK315020; BAG37510.1; -; mRNA.
DR EMBL; AC009167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092291; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85110.1; -; Genomic_DNA.
DR EMBL; BC050029; AAH50029.1; -; mRNA.
DR RefSeq; NP_001127949.1; NM_001134477.2.
DR RefSeq; NP_001229921.1; NM_001242992.1.
DR RefSeq; NP_002573.1; NM_002582.3.
DR UniGene; Hs.253197; -.
DR PDB; 2A1R; X-ray; 2.60 A; A/B=1-430.
DR PDB; 2A1S; X-ray; 2.60 A; A/B/C/D=1-430.
DR PDB; 3CTR; X-ray; 2.10 A; A=445-540.
DR PDBsum; 2A1R; -.
DR PDBsum; 2A1S; -.
DR PDBsum; 3CTR; -.
DR ProteinModelPortal; O95453; -.
DR SMR; O95453; 1-514.
DR DIP; DIP-31124N; -.
DR IntAct; O95453; 5.
DR MINT; MINT-3002980; -.
DR STRING; 9606.ENSP00000387911; -.
DR PhosphoSite; O95453; -.
DR SWISS-2DPAGE; O95453; -.
DR PaxDb; O95453; -.
DR PRIDE; O95453; -.
DR DNASU; 2987; -.
DR DNASU; 5073; -.
DR Ensembl; ENST00000341484; ENSP00000345456; ENSG00000140694.
DR Ensembl; ENST00000420015; ENSP00000410525; ENSG00000140694.
DR Ensembl; ENST00000437198; ENSP00000387911; ENSG00000140694.
DR GeneID; 5073; -.
DR KEGG; hsa:5073; -.
DR UCSC; uc010uzc.2; human.
DR CTD; 5073; -.
DR GeneCards; GC16M014529; -.
DR HGNC; HGNC:8609; PARN.
DR HPA; CAB011673; -.
DR HPA; HPA006314; -.
DR HPA; HPA012010; -.
DR MIM; 604212; gene.
DR neXtProt; NX_O95453; -.
DR PharmGKB; PA29072; -.
DR PharmGKB; PA32949; -.
DR eggNOG; NOG145331; -.
DR HOGENOM; HOG000007285; -.
DR HOVERGEN; HBG053512; -.
DR InParanoid; O95453; -.
DR KO; K01148; -.
DR OMA; LEQTDSC; -.
DR OrthoDB; EOG7GN2MD; -.
DR BRENDA; 3.1.13.4; 2681.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PARN; human.
DR EvolutionaryTrace; O95453; -.
DR GeneWiki; PARN; -.
DR GeneWiki; Poly(A)-specific_ribonuclease; -.
DR GenomeRNAi; 5073; -.
DR NextBio; 11844; -.
DR PRO; PR:O95453; -.
DR ArrayExpress; O95453; -.
DR Bgee; O95453; -.
DR CleanEx; HS_PARN; -.
DR Genevestigator; O95453; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; TAS:ProtInc.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; TAS:Reactome.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:0009451; P:RNA modification; TAS:ProtInc.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR014789; PolyA-riboNase_RNA_binding.
DR InterPro; IPR001374; R3H_ss-bd.
DR InterPro; IPR006941; RNase_CAF1.
DR InterPro; IPR012337; RNaseH-like_dom.
DR Pfam; PF04857; CAF1; 1.
DR Pfam; PF08675; RNA_bind; 1.
DR SUPFAM; SSF53098; SSF53098; 2.
DR PROSITE; PS51061; R3H; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW Nonsense-mediated mRNA decay; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding.
FT CHAIN 1 639 Poly(A)-specific ribonuclease PARN.
FT /FTId=PRO_0000212851.
FT DOMAIN 178 245 R3H.
FT METAL 28 28 Divalent metal cation; catalytic
FT (Probable).
FT METAL 30 30 Divalent metal cation; catalytic
FT (Probable).
FT METAL 292 292 Divalent metal cation; catalytic
FT (Probable).
FT METAL 382 382 Divalent metal cation; catalytic
FT (Probable).
FT SITE 326 326 Interaction with poly(A).
FT MOD_RES 163 163 Phosphoserine.
FT MOD_RES 220 220 N6-acetyllysine.
FT MOD_RES 499 499 N6-acetyllysine.
FT MOD_RES 557 557 Phosphoserine; by MAPKAPK2.
FT MOD_RES 619 619 Phosphoserine.
FT MOD_RES 623 623 Phosphoserine.
FT MOD_RES 628 628 Phosphoserine.
FT MOD_RES 631 631 Phosphothreonine.
FT VAR_SEQ 1 61 Missing (in isoform 2).
FT /FTId=VSP_042846.
FT VAR_SEQ 53 98 Missing (in isoform 3).
FT /FTId=VSP_042847.
FT MUTAGEN 28 28 D->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 28 28 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 30 30 E->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 30 30 E->C: Loss of function in the presence of
FT Mg(2+), Mn(2+), Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 31 31 F->A: Reduced affinity for poly(A). Loss
FT of activity.
FT MUTAGEN 34 34 I->A: Reduced affinity for poly(A).
FT Strongly reduced activity.
FT MUTAGEN 113 113 I->A: Loss of dimerization. Loss of
FT activity.
FT MUTAGEN 115 115 F->A: Reduced affinity for poly(A).
FT Little effect on activity.
FT MUTAGEN 123 123 F->A: Loss of dimerization. Loss of
FT activity.
FT MUTAGEN 292 292 D->A: Loss of function but does not
FT abolish ability to bind RNA.
FT MUTAGEN 292 292 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 326 326 K->A: Reduced affinity for poly(A).
FT Little effect on activity.
FT MUTAGEN 377 377 H->A: Loss of activity.
FT MUTAGEN 382 382 D->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 382 382 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 557 557 S->A: Strong reduction of phosphorylation
FT by MAPKAPK2.
FT HELIX 5 21
FT STRAND 23 32
FT STRAND 36 38
FT HELIX 50 60
FT TURN 61 63
FT STRAND 66 77
FT TURN 78 81
FT STRAND 82 92
FT STRAND 97 101
FT STRAND 105 109
FT HELIX 110 118
FT HELIX 123 127
FT HELIX 136 141
FT HELIX 175 177
FT HELIX 178 192
FT HELIX 207 217
FT TURN 222 224
FT STRAND 228 231
FT STRAND 237 240
FT STRAND 245 248
FT TURN 249 252
FT HELIX 260 265
FT HELIX 271 280
FT STRAND 283 288
FT HELIX 290 300
FT HELIX 308 318
FT STRAND 320 324
FT HELIX 325 329
FT TURN 332 337
FT HELIX 343 349
FT STRAND 360 362
FT HELIX 379 397
FT HELIX 398 400
FT STRAND 401 403
FT TURN 413 415
FT HELIX 416 418
FT STRAND 419 429
FT STRAND 445 451
FT HELIX 458 464
FT TURN 465 467
FT STRAND 468 477
FT STRAND 480 488
FT HELIX 490 498
FT HELIX 509 513
SQ SEQUENCE 639 AA; 73451 MW; 6994BE39384DF7AC CRC64;
MEIIRSNFKS NLHKVYQAIE EADFFAIDGE FSGISDGPSV SALTNGFDTP EERYQKLKKH
SMDFLLFQFG LCTFKYDYTD SKYITKSFNF YVFPKPFNRS SPDVKFVCQS SSIDFLASQG
FDFNKVFRNG IPYLNQEEER QLREQYDEKR SQANGAGALS YVSPNTSKCP VTIPEDQKKF
IDQVVEKIED LLQSEENKNL DLEPCTGFQR KLIYQTLSWK YPKGIHVETL ETEKKERYIV
ISKVDEEERK RREQQKHAKE QEELNDAVGF SRVIHAIANS GKLVIGHNML LDVMHTVHQF
YCPLPADLSE FKEMTTCVFP RLLDTKLMAS TQPFKDIINN TSLAELEKRL KETPFNPPKV
ESAEGFPSYD TASEQLHEAG YDAYITGLCF ISMANYLGSF LSPPKIHVSA RSKLIEPFFN
KLFLMRVMDI PYLNLEGPDL QPKRDHVLHV TFPKEWKTSD LYQLFSAFGN IQISWIDDTS
AFVSLSQPEQ VKIAVNTSKY AESYRIQTYA EYMGRKQEEK QIKRKWTEDS WKEADSKRLN
PQCIPYTLQN HYYRNNSFTA PSTVGKRNLS PSQEEAGLED GVSGEISDTE LEQTDSCAEP
LSEGRKKAKK LKRMKKELSP AGSISKNSPA TLFEVPDTW
//
ID PARN_HUMAN Reviewed; 639 AA.
AC O95453; B2RCB3; B4DDG8; B4DWR4; B4E1H6;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Poly(A)-specific ribonuclease PARN;
DE EC=3.1.13.4;
DE AltName: Full=Deadenylating nuclease;
DE AltName: Full=Deadenylation nuclease;
DE AltName: Full=Polyadenylate-specific ribonuclease;
GN Name=PARN; Synonyms=DAN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME ACTIVITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9736620; DOI=10.1093/emboj/17.18.5427;
RA Koerner C.G., Wormington M., Muckenthaler M., Schneider S., Dehlin E.,
RA Wahle E.;
RT "The deadenylating nuclease (DAN) is involved in poly(A) tail removal
RT during the meiotic maturation of Xenopus oocytes.";
RL EMBO J. 17:5427-5437(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Adrenal gland, Esophagus, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10640832;
RA Buiting K., Koerner C., Ulrich B., Wahle E., Horsthemke B.;
RT "The human gene for the poly(A)-specific ribonuclease (PARN) maps to
RT 16p13 and has a truncated copy in the Prader-Willi/Angelman syndrome
RT region on 15q11-->q13.";
RL Cytogenet. Cell Genet. 87:125-131(1999).
RN [7]
RP ENZYME ACTIVITY, SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10801819; DOI=10.1074/jbc.M001705200;
RA Martinez J., Ren Y.-G., Thuresson A.-C., Hellman U., Aastroem J.,
RA Virtanen A.;
RT "A 54-kDa fragment of the Poly(A)-specific ribonuclease is an
RT oligomeric, processive, and cap-interacting Poly(A)-specific 3'
RT exonuclease.";
RL J. Biol. Chem. 275:24222-24230(2000).
RN [8]
RP FUNCTION.
RX PubMed=10882133; DOI=10.1016/S1097-2765(00)80442-6;
RA Gao M., Fritz D.T., Ford L.P., Wilusz J.;
RT "Interaction between a poly(A)-specific ribonuclease and the 5' cap
RT influences mRNA deadenylation rates in vitro.";
RL Mol. Cell 5:479-488(2000).
RN [9]
RP FUNCTION, AND COFACTOR.
RX PubMed=11359775; DOI=10.1074/jbc.M102270200;
RA Martinez J., Ren Y.-G., Nilsson P., Ehrenberg M., Virtanen A.;
RT "The mRNA cap structure stimulates rate of poly(A) removal and
RT amplifies processivity of degradation.";
RL J. Biol. Chem. 276:27923-27929(2001).
RN [10]
RP MUTAGENESIS OF ASP-28; GLU-30; ASP-292 AND ASP-382.
RX PubMed=11742007; DOI=10.1074/jbc.M111515200;
RA Ren Y.-G., Martinez J., Virtanen A.;
RT "Identification of the active site of poly(A)-specific ribonuclease by
RT site-directed mutagenesis and Fe(2+)-mediated cleavage.";
RL J. Biol. Chem. 277:5982-5987(2002).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.E02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [12]
RP IDENTIFICATION IN A MRNA DECAY COMPLEX WITH RENT1; RENT2 AND RENT3B.
RX PubMed=14527413; DOI=10.1016/S1097-2765(03)00349-6;
RA Lejeune F., Li X., Maquat L.E.;
RT "Nonsense-mediated mRNA decay in mammalian cells involves decapping,
RT deadenylating, and exonucleolytic activities.";
RL Mol. Cell 12:675-687(2003).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ASP-28; GLU-30 AND ASP-382.
RX PubMed=12748283; DOI=10.1128/MCB.23.11.3798-3812.2003;
RA Lai W.S., Kennington E.A., Blackshear P.J.;
RT "Tristetraprolin and its family members can promote the cell-free
RT deadenylation of AU-rich element-containing mRNAs by poly(A)
RT ribonuclease.";
RL Mol. Cell. Biol. 23:3798-3812(2003).
RN [14]
RP FUNCTION, AND INTERACTION WITH KHSRP.
RX PubMed=15175153; DOI=10.1016/j.molcel.2004.05.002;
RA Gherzi R., Lee K.-Y., Briata P., Wegmueller D., Moroni C., Karin M.,
RA Chen C.-Y.;
RT "A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA
RT turnover by recruiting the degradation machinery.";
RL Mol. Cell 14:571-583(2004).
RN [15]
RP COFACTOR, AND MUTAGENESIS OF ASP-28; GLU-30; ASP-292 AND ASP-382.
RX PubMed=15358788; DOI=10.1074/jbc.M403858200;
RA Ren Y.-G., Kirsebom L.A., Virtanen A.;
RT "Coordination of divalent metal ions in the active site of poly(A)-
RT specific ribonuclease.";
RL J. Biol. Chem. 279:48702-48706(2004).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163 AND SER-557, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP INTERACTION WITH CELF1.
RX PubMed=16601207; DOI=10.1261/rna.59606;
RA Moraes K.C., Wilusz C.J., Wilusz J.;
RT "CUG-BP binds to RNA substrates and recruits PARN deadenylase.";
RL RNA 12:1084-1091(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220 AND LYS-499, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619; SER-628
RP AND THR-631, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
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.,
RA Buerckstuemmer T., 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 [24]
RP INTERACTION WITH ZC3HAV1.
RX PubMed=21876179; DOI=10.1073/pnas.1101676108;
RA Zhu Y., Chen G., Lv F., Wang X., Ji X., Xu Y., Sun J., Wu L.,
RA Zheng Y.T., Gao G.;
RT "Zinc-finger antiviral protein inhibits HIV-1 infection by selectively
RT targeting multiply spliced viral mRNAs for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:15834-15839(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619 AND
RP SER-623, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-430 IN COMPLEX WITH DNA,
RP MUTAGENESIS OF PHE-31; ILE-34; ILE-113; PHE-123 AND HIS-377, AND
RP SUBUNIT.
RX PubMed=16281054; DOI=10.1038/sj.emboj.7600869;
RA Wu M., Reuter M., Lilie H., Liu Y., Wahle E., Song H.;
RT "Structural insight into poly(A) binding and catalytic mechanism of
RT human PARN.";
RL EMBO J. 24:4082-4093(2005).
RN [27]
RP PHOSPHORYLATION AT SER-557 BY MAPKAPK2, AND PHOSPHORYLATION AT
RP SER-557.
RX PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018;
RA Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S.,
RA van Vugt M.A., Wang X., Linding R., Ong S.E., Weaver D., Carr S.A.,
RA Yaffe M.B.;
RT "DNA damage activates a spatially distinct late cytoplasmic cell-cycle
RT checkpoint network controlled by MK2-mediated RNA stabilization.";
RL Mol. Cell 40:34-49(2010).
CC -!- FUNCTION: 3'-exoribonuclease that has a preference for poly(A)
CC tails of mRNAs, thereby efficiently degrading poly(A) tails.
CC Exonucleolytic degradation of the poly(A) tail is often the first
CC step in the decay of eukaryotic mRNAs and is also used to silence
CC certain maternal mRNAs translationally during oocyte maturation
CC and early embryonic development. Interacts with both the 3'-end
CC poly(A) tail and the 5'-end cap structure during degradation, the
CC interaction with the cap structure being required for an efficient
CC degradation of poly(A) tails. Involved in nonsense-mediated mRNA
CC decay, a critical process of selective degradation of mRNAs that
CC contain premature stop codons. Also involved in degradation of
CC inherently unstable mRNAs that contain AU-rich elements (AREs) in
CC their 3'-UTR, possibly via its interaction with KHSRP. Probably
CC mediates the removal of poly(A) tails of AREs mRNAs, which
CC constitutes the first step of destabilization.
CC -!- CATALYTIC ACTIVITY: Exonucleolytic cleavage of poly(A) to 5'-AMP.
CC -!- COFACTOR: Divalent metal cations. Mg(2+) is the most probable.
CC -!- SUBUNIT: Homodimer. Interacts with KHSRP and CELF1/CUGBP1. Found
CC in a mRNA decay complex with RENT1, RENT2 and RENT3B. Interacts
CC with ZC3HAV1 in an RNA-independent manner.
CC -!- INTERACTION:
CC Q99728:BARD1; NbExp=4; IntAct=EBI-372832, EBI-473181;
CC P33240:CSTF2; NbExp=5; IntAct=EBI-372832, EBI-711360;
CC Q09161:NCBP1; NbExp=2; IntAct=EBI-372832, EBI-464743;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus, nucleolus.
CC Note=Some nuclear fraction is nucleolar.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95453-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95453-2; Sequence=VSP_042846;
CC Note=No experimental confirmation available. Non canonical
CC splice junctions;
CC Name=3;
CC IsoId=O95453-3; Sequence=VSP_042847;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- PTM: Phosphorylation by MAPKAPK2, preventing GADD45A mRNA
CC degradation after genotoxic stress.
CC -!- SIMILARITY: Belongs to the CAF1 family.
CC -!- SIMILARITY: Contains 1 R3H domain.
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DR EMBL; AJ005698; CAA06683.1; -; mRNA.
DR EMBL; AK293189; BAG56729.1; -; mRNA.
DR EMBL; AK301648; BAG63126.1; -; mRNA.
DR EMBL; AK315020; BAG37510.1; -; mRNA.
DR EMBL; AC009167; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092291; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85110.1; -; Genomic_DNA.
DR EMBL; BC050029; AAH50029.1; -; mRNA.
DR RefSeq; NP_001127949.1; NM_001134477.2.
DR RefSeq; NP_001229921.1; NM_001242992.1.
DR RefSeq; NP_002573.1; NM_002582.3.
DR UniGene; Hs.253197; -.
DR PDB; 2A1R; X-ray; 2.60 A; A/B=1-430.
DR PDB; 2A1S; X-ray; 2.60 A; A/B/C/D=1-430.
DR PDB; 3CTR; X-ray; 2.10 A; A=445-540.
DR PDBsum; 2A1R; -.
DR PDBsum; 2A1S; -.
DR PDBsum; 3CTR; -.
DR ProteinModelPortal; O95453; -.
DR SMR; O95453; 1-514.
DR DIP; DIP-31124N; -.
DR IntAct; O95453; 5.
DR MINT; MINT-3002980; -.
DR STRING; 9606.ENSP00000387911; -.
DR PhosphoSite; O95453; -.
DR SWISS-2DPAGE; O95453; -.
DR PaxDb; O95453; -.
DR PRIDE; O95453; -.
DR DNASU; 2987; -.
DR DNASU; 5073; -.
DR Ensembl; ENST00000341484; ENSP00000345456; ENSG00000140694.
DR Ensembl; ENST00000420015; ENSP00000410525; ENSG00000140694.
DR Ensembl; ENST00000437198; ENSP00000387911; ENSG00000140694.
DR GeneID; 5073; -.
DR KEGG; hsa:5073; -.
DR UCSC; uc010uzc.2; human.
DR CTD; 5073; -.
DR GeneCards; GC16M014529; -.
DR HGNC; HGNC:8609; PARN.
DR HPA; CAB011673; -.
DR HPA; HPA006314; -.
DR HPA; HPA012010; -.
DR MIM; 604212; gene.
DR neXtProt; NX_O95453; -.
DR PharmGKB; PA29072; -.
DR PharmGKB; PA32949; -.
DR eggNOG; NOG145331; -.
DR HOGENOM; HOG000007285; -.
DR HOVERGEN; HBG053512; -.
DR InParanoid; O95453; -.
DR KO; K01148; -.
DR OMA; LEQTDSC; -.
DR OrthoDB; EOG7GN2MD; -.
DR BRENDA; 3.1.13.4; 2681.
DR Reactome; REACT_21257; Metabolism of RNA.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; PARN; human.
DR EvolutionaryTrace; O95453; -.
DR GeneWiki; PARN; -.
DR GeneWiki; Poly(A)-specific_ribonuclease; -.
DR GenomeRNAi; 5073; -.
DR NextBio; 11844; -.
DR PRO; PR:O95453; -.
DR ArrayExpress; O95453; -.
DR Bgee; O95453; -.
DR CleanEx; HS_PARN; -.
DR Genevestigator; O95453; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; TAS:ProtInc.
DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; TAS:Reactome.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
DR GO; GO:0009451; P:RNA modification; TAS:ProtInc.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait.
DR InterPro; IPR014789; PolyA-riboNase_RNA_binding.
DR InterPro; IPR001374; R3H_ss-bd.
DR InterPro; IPR006941; RNase_CAF1.
DR InterPro; IPR012337; RNaseH-like_dom.
DR Pfam; PF04857; CAF1; 1.
DR Pfam; PF08675; RNA_bind; 1.
DR SUPFAM; SSF53098; SSF53098; 2.
DR PROSITE; PS51061; R3H; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW Nonsense-mediated mRNA decay; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; RNA-binding.
FT CHAIN 1 639 Poly(A)-specific ribonuclease PARN.
FT /FTId=PRO_0000212851.
FT DOMAIN 178 245 R3H.
FT METAL 28 28 Divalent metal cation; catalytic
FT (Probable).
FT METAL 30 30 Divalent metal cation; catalytic
FT (Probable).
FT METAL 292 292 Divalent metal cation; catalytic
FT (Probable).
FT METAL 382 382 Divalent metal cation; catalytic
FT (Probable).
FT SITE 326 326 Interaction with poly(A).
FT MOD_RES 163 163 Phosphoserine.
FT MOD_RES 220 220 N6-acetyllysine.
FT MOD_RES 499 499 N6-acetyllysine.
FT MOD_RES 557 557 Phosphoserine; by MAPKAPK2.
FT MOD_RES 619 619 Phosphoserine.
FT MOD_RES 623 623 Phosphoserine.
FT MOD_RES 628 628 Phosphoserine.
FT MOD_RES 631 631 Phosphothreonine.
FT VAR_SEQ 1 61 Missing (in isoform 2).
FT /FTId=VSP_042846.
FT VAR_SEQ 53 98 Missing (in isoform 3).
FT /FTId=VSP_042847.
FT MUTAGEN 28 28 D->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 28 28 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 30 30 E->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 30 30 E->C: Loss of function in the presence of
FT Mg(2+), Mn(2+), Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 31 31 F->A: Reduced affinity for poly(A). Loss
FT of activity.
FT MUTAGEN 34 34 I->A: Reduced affinity for poly(A).
FT Strongly reduced activity.
FT MUTAGEN 113 113 I->A: Loss of dimerization. Loss of
FT activity.
FT MUTAGEN 115 115 F->A: Reduced affinity for poly(A).
FT Little effect on activity.
FT MUTAGEN 123 123 F->A: Loss of dimerization. Loss of
FT activity.
FT MUTAGEN 292 292 D->A: Loss of function but does not
FT abolish ability to bind RNA.
FT MUTAGEN 292 292 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 326 326 K->A: Reduced affinity for poly(A).
FT Little effect on activity.
FT MUTAGEN 377 377 H->A: Loss of activity.
FT MUTAGEN 382 382 D->A: Loss of function but does not
FT abolish ability to bind RNA. Induces a
FT decrease in degradation of mRNAs
FT containing AREs.
FT MUTAGEN 382 382 D->C: Loss of function in the presence of
FT Mg(2+) but not in the presence of Mn(2+),
FT Zn(2+), Co(2+) or Cd(2+).
FT MUTAGEN 557 557 S->A: Strong reduction of phosphorylation
FT by MAPKAPK2.
FT HELIX 5 21
FT STRAND 23 32
FT STRAND 36 38
FT HELIX 50 60
FT TURN 61 63
FT STRAND 66 77
FT TURN 78 81
FT STRAND 82 92
FT STRAND 97 101
FT STRAND 105 109
FT HELIX 110 118
FT HELIX 123 127
FT HELIX 136 141
FT HELIX 175 177
FT HELIX 178 192
FT HELIX 207 217
FT TURN 222 224
FT STRAND 228 231
FT STRAND 237 240
FT STRAND 245 248
FT TURN 249 252
FT HELIX 260 265
FT HELIX 271 280
FT STRAND 283 288
FT HELIX 290 300
FT HELIX 308 318
FT STRAND 320 324
FT HELIX 325 329
FT TURN 332 337
FT HELIX 343 349
FT STRAND 360 362
FT HELIX 379 397
FT HELIX 398 400
FT STRAND 401 403
FT TURN 413 415
FT HELIX 416 418
FT STRAND 419 429
FT STRAND 445 451
FT HELIX 458 464
FT TURN 465 467
FT STRAND 468 477
FT STRAND 480 488
FT HELIX 490 498
FT HELIX 509 513
SQ SEQUENCE 639 AA; 73451 MW; 6994BE39384DF7AC CRC64;
MEIIRSNFKS NLHKVYQAIE EADFFAIDGE FSGISDGPSV SALTNGFDTP EERYQKLKKH
SMDFLLFQFG LCTFKYDYTD SKYITKSFNF YVFPKPFNRS SPDVKFVCQS SSIDFLASQG
FDFNKVFRNG IPYLNQEEER QLREQYDEKR SQANGAGALS YVSPNTSKCP VTIPEDQKKF
IDQVVEKIED LLQSEENKNL DLEPCTGFQR KLIYQTLSWK YPKGIHVETL ETEKKERYIV
ISKVDEEERK RREQQKHAKE QEELNDAVGF SRVIHAIANS GKLVIGHNML LDVMHTVHQF
YCPLPADLSE FKEMTTCVFP RLLDTKLMAS TQPFKDIINN TSLAELEKRL KETPFNPPKV
ESAEGFPSYD TASEQLHEAG YDAYITGLCF ISMANYLGSF LSPPKIHVSA RSKLIEPFFN
KLFLMRVMDI PYLNLEGPDL QPKRDHVLHV TFPKEWKTSD LYQLFSAFGN IQISWIDDTS
AFVSLSQPEQ VKIAVNTSKY AESYRIQTYA EYMGRKQEEK QIKRKWTEDS WKEADSKRLN
PQCIPYTLQN HYYRNNSFTA PSTVGKRNLS PSQEEAGLED GVSGEISDTE LEQTDSCAEP
LSEGRKKAKK LKRMKKELSP AGSISKNSPA TLFEVPDTW
//
MIM
604212
*RECORD*
*FIELD* NO
604212
*FIELD* TI
*604212 POLYADENYLATE-SPECIFIC RIBONUCLEASE; PARN
;;POLY(A)-SPECIFIC RIBONUCLEASE;;
read moreDEADENYLATING NUCLEASE; DAN
*FIELD* TX
Exonucleolytic degradation of the poly(A) tail is often the first step
in the decay of eukaryotic mRNAs. Korner and Wahle (1997) purified the
enzyme for deadenylation, PARN, which they named DAN, from calf thymus.
Korner et al. (1998) partially sequenced the bovine PARN protein. By
searching an EST database with the bovine PARN peptide sequences, they
identified a human PARN EST encoding a deduced 639-amino acid protein.
The calculated molecular mass of human PARN is 73.5 kD, which was the
mass of recombinant PARN expressed in E. coli. The human PARN protein
shows sequence similarity to the RNase D family of 3-prime exonucleases,
which includes E. coli polymerase I. PARN is a 3-prime exonuclease that
prefers poly(A) as the substrate. In an in vitro assay, PARN activity
was partially inhibited by PAB1 (604679), resulting in phased shortening
of the poly(A) tail of the polyadenylated RNA substrate. The PARN
protein is located in both the nucleus and the cytoplasm. It is not
stably associated with polysomes or ribosomal subunits. Northern blot
analysis detected a 3.1-kb PARN transcript in HeLa cell extracts. The
authors noted that the PARN gene is widely expressed.
Korner et al. (1998) noted that the PARN gene maps to chromosome 16.
*FIELD* RF
1. Korner, C. G.; Wahle, E.: Poly(A) tail shortening by a mammalian
poly(A)-specific 3-prime-exoribonuclease. J. Biol. Chem. 272: 10448-10456,
1997.
2. Korner, C. G.; Wormington, M.; Muckenthaler, M.; Schneider, S.;
Dehlin, E.; Wahle, E.: The deadenylating nuclease (DAN) is involved
in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO
J. 17: 5427-5437, 1998.
*FIELD* CN
Patti M. Sherman - updated: 10/5/1999
*FIELD* CD
Barbara J. Biery: 9/30/1999
*FIELD* ED
mgross: 03/14/2000
mgross: 10/5/1999
psherman: 10/5/1999
psherman: 10/1/1999
*RECORD*
*FIELD* NO
604212
*FIELD* TI
*604212 POLYADENYLATE-SPECIFIC RIBONUCLEASE; PARN
;;POLY(A)-SPECIFIC RIBONUCLEASE;;
read moreDEADENYLATING NUCLEASE; DAN
*FIELD* TX
Exonucleolytic degradation of the poly(A) tail is often the first step
in the decay of eukaryotic mRNAs. Korner and Wahle (1997) purified the
enzyme for deadenylation, PARN, which they named DAN, from calf thymus.
Korner et al. (1998) partially sequenced the bovine PARN protein. By
searching an EST database with the bovine PARN peptide sequences, they
identified a human PARN EST encoding a deduced 639-amino acid protein.
The calculated molecular mass of human PARN is 73.5 kD, which was the
mass of recombinant PARN expressed in E. coli. The human PARN protein
shows sequence similarity to the RNase D family of 3-prime exonucleases,
which includes E. coli polymerase I. PARN is a 3-prime exonuclease that
prefers poly(A) as the substrate. In an in vitro assay, PARN activity
was partially inhibited by PAB1 (604679), resulting in phased shortening
of the poly(A) tail of the polyadenylated RNA substrate. The PARN
protein is located in both the nucleus and the cytoplasm. It is not
stably associated with polysomes or ribosomal subunits. Northern blot
analysis detected a 3.1-kb PARN transcript in HeLa cell extracts. The
authors noted that the PARN gene is widely expressed.
Korner et al. (1998) noted that the PARN gene maps to chromosome 16.
*FIELD* RF
1. Korner, C. G.; Wahle, E.: Poly(A) tail shortening by a mammalian
poly(A)-specific 3-prime-exoribonuclease. J. Biol. Chem. 272: 10448-10456,
1997.
2. Korner, C. G.; Wormington, M.; Muckenthaler, M.; Schneider, S.;
Dehlin, E.; Wahle, E.: The deadenylating nuclease (DAN) is involved
in poly(A) tail removal during the meiotic maturation of Xenopus oocytes. EMBO
J. 17: 5427-5437, 1998.
*FIELD* CN
Patti M. Sherman - updated: 10/5/1999
*FIELD* CD
Barbara J. Biery: 9/30/1999
*FIELD* ED
mgross: 03/14/2000
mgross: 10/5/1999
psherman: 10/5/1999
psherman: 10/1/1999