PARN_HUMAN
ID PARN_HUMAN Reviewed; 639 AA.
AC O95453; B2RCB3; B4DDG8; B4DSB0; B4DWR4; B4E1H6;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 189.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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; 3 AND 4).
RC TISSUE=Adrenal gland, Brain, 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., 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., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10640832; DOI=10.1159/000015378;
RA Buiting K., Koerner C., Ulrich B., Wahle E., Horsthemke B.;
RT "The human gene for the poly(A)-specific ribonuclease (PARN) maps to 16p13
RT and has a truncated copy in the Prader-Willi/Angelman syndrome region on
RT 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 oligomeric,
RT processive, and cap-interacting Poly(A)-specific 3' 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 amplifies
RT 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].
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 INTERACTION WITH DHX36.
RX PubMed=14731398; DOI=10.1016/s1097-2765(03)00481-7;
RA Tran H., Schilling M., Wirbelauer C., Hess D., Nagamine Y.;
RT "Facilitation of mRNA deadenylation and decay by the exosome-bound, DExH
RT protein RHAU.";
RL Mol. Cell 13:101-111(2004).
RN [15]
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 turnover
RT by recruiting the degradation machinery.";
RL Mol. Cell 14:571-583(2004).
RN [16]
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)-specific
RT ribonuclease.";
RL J. Biol. Chem. 279:48702-48706(2004).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163 AND SER-557, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [20]
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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220 AND LYS-499, 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 [23]
RP PHOSPHORYLATION AT SER-557 BY MAPKAPK2, AND PHOSPHORYLATION AT SER-557.
RX PubMed=20932473; DOI=10.1016/j.molcel.2010.09.018;
RA Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S., van Vugt M.A.,
RA Wang X., Linding R., Ong S.E., Weaver D., Carr S.A., 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).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619; SER-628 AND
RP THR-631, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
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 [26]
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., Zheng Y.T.,
RA 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557; SER-619 AND SER-623, AND
RP IDENTIFICATION BY 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 [28]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22442037; DOI=10.1261/rna.032292.112;
RA Berndt H., Harnisch C., Rammelt C., Stoehr N., Zirkel A., Dohm J.C.,
RA Himmelbauer H., Tavanez J.P., Huettelmaier S., Wahle E.;
RT "Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and
RT PARN-dependent trimming.";
RL RNA 18:958-972(2012).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163; SER-167; SER-530;
RP SER-557; SER-619 AND SER-623, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-557, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP FUNCTION.
RX PubMed=25049417; DOI=10.1073/pnas.1317751111;
RA Boele J., Persson H., Shin J.W., Ishizu Y., Newie I.S., Soekilde R.,
RA Hawkins S.M., Coarfa C., Ikeda K., Takayama K., Horie-Inoue K., Ando Y.,
RA Burroughs A.M., Sasaki C., Suzuki C., Sakai M., Aoki S., Ogawa A.,
RA Hasegawa A., Lizio M., Kaida K., Teusink B., Carninci P., Suzuki H.,
RA Inoue S., Gunaratne P.H., Rovira C., Hayashizaki Y., de Hoon M.J.;
RT "PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is
RT disrupted in proliferative disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:11467-11472(2014).
RN [32]
RP INVOLVEMENT IN DKCB6, AND VARIANT DKCB6 VAL-383.
RX PubMed=25893599; DOI=10.1172/jci78963;
RA Tummala H., Walne A., Collopy L., Cardoso S., de la Fuente J., Lawson S.,
RA Powell J., Cooper N., Foster A., Mohammed S., Plagnol V., Vulliamy T.,
RA Dokal I.;
RT "Poly(A)-specific ribonuclease deficiency impacts telomere biology and
RT causes dyskeratosis congenita.";
RL J. Clin. Invest. 125:2151-2160(2015).
RN [33]
RP INVOLVEMENT IN PFBMFT4, AND VARIANT PFBMFT4 ARG-421.
RX PubMed=25848748; DOI=10.1038/ng.3278;
RA Stuart B.D., Choi J., Zaidi S., Xing C., Holohan B., Chen R., Choi M.,
RA Dharwadkar P., Torres F., Girod C.E., Weissler J., Fitzgerald J.,
RA Kershaw C., Klesney-Tait J., Mageto Y., Shay J.W., Ji W., Bilguvar K.,
RA Mane S., Lifton R.P., Garcia C.K.;
RT "Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary
RT fibrosis and telomere shortening.";
RL Nat. Genet. 47:512-517(2015).
RN [34]
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 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 human
RT PARN.";
RL EMBO J. 24:4082-4093(2005).
CC -!- FUNCTION: 3'-exoribonuclease that has a preference for poly(A) tails of
CC mRNAs, thereby efficiently degrading poly(A) tails. Exonucleolytic
CC degradation of the poly(A) tail is often the first step in the decay of
CC eukaryotic mRNAs and is also used to silence certain maternal mRNAs
CC translationally during oocyte maturation and early embryonic
CC development. Interacts with both the 3'-end poly(A) tail and the 5'-end
CC cap structure during degradation, the interaction with the cap
CC structure being required for an efficient degradation of poly(A) tails.
CC Involved in nonsense-mediated mRNA decay, a critical process of
CC selective degradation of mRNAs that contain premature stop codons. Also
CC involved in degradation of inherently unstable mRNAs that contain AU-
CC rich elements (AREs) in their 3'-UTR, possibly via its interaction with
CC KHSRP. Probably mediates the removal of poly(A) tails of AREs mRNAs,
CC which constitutes the first step of destabilization (PubMed:10882133,
CC PubMed:11359775, PubMed:12748283, PubMed:15175153, PubMed:9736620).
CC Also able to recognize and trim poly(A) tails of microRNAs such as
CC MIR21 and H/ACA box snoRNAs (small nucleolar RNAs) leading to microRNAs
CC degradation or snoRNA increased stability (PubMed:25049417,
CC PubMed:22442037). {ECO:0000269|PubMed:10882133,
CC ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:12748283,
CC ECO:0000269|PubMed:15175153, ECO:0000269|PubMed:22442037,
CC ECO:0000269|PubMed:25049417, ECO:0000269|PubMed:9736620}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000269|PubMed:10801819, ECO:0000269|PubMed:9736620};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:15358788};
CC Note=Divalent metal cations. Mg(2+) is the most probable.
CC {ECO:0000269|PubMed:11359775, ECO:0000269|PubMed:15358788};
CC -!- SUBUNIT: Homodimer (PubMed:10801819, PubMed:16281054). Found in a mRNA
CC decay complex with RENT1, RENT2 and RENT3B (PubMed:14527413). Interacts
CC with KHSRP (PubMed:15175153). Interacts with CELF1/CUGBP1
CC (PubMed:16601207). Interacts with ZC3HAV1 in an RNA-independent manner
CC (PubMed:21876179). Interacts with DHX36 (PubMed:14731398).
CC {ECO:0000269|PubMed:10801819, ECO:0000269|PubMed:14527413,
CC ECO:0000269|PubMed:14731398, ECO:0000269|PubMed:15175153,
CC ECO:0000269|PubMed:16281054, ECO:0000269|PubMed:16601207,
CC ECO:0000269|PubMed:21876179}.
CC -!- INTERACTION:
CC O95453; Q99728: BARD1; NbExp=4; IntAct=EBI-372832, EBI-473181;
CC O95453; P33240: CSTF2; NbExp=5; IntAct=EBI-372832, EBI-711360;
CC O95453; Q09161: NCBP1; NbExp=2; IntAct=EBI-372832, EBI-464743;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9736620}. Cytoplasm
CC {ECO:0000269|PubMed:9736620}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:22442037}. Note=Some
CC nuclear fraction is nucleolar.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O95453-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95453-2; Sequence=VSP_042846;
CC Name=3;
CC IsoId=O95453-3; Sequence=VSP_042847;
CC Name=4;
CC IsoId=O95453-4; Sequence=VSP_057269;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10640832,
CC ECO:0000269|PubMed:9736620}.
CC -!- PTM: Phosphorylation by MAPKAPK2, preventing GADD45A mRNA degradation
CC after genotoxic stress. {ECO:0000269|PubMed:20932473}.
CC -!- DISEASE: Dyskeratosis congenita, autosomal recessive, 6 (DKCB6)
CC [MIM:616353]: A form of dyskeratosis congenita, a rare multisystem
CC disorder caused by defective telomere maintenance. It is characterized
CC by progressive bone marrow failure, and the clinical triad of
CC reticulated skin hyperpigmentation, nail dystrophy, and mucosal
CC leukoplakia. Common but variable features include premature graying,
CC aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and
CC liver fibrosis among others. Early mortality is often associated with
CC bone marrow failure, infections, fatal pulmonary complications, or
CC malignancy. {ECO:0000269|PubMed:25893599}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- DISEASE: Pulmonary fibrosis, and/or bone marrow failure, telomere-
CC related, 4 (PFBMFT4) [MIM:616371]: An autosomal dominant disease
CC associated with shortened telomeres. Pulmonary fibrosis is the most
CC common manifestation. Other manifestations include aplastic anemia due
CC to bone marrow failure, hepatic fibrosis, and increased cancer risk,
CC particularly myelodysplastic syndrome and acute myeloid leukemia.
CC Phenotype, age at onset, and severity are determined by telomere
CC length. {ECO:0000269|PubMed:25848748}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Non canonical splice junctions.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CAF1 family. {ECO:0000305}.
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DR EMBL; AJ005698; CAA06683.1; -; mRNA.
DR EMBL; AK293189; BAG56729.1; -; mRNA.
DR EMBL; AK299653; BAG61572.1; -; 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; KF456163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85110.1; -; Genomic_DNA.
DR EMBL; BC050029; AAH50029.1; -; mRNA.
DR CCDS; CCDS45419.1; -. [O95453-1]
DR CCDS; CCDS45420.1; -. [O95453-2]
DR CCDS; CCDS58425.1; -. [O95453-3]
DR RefSeq; NP_001127949.1; NM_001134477.2. [O95453-2]
DR RefSeq; NP_001229921.1; NM_001242992.1. [O95453-3]
DR RefSeq; NP_002573.1; NM_002582.3. [O95453-1]
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 AlphaFoldDB; O95453; -.
DR SMR; O95453; -.
DR BioGRID; 111107; 116.
DR CORUM; O95453; -.
DR DIP; DIP-31124N; -.
DR IntAct; O95453; 26.
DR MINT; O95453; -.
DR STRING; 9606.ENSP00000387911; -.
DR BindingDB; O95453; -.
DR ChEMBL; CHEMBL3616362; -.
DR GlyGen; O95453; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95453; -.
DR PhosphoSitePlus; O95453; -.
DR SwissPalm; O95453; -.
DR BioMuta; PARN; -.
DR SWISS-2DPAGE; O95453; -.
DR EPD; O95453; -.
DR jPOST; O95453; -.
DR MassIVE; O95453; -.
DR MaxQB; O95453; -.
DR PaxDb; O95453; -.
DR PeptideAtlas; O95453; -.
DR PRIDE; O95453; -.
DR ProteomicsDB; 5011; -.
DR ProteomicsDB; 50886; -. [O95453-1]
DR ProteomicsDB; 50887; -. [O95453-2]
DR ProteomicsDB; 50888; -. [O95453-3]
DR Antibodypedia; 1739; 432 antibodies from 28 providers.
DR DNASU; 2987; -.
DR DNASU; 5073; -.
DR Ensembl; ENST00000341484.11; ENSP00000345456.7; ENSG00000140694.17. [O95453-2]
DR Ensembl; ENST00000420015.6; ENSP00000410525.2; ENSG00000140694.17. [O95453-3]
DR Ensembl; ENST00000437198.7; ENSP00000387911.2; ENSG00000140694.17. [O95453-1]
DR Ensembl; ENST00000539279.5; ENSP00000444381.1; ENSG00000140694.17. [O95453-4]
DR Ensembl; ENST00000615183.4; ENSP00000478668.1; ENSG00000274829.4. [O95453-1]
DR Ensembl; ENST00000618929.2; ENSP00000484279.1; ENSG00000274829.4. [O95453-3]
DR Ensembl; ENST00000631868.1; ENSP00000488554.1; ENSG00000274829.4. [O95453-4]
DR Ensembl; ENST00000634004.1; ENSP00000487634.1; ENSG00000274829.4. [O95453-2]
DR GeneID; 5073; -.
DR KEGG; hsa:5073; -.
DR MANE-Select; ENST00000437198.7; ENSP00000387911.2; NM_002582.4; NP_002573.1.
DR UCSC; uc010uzc.3; human. [O95453-1]
DR CTD; 5073; -.
DR DisGeNET; 5073; -.
DR GeneCards; PARN; -.
DR GeneReviews; PARN; -.
DR HGNC; HGNC:8609; PARN.
DR HPA; ENSG00000140694; Low tissue specificity.
DR MalaCards; PARN; -.
DR MIM; 604212; gene.
DR MIM; 616353; phenotype.
DR MIM; 616371; phenotype.
DR neXtProt; NX_O95453; -.
DR OpenTargets; ENSG00000140694; -.
DR Orphanet; 1775; Dyskeratosis congenita.
DR Orphanet; 3322; Hoyeraal-Hreidarsson syndrome.
DR Orphanet; 2032; Idiopathic pulmonary fibrosis.
DR PharmGKB; PA29072; -.
DR PharmGKB; PA32949; -.
DR VEuPathDB; HostDB:ENSG00000140694; -.
DR eggNOG; KOG1990; Eukaryota.
DR GeneTree; ENSGT00940000153167; -.
DR HOGENOM; CLU_018030_1_1_1; -.
DR InParanoid; O95453; -.
DR PhylomeDB; O95453; -.
DR TreeFam; TF314502; -.
DR PathwayCommons; O95453; -.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-429947; Deadenylation of mRNA.
DR Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR SignaLink; O95453; -.
DR SIGNOR; O95453; -.
DR BioGRID-ORCS; 5073; 161 hits in 1080 CRISPR screens.
DR ChiTaRS; PARN; human.
DR EvolutionaryTrace; O95453; -.
DR GeneWiki; PARN; -.
DR GeneWiki; Poly(A)-specific_ribonuclease; -.
DR GenomeRNAi; 5073; -.
DR Pharos; O95453; Tbio.
DR PRO; PR:O95453; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O95453; protein.
DR Bgee; ENSG00000140694; Expressed in calcaneal tendon and 108 other tissues.
DR ExpressionAtlas; O95453; baseline and differential.
DR Genevisible; O95453; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IBA:GO_Central.
DR GO; GO:0043169; F:cation binding; IMP:UniProtKB.
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:0004518; F:nuclease activity; TAS:ProtInc.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0070034; F:telomerase RNA binding; IC:BHF-UCL.
DR GO; GO:0000495; P:box H/ACA RNA 3'-end processing; IDA:UniProtKB.
DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc.
DR GO; GO:0010587; P:miRNA catabolic process; IDA:UniProtKB.
DR GO; GO:0110008; P:ncRNA deadenylation; IMP:BHF-UCL.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IBA:GO_Central.
DR GO; GO:0071051; P:polyadenylation-dependent snoRNA 3'-end processing; IDA:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:1904872; P:regulation of telomerase RNA localization to Cajal body; IMP:BHF-UCL.
DR GO; GO:0009451; P:RNA modification; TAS:ProtInc.
DR GO; GO:0090503; P:RNA phosphodiester bond hydrolysis, exonucleolytic; IMP:BHF-UCL.
DR GO; GO:0090669; P:telomerase RNA stabilization; IMP:BHF-UCL.
DR CDD; cd02637; R3H_PARN; 1.
DR Gene3D; 3.30.420.10; -; 2.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR034042; PARN_R3H.
DR InterPro; IPR014789; PolyA-riboNase_RNA-binding.
DR InterPro; IPR001374; R3H_dom.
DR InterPro; IPR036867; R3H_dom_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR006941; RNase_CAF1.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF04857; CAF1; 1.
DR Pfam; PF08675; RNA_bind; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR SUPFAM; SSF82708; SSF82708; 1.
DR PROSITE; PS51061; R3H; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Disease variant; Dyskeratosis congenita; Exonuclease; Hydrolase; Magnesium;
KW Metal-binding; Nonsense-mediated mRNA decay; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding.
FT CHAIN 1..639
FT /note="Poly(A)-specific ribonuclease PARN"
FT /id="PRO_0000212851"
FT DOMAIN 178..245
FT /note="R3H"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00382"
FT REGION 560..639
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 621..639
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 28
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 30
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 292
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT BINDING 382
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305"
FT SITE 326
FT /note="Interaction with poly(A)"
FT /evidence="ECO:0000269|PubMed:16281054"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 220
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 499
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 530
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 557
FT /note="Phosphoserine; by MAPKAPK2"
FT /evidence="ECO:0000269|PubMed:20932473,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDG3"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDG3"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 628
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 631
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042846"
FT VAR_SEQ 53..98
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042847"
FT VAR_SEQ 59..233
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057269"
FT VARIANT 383
FT /note="A -> V (in DKCB6; dbSNP:rs786200999)"
FT /evidence="ECO:0000269|PubMed:25893599"
FT /id="VAR_073782"
FT VARIANT 421
FT /note="K -> R (in PFBMFT4; dbSNP:rs777090017)"
FT /evidence="ECO:0000269|PubMed:25848748"
FT /id="VAR_073783"
FT MUTAGEN 28
FT /note="D->A: Loss of function but does not abolish ability
FT to bind RNA. Induces a decrease in degradation of mRNAs
FT containing AREs."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 28
FT /note="D->C: Loss of function in the presence of Mg(2+) but
FT not in the presence of Mn(2+), Zn(2+), Co(2+) or Cd(2+)."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 30
FT /note="E->A: Loss of function but does not abolish ability
FT to bind RNA. Induces a decrease in degradation of mRNAs
FT containing AREs."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 30
FT /note="E->C: Loss of function in the presence of Mg(2+),
FT Mn(2+), Zn(2+), Co(2+) or Cd(2+)."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 31
FT /note="F->A: Reduced affinity for poly(A). Loss of
FT activity."
FT /evidence="ECO:0000269|PubMed:16281054"
FT MUTAGEN 34
FT /note="I->A: Reduced affinity for poly(A). Strongly reduced
FT activity."
FT /evidence="ECO:0000269|PubMed:16281054"
FT MUTAGEN 113
FT /note="I->A: Loss of dimerization. Loss of activity."
FT /evidence="ECO:0000269|PubMed:16281054"
FT MUTAGEN 115
FT /note="F->A: Reduced affinity for poly(A). Little effect on
FT activity."
FT MUTAGEN 123
FT /note="F->A: Loss of dimerization. Loss of activity."
FT /evidence="ECO:0000269|PubMed:16281054"
FT MUTAGEN 292
FT /note="D->A: Loss of function but does not abolish ability
FT to bind RNA."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:15358788"
FT MUTAGEN 292
FT /note="D->C: Loss of function in the presence of Mg(2+) but
FT not in the presence of Mn(2+), Zn(2+), Co(2+) or Cd(2+)."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:15358788"
FT MUTAGEN 326
FT /note="K->A: Reduced affinity for poly(A). Little effect on
FT activity."
FT MUTAGEN 377
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16281054"
FT MUTAGEN 382
FT /note="D->A: Loss of function but does not abolish ability
FT to bind RNA. Induces a decrease in degradation of mRNAs
FT containing AREs."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 382
FT /note="D->C: Loss of function in the presence of Mg(2+) but
FT not in the presence of Mn(2+), Zn(2+), Co(2+) or Cd(2+)."
FT /evidence="ECO:0000269|PubMed:11742007,
FT ECO:0000269|PubMed:12748283, ECO:0000269|PubMed:15358788"
FT MUTAGEN 557
FT /note="S->A: Strong reduction of phosphorylation by
FT MAPKAPK2."
FT HELIX 5..21
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 50..60
FT /evidence="ECO:0007829|PDB:2A1R"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 66..77
FT /evidence="ECO:0007829|PDB:2A1R"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 82..92
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 110..118
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 123..127
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 136..141
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:2A1S"
FT HELIX 178..192
FT /evidence="ECO:0007829|PDB:2A1S"
FT HELIX 207..217
FT /evidence="ECO:0007829|PDB:2A1S"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:2A1S"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:2A1S"
FT STRAND 237..240
FT /evidence="ECO:0007829|PDB:2A1S"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:2A1S"
FT TURN 249..252
FT /evidence="ECO:0007829|PDB:2A1S"
FT HELIX 260..265
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 290..300
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 308..318
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 325..329
FT /evidence="ECO:0007829|PDB:2A1R"
FT TURN 332..337
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 343..349
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 379..397
FT /evidence="ECO:0007829|PDB:2A1R"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:2A1R"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:2A1S"
FT HELIX 416..418
FT /evidence="ECO:0007829|PDB:2A1R"
FT STRAND 419..429
FT /evidence="ECO:0007829|PDB:2A1S"
FT STRAND 445..451
FT /evidence="ECO:0007829|PDB:3CTR"
FT HELIX 458..464
FT /evidence="ECO:0007829|PDB:3CTR"
FT TURN 465..467
FT /evidence="ECO:0007829|PDB:3CTR"
FT STRAND 468..477
FT /evidence="ECO:0007829|PDB:3CTR"
FT STRAND 480..488
FT /evidence="ECO:0007829|PDB:3CTR"
FT HELIX 490..498
FT /evidence="ECO:0007829|PDB:3CTR"
FT HELIX 509..513
FT /evidence="ECO:0007829|PDB:3CTR"
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
