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 27-MAR-2024, entry version 198. 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 syndrome, CC telomere-related, 4 (PFBMFT4) [MIM:616371]: An autosomal dominant CC disease associated with shortened telomeres. Pulmonary fibrosis is the CC most common manifestation. Other manifestations include aplastic anemia CC due to bone marrow failure, hepatic fibrosis, and increased cancer CC risk, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 150. DR CORUM; O95453; -. DR DIP; DIP-31124N; -. DR IntAct; O95453; 27. 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 EPD; O95453; -. DR jPOST; O95453; -. DR MassIVE; O95453; -. DR MaxQB; O95453; -. DR PaxDb; 9606-ENSP00000387911; -. DR PeptideAtlas; O95453; -. DR ProteomicsDB; 5011; -. DR ProteomicsDB; 50886; -. [O95453-1] DR ProteomicsDB; 50887; -. [O95453-2] DR ProteomicsDB; 50888; -. [O95453-3] DR Pumba; O95453; -. DR Antibodypedia; 1739; 486 antibodies from 28 providers. DR DNASU; 2987; -. DR DNASU; 5073; -. DR Ensembl; ENST00000341484.11; ENSP00000345456.7; ENSG00000140694.18. [O95453-2] DR Ensembl; ENST00000420015.6; ENSP00000410525.2; ENSG00000140694.18. [O95453-3] DR Ensembl; ENST00000437198.7; ENSP00000387911.2; ENSG00000140694.18. [O95453-1] DR Ensembl; ENST00000539279.5; ENSP00000444381.1; ENSG00000140694.18. [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 AGR; HGNC:8609; -. 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 OrthoDB; 276176at2759; -. 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; 179 hits in 1158 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 cell types or tissues. DR ExpressionAtlas; O95453; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. 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:0098794; C:postsynapse; IEA:Ensembl. 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:0090669; P:telomerase RNA stabilization; IMP:BHF-UCL. DR CDD; cd02637; R3H_PARN; 1. DR CDD; cd12428; RRM_PARN; 1. DR Gene3D; 3.30.70.330; -; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 2. 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 PANTHER; PTHR15092; POLY A -SPECIFIC RIBONUCLEASE/TARGET OF EGR1, MEMBER 1; 1. DR PANTHER; PTHR15092:SF44; POLY(A)-SPECIFIC RIBONUCLEASE PARN; 1. DR Pfam; PF04857; CAF1; 1. DR Pfam; PF08675; RNA_bind; 1. DR SUPFAM; SSF82708; R3H domain; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS51061; R3H; 1. DR SWISS-2DPAGE; O95453; -. DR Genevisible; O95453; HS. 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 //