ID RIF1_HUMAN Reviewed; 2472 AA. AC Q5UIP0; A6NC27; C9JBR1; Q5H9R3; Q5UIP2; Q66YK6; Q6PRU2; Q8TE94; Q99772; AC Q9H830; Q9H9B9; Q9NVP5; Q9Y4R4; DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2005, sequence version 2. DT 27-MAR-2024, entry version 173. DE RecName: Full=Telomere-associated protein RIF1 {ECO:0000305}; DE AltName: Full=Rap1-interacting factor 1 homolog {ECO:0000305|PubMed:15342490}; GN Name=RIF1 {ECO:0000303|PubMed:15342490, ECO:0000312|HGNC:HGNC:23207}; 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, SUBCELLULAR LOCATION, AND RP VARIANTS TYR-2021 AND VAL-2418. RX PubMed=15342490; DOI=10.1101/gad.1216004; RA Silverman J., Takai H., Buonomo S.B.C., Eisenhaber F., De Lange T.; RT "Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and RT 53BP1 and functions in the S-phase checkpoint."; RL Genes Dev. 18:2108-2119(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, DEVELOPMENTAL STAGE, AND VARIANTS SER-836; MET-1362; TYR-2021 RP AND VAL-2418. RX PubMed=15583028; DOI=10.1083/jcb.200408181; RA Xu L., Blackburn E.H.; RT "Human Rif1 protein binds aberrant telomeres and aligns along anaphase RT midzone microtubules."; RL J. Cell Biol. 167:819-830(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Simonsson T.; RT "Identification and characterization of human Rif1."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-853 AND 1728-2472 (ISOFORM 1), RP AND VARIANTS TYR-2021 AND VAL-2418. RC TISSUE=Testis, and Testis carcinoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 161-1499 AND 2217-2472 (ISOFORM RP 1), AND VARIANTS SER-836; MET-1362 AND VAL-2418. 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2108-2472 (ISOFORM 2), AND RP VARIANT VAL-2418. RC TISSUE=Brain; RX PubMed=9110174; DOI=10.1101/gr.7.4.353; RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.; RT "Large-scale concatenation cDNA sequencing."; RL Genome Res. 7:353-358(1997). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1454 AND SER-1688, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-409 AND SER-1579, 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1513; THR-1518 AND SER-1542, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-402; THR-409; SER-1162; RP SER-1236; SER-1238; SER-1422; SER-1554; SER-1616; SER-1688; SER-1693; RP SER-1810; SER-2144; SER-2172; SER-2196; SER-2205; SER-2260; SER-2339; RP SER-2391; SER-2393; SER-2465 AND SER-2471, AND IDENTIFICATION BY MASS RP 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 [12] 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979; THR-1047; SER-1552; RP SER-1554; SER-1579; SER-1688; THR-1806; SER-1971 AND SER-2196, AND RP IDENTIFICATION BY 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 [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1238; SER-1454; SER-1579; RP SER-1688; SER-1810; SER-1873; SER-1876; SER-2161; SER-2172; SER-2176; RP SER-2196; SER-2205 AND SER-2393, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-782; SER-1422; SER-1454; RP SER-1542; SER-1554; SER-1576; SER-1579; SER-1688; SER-1873; SER-2144; RP SER-2161; THR-2167 AND SER-2393, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-402; SER-782; SER-1008; RP SER-1162; THR-1220; SER-1236; SER-1238; SER-1422; SER-1454; SER-1513; RP SER-1542; SER-1552; SER-1554; SER-1556; SER-1579; SER-1613; SER-1616; RP SER-1688; SER-1706; SER-1709; THR-1806; SER-1810; SER-1926; SER-2144; RP SER-2161; SER-2172; SER-2176; SER-2196; SER-2205 AND SER-2339, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP FUNCTION, AND INTERACTION WITH TP53BP1. RX PubMed=23333306; DOI=10.1016/j.molcel.2013.01.001; RA Escribano-Diaz C., Orthwein A., Fradet-Turcotte A., Xing M., Young J.T., RA Tkac J., Cook M.A., Rosebrock A.P., Munro M., Canny M.D., Xu D., RA Durocher D.; RT "A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and RT BRCA1-CtIP controls DNA repair pathway choice."; RL Mol. Cell 49:872-883(2013). RN [20] RP IDENTIFICATION BY 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 [21] RP INTERACTION WITH ERCC6. RX PubMed=29203878; DOI=10.1038/s41467-017-02114-x; RA Batenburg N.L., Walker J.R., Noordermeer S.M., Moatti N., Durocher D., RA Zhu X.D.; RT "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair RT pathway choice."; RL Nat. Commun. 8:1921-1921(2017). RN [22] RP FUNCTION, AND INTERACTION WITH TP53BP1. RX PubMed=28241136; DOI=10.1038/nature21358; RA Drane P., Brault M.E., Cui G., Meghani K., Chaubey S., Detappe A., RA Parnandi N., He Y., Zheng X.F., Botuyan M.V., Kalousi A., Yewdell W.T., RA Muench C., Harper J.W., Chaudhuri J., Soutoglou E., Mer G., Chowdhury D.; RT "TIRR regulates 53BP1 by masking its histone methyl-lysine binding RT function."; RL Nature 543:211-216(2017). RN [23] RP INTERACTION WITH SHLD2, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=29789392; DOI=10.15252/embj.201899543; RA Tomida J., Takata K.I., Bhetawal S., Person M.D., Chao H.P., Tang D.G., RA Wood R.D.; RT "FAM35A associates with REV7 and modulates DNA damage responses of normal RT and BRCA1-defective cells."; RL EMBO J. 37:0-0(2018). RN [24] RP VARIANTS [LARGE SCALE ANALYSIS] LYS-1784 AND HIS-1955. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Key regulator of TP53BP1 that plays a key role in the repair CC of double-strand DNA breaks (DSBs) in response to DNA damage: acts by CC promoting non-homologous end joining (NHEJ)-mediated repair of DSBs CC (PubMed:15342490, PubMed:28241136). In response to DNA damage, CC interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, CC PubMed:28241136). Interaction with TP53BP1 leads to dissociate the CC interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the CC tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA CC DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by CC promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same CC time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by CC blocking DSBs resection via homologous recombination (HR) during G1 CC phase (PubMed:23333306). Also required for immunoglobulin class-switch CC recombination (CSR) during antibody genesis, a process that involves CC the generation of DNA DSBs (By similarity). Promotes NHEJ of CC dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, CC ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, CC ECO:0000269|PubMed:28241136}. CC -!- SUBUNIT: Interacts with TP53BP1 (when phosphorylated by ATM) CC (PubMed:23333306, PubMed:28241136). May interact with TRF2 (By CC similarity). Interacts with SHLD2 (PubMed:29789392). Interacts with CC ERCC6 (via WHD region) (PubMed:29203878). CC {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:23333306, CC ECO:0000269|PubMed:28241136, ECO:0000269|PubMed:29203878, CC ECO:0000269|PubMed:29789392}. CC -!- INTERACTION: CC Q5UIP0; P62136: PPP1CA; NbExp=4; IntAct=EBI-711331, EBI-357253; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15583028}. Chromosome CC {ECO:0000250|UniProtKB:Q6PR54}. Chromosome, telomere CC {ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:15583028}. Cytoplasm, CC cytoskeleton, spindle {ECO:0000269|PubMed:15583028}. Note=Following CC interaction with TP53BP1, recruited to sites of DNA damage, such as CC DSBs (By similarity). Exhibits ATM- and TP53BP1-dependent localization CC to uncapped or aberrant telomeres and to DNA double strand breaks CC (DSBs) (PubMed:15342490). Does not associate with normal telomere CC structures (PubMed:15342490, PubMed:15583028). Localizes to CC microtubules of the midzone of the mitotic spindle during anaphase, and CC to condensed chromosomes in telophase (PubMed:15583028). CC {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, CC ECO:0000269|PubMed:15583028}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5UIP0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5UIP0-2; Sequence=VSP_014431; CC -!- TISSUE SPECIFICITY: Highly expressed in testis. CC {ECO:0000269|PubMed:15583028}. CC -!- DEVELOPMENTAL STAGE: Expression peaks in late G2/S phase of the cell CC cycle. {ECO:0000269|PubMed:15583028}. CC -!- SIMILARITY: Belongs to the RIF1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91705.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB14313.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB14792.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB85058.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI45961.1; Type=Frameshift; Evidence={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; AY585745; AAT40745.1; -; mRNA. DR EMBL; AY727910; AAV51401.1; -; mRNA. DR EMBL; AY727911; AAV51402.1; -; mRNA. DR EMBL; AY727912; AAV51403.1; -; mRNA. DR EMBL; AY727913; AAV51404.1; -; mRNA. DR EMBL; AY584066; AAS94233.1; -; mRNA. DR EMBL; AC009311; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC009497; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL080129; CAB45727.1; -; mRNA. DR EMBL; CR933663; CAI45961.1; ALT_SEQ; mRNA. DR EMBL; AK001461; BAA91705.1; ALT_INIT; mRNA. DR EMBL; AK022932; BAB14313.1; ALT_INIT; mRNA. DR EMBL; AK024033; BAB14792.1; ALT_INIT; mRNA. DR EMBL; AK074349; BAB85058.1; ALT_INIT; mRNA. DR EMBL; U79263; AAB50209.1; -; mRNA. DR CCDS; CCDS2194.1; -. [Q5UIP0-1] DR CCDS; CCDS54406.1; -. [Q5UIP0-2] DR PIR; T12518; T12518. DR RefSeq; NP_001171134.1; NM_001177663.1. [Q5UIP0-2] DR RefSeq; NP_001171135.1; NM_001177664.1. [Q5UIP0-2] DR RefSeq; NP_001171136.1; NM_001177665.1. [Q5UIP0-2] DR RefSeq; NP_060621.3; NM_018151.4. [Q5UIP0-1] DR RefSeq; XP_005246722.1; XM_005246665.3. [Q5UIP0-1] DR AlphaFoldDB; Q5UIP0; -. DR SMR; Q5UIP0; -. DR BioGRID; 120482; 202. DR IntAct; Q5UIP0; 165. DR MINT; Q5UIP0; -. DR STRING; 9606.ENSP00000243326; -. DR GlyConnect; 1791; 3 N-Linked glycans (1 site). DR GlyCosmos; Q5UIP0; 1 site, 3 glycans. DR GlyGen; Q5UIP0; 2 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q5UIP0; -. DR MetOSite; Q5UIP0; -. DR PhosphoSitePlus; Q5UIP0; -. DR SwissPalm; Q5UIP0; -. DR BioMuta; RIF1; -. DR DMDM; 68565701; -. DR CPTAC; CPTAC-3254; -. DR CPTAC; CPTAC-5981; -. DR EPD; Q5UIP0; -. DR jPOST; Q5UIP0; -. DR MassIVE; Q5UIP0; -. DR MaxQB; Q5UIP0; -. DR PaxDb; 9606-ENSP00000243326; -. DR PeptideAtlas; Q5UIP0; -. DR ProteomicsDB; 65248; -. [Q5UIP0-1] DR ProteomicsDB; 65249; -. [Q5UIP0-2] DR Pumba; Q5UIP0; -. DR Antibodypedia; 33653; 156 antibodies from 29 providers. DR DNASU; 55183; -. DR Ensembl; ENST00000243326.9; ENSP00000243326.4; ENSG00000080345.18. [Q5UIP0-1] DR Ensembl; ENST00000428287.6; ENSP00000415691.2; ENSG00000080345.18. [Q5UIP0-2] DR Ensembl; ENST00000430328.6; ENSP00000416123.2; ENSG00000080345.18. [Q5UIP0-2] DR Ensembl; ENST00000444746.7; ENSP00000390181.2; ENSG00000080345.18. [Q5UIP0-1] DR Ensembl; ENST00000453091.6; ENSP00000414615.2; ENSG00000080345.18. [Q5UIP0-2] DR GeneID; 55183; -. DR KEGG; hsa:55183; -. DR MANE-Select; ENST00000444746.7; ENSP00000390181.2; NM_018151.5; NP_060621.3. DR UCSC; uc002txl.4; human. [Q5UIP0-1] DR AGR; HGNC:23207; -. DR CTD; 55183; -. DR DisGeNET; 55183; -. DR GeneCards; RIF1; -. DR HGNC; HGNC:23207; RIF1. DR HPA; ENSG00000080345; Low tissue specificity. DR MalaCards; RIF1; -. DR MIM; 608952; gene. DR neXtProt; NX_Q5UIP0; -. DR OpenTargets; ENSG00000080345; -. DR PharmGKB; PA134933858; -. DR VEuPathDB; HostDB:ENSG00000080345; -. DR eggNOG; ENOG502QV6C; Eukaryota. DR GeneTree; ENSGT00390000012204; -. DR HOGENOM; CLU_000989_0_0_1; -. DR InParanoid; Q5UIP0; -. DR OMA; KISGMEI; -. DR OrthoDB; 2965734at2759; -. DR PhylomeDB; Q5UIP0; -. DR TreeFam; TF323789; -. DR PathwayCommons; Q5UIP0; -. DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ). DR SignaLink; Q5UIP0; -. DR SIGNOR; Q5UIP0; -. DR BioGRID-ORCS; 55183; 213 hits in 1158 CRISPR screens. DR ChiTaRS; RIF1; human. DR GeneWiki; RIF1; -. DR GenomeRNAi; 55183; -. DR Pharos; Q5UIP0; Tbio. DR PRO; PR:Q5UIP0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q5UIP0; Protein. DR Bgee; ENSG00000080345; Expressed in buccal mucosa cell and 201 other cell types or tissues. DR ExpressionAtlas; Q5UIP0; baseline and differential. DR GO; GO:0000785; C:chromatin; ISS:BHF-UCL. DR GO; GO:0140445; C:chromosome, telomeric repeat region; ISS:BHF-UCL. DR GO; GO:0000793; C:condensed chromosome; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0001939; C:female pronucleus; IEA:Ensembl. DR GO; GO:0001940; C:male pronucleus; IEA:Ensembl. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0051233; C:spindle midzone; IDA:BHF-UCL. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB. DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0031509; P:subtelomeric heterochromatin formation; ISS:BHF-UCL. DR GO; GO:0000723; P:telomere maintenance; ISS:BHF-UCL. DR GO; GO:0043247; P:telomere maintenance in response to DNA damage; IDA:BHF-UCL. DR CDD; cd14267; Rif1_CTD_C-II_like; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR022031; Rif1_N. DR PANTHER; PTHR22928; TELOMERE-ASSOCIATED PROTEIN RIF1; 1. DR PANTHER; PTHR22928:SF3; TELOMERE-ASSOCIATED PROTEIN RIF1; 1. DR Pfam; PF12231; Rif1_N; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR Genevisible; Q5UIP0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; KW DNA damage; DNA repair; Nucleus; Phosphoprotein; Reference proteome; KW Telomere. FT CHAIN 1..2472 FT /note="Telomere-associated protein RIF1" FT /id="PRO_0000097333" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1145..1192 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1265..1318 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1398..1464 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1479..1587 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1762..1782 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1846..1889 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1924..2472 FT /note="Interaction with condensed chromosomes in telophase" FT REGION 1992..2021 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2170..2446 FT /note="Interaction with ERCC6" FT /evidence="ECO:0000269|PubMed:29203878" FT REGION 2227..2269 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1146..1165 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1166..1180 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1398..1413 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1416..1464 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1498..1534 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1536..1553 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1554..1587 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1767..1782 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1874..1889 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2005..2019 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2227..2267 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 402 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 409 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648" FT MOD_RES 782 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 979 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1008 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1047 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1162 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1220 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1236 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1238 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1422 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1454 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1513 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1518 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 1542 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1552 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1554 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1556 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1564 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PR54" FT MOD_RES 1576 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1579 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1613 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1616 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1688 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1693 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1706 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1709 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1806 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1810 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 1873 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT MOD_RES 1876 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1926 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1971 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 2144 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 2161 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 2167 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 2172 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 2176 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2195 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6PR54" FT MOD_RES 2196 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2205 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 2260 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 2391 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2393 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 2465 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 2471 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT VAR_SEQ 2250..2275 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15583028, FT ECO:0000303|PubMed:9110174" FT /id="VSP_014431" FT VARIANT 836 FT /note="G -> S (in dbSNP:rs2444263)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15583028" FT /id="VAR_022788" FT VARIANT 1362 FT /note="V -> M (in dbSNP:rs2123465)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15583028" FT /id="VAR_022789" FT VARIANT 1686 FT /note="R -> G (in dbSNP:rs3732305)" FT /id="VAR_022790" FT VARIANT 1784 FT /note="E -> K (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035983" FT VARIANT 1862 FT /note="V -> I (in dbSNP:rs2444258)" FT /id="VAR_022791" FT VARIANT 1955 FT /note="D -> H (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035984" FT VARIANT 2021 FT /note="N -> Y (in dbSNP:rs2444257)" FT /evidence="ECO:0000269|PubMed:15342490, FT ECO:0000269|PubMed:15583028, ECO:0000269|PubMed:17974005" FT /id="VAR_022792" FT VARIANT 2165 FT /note="M -> R (in dbSNP:rs16830057)" FT /id="VAR_022793" FT VARIANT 2418 FT /note="L -> V (in dbSNP:rs1065177)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:15583028, FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:9110174" FT /id="VAR_022794" FT CONFLICT 96 FT /note="N -> D (in Ref. 1; AAT40745)" FT /evidence="ECO:0000305" FT CONFLICT 699 FT /note="A -> P (in Ref. 6; BAA91705)" FT /evidence="ECO:0000305" FT CONFLICT 1256 FT /note="M -> V (in Ref. 6; BAA91705)" FT /evidence="ECO:0000305" FT CONFLICT 2316 FT /note="R -> G (in Ref. 6; BAB85058)" FT /evidence="ECO:0000305" FT CONFLICT 2392 FT /note="L -> F (in Ref. 6; BAB85058)" FT /evidence="ECO:0000305" FT CONFLICT 2445..2446 FT /note="HE -> RV (in Ref. 6; BAB85058)" FT /evidence="ECO:0000305" FT CONFLICT 2464 FT /note="R -> G (in Ref. 6; BAB85058)" FT /evidence="ECO:0000305" SQ SEQUENCE 2472 AA; 274466 MW; A45DCE3C5F9E052D CRC64; MTARGQSPLA PLLETLEDPS ASHGGQTDAY LTLTSRMTGE EGKEVITEIE KKLPRLYKVL KTHISSQNSE LSSAALQALG FCLYNPKITS ELSEANALEL LSKLNDTIKN SDKNVRTRAL WVISKQTFPS EVVGKMVSSI IDSLEILFNK GETHSAVVDF EALNVIVRLI EQAPIQMGEE AVRWAKLVIP LVVHSAQKVH LRGATALEMG MPLLLQKQQE IASITEQLMT TKLISELQKL FMSKNETYVL KLWPLFVKLL GRTLHRSGSF INSLLQLEEL GFRSGAPMIK KIAFIAWKSL IDNFALNPDI LCSAKRLKLL MQPLSSIHVR TETLALTKLE VWWYLLMRLG PHLPANFEQV CVPLIQSTIS IDSNASPQGN SCHVATSPGL NPMTPVHKGA SSPYGAPGTP RMNLSSNLGG MATIPSIQLL GLEMLLHFLL GPEALSFAKQ NKLVLSLEPL EHPLISSPSF FSKHANTLIT AVHDSFVAVG KDAPDVVVSA IWKELISLVK SVTESGNKKE KPGSEVLTLL LKSLESIVKS EVFPVSKTLV LMEITIKGLP QKVLGSPAYQ VANMDILNGT PALFLIQLIF NNFLECGVSD ERFFLSLESL VGCVLSGPTS PLAFSDSVLN VINQNAKQLE NKEHLWKMWS VIVTPLTELI NQTNEVNQGD ALEHNFSAIY GALTLPVNHI FSEQRFPVAT MKTLLRTWSE LYRAFARCAA LVATAEENLC CEELSSKIMS SLEDEGFSNL LFVDRIIYII TVMVDCIDFS PYNIKYQPKV KSPQRPSDWS KKKNEPLGKL TSLFKLIVKV IYSFHTLSFK EAHSDTLFTI GNSITGIISS VLGHISLPSM IRKIFATLTR PLALFYENSK LDEVPKVYSC LNNKLEKLLG EIIACLQFSY TGTYDSELLE QLSPLLCIIF LHKNKQIRKQ SAQFWNATFA KVMMLVYPEE LKPVLTQAKQ KFLLLLPGLE TVEMMEESSG PYSDGTENSQ LNVKISGMER KSNGKRDSFL AQTKNKKENM KPAAKLKLES SSLKVKGEIL LEEEKSTDFV FIPPEGKDAK ERILTDHQKE VLKTKRCDIP AMYNNLDVSQ DTLFTQYSQE EPMEIPTLTR KPKEDSKMMI TEEQMDSDIV IPQDVTEDCG MAEHLEKSSL SNNECGSLDK TSPEMSNSNN DERKKALISS RKTSTECASS TENSFVVSSS SVSNTTVAGT PPYPTSRRQT FITLEKFDGS ENRPFSPSPL NNISSTVTVK NNQETMIKTD FLPKAKQREG TFSKSDSEKI VNGTKRSSRR AGKAEQTGNK RSKPLMRSEP EKNTEESVEG IVVLENNPPG LLNQTECVSD NQVHLSESTM EHDNTKLKAA TVENAVLLET NTVEEKNVEI NLESKENTPP VVISADQMVN EDSQVQITPN QKTLRRSSRR RSEVVESTTE SQDKENSHQK KERRKEEEKP LQKSPLHIKD DVLPKQKLIA EQTLQENLIE KGSNLHEKTL GETSANAETE QNKKKADPEN IKSEGDGTQD IVDKSSEKLV RGRTRYQTRR ASQGLLSSIE NSESDSSEAK EEGSRKKRSG KWKNKSNESV DIQDQEEKVV KQECIKAENQ SHDYKATSEE DVSIKSPICE KQDESNTVIC QDSTVTSDLL QVPDDLPNVC EEKNETSKYA EYSFTSLPVP ESNLRTRNAI KRLHKRDSFD NCSLGESSKI GISDISSLSE KTFQTLECQH KRSRRVRRSK GCDCCGEKSQ PQEKSLIGLK NTENNDVEIS ETKKADVQAP VSPSETSQAN PYSEGQFLDE HHSVNFHLGL KEDNDTINDS LIVSETKSKE NTMQESLPSG IVNFREEICD MDSSEAMSLE SQESPNENFK TVGPCLGDSK NVSQESLETK EEKPEETPKM ELSLENVTVE GNACKVTESN LEKAKTMELN VGNEASFHGQ ERTKTGISEE AAIEENKRND DSEADTAKLN AKEVATEEFN SDISLSDNTT PVKLNAQTEI SEQTAAGELD GGNDVSDLHS SEETNTKMKN NEEMMIGEAM AETGHDGETE NEGITTKTSK PDEAETNMLT AEMDNFVCDT VEMSTEEGII DANKTETNTE YSKSEEKLDN NQMVMESDIL QEDHHTSQKV EEPSQCLASG TAISELIIED NNASPQKLRE LDPSLVSAND SPSGMQTRCV WSPLASPSTS ILKRGLKRSQ EDEISSPVNK VRRVSFADPI YQAGLADDID RRCSIVRSHS SNSSPIGKSV KTSPTTQSKH NTTSAKGFLS PGSRSPKFKS SKKCLISEMA KESIPCPTES VYPPLVNCVA PVDIILPQIT SNMWARGLGQ LIRAKNIKTI GDLSTLTASE IKTLPIRSPK VSNVKKALRI YHEQQVKTRG LEEIPVFDIS EKTVNGIENK SLSPDEERLV SDIIDPVALE IPLSKNLLAQ ISALALQLDS EDLHNYSGSQ LFEMHEKLSC MANSVIKNLQ SRWRSPSHEN SI //