RIF1_HUMAN
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 03-AUG-2022, entry version 164.
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};
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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; 170.
DR IntAct; Q5UIP0; 163.
DR MINT; Q5UIP0; -.
DR STRING; 9606.ENSP00000243326; -.
DR GlyConnect; 1791; 3 N-Linked glycans (1 site).
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 EPD; Q5UIP0; -.
DR jPOST; Q5UIP0; -.
DR MassIVE; Q5UIP0; -.
DR MaxQB; Q5UIP0; -.
DR PaxDb; Q5UIP0; -.
DR PeptideAtlas; Q5UIP0; -.
DR PRIDE; Q5UIP0; -.
DR ProteomicsDB; 65248; -. [Q5UIP0-1]
DR ProteomicsDB; 65249; -. [Q5UIP0-2]
DR Antibodypedia; 33653; 140 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 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; NKNETYV; -.
DR OrthoDB; 10400at2759; -.
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; 195 hits in 1080 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 200 other tissues.
DR ExpressionAtlas; Q5UIP0; baseline and differential.
DR Genevisible; Q5UIP0; HS.
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:0016604; C:nuclear body; IDA:HPA.
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:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
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:0051574; P:positive regulation of histone H3-K9 methylation; ISS:BHF-UCL.
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 assembly; 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 Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR028566; Rif1.
DR InterPro; IPR022031; Rif1_N.
DR PANTHER; PTHR22928; PTHR22928; 3.
DR Pfam; PF12231; Rif1_N; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
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
