FBRL_HUMAN
ID FBRL_HUMAN Reviewed; 321 AA.
AC P22087; B5BUE8; O75259; Q6IAT5; Q9UPI6;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=rRNA 2'-O-methyltransferase fibrillarin;
DE EC=2.1.1.- {ECO:0000269|PubMed:24352239, ECO:0000305|PubMed:32017898};
DE AltName: Full=34 kDa nucleolar scleroderma antigen;
DE AltName: Full=Histone-glutamine methyltransferase;
DE AltName: Full=U6 snRNA 2'-O-methyltransferase fibrillarin {ECO:0000305};
GN Name=FBL {ECO:0000312|HGNC:HGNC:3599}; Synonyms=FIB1, FLRN;
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].
RX PubMed=1846968; DOI=10.1073/pnas.88.3.931;
RA Aris J.P., Blobel G.;
RT "cDNA cloning and sequencing of human fibrillarin, a conserved nucleolar
RT protein recognized by autoimmune antisera.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:931-935(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=2026646; DOI=10.1083/jcb.113.4.715;
RA Jansen R.P., Hurt E.C., Kern H., Lehtonen H., Carmo-Fonseca M., Lapeyre B.,
RA Tollervey D.;
RT "Evolutionary conservation of the human nucleolar protein fibrillarin and
RT its functional expression in yeast.";
RL J. Cell Biol. 113:715-729(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [9]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=2414294; DOI=10.1016/s0021-9258(17)38718-5;
RA Lischwe M.A., Ochs R.L., Reddy R., Cook R.G., Yeoman L.C., Tan E.M.,
RA Reichlin M., Busch H.;
RT "Purification and partial characterization of a nucleolar scleroderma
RT antigen (Mr = 34,000; pI, 8.5) rich in NG,NG-dimethylarginine.";
RL J. Biol. Chem. 260:14304-14310(1985).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH SMALL NUCLEOLAR RNA U3; U8; U13; X AND Y.
RX PubMed=1714385; DOI=10.1002/j.1460-2075.1991.tb07807.x;
RA Baserga S.J., Yang X.D., Steitz J.A.;
RT "An intact Box C sequence in the U3 snRNA is required for binding of
RT fibrillarin, the protein common to the major family of nucleolar snRNPs.";
RL EMBO J. 10:2645-2651(1991).
RN [11]
RP INTERACTION WITH DDX5.
RX PubMed=10837141; DOI=10.1006/excr.2000.4886;
RA Nicol S.M., Causevic M., Prescott A.R., Fuller-Pace F.V.;
RT "The nuclear DEAD box RNA helicase p68 interacts with the nucleolar protein
RT fibrillarin and colocalizes specifically in nascent nucleoli during
RT telophase.";
RL Exp. Cell Res. 257:272-280(2000).
RN [12]
RP INTERACTION WITH PRMT5, IDENTIFICATION IN A COMPLEX WITH NOP5 AND NOP56,
RP IDENTIFICATION IN A COMPLEX WITH RIBOSOMAL PROTEINS AND WITH NUMEROUS
RP NUCLEOLAR PROTEINS, IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=14583623; DOI=10.1074/jbc.m305604200;
RA Yanagida M., Hayano T., Yamauchi Y., Shinkawa T., Natsume T., Isobe T.,
RA Takahashi N.;
RT "Human fibrillarin forms a sub-complex with splicing factor 2-associated
RT p32, protein arginine methyltransferases, and tubulins alpha 3 and beta 1
RT that is independent of its association with preribosomal ribonucleoprotein
RT complexes.";
RL J. Biol. Chem. 279:1607-1614(2004).
RN [13]
RP INTERACTION WITH UTP20.
RX PubMed=17498821; DOI=10.1016/j.bbamcr.2007.04.002;
RA Wang Y., Liu J., Zhao H., Lue W., Zhao J., Yang L., Li N., Du X., Ke Y.;
RT "Human 1A6/DRIM, the homolog of yeast Utp20, functions in the 18S rRNA
RT processing.";
RL Biochim. Biophys. Acta 1773:863-868(2007).
RN [14]
RP INTERACTION WITH PIH1D1.
RX PubMed=17636026; DOI=10.1128/mcb.01097-07;
RA McKeegan K.S., Debieux C.M., Boulon S., Bertrand E., Watkins N.J.;
RT "A dynamic scaffold of pre-snoRNP factors facilitates human box C/D snoRNP
RT assembly.";
RL Mol. Cell. Biol. 27:6782-6793(2007).
RN [15]
RP IDENTIFICATION BY 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 [16]
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND DEUBIQUITINATION BY USP36.
RX PubMed=19208757; DOI=10.1242/jcs.044461;
RA Endo A., Matsumoto M., Inada T., Yamamoto A., Nakayama K.I., Kitamura N.,
RA Komada M.;
RT "Nucleolar structure and function are regulated by the deubiquitylating
RT enzyme USP36.";
RL J. Cell Sci. 122:678-686(2009).
RN [17]
RP INTERACTION WITH RRP1B.
RX PubMed=20926688; DOI=10.1091/mbc.e10-04-0287;
RA Chamousset D., De Wever V., Moorhead G.B., Chen Y., Boisvert F.M.,
RA Lamond A.I., Trinkle-Mulcahy L.;
RT "RRP1B targets PP1 to mammalian cell nucleoli and is associated with pre-
RT 60S ribosomal subunits.";
RL Mol. Biol. Cell 21:4212-4226(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, AND IDENTIFICATION BY
RP 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 [19]
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 [20]
RP INTERACTION WITH C1QBP.
RX PubMed=21536856; DOI=10.1074/mcp.m110.006148;
RA Yoshikawa H., Komatsu W., Hayano T., Miura Y., Homma K., Izumikawa K.,
RA Ishikawa H., Miyazawa N., Tachikawa H., Yamauchi Y., Isobe T.,
RA Takahashi N.;
RT "Splicing factor 2-associated protein p32 participates in ribosome
RT biogenesis by regulating the binding of Nop52 and fibrillarin to
RT preribosome particles.";
RL Mol. Cell. Proteomics 10:0-0(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, AND IDENTIFICATION BY
RP 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 [22]
RP INTERACTION WITH NOL11.
RX PubMed=22916032; DOI=10.1371/journal.pgen.1002892;
RA Freed E.F., Prieto J.L., McCann K.L., McStay B., Baserga S.J.;
RT "NOL11, implicated in the pathogenesis of North American Indian childhood
RT cirrhosis, is required for pre-rRNA transcription and processing.";
RL PLoS Genet. 8:E1002892-E1002892(2012).
RN [23]
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-116; SER-124 AND SER-126, 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124, 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 [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=24352239; DOI=10.1038/nature12819;
RA Tessarz P., Santos-Rosa H., Robson S.C., Sylvestersen K.B., Nelson C.J.,
RA Nielsen M.L., Kouzarides T.;
RT "Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated
RT modification.";
RL Nature 505:564-568(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-84; LYS-102; LYS-109; LYS-131;
RP LYS-143 AND LYS-158, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [28]
RP FUNCTION, ACETYLATION AT LYS-102; LYS-121; LYS-205 AND LYS-206, AND
RP MUTAGENESIS OF LYS-102; LYS-121 AND 205-LYS-LYS-206.
RX PubMed=30540930; DOI=10.1016/j.celrep.2018.11.051;
RA Iyer-Bierhoff A., Krogh N., Tessarz P., Ruppert T., Nielsen H., Grummt I.;
RT "SIRT7-dependent deacetylation of fibrillarin controls histone H2A
RT methylation and rRNA synthesis during the cell cycle.";
RL Cell Rep. 25:2946-2954(2018).
RN [29]
RP FUNCTION, IDENTIFICATION IN BOX C/D RNP COMPLEX, AND CATALYTIC ACTIVITY.
RX PubMed=32017898; DOI=10.1016/j.molcel.2020.01.001;
RA Hasler D., Meduri R., Bak M., Lehmann G., Heizinger L., Wang X., Li Z.T.,
RA Sement F.M., Bruckmann A., Dock-Bregeon A.C., Merkl R., Kalb R., Grauer E.,
RA Kunstmann E., Zavolan M., Liu M.F., Fischer U., Meister G.;
RT "The Alazami syndrome-associated protein LARP7 guides U6 small nuclear RNA
RT modification and contributes to splicing robustness.";
RL Mol. Cell 0:0-0(2020).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 83-315 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human fibrillarin in complex with SAH.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that has
CC the ability to methylate both RNAs and proteins (PubMed:24352239,
CC PubMed:30540930, PubMed:32017898). Involved in pre-rRNA processing by
CC catalyzing the site-specific 2'-hydroxyl methylation of ribose moieties
CC in pre-ribosomal RNA (PubMed:30540930). Site specificity is provided by
CC a guide RNA that base pairs with the substrate (By similarity).
CC Methylation occurs at a characteristic distance from the sequence
CC involved in base pairing with the guide RNA (By similarity). Probably
CC catalyzes 2'-O-methylation of U6 snRNAs in box C/D RNP complexes
CC (PubMed:32017898). U6 snRNA 2'-O-methylation is required for mRNA
CC splicing fidelity (PubMed:32017898). Also acts as a protein
CC methyltransferase by mediating methylation of 'Gln-105' of histone H2A
CC (H2AQ104me), a modification that impairs binding of the FACT complex
CC and is specifically present at 35S ribosomal DNA locus
CC (PubMed:24352239, PubMed:30540930). {ECO:0000250|UniProtKB:P15646,
CC ECO:0000269|PubMed:24352239, ECO:0000269|PubMed:30540930,
CC ECO:0000269|PubMed:32017898}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-glutaminyl-[histone H2A] + S-adenosyl-L-methionine = H(+) +
CC N(5)-methyl-L-glutaminyl-[histone H2A] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:50904, Rhea:RHEA-COMP:12837, Rhea:RHEA-COMP:12839,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30011, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61891;
CC Evidence={ECO:0000269|PubMed:24352239};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleotide in rRNA + S-adenosyl-L-methionine = a 2'-O-
CC methylribonucleotide in rRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:48628, Rhea:RHEA-COMP:12164, Rhea:RHEA-COMP:12165,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:90675, ChEBI:CHEBI:90676;
CC Evidence={ECO:0000250|UniProtKB:P15646};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48629;
CC Evidence={ECO:0000250|UniProtKB:P15646};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleotide in U6 snRNA + S-adenosyl-L-methionine = a 2'-
CC O-methylribonucleotide in U6 snRNA + H(+) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:63088, Rhea:RHEA-COMP:16262, Rhea:RHEA-
CC COMP:16263, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:90675, ChEBI:CHEBI:90676;
CC Evidence={ECO:0000305|PubMed:32017898};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63089;
CC Evidence={ECO:0000305|PubMed:32017898};
CC -!- SUBUNIT: Component of box C/D small nucleolar ribonucleoprotein
CC (snoRNP) particles that contain SNU13, FBL, NOP5 and NOP56, plus a
CC guide RNA (PubMed:1714385, PubMed:32017898). It is associated with the
CC U3, U8, U13, X and Y small nuclear RNAs (PubMed:1714385). Component of
CC several ribosomal and nucleolar protein complexes. Interacts with PRMT5
CC and UTP20 (PubMed:14583623, PubMed:17498821). Interacts with DDX5 and
CC C1QBP (PubMed:10837141, PubMed:21536856). Interacts with NOL11
CC (PubMed:22916032). Interacts with PIH1D1 (PubMed:17636026). Interacts
CC with RRP1B (PubMed:20926688). Interacts with NOLC1 (By similarity).
CC {ECO:0000250|UniProtKB:P22509, ECO:0000269|PubMed:10837141,
CC ECO:0000269|PubMed:14583623, ECO:0000269|PubMed:1714385,
CC ECO:0000269|PubMed:17498821, ECO:0000269|PubMed:17636026,
CC ECO:0000269|PubMed:20926688, ECO:0000269|PubMed:21536856,
CC ECO:0000269|PubMed:22916032, ECO:0000269|PubMed:2414294}.
CC -!- INTERACTION:
CC P22087; P17844: DDX5; NbExp=6; IntAct=EBI-358318, EBI-351962;
CC P22087; Q14684: RRP1B; NbExp=4; IntAct=EBI-358318, EBI-372051;
CC P22087; Q96RS0: TGS1; NbExp=2; IntAct=EBI-358318, EBI-949244;
CC P22087; Q3KQV3: ZNF792; NbExp=3; IntAct=EBI-358318, EBI-10240849;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:14583623,
CC ECO:0000269|PubMed:19208757, ECO:0000269|PubMed:2026646,
CC ECO:0000269|PubMed:2414294, ECO:0000269|PubMed:24352239}. Nucleus,
CC nucleoplasm {ECO:0000250|UniProtKB:P35550}. Note=Fibrillar region of
CC the nucleolus.
CC -!- PTM: Ubiquitinated. Ubiquitination leads to proteasomal degradation
CC (PubMed:19208757). Deubiquitinated by USP36 (PubMed:19208757).
CC {ECO:0000269|PubMed:19208757}.
CC -!- PTM: By homology to other fibrillarins, some or all of the N-terminal
CC domain arginines are modified to asymmetric dimethylarginine (DMA).
CC {ECO:0000250|UniProtKB:P22509}.
CC -!- PTM: Acetylated by CREBBP/CBP, preventing methylation of 'Gln-105' of
CC histone H2A (H2AQ104me), without affecting rRNA methylation
CC (PubMed:30540930). Deacetylation by SIRT7 restores methylation of 'Gln-
CC 105' of histone H2A (H2AQ104me) (PubMed:30540930).
CC {ECO:0000269|PubMed:30540930}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. Fibrillarin
CC family. {ECO:0000305}.
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DR EMBL; M59849; AAA52453.1; -; mRNA.
DR EMBL; X56597; CAA39935.1; -; mRNA.
DR EMBL; BT006830; AAP35476.1; -; mRNA.
DR EMBL; BT020144; AAV38946.1; -; mRNA.
DR EMBL; CR457069; CAG33350.1; -; mRNA.
DR EMBL; AB451384; BAG70198.1; -; mRNA.
DR EMBL; AC006950; AAD15623.1; -; Genomic_DNA.
DR EMBL; AC005393; AAC28913.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW56925.1; -; Genomic_DNA.
DR EMBL; BC019260; AAH19260.1; -; mRNA.
DR CCDS; CCDS12545.1; -.
DR PIR; A38712; A38712.
DR RefSeq; NP_001427.2; NM_001436.3.
DR PDB; 2IPX; X-ray; 1.82 A; A=83-315.
DR PDB; 7MQ8; EM; 3.60 A; SC/SD=1-321.
DR PDB; 7MQ9; EM; 3.87 A; SC/SD=1-321.
DR PDB; 7MQA; EM; 2.70 A; SC/SD=1-321.
DR PDB; 7SE6; X-ray; 1.99 A; A=83-321.
DR PDB; 7SE7; X-ray; 1.75 A; A=83-321.
DR PDB; 7SE8; X-ray; 1.75 A; A/B=83-321.
DR PDB; 7SE9; X-ray; 1.75 A; A/B=83-321.
DR PDB; 7SEA; X-ray; 1.91 A; A=83-321.
DR PDB; 7SEB; X-ray; 1.81 A; A=83-321.
DR PDB; 7SEC; X-ray; 1.90 A; A/B=83-321.
DR PDB; 7SED; X-ray; 1.90 A; A=83-321.
DR PDBsum; 2IPX; -.
DR PDBsum; 7MQ8; -.
DR PDBsum; 7MQ9; -.
DR PDBsum; 7MQA; -.
DR PDBsum; 7SE6; -.
DR PDBsum; 7SE7; -.
DR PDBsum; 7SE8; -.
DR PDBsum; 7SE9; -.
DR PDBsum; 7SEA; -.
DR PDBsum; 7SEB; -.
DR PDBsum; 7SEC; -.
DR PDBsum; 7SED; -.
DR AlphaFoldDB; P22087; -.
DR SMR; P22087; -.
DR BioGRID; 108399; 592.
DR CORUM; P22087; -.
DR DIP; DIP-27569N; -.
DR IntAct; P22087; 325.
DR MINT; P22087; -.
DR STRING; 9606.ENSP00000221801; -.
DR GlyGen; P22087; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P22087; -.
DR MetOSite; P22087; -.
DR PhosphoSitePlus; P22087; -.
DR SwissPalm; P22087; -.
DR BioMuta; FBL; -.
DR DMDM; 14549159; -.
DR SWISS-2DPAGE; P22087; -.
DR EPD; P22087; -.
DR jPOST; P22087; -.
DR MassIVE; P22087; -.
DR MaxQB; P22087; -.
DR PaxDb; P22087; -.
DR PeptideAtlas; P22087; -.
DR PRIDE; P22087; -.
DR ProteomicsDB; 53959; -.
DR Antibodypedia; 3594; 401 antibodies from 40 providers.
DR DNASU; 2091; -.
DR Ensembl; ENST00000221801.8; ENSP00000221801.2; ENSG00000105202.9.
DR Ensembl; ENST00000625241.3; ENSP00000487390.1; ENSG00000280548.4.
DR GeneID; 2091; -.
DR KEGG; hsa:2091; -.
DR MANE-Select; ENST00000221801.8; ENSP00000221801.2; NM_001436.4; NP_001427.2.
DR UCSC; uc002omn.4; human.
DR CTD; 2091; -.
DR DisGeNET; 2091; -.
DR GeneCards; FBL; -.
DR HGNC; HGNC:3599; FBL.
DR HPA; ENSG00000105202; Low tissue specificity.
DR MIM; 134795; gene.
DR neXtProt; NX_P22087; -.
DR OpenTargets; ENSG00000105202; -.
DR PharmGKB; PA28012; -.
DR VEuPathDB; HostDB:ENSG00000105202; -.
DR eggNOG; KOG1596; Eukaryota.
DR GeneTree; ENSGT00550000074792; -.
DR OMA; INMATHR; -.
DR OrthoDB; 1411035at2759; -.
DR PhylomeDB; P22087; -.
DR TreeFam; TF300639; -.
DR PathwayCommons; P22087; -.
DR Reactome; R-HSA-6790901; rRNA modification in the nucleus and cytosol.
DR Reactome; R-HSA-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR SignaLink; P22087; -.
DR BioGRID-ORCS; 2091; 681 hits in 1096 CRISPR screens.
DR ChiTaRS; FBL; human.
DR EvolutionaryTrace; P22087; -.
DR GeneWiki; Fibrillarin; -.
DR GenomeRNAi; 2091; -.
DR Pharos; P22087; Tbio.
DR PRO; PR:P22087; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P22087; protein.
DR Bgee; ENSG00000105202; Expressed in ganglionic eminence and 97 other tissues.
DR ExpressionAtlas; P22087; baseline and differential.
DR Genevisible; P22087; HS.
DR GO; GO:0031428; C:box C/D RNP complex; IBA:GO_Central.
DR GO; GO:0015030; C:Cajal body; IDA:BHF-UCL.
DR GO; GO:0005694; C:chromosome; IEA:Ensembl.
DR GO; GO:0001651; C:dense fibrillar component; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0001652; C:granular component; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032040; C:small-subunit processome; IBA:GO_Central.
DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB.
DR GO; GO:1990259; F:histone-glutamine methyltransferase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008649; F:rRNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; IPI:UniProtKB.
DR GO; GO:0000494; P:box C/D RNA 3'-end processing; IBA:GO_Central.
DR GO; GO:1990258; P:histone glutamine methylation; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR GO; GO:0031167; P:rRNA methylation; IDA:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; TAS:ProtInc.
DR GO; GO:0048254; P:snoRNA localization; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR HAMAP; MF_00351; RNA_methyltransf_FlpA; 1.
DR InterPro; IPR000692; Fibrillarin.
DR InterPro; IPR020813; Fibrillarin_CS.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01269; Fibrillarin; 1.
DR PRINTS; PR00052; FIBRILLARIN.
DR SMART; SM01206; Fibrillarin; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS00566; FIBRILLARIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Isopeptide bond; Methylation; Methyltransferase;
KW Nucleus; Phosphoprotein; Reference proteome; Ribonucleoprotein;
KW RNA-binding; rRNA processing; S-adenosyl-L-methionine; Transferase;
KW Ubl conjugation.
FT CHAIN 1..321
FT /note="rRNA 2'-O-methyltransferase fibrillarin"
FT /id="PRO_0000148507"
FT REGION 1..87
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..306
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 172..173
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y9U3"
FT BINDING 191..192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.30"
FT BINDING 216..217
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.30"
FT BINDING 236..239
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.30"
FT MOD_RES 8
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 15
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 21
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 24
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 27
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 102
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:30540930"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 121
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:30540930"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 205
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:30540930"
FT MOD_RES 206
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:30540930"
FT CROSSLNK 84
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 102
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 109
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 131
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 143
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 158
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT MUTAGEN 102
FT /note="K->Q: Mimics acetylation; impaired ability to
FT methylate histone H2A; when associated with Q-121 and 205-
FT Q-Q-206."
FT /evidence="ECO:0000269|PubMed:30540930"
FT MUTAGEN 102
FT /note="K->R: Decreased acetylation; restores ability to
FT methylate histone H2A; when associated with R-121 and 205-
FT R-R-206."
FT /evidence="ECO:0000269|PubMed:30540930"
FT MUTAGEN 121
FT /note="K->Q: Mimics acetylation; impaired ability to
FT methylate histone H2A; when associated with Q-102 and 205-
FT Q-Q-206."
FT /evidence="ECO:0000269|PubMed:30540930"
FT MUTAGEN 121
FT /note="K->R: Decreased acetylation; restores ability to
FT methylate histone H2A; when associated with R-102 and 205-
FT R-R-206."
FT /evidence="ECO:0000269|PubMed:30540930"
FT MUTAGEN 205..206
FT /note="KK->QQ: Mimics acetylation; impaired ability to
FT methylate histone H2A; when associated with Q-102 and Q-
FT 121."
FT /evidence="ECO:0000269|PubMed:30540930"
FT MUTAGEN 205..206
FT /note="KK->RR: Decreased acetylation; restores ability to
FT methylate histone H2A; when associated with R-102 and R-
FT 121."
FT /evidence="ECO:0000269|PubMed:30540930"
FT CONFLICT 132
FT /note="I -> F (in Ref. 1; AAA52453)"
FT /evidence="ECO:0000305"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 117..119
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:2IPX"
FT TURN 139..141
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 143..149
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 172..181
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 186..190
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 194..206
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 210..213
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 220..226
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 230..235
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 242..253
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 254..265
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:2IPX"
FT HELIX 285..289
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 291..298
FT /evidence="ECO:0007829|PDB:2IPX"
FT TURN 300..302
FT /evidence="ECO:0007829|PDB:2IPX"
FT STRAND 303..313
FT /evidence="ECO:0007829|PDB:2IPX"
SQ SEQUENCE 321 AA; 33784 MW; 2123F41E01EC557A CRC64;
MKPGFSPRGG GFGGRGGFGD RGGRGGRGGF GGGRGRGGGF RGRGRGGGGG GGGGGGGGRG
GGGFHSGGNR GRGRGGKRGN QSGKNVMVEP HRHEGVFICR GKEDALVTKN LVPGESVYGE
KRVSISEGDD KIEYRAWNPF RSKLAAAILG GVDQIHIKPG AKVLYLGAAS GTTVSHVSDI
VGPDGLVYAV EFSHRSGRDL INLAKKRTNI IPVIEDARHP HKYRMLIAMV DVIFADVAQP
DQTRIVALNA HTFLRNGGHF VISIKANCID STASAEAVFA SEVKKMQQEN MKPQEQLTLE
PYERDHAVVV GVYRPPPKVK N
