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 27-MAR-2024, entry version 226. 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 INTERACTION WITH SDE2. RX PubMed=34365507; DOI=10.1093/nar/gkab647; RA Floro J., Dai A., Metzger A., Mora-Martin A., Ganem N.J., Cifuentes D., RA Wu C.S., Dalal J., Lyons S.M., Labadorf A., Flynn R.L.; RT "SDE2 is an essential gene required for ribosome biogenesis and the RT regulation of alternative splicing."; RL Nucleic Acids Res. 49:9424-9443(2021). RN [31] 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. RN [32] {ECO:0007744|PDB:7MQ8, ECO:0007744|PDB:7MQ9, ECO:0007744|PDB:7MQA} RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS), FUNCTION, IDENTIFICATION RP IN THE DCX(DCAF13) COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=34516797; DOI=10.1126/science.abj5338; RA Singh S., Vanden Broeck A., Miller L., Chaker-Margot M., Klinge S.; RT "Nucleolar maturation of the human small subunit processome."; RL Science 373:eabj5338-eabj5338(2021). 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). Part of the small subunit (SSU) CC processome, first precursor of the small eukaryotic ribosomal subunit. CC During the assembly of the SSU processome in the nucleolus, many CC ribosome biogenesis factors, an RNA chaperone and ribosomal proteins CC associate with the nascent pre-rRNA and work in concert to generate RNA CC folding, modifications, rearrangements and cleavage as well as targeted CC degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). CC {ECO:0000250|UniProtKB:P15646, ECO:0000269|PubMed:24352239, CC ECO:0000269|PubMed:30540930, ECO:0000269|PubMed:32017898, CC ECO:0000269|PubMed:34516797}. 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. Part of the small CC subunit (SSU) processome, composed of more than 70 proteins and the RNA CC chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Interacts CC with PRMT5 and UTP20 (PubMed:14583623, PubMed:17498821). Interacts with CC DDX5 and 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 Interacts with SDE2 (PubMed:34365507). {ECO:0000250|UniProtKB:P22509, CC ECO:0000269|PubMed:10837141, ECO:0000269|PubMed:14583623, CC ECO:0000269|PubMed:1714385, ECO:0000269|PubMed:17498821, CC ECO:0000269|PubMed:17636026, ECO:0000269|PubMed:20926688, CC ECO:0000269|PubMed:21536856, ECO:0000269|PubMed:22916032, CC ECO:0000269|PubMed:2414294, ECO:0000269|PubMed:34365507, CC ECO:0000269|PubMed:34516797}. 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, CC ECO:0000269|PubMed:34516797}. Nucleus, nucleoplasm CC {ECO:0000250|UniProtKB:P35550}. Note=Fibrillar region of 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}. 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; 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 EMDB; EMD-23936; -. DR EMDB; EMD-23937; -. DR EMDB; EMD-23938; -. DR SMR; P22087; -. DR BioGRID; 108399; 636. DR ComplexPortal; CPX-2511; Small ribosomal subunit processome. DR CORUM; P22087; -. DR DIP; DIP-27569N; -. DR IntAct; P22087; 331. DR MINT; P22087; -. DR STRING; 9606.ENSP00000221801; -. DR GlyCosmos; P22087; 1 site, 1 glycan. 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 EPD; P22087; -. DR jPOST; P22087; -. DR MassIVE; P22087; -. DR MaxQB; P22087; -. DR PaxDb; 9606-ENSP00000221801; -. DR PeptideAtlas; P22087; -. DR ProteomicsDB; 53959; -. DR Pumba; P22087; -. DR Antibodypedia; 3594; 455 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 AGR; HGNC:3599; -. 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 InParanoid; P22087; -. DR OMA; WNPNKSK; -. DR OrthoDB; 5483592at2759; -. 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 SIGNOR; P22087; -. DR BioGRID-ORCS; 2091; 717 hits in 1177 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 99 other cell types or tissues. DR ExpressionAtlas; P22087; baseline and differential. 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: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; IDA:UniProtKB. DR GO; GO:0051117; F:ATPase binding; IPI:UniProtKB. DR GO; GO:1990259; F:histone H2AQ104 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:0001649; P:osteoblast differentiation; HDA:UniProtKB. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IDA: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; Vaccinia Virus protein VP39; 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 PANTHER; PTHR10335:SF4; RRNA 2'-O-METHYLTRANSFERASE FIBRILLARIN; 1. DR PANTHER; PTHR10335; RRNA 2-O-METHYLTRANSFERASE FIBRILLARIN; 1. DR Pfam; PF01269; Fibrillarin; 1. DR PRINTS; PR00052; FIBRILLARIN. DR SMART; SM01206; Fibrillarin; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR PROSITE; PS00566; FIBRILLARIN; 1. DR SWISS-2DPAGE; P22087; -. DR Genevisible; P22087; HS. 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.31" FT BINDING 216..217 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.31" FT BINDING 236..239 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.31" 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 FT 205-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 FT 205-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 FT 205-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 FT 205-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 FT Q-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 FT R-121." FT /evidence="ECO:0000269|PubMed:30540930" FT CONFLICT 132 FT /note="I -> F (in Ref. 1; AAA52453)" FT /evidence="ECO:0000305" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 106..109 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 122..127 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 130..136 FT /evidence="ECO:0007829|PDB:7SE7" FT TURN 139..141 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 143..149 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 162..166 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 172..181 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 185..190 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 194..206 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 210..213 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 220..222 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 230..235 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 242..253 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 254..265 FT /evidence="ECO:0007829|PDB:7SE7" FT HELIX 266..269 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:2IPX" FT HELIX 275..288 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 291..298 FT /evidence="ECO:0007829|PDB:7SE7" FT TURN 300..302 FT /evidence="ECO:0007829|PDB:7SE7" FT STRAND 303..313 FT /evidence="ECO:0007829|PDB:7SE7" 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 //