FBRL_MOUSE
ID FBRL_MOUSE Reviewed; 327 AA.
AC P35550; Q99L58;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=rRNA 2'-O-methyltransferase fibrillarin;
DE EC=2.1.1.- {ECO:0000305|PubMed:32017896};
DE AltName: Full=Histone-glutamine methyltransferase;
DE AltName: Full=Nucleolar protein 1;
DE AltName: Full=U6 snRNA 2'-O-methyltransferase fibrillarin {ECO:0000305};
GN Name=Fbl {ECO:0000312|MGI:MGI:95486};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Macrophage;
RX PubMed=8218401; DOI=10.1016/0167-4781(93)90046-g;
RA Turley S.J., Tan E.M., Pollard K.M.;
RT "Molecular cloning and sequence analysis of U3 snoRNA-associated mouse
RT fibrillarin.";
RL Biochim. Biophys. Acta 1216:119-122(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver, and Mammary tumor;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, IDENTIFICATION IN BOX C/D RNP COMPLEX, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=32017896; DOI=10.1016/j.molcel.2020.01.002;
RA Wang X., Li Z.T., Yan Y., Lin P., Tang W., Hasler D., Meduri R., Li Y.,
RA Hua M.M., Qi H.T., Lin D.H., Shi H.J., Hui J., Li J., Li D., Yang J.H.,
RA Lin J., Meister G., Fischer U., Liu M.F.;
RT "LARP7-mediated U6 snRNA modification ensures splicing fidelity and
RT spermatogenesis in mice.";
RL Mol. Cell 0:0-0(2020).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that has
CC the ability to methylate both RNAs and proteins (PubMed:32017896).
CC Involved in pre-rRNA processing by catalyzing the site-specific 2'-
CC hydroxyl methylation of ribose moieties in pre-ribosomal RNA (By
CC similarity). Site specificity is provided by a guide RNA that base
CC pairs with the substrate (By similarity). Methylation occurs at a
CC characteristic distance from the sequence involved in base pairing with
CC the guide RNA (By similarity). Probably catalyzes 2'-O-methylation of
CC U6 snRNAs in box C/D RNP complexes (PubMed:32017896). U6 snRNA 2'-O-
CC methylation is required for mRNA splicing fidelity (PubMed:32017896).
CC Also acts as a protein methyltransferase by mediating methylation of
CC 'Gln-105' of histone H2A (H2AQ104me), a modification that impairs
CC binding of the FACT complex and is specifically present at 35S
CC ribosomal DNA locus (By similarity). {ECO:0000250|UniProtKB:P15646,
CC ECO:0000250|UniProtKB:P22087, ECO:0000269|PubMed:32017896}.
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:0000250|UniProtKB:P22087};
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:32017896};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63089;
CC Evidence={ECO:0000305|PubMed:32017896};
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. It is associated with the U3, U8, U13, X and Y small nuclear
CC RNAs. Component of several ribosomal and nucleolar protein complexes.
CC Interacts with PRMT5 and UTP20. Interacts with DDX5 and C1QBP.
CC Interacts with NOL11. Interacts with PIH1D1. Interacts with RRP1B (By
CC similarity). Interacts with NOLC1 (By similarity).
CC {ECO:0000250|UniProtKB:P22087, ECO:0000250|UniProtKB:P22509}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:P22087}. Nucleus, nucleoplasm
CC {ECO:0000305|PubMed:32017896}. Note=Fibrillar region of the nucleolus.
CC {ECO:0000250|UniProtKB:P22087}.
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: Ubiquitinated. Ubiquitination leads to proteasomal degradation.
CC Deubiquitinated by USP36. {ECO:0000250|UniProtKB:P22087}.
CC -!- PTM: Acetylated by CREBBP/CBP, preventing methylation of 'Gln-105' of
CC histone H2A (H2AQ104me), without affecting rRNA methylation.
CC Deacetylation by SIRT7 restores methylation of 'Gln-105' of histone H2A
CC (H2AQ104me). {ECO:0000250|UniProtKB:P22087}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. Fibrillarin
CC family. {ECO:0000305}.
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DR EMBL; Z22593; CAA80307.1; -; mRNA.
DR EMBL; BC003813; AAH03813.1; -; mRNA.
DR EMBL; BC092274; AAH92274.1; -; mRNA.
DR CCDS; CCDS21036.1; -.
DR PIR; S38342; S38342.
DR RefSeq; NP_032017.2; NM_007991.3.
DR AlphaFoldDB; P35550; -.
DR SMR; P35550; -.
DR BioGRID; 199604; 36.
DR CORUM; P35550; -.
DR IntAct; P35550; 38.
DR MINT; P35550; -.
DR STRING; 10090.ENSMUSP00000037613; -.
DR iPTMnet; P35550; -.
DR PhosphoSitePlus; P35550; -.
DR SwissPalm; P35550; -.
DR EPD; P35550; -.
DR jPOST; P35550; -.
DR MaxQB; P35550; -.
DR PaxDb; P35550; -.
DR PeptideAtlas; P35550; -.
DR PRIDE; P35550; -.
DR ProteomicsDB; 270959; -.
DR Antibodypedia; 3594; 401 antibodies from 40 providers.
DR DNASU; 14113; -.
DR Ensembl; ENSMUST00000042405; ENSMUSP00000037613; ENSMUSG00000046865.
DR GeneID; 14113; -.
DR KEGG; mmu:14113; -.
DR UCSC; uc009fxy.1; mouse.
DR CTD; 2091; -.
DR MGI; MGI:95486; Fbl.
DR VEuPathDB; HostDB:ENSMUSG00000046865; -.
DR eggNOG; KOG1596; Eukaryota.
DR GeneTree; ENSGT00550000074792; -.
DR HOGENOM; CLU_059055_1_0_1; -.
DR InParanoid; P35550; -.
DR OMA; INMATHR; -.
DR OrthoDB; 1411035at2759; -.
DR PhylomeDB; P35550; -.
DR TreeFam; TF300639; -.
DR Reactome; R-MMU-6791226; Major pathway of rRNA processing in the nucleolus and cytosol.
DR BioGRID-ORCS; 14113; 22 hits in 72 CRISPR screens.
DR ChiTaRS; Fbl; mouse.
DR PRO; PR:P35550; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P35550; protein.
DR Bgee; ENSMUSG00000046865; Expressed in ectoplacental cone and 67 other tissues.
DR ExpressionAtlas; P35550; baseline and differential.
DR Genevisible; P35550; MM.
DR GO; GO:0031428; C:box C/D RNP complex; IBA:GO_Central.
DR GO; GO:0015030; C:Cajal body; IDA:MGI.
DR GO; GO:0005694; C:chromosome; ISO:MGI.
DR GO; GO:0001651; C:dense fibrillar component; ISO:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0001652; C:granular component; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; ISO:MGI.
DR GO; GO:1990259; F:histone-glutamine methyltransferase activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IPI:MGI.
DR GO; GO:0008649; F:rRNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; ISO:MGI.
DR GO; GO:0000494; P:box C/D RNA 3'-end processing; IBA:GO_Central.
DR GO; GO:1990258; P:histone glutamine methylation; ISS:UniProtKB.
DR GO; GO:0031167; P:rRNA methylation; ISS:UniProtKB.
DR GO; GO:0016074; P:sno(s)RNA metabolic process; IMP:MGI.
DR GO; GO:0048254; P:snoRNA localization; ISO:MGI.
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 Acetylation; Isopeptide bond; Methylation; Methyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; Ribonucleoprotein; RNA-binding;
KW rRNA processing; S-adenosyl-L-methionine; Transferase; Ubl conjugation.
FT CHAIN 1..327
FT /note="rRNA 2'-O-methyltransferase fibrillarin"
FT /id="PRO_0000148508"
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 178..179
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y9U3"
FT BINDING 197..198
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT BINDING 222..223
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT BINDING 242..245
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P22087"
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 28
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 31
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P22509"
FT MOD_RES 108
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 127
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 211
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT MOD_RES 212
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 90
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 108
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 115
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 137
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 149
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CROSSLNK 164
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P22087"
FT CONFLICT 6
FT /note="S -> R (in Ref. 1; CAA80307)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="G -> V (in Ref. 1; CAA80307)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="V -> F (in Ref. 1; CAA80307)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="K -> T (in Ref. 1; CAA80307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 327 AA; 34307 MW; 0E22FE7C758089C3 CRC64;
MKPGFSPRGG GFGGRGGFGD RGGRGGGRGG RGGFGGGRGG FGGGGRGRGG GGGGFRGRGG
GGGRGGGFQS GGNRGRGGGR GGKRGNQSGK NVMVEPHRHE GVFICRGKED ALVTKNLVPG
ESVYGEKRVS ISEGDDKIEY RAWNPFRSKL AAAILGGVDQ IHIKPGAKVL YLGAASGTTV
SHVSDIVGPD GLVYAVEFSH RSGRDLINLA KKRTNIIPVI EDARHPHKYR MLIAMVDVIF
ADVAQPDQTR IVALNAHTFL RNGGHFVISI KANCIDSTAS AEAVFASEVK KMQQENMKPQ
EQLTLEPYER DHAVVVGVYR PPPKVKN
