ID RRP8_HUMAN Reviewed; 456 AA. AC O43159; Q7KZ78; Q9BVM6; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2005, sequence version 2. DT 27-MAR-2024, entry version 188. DE RecName: Full=Ribosomal RNA-processing protein 8; DE EC=2.1.1.-; DE AltName: Full=Cerebral protein 1; DE AltName: Full=Nucleomethylin; GN Name=RRP8; Synonyms=KIAA0409, NML; ORFNames=hucep-1; 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]. RC TISSUE=Brain; RA Yazaki M., Takayama K., Matsumoto K., Yoshimoto M.; RT "Cloning and characterization of a novel gene which is expressed in the RT human brain."; RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=9455477; DOI=10.1093/dnares/4.5.307; RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. VIII. 78 RT new cDNA clones from brain which code for large proteins in vitro."; RL DNA Res. 4:307-313(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [4] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=12429849; DOI=10.1091/mbc.e02-05-0271; RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., RA Greco A., Hochstrasser D.F., Diaz J.-J.; RT "Functional proteomic analysis of human nucleolus."; RL Mol. Biol. Cell 13:4100-4109(2002). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=11790298; DOI=10.1016/s0960-9822(01)00650-9; RA Andersen J.S., Lyon C.E., Fox A.H., Leung A.K.L., Lam Y.W., Steen H., RA Mann M., Lamond A.I.; RT "Directed proteomic analysis of the human nucleolus."; RL Curr. Biol. 12:1-11(2002). RN [6] 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-64; SER-171 AND RP SER-223, AND 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 [8] 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-64, 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 [10] RP IDENTIFICATION BY 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104; SER-176 AND SER-223, 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171, 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 [13] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 242-456 IN COMPLEX WITH RP S-ADENOSYL-L-HOMOCYSTEINE, IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, RP SUBCELLULAR LOCATION, AND H3K9ME2-BINDING. RX PubMed=18485871; DOI=10.1016/j.cell.2008.03.030; RA Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K., RA Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A., RA Kimura K., Shimizu T., Yanagisawa J.; RT "Epigenetic control of rDNA loci in response to intracellular energy RT status."; RL Cell 133:627-639(2008). CC -!- FUNCTION: Essential component of the eNoSC (energy-dependent nucleolar CC silencing) complex, a complex that mediates silencing of rDNA in CC response to intracellular energy status and acts by recruiting histone- CC modifying enzymes. The eNoSC complex is able to sense the energy status CC of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio CC activates SIRT1, leading to histone H3 deacetylation followed by CC dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation CC of silent chromatin in the rDNA locus. In the complex, RRP8 binds to CC H3K9me2 and probably acts as a methyltransferase. Its substrates are CC however unknown. {ECO:0000269|PubMed:18485871}. CC -!- SUBUNIT: Component of the eNoSC complex, composed of SIRT1, SUV39H1 and CC RRP8. {ECO:0000269|PubMed:18485871}. CC -!- INTERACTION: CC O43159; Q92997: DVL3; NbExp=3; IntAct=EBI-2008793, EBI-739789; CC O43159; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2008793, EBI-16439278; CC O43159; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-2008793, EBI-79165; CC O43159; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-2008793, EBI-1802965; CC O43159; O43463: SUV39H1; NbExp=3; IntAct=EBI-2008793, EBI-349968; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:11790298, CC ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:18485871}. CC Note=Localizes at rDNA locus. CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. RRP8 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA23705.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D87060; BAB46916.1; -; mRNA. DR EMBL; AB007869; BAA23705.1; ALT_INIT; mRNA. DR EMBL; BC001071; AAH01071.1; -; mRNA. DR CCDS; CCDS31411.1; -. DR RefSeq; NP_056139.1; NM_015324.3. DR PDB; 2ZFU; X-ray; 2.00 A; A/B=242-456. DR PDBsum; 2ZFU; -. DR AlphaFoldDB; O43159; -. DR SMR; O43159; -. DR BioGRID; 116954; 261. DR ComplexPortal; CPX-467; eNoSc complex. DR DIP; DIP-46686N; -. DR IntAct; O43159; 134. DR MINT; O43159; -. DR STRING; 9606.ENSP00000254605; -. DR GlyGen; O43159; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; O43159; -. DR PhosphoSitePlus; O43159; -. DR SwissPalm; O43159; -. DR BioMuta; RRP8; -. DR EPD; O43159; -. DR jPOST; O43159; -. DR MassIVE; O43159; -. DR MaxQB; O43159; -. DR PaxDb; 9606-ENSP00000254605; -. DR PeptideAtlas; O43159; -. DR ProteomicsDB; 48780; -. DR Pumba; O43159; -. DR Antibodypedia; 23905; 194 antibodies from 29 providers. DR DNASU; 23378; -. DR Ensembl; ENST00000254605.11; ENSP00000254605.6; ENSG00000132275.11. DR GeneID; 23378; -. DR KEGG; hsa:23378; -. DR MANE-Select; ENST00000254605.11; ENSP00000254605.6; NM_015324.4; NP_056139.1. DR UCSC; uc001med.4; human. DR AGR; HGNC:29030; -. DR CTD; 23378; -. DR DisGeNET; 23378; -. DR GeneCards; RRP8; -. DR HGNC; HGNC:29030; RRP8. DR HPA; ENSG00000132275; Low tissue specificity. DR MIM; 615818; gene. DR neXtProt; NX_O43159; -. DR OpenTargets; ENSG00000132275; -. DR PharmGKB; PA164725550; -. DR VEuPathDB; HostDB:ENSG00000132275; -. DR eggNOG; KOG3045; Eukaryota. DR GeneTree; ENSGT00390000006189; -. DR HOGENOM; CLU_027694_2_3_1; -. DR InParanoid; O43159; -. DR OMA; QNQVKKW; -. DR OrthoDB; 1694at2759; -. DR PhylomeDB; O43159; -. DR TreeFam; TF313749; -. DR BRENDA; 2.1.1.B128; 2681. DR PathwayCommons; O43159; -. DR Reactome; R-HSA-427359; SIRT1 negatively regulates rRNA expression. DR SignaLink; O43159; -. DR BioGRID-ORCS; 23378; 20 hits in 1162 CRISPR screens. DR ChiTaRS; RRP8; human. DR EvolutionaryTrace; O43159; -. DR GeneWiki; KIAA0409; -. DR GenomeRNAi; 23378; -. DR Pharos; O43159; Tbio. DR PRO; PR:O43159; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O43159; Protein. DR Bgee; ENSG00000132275; Expressed in muscle layer of sigmoid colon and 163 other cell types or tissues. DR ExpressionAtlas; O43159; baseline and differential. DR GO; GO:0005677; C:chromatin silencing complex; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0061773; C:eNoSc complex; IPI:ComplexPortal. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0033553; C:rDNA heterochromatin; IDA:UniProtKB. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; TAS:UniProtKB. DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; IMP:ComplexPortal. DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:ComplexPortal. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:ComplexPortal. DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:ComplexPortal. DR GO; GO:0000183; P:rDNA heterochromatin formation; IDA:UniProtKB. DR GO; GO:1903450; P:regulation of G1 to G0 transition; IMP:UniProtKB. DR GO; GO:0046015; P:regulation of transcription by glucose; IMP:UniProtKB. DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW. DR CDD; cd02440; AdoMet_MTases; 1. DR Gene3D; 1.10.10.2150; Ribosomal RNA-processing protein 8, N-terminal domain; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR007823; RRP8. DR InterPro; IPR042036; RRP8_N. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR InterPro; IPR023576; UbiE/COQ5_MeTrFase_CS. DR PANTHER; PTHR12787:SF0; RIBOSOMAL RNA-PROCESSING PROTEIN 8; 1. DR PANTHER; PTHR12787; UNCHARACTERIZED; 1. DR Pfam; PF05148; Methyltransf_8; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. DR SWISS-2DPAGE; O43159; -. DR Genevisible; O43159; HS. PE 1: Evidence at protein level; KW 3D-structure; Chromatin regulator; Methyltransferase; Nucleus; KW Phosphoprotein; Reference proteome; Repressor; rRNA processing; KW S-adenosyl-L-methionine; Transcription; Transcription regulation; KW Transferase. FT CHAIN 1..456 FT /note="Ribosomal RNA-processing protein 8" FT /id="PRO_0000084090" FT REGION 1..39 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 52..231 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 61..77 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 88..136 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 143..183 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 184..200 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 281 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT BINDING 316 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT BINDING 334 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT BINDING 346 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT BINDING 347 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT BINDING 363 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|PubMed:18485871, FT ECO:0007744|PDB:2ZFU" FT MOD_RES 62 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 64 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332" FT MOD_RES 104 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 171 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 176 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 223 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VARIANT 145 FT /note="A -> P (in dbSNP:rs11040934)" FT /id="VAR_051034" FT VARIANT 329 FT /note="P -> S (in dbSNP:rs17834692)" FT /id="VAR_051035" FT HELIX 244..260 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 263..272 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 274..288 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 295..304 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 312..316 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 321..325 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 330..336 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 342..345 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 357..364 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 371..381 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 382..392 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 394..396 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 400..409 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 412..418 FT /evidence="ECO:0007829|PDB:2ZFU" FT STRAND 425..431 FT /evidence="ECO:0007829|PDB:2ZFU" FT HELIX 444..446 FT /evidence="ECO:0007829|PDB:2ZFU" SQ SEQUENCE 456 AA; 50715 MW; 49251E2A488DA1C4 CRC64; MFEEPEWAEA APVAAGLGPV ISRPPPAASS QNKGSKRRQL LATLRALEAA SLSQHPPSLC ISDSEEEEEE RKKKCPKKAS FASASAEVGK KGKKKCQKQG PPCSDSEEEV ERKKKCHKQA LVGSDSAEDE KRKRKCQKHA PINSAQHLDN VDQTGPKAWK GSTTNDPPKQ SPGSTSPKPP HTLSRKQWRN RQKNKRRCKN KFQPPQVPDQ APAEAPTEKT EVSPVPRTDS HEARAGALRA RMAQRLDGAR FRYLNEQLYS GPSSAAQRLF QEDPEAFLLY HRGFQSQVKK WPLQPVDRIA RDLRQRPASL VVADFGCGDC RLASSIRNPV HCFDLASLDP RVTVCDMAQV PLEDESVDVA VFCLSLMGTN IRDFLEEANR VLKPGGLLKV AEVSSRFEDV RTFLRAVTKL GFKIVSKDLT NSHFFLFDFQ KTGPPLVGPK AQLSGLQLQP CLYKRR //