RRP8_HUMAN
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 03-AUG-2022, entry version 179.
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};
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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; 245.
DR ComplexPortal; CPX-467; eNoSc complex.
DR DIP; DIP-46686N; -.
DR IntAct; O43159; 133.
DR MINT; O43159; -.
DR STRING; 9606.ENSP00000254605; -.
DR GlyGen; O43159; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43159; -.
DR PhosphoSitePlus; O43159; -.
DR BioMuta; RRP8; -.
DR SWISS-2DPAGE; O43159; -.
DR EPD; O43159; -.
DR jPOST; O43159; -.
DR MassIVE; O43159; -.
DR MaxQB; O43159; -.
DR PaxDb; O43159; -.
DR PeptideAtlas; O43159; -.
DR PRIDE; O43159; -.
DR ProteomicsDB; 48780; -.
DR Antibodypedia; 23905; 154 antibodies from 28 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 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; 945819at2759; -.
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 1084 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 161 other tissues.
DR ExpressionAtlas; O43159; baseline and differential.
DR Genevisible; O43159; HS.
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 transcription, DNA-templated; IMP:ComplexPortal.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:ComplexPortal.
DR GO; GO:0031062; P:positive regulation of histone methylation; IMP:ComplexPortal.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; 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 Gene3D; 1.10.10.2150; -; 1.
DR Gene3D; 3.40.50.150; -; 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; PTHR12787; 1.
DR Pfam; PF05148; Methyltransf_8; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
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
