Reviewed, UniProtKB/Swiss-Prot O43159 (RRP8_HUMAN)

Names and origin

Protein names

Recommended name:
    Ribosomal RNA-processing protein 8
    EC=2.1.1.-
Alternative name(s):
    Nucleomethylin
    Cerebral protein 1

Gene names

Name:	RRP8
Synonyms:	KIAA0409, NML
ORF Names:	hucep-1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	456 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD+/NADP+ ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and probably acts as a methyltransferase. Its substrates are however unknown. Ref.15
Subunit structure	Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8.
Subcellular location	Nucleus › nucleolus. Nucleus › nucleolus. Note: Localizes at rDNA locus. Ref.15 Ref.4 Ref.5
Sequence similarities	Belongs to the methyltransferase superfamily. RRP8 family.

Ontologies

Keywords
Biological process	Transcription Transcription regulation rRNA processing
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW chromatin silencing at rDNA Ref.15 Inferred from direct assay. Source: UniProtKB rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	chromatin silencing complex Ref.15 Inferred from direct assay. Source: UniProtKB nucleolus Ref.15 Inferred from direct assay. Source: UniProtKB rDNA heterochromatin Ref.15 Inferred from direct assay. Source: UniProtKB
Molecular function	S-adenosylmethionine-dependent methyltransferase activity Ref.15 Traceable author statement. Source: UniProtKB methylated histone residue binding Ref.15 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SIRT1	Q96EB6	1	EBI-2008793,EBI-1802965
SUV39H1	O43463	1	EBI-2008793,EBI-349968

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 456

456

Ribosomal RNA-processing protein 8

PRO_0000084090

Regions

Compositional bias

65 – 70

6

Poly-Glu

Sites

Binding site

281

1

S-adenosyl-L-methionine

Binding site

316

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

334

1

S-adenosyl-L-methionine

Binding site

346

1

S-adenosyl-L-methionine

Binding site

347

1

S-adenosyl-L-methionine

Binding site

363

1

S-adenosyl-L-methionine; via carbonyl oxygen

Amino acid modifications

Modified residue

58

1

Phosphoserine By similarity

Modified residue

62

1

Phosphoserine Ref.6 Ref.11 Ref.12 Ref.13 Ref.14

Modified residue

64

1

Phosphoserine Ref.6 Ref.11 Ref.12 Ref.13 Ref.14

Modified residue

104

1

Phosphoserine Ref.6 Ref.13

Modified residue

106

1

Phosphoserine Ref.6 Ref.13

Modified residue

124

1

Phosphoserine Ref.13 Ref.9

Modified residue

126

1

Phosphoserine Ref.13 Ref.9 Ref.10

Modified residue

171

1

Phosphoserine Ref.12 Ref.8

Modified residue

175

1

Phosphothreonine Ref.12

Modified residue

176

1

Phosphoserine Ref.8

Modified residue

223

1

Phosphoserine Ref.12 Ref.7

Natural variations

Natural variant

145

1

A → P: dbSNP rs11040934.

VAR_051034

Natural variant

329

1

P → S: dbSNP rs17834692.

VAR_051035

Secondary structure

1

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456

Helix Strand Turn

Details...

Turn

244 – 246

3

Helix

250 – 259

10

Helix

263 – 272

10

Helix

274 – 281

8

Helix

285 – 288

4

Beta strand

291 – 293

3

Helix

295 – 304

10

Beta strand

312 – 314

3

Helix

321 – 325

5

Beta strand

330 – 336

7

Beta strand

342 – 345

4

Beta strand

357 – 364

8

Helix

371 – 381

11

Beta strand

388 – 392

5

Helix

394 – 396

3

Helix

400 – 409

10

Beta strand

413 – 418

6

Beta strand

425 – 430

6

Sequences

	Sequence		Length	Mass (Da)
	O43159-1 [UniParc]. Last modified April 26, 2005. Version 2. Checksum: 49251E2A488DA1C4	FASTA	456	50,715
	10 20 30 40 50 60 MFEEPEWAEA APVAAGLGPV ISRPPPAASS QNKGSKRRQL LATLRALEAA SLSQHPPSLC 70 80 90 100 110 120 ISDSEEEEEE RKKKCPKKAS FASASAEVGK KGKKKCQKQG PPCSDSEEEV ERKKKCHKQA 130 140 150 160 170 180 LVGSDSAEDE KRKRKCQKHA PINSAQHLDN VDQTGPKAWK GSTTNDPPKQ SPGSTSPKPP 190 200 210 220 230 240 HTLSRKQWRN RQKNKRRCKN KFQPPQVPDQ APAEAPTEKT EVSPVPRTDS HEARAGALRA 250 260 270 280 290 300 RMAQRLDGAR FRYLNEQLYS GPSSAAQRLF QEDPEAFLLY HRGFQSQVKK WPLQPVDRIA 310 320 330 340 350 360 RDLRQRPASL VVADFGCGDC RLASSIRNPV HCFDLASLDP RVTVCDMAQV PLEDESVDVA 370 380 390 400 410 420 VFCLSLMGTN IRDFLEEANR VLKPGGLLKV AEVSSRFEDV RTFLRAVTKL GFKIVSKDLT 430 440 450 NSHFFLFDFQ KTGPPLVGPK AQLSGLQLQP CLYKRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of a novel gene which is expressed in the human brain." Yazaki M., Takayama K., Matsumoto K., Yoshimoto M. Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed: 9455477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed: 12429849] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[5]	"Directed proteomic analysis of the human nucleolus." Andersen J.S., Lyon C.E., Fox A.H., Leung A.K.L., Lam Y.W., Steen H., Mann M., Lamond A.I. Curr. Biol. 12:1-11(2002) [PubMed: 11790298] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-64; SER-104 AND SER-106, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171 AND SER-176, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124 AND SER-126, MASS SPECTROMETRY.
[10]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, MASS SPECTROMETRY.
[11]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-64, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-64; SER-171; THR-175 AND SER-223, MASS SPECTROMETRY.
[13]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62; SER-64; SER-104; SER-106; SER-124 AND SER-126, MASS SPECTROMETRY.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62 AND SER-64, MASS SPECTROMETRY. Tissue: T-cell.
[15]	"Epigenetic control of rDNA loci in response to intracellular energy status." Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K., Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A., Kimura K., Shimizu T., Yanagisawa J. Cell 133:627-639(2008) [PubMed: 18485871] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 242-456 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, SUBCELLULAR LOCATION, H3K9ME2-BINDING.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D87060 mRNA. Translation: BAB46916.1.
AB007869 mRNA. Translation: BAA23705.1. Different initiation.
BC001071 mRNA. Translation: AAH01071.1.

IPI

IPI00304932.

RefSeq

NP_056139.1.

UniGene

Hs.652255

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZFU	X-ray	2.00	A/B	242-456	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O43159. 4 interactions.

STRING

O43159.

PTM databases

PhosphoSite

O43159.

2-D gel databases

SWISS-2DPAGE

O43159.

Proteomic databases

PeptideAtlas

O43159.

PRIDE

O43159.

Genome annotation databases

Ensembl

ENST00000254605; ENSP00000254605; ENSG00000132275; Homo sapiens. [Genome view]

GeneID

23378.

KEGG

hsa:23378.

UCSC

uc001med.1. human.

Organism-specific databases

CTD

23378.

GeneCards

GC11M006573.

H-InvDB

HIX0009407.

HGNC

HGNC:29030. RRP8.

PharmGKB

PA142671626.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19436.

HOVERGEN

O43159.

InParanoid

O43159.

OMA

MGTNIRD.

OrthoDB

EOG92Z79B.

PhylomeDB

O43159.

Gene expression databases

ArrayExpress

O43159.

Bgee

O43159.

CleanEx

HS_KIAA0409.

Genevestigator

O43159.

GermOnline

ENSG00000132275. Homo sapiens.

Family and domain databases

InterPro

IPR007823. Methyltransferase-rel.
IPR004033. UbiE/COQ5_MeTrFase.
[Graphical view]

PANTHER

PTHR12787. mtransfer. 1 hit.

Pfam

PF05148. Methyltransf_8. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

45466.

Entry information

Entry name

RRP8_HUMAN

Accession

Primary (citable) accession number: O43159
Secondary accession number(s): Q7KZ78, Q9BVM6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	April 26, 2005
Last modified:	February 9, 2010
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.