Q96B26 (EXOS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exosome complex component RRP43

Alternative name(s):
Exosome component 8
Opa-interacting protein 2
Short name=OIP-2
Ribosomal RNA-processing protein 43
p9

Gene names

Name:	EXOSC8
Synonyms:	OIP2, RRP43

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	276 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as anti-sense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC8 binds to ARE-containing RNAs. Ref.8 Ref.9
Subunit structure	Component of the RNA exosome complex. Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Binds outer membrane protein opap from Neisseria gonorrhoeae.
Subcellular location	Cytoplasm. Nucleus. Nucleus › nucleolus By similarity Ref.9.
Sequence similarities	Belongs to the RNase PH family.
Caution	The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.
Sequence caution	The sequence CAI14013.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence EAX08581.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	rRNA processing
Cellular component	Cytoplasm Exosome Nucleus
Ligand	RNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Traceable author statement. Source: Reactome rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome exosome (RNase complex) Inferred from direct assay Ref.10. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	AU-rich element binding Inferred from direct assay Ref.8. Source: UniProtKB protein binding Inferred from physical interaction Ref.6Ref.10. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXOSC3	Q9NQT5	3	EBI-371922,EBI-371866
EXOSC5	Q9NQT4	4	EBI-371922,EBI-371876

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 276

276

Exosome complex component RRP43

PRO_0000139967

Experimental info

Sequence conflict

265 – 276

12

LMDEV…SMKPK → TDG in AAC39558. Ref.4

Secondary structure

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276

Helix Strand Turn

Details...

Helix

11 – 19

9

Beta strand

49 – 52

4

Beta strand

57 – 60

4

Beta strand

63 – 66

4

Beta strand

71 – 73

3

Beta strand

80 – 84

5

Beta strand

87 – 89

3

Helix

101 – 116

16

Helix

121 – 124

4

Beta strand

133 – 143

11

Helix

150 – 161

12

Beta strand

172 – 175

4

Beta strand

194 – 199

6

Turn

202 – 204

3

Beta strand

207 – 209

3

Turn

214 – 216

3

Beta strand

222 – 226

5

Beta strand

232 – 237

6

Helix

247 – 267

21

Turn

268 – 273

6

Sequences

	Sequence		Length	Mass (Da)
	Q96B26 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: FC8F5BAE74A1FF55	FASTA	276	30,040
	10 20 30 40 50 60 MAAGFKTVEP LEYYRRFLKE NCRPDGRELG EFRTTTVNIG SISTADGSAL VKLGNTTVIC 70 80 90 100 110 120 GVKAEFAAPS TDAPDKGYVV PNVDLPPLCS SRFRSGPPGE EAQVASQFIA DVIENSQIIQ 130 140 150 160 170 180 KEDLCISPGK LVWVLYCDLI CLDYDGNILD ACTFALLAAL KNVQLPEVTI NEETALAEVN 190 200 210 220 230 240 LKKKSYLNIR THPVATSFAV FDDTLLIVDP TGEEEHLATG TLTIVMDEEG KLCCLHKPGG 250 260 270 SGLTGAKLQD CMSRAVTRHK EVKKLMDEVI KSMKPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]. Tissue: Uterus.
[4]	"Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth." Williams J.M., Chen G.-C., Zhu L., Rest R.F. Mol. Microbiol. 27:171-186(1998) [PubMed: 9466265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-276.
[5]	"AU binding proteins recruit the exosome to degrade ARE-containing mRNAs." Chen C.-Y., Gherzi R., Ong S.-E., Chan E.L., Raijmakers R., Pruijn G.J.M., Stoecklin G., Moroni C., Mann M., Karin M. Cell 107:451-464(2001) [PubMed: 11719186] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RNA EXOSOME CORE COMPLEX.
[6]	"Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring." Raijmakers R., Vree Egberts W., van Venrooij W.J., Pruijn G.J.M. J. Mol. Biol. 323:653-663(2002) [PubMed: 12419256] [Abstract] Cited for: PROTEIN INTERACTION.
[7]	"A protein interaction framework for human mRNA degradation." Lehner B., Sanderson C.M. Genome Res. 14:1315-1323(2004) [PubMed: 15231747] [Abstract] Cited for: PROTEIN INTERACTION.
[8]	"Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome." Anderson J.R., Mukherjee D., Muthukumaraswamy K., Moraes K.C., Wilusz C.J., Wilusz J. RNA 12:1810-1816(2006) [PubMed: 16912217] [Abstract] Cited for: FUNCTION IN ARE-CONTAINING MRNA BINDING.
[9]	"Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways." van Dijk E.L., Schilders G., Pruijn G.J. RNA 13:1027-1035(2007) [PubMed: 17545563] [Abstract] Cited for: FUNCTION IN MRNA DEGRADATION, SUBCELLULAR LOCATION.
[10]	"Dis3-like 1: a novel exoribonuclease associated with the human exosome." Staals R.H., Bronkhorst A.W., Schilders G., Slomovic S., Schuster G., Heck A.J., Raijmakers R., Pruijn G.J. EMBO J. 29:2358-2367(2010) [PubMed: 20531389] [Abstract] Cited for: IDENTIFICATION IN THE RNA EXOSOME COMPLEX, MASS SPECTROMETRY.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Reconstitution, activities, and structure of the eukaryotic RNA exosome." Liu Q., Greimann J.C., Lima C.D. Cell 127:1223-1237(2006) [PubMed: 17174896] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS), LACK OF CATALYTIC ACTIVITY, RECONSTITUTION OF THE RNA EXOSOME CORE COMPLEX.
[13]	Erratum Liu Q., Greimann J.C., Lima C.D. Cell 131:188-189(2007)
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AL138706 Genomic DNA. Translation: CAI14013.1. Sequence problems.
CH471075 Genomic DNA. Translation: EAX08581.1. Sequence problems.
BC020773 mRNA. Translation: AAH20773.1.
AF025438 mRNA. Translation: AAC39558.1.

IPI

IPI00552920.

RefSeq

NP_852480.1. NM_181503.2.

UniGene

Hs.294041.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NN6	X-ray	3.35	C	1-276	[»]

ProteinModelPortal

Q96B26.

SMR

Q96B26. Positions 7-275.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q96B26. 23 interactions.

STRING

Q96B26.

Polymorphism databases

DMDM

21759409.

2D gel databases

SWISS-2DPAGE

Q96B26.

Proteomic databases

PeptideAtlas

Q96B26.

PRIDE

Q96B26.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000389704; ENSP00000374354; ENSG00000120699.

GeneID

11340.

KEGG

hsa:11340.

UCSC

uc001uwa.1. human.

Organism-specific databases

CTD

11340.

GeneCards

GC13P037572.

H-InvDB

HIX0017428.

HGNC

HGNC:17035. EXOSC8.

MIM

606019. gene.

neXtProt

NX_Q96B26.

PharmGKB

PA134922251.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04174.

GeneTree

ENSGT00530000063093.

HOGENOM

HBG737187.

HOVERGEN

HBG051522.

InParanoid

Q96B26.

OMA

FAVFDDT.

OrthoDB

EOG47M1ZJ.

PhylomeDB

Q96B26.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q96B26.

Bgee

Q96B26.

CleanEx

HS_EXOSC8.

Genevestigator

Q96B26.

GermOnline

ENSG00000120699. Homo sapiens.

Family and domain databases

InterPro

IPR001247. ExoRNase_PH_dom1.
IPR015847. ExoRNase_PH_dom2.
IPR020568. Ribosomal_S5_D2-typ_fold.
[Graphical view]

KO

K12586.

Pfam

PF01138. RNase_PH. 1 hit.
PF03725. RNase_PH_C. 1 hit.
[Graphical view]

SUPFAM

SSF55666. 3_ExoRNase. 1 hit.
SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit.

ProtoNet

Search...

Other

NextBio

43089.

SOURCE

Search...

Entry information

Entry name

EXOS8_HUMAN

Accession

Primary (citable) accession number: Q96B26
Secondary accession number(s): O43480, Q5TBA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2002
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.