Q5RKV6 (EXOS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exosome complex component MTR3

Alternative name(s):
Exosome component 6
mRNA transport regulator 3 homolog
Short name=hMtr3
p11

Gene names

Name:	EXOSC6
Synonyms:	MTR3

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	272 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. Ref.8
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.
Subcellular location	Cytoplasm Probable. Nucleus › nucleolus Probable. Nucleus Probable.
Sequence similarities	Belongs to the RNase PH family.
Caution	The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.

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	DNA deamination Inferred from direct assay Ref.8. Source: UniProtKB exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Traceable author statement. Source: Reactome isotype switching Inferred from sequence or structural similarity. Source: UniProtKB 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.6. Source: UniProtKB nucleolus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	RNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 272

272

Exosome complex component MTR3

PRO_0000287478

Secondary structure

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272

Helix Strand Turn

Details...

Beta strand

47 – 53

7

Beta strand

57 – 59

3

Beta strand

61 – 70

10

Beta strand

95 – 102

8

Beta strand

106 – 109

4

Helix

116 – 130

15

Turn

131 – 133

3

Beta strand

143 – 152

10

Helix

157 – 172

16

Beta strand

176 – 178

3

Beta strand

181 – 184

4

Turn

201 – 203

3

Helix

204 – 206

3

Beta strand

208 – 216

9

Turn

217 – 220

4

Beta strand

221 – 228

8

Turn

234 – 237

4

Helix

238 – 267

30

Sequences

	Sequence		Length	Mass (Da)
	Q5RKV6 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: F31729E0D1545F94	FASTA	272	28,235
	10 20 30 40 50 60 MPGDHRRIRG PEESQPPQLY AADEEEAPGT RDPTRLRPVY ARAGLLSQAK GSAYLEAGGT 70 80 90 100 110 120 KVLCAVSGPR QAEGGERGGG PAGAGGEAPA ALRGRLLCDF RRAPFAGRRR RAPPGGCEER 130 140 150 160 170 180 ELALALQEAL EPAVRLGRYP RAQLEVSALL LEDGGSALAA ALTAAALALA DAGVEMYDLV 190 200 210 220 230 240 VGCGLSLAPG PAPTWLLDPT RLEEERAAAG LTVALMPVLN QVAGLLGSGE GGLTESWAEA 250 260 270 VRLGLEGCQR LYPVLQQSLV RAARRRGAAA QP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Tissue: Salivary gland.
[2]	"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: Salivary gland.
[3]	"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.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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].
[8]	"The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates." Basu U., Meng F.L., Keim C., Grinstein V., Pefanis E., Eccleston J., Zhang T., Myers D., Wasserman C.R., Wesemann D.R., Januszyk K., Gregory R.I., Deng H., Lima C.D., Alt F.W. Cell 144:353-363(2011) [PubMed: 21255825] [Abstract] Cited for: FUNCTION IN DEAMINATION OF TRANSCRIBED DNA SUBSTRATE.
[9]	"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.
[10]	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

AC009060 Genomic DNA. No translation available.
BC052252 mRNA. Translation: AAH52252.1.

IPI

IPI00073602.

RefSeq

NP_478126.1. NM_058219.2.

UniGene

Hs.660633.
Hs.728918.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NN6	X-ray	3.35	F	1-272	[»]

ProteinModelPortal

Q5RKV6.

SMR

Q5RKV6. Positions 29-260.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q5RKV6. 6 interactions.

STRING

Q5RKV6.

Polymorphism databases

DMDM

74736141.

Proteomic databases

PeptideAtlas

Q5RKV6.

PRIDE

Q5RKV6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000435634; ENSP00000398597; ENSG00000223496.

GeneID

118460.

KEGG

hsa:118460.

UCSC

uc002eym.1. human.

Organism-specific databases

CTD

118460.

GeneCards

GC16M070284.

H-InvDB

HIX0017377.

HGNC

HGNC:19055. EXOSC6.

MIM

606490. gene.

neXtProt

NX_Q5RKV6.

PharmGKB

PA134932096.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09362.

GeneTree

ENSGT00550000074804.

HOGENOM

HBG737187.

HOVERGEN

HBG057826.

InParanoid

Q5RKV6.

OMA

DHRRIRG.

OrthoDB

EOG4D7Z6K.

PhylomeDB

Q5RKV6.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q5RKV6.

Bgee

Q5RKV6.

CleanEx

HS_EXOSC6.

Genevestigator

Q5RKV6.

Family and domain databases

InterPro

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

KO

K12587.

Pfam

PF01138. RNase_PH. 1 hit.
[Graphical view]

SUPFAM

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

ProtoNet

Search...

Other

NextBio

80292.

SOURCE

Search...

Entry information

Entry name

EXOS6_HUMAN

Accession

Primary (citable) accession number: Q5RKV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 15, 2007
Last sequence update:	December 21, 2004
Last modified:	January 25, 2012
This is version 70 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.