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Q9NQT4 (EXOS5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Exosome complex component RRP46
Alternative name(s):
Chronic myelogenous leukemia tumor antigen 28
Exosome component 5
Ribosomal RNA-processing protein 46
p12B
Gene names
Name:EXOSC5
Synonyms:CML28, RRP46
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length235 AA.
Sequence statusComplete.
Protein existenceEvidence 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 antisense 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.7 Ref.14

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. Interacts with EXOSC1. Interacts with GTPBP1. Interacts with ZC3HAV1. Interacts with DDX17 only in the presence of ZC3HAV1 in an RNA-independent manner. Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.15

Subcellular location

Nucleusnucleolus. Cytoplasm Probable. Nucleus Probable Ref.8.

Tissue specificity

Highly expressed in a variety of hematopoietic and epithelial tumor cell lines, but not in normal hematopoietic tissues or other normal tissue, with the exception of testis.

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 AAM75154.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processrRNA processing
   Cellular componentCytoplasm
Exosome
Nucleus
   Coding sequence diversityPolymorphism
   LigandRNA-binding
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA deamination

Inferred from direct assay Ref.14. Source: UniProtKB

RNA metabolic process

Traceable author statement. Source: Reactome

RNA phosphodiester bond hydrolysis, exonucleolytic

Non-traceable author statement Ref.1. Source: GOC

defense response to virus

Inferred from mutant phenotype PubMed 21791617. Source: MGI

exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay

Inferred from mutant phenotype Ref.7. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

mRNA metabolic process

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Traceable author statement. Source: Reactome

rRNA processing

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Non-traceable author statement Ref.1. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

exosome (RNase complex)

Inferred from direct assay Ref.11. Source: UniProtKB

nucleolus

Non-traceable author statement Ref.1. Source: UniProtKB

transcriptionally active chromatin

Inferred from mutant phenotype PubMed 20699273. Source: UniProtKB

   Molecular_function3'-5'-exoribonuclease activity

Non-traceable author statement Ref.1. Source: UniProtKB

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.8Ref.9. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 235235Exosome complex component RRP46
PRO_0000139975

Amino acid modifications

Modified residue201Phosphoserine Ref.12

Natural variations

Natural variant51T → M. Ref.4
Corresponds to variant rs10853751 [ dbSNP | Ensembl ].
VAR_030788
Natural variant331C → W.
Corresponds to variant rs34500671 [ dbSNP | Ensembl ].
VAR_051868

Secondary structure

................................ 235
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NQT4 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: C3C1FCB39D85B1EE

FASTA23525,249
        10         20         30         40         50         60 
MEEETHTDAK IRAENGTGSS PRGPGCSLRH FACEQNLLSR PDGSASFLQG DTSVLAGVYG 

        70         80         90        100        110        120 
PAEVKVSKEI FNKATLEVIL RPKIGLPGVA EKSRERLIRN TCEAVVLGTL HPRTSITVVL 

       130        140        150        160        170        180 
QVVSDAGSLL ACCLNAACMA LVDAGVPMRA LFCGVACALD SDGTLVLDPT SKQEKEARAV 

       190        200        210        220        230 
LTFALDSVER KLLMSSTKGL YSDTELQQCL AAAQAASQHV FRFYRESLQR RYSKS 

« Hide

References

« Hide 'large scale' references
[1]"Three novel components of the human exosome."
Brouwer R., Allmang C., Raijmakers R., van Aarssen Y., Egberts W.V., Petfalski E., van Venrooij W.J., Tollervey D., Pruijn G.J.M.
J. Biol. Chem. 276:6177-6184(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[2]"CML28 is a broadly immunogenic antigen, which is overexpressed in tumor cells."
Yang X.-F., Wu C.J., Chen L., Alyea E.P., Canning C., Kantoff P., Soiffer R.J., Dranoff G., Ritz J.
Cancer Res. 62:5517-5522(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-5.
Tissue: B-cell.
[5]"The yeast exosome and human PM-Scl are related complexes of 3'-->5' exonucleases."
Allmang C., Petfalski E., Podtelejnikov A., Mann M., Tollervey D., Mitchell P.
Genes Dev. 13:2148-2158(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[6]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RNA EXOSOME CORE COMPLEX.
[7]"The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements."
Mukherjee D., Gao M., O'Connor J.P., Raijmakers R., Pruijn G., Lutz C.S., Wilusz J.
EMBO J. 21:165-174(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYTOPLASMIC MRNA DEGRADATION.
[8]"Protein-protein interactions of hCsl4p with other human exosome subunits."
Raijmakers R., Noordman Y.E., van Venrooij W.J., Pruijn G.J.M.
J. Mol. Biol. 315:809-818(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH EXOSC1.
[9]"The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA."
Guo X., Ma J., Sun J., Gao G.
Proc. Natl. Acad. Sci. U.S.A. 104:151-156(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZC3HAV1.
[10]"p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein."
Chen G., Guo X., Lv F., Xu Y., Gao G.
Proc. Natl. Acad. Sci. U.S.A. 105:4352-4357(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX17.
[11]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE RNA EXOSOME COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEAMINATION OF TRANSCRIBED DNA SUBSTRATE.
[15]"Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs."
Woo K.C., Kim T.D., Lee K.H., Kim D.Y., Kim S., Lee H.R., Kang H.J., Chung S.J., Senju S., Nishimura Y., Kim K.T.
FASEB J. 25:2757-2769(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GTPBP1.
[16]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Reconstitution, activities, and structure of the eukaryotic RNA exosome."
Liu Q., Greimann J.C., Lima C.D.
Cell 127:1223-1237(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS), LACK OF CATALYTIC ACTIVITY, RECONSTITUTION OF THE RNA EXOSOME CORE COMPLEX.
[18]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
AF281134 mRNA. Translation: AAF82135.1.
AF285785 mRNA. Translation: AAM75154.1. Different initiation.
AC011462 Genomic DNA. No translation available.
BC007742 mRNA. Translation: AAH07742.1.
BC107696 mRNA. Translation: AAI07697.1.
CCDSCCDS12580.1.
RefSeqNP_064543.3. NM_020158.3.
UniGeneHs.283741.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2NN6X-ray3.35D1-235[»]
ProteinModelPortalQ9NQT4.
SMRQ9NQT4. Positions 25-234.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121243. 30 interactions.
DIPDIP-29846N.
IntActQ9NQT4. 21 interactions.
MINTMINT-1479651.
STRING9606.ENSP00000221233.

PTM databases

PhosphoSiteQ9NQT4.

Polymorphism databases

DMDM14285757.

Proteomic databases

MaxQBQ9NQT4.
PaxDbQ9NQT4.
PRIDEQ9NQT4.

Protocols and materials databases

DNASU56915.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221233; ENSP00000221233; ENSG00000077348.
GeneID56915.
KEGGhsa:56915.
UCSCuc002oqo.3. human.

Organism-specific databases

CTD56915.
GeneCardsGC19M041892.
HGNCHGNC:24662. EXOSC5.
HPAHPA053150.
MIM606492. gene.
neXtProtNX_Q9NQT4.
PharmGKBPA134890468.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0689.
HOGENOMHOG000229515.
HOVERGENHBG051520.
InParanoidQ9NQT4.
KOK12590.
OMATCEASLL.
PhylomeDBQ9NQT4.
TreeFamTF315920.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9NQT4.
BgeeQ9NQT4.
CleanExHS_EXOSC5.
GenevestigatorQ9NQT4.

Family and domain databases

Gene3D3.30.230.70. 1 hit.
InterProIPR001247. ExoRNase_PH_dom1.
IPR015847. ExoRNase_PH_dom2.
IPR027408. PNPase/RNase_PH_dom.
IPR020568. Ribosomal_S5_D2-typ_fold.
[Graphical view]
PfamPF01138. RNase_PH. 1 hit.
PF03725. RNase_PH_C. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55666. SSF55666. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9NQT4.
GeneWikiExosome_component_5.
GenomeRNAi56915.
NextBio62403.
PROQ9NQT4.
SOURCESearch...

Entry information

Entry nameEXOS5_HUMAN
AccessionPrimary (citable) accession number: Q9NQT4
Secondary accession number(s): Q32Q81, Q8NG16, Q96I89
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM