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Q9NPD3 (EXOS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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 RRP41
Alternative name(s):
Exosome component 4
Ribosomal RNA-processing protein 41
p12A
Gene names
Name:EXOSC4
Synonyms:RRP41, SKI6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length245 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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. EXOSC4 binds to ARE-containing RNAs. Ref.8 Ref.9 Ref.10 Ref.13 Ref.15

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 DDX60. Ref.7 Ref.12 Ref.16

Subcellular location

Cytoplasm. Nucleusnucleolus. Nucleus 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.

Ontologies

Keywords
   Biological processrRNA processing
   Cellular componentCytoplasm
Exosome
Nucleus
   LigandRNA-binding
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA deamination

Inferred from direct assay Ref.15. 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 Ref.16. Source: MGI

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

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

histone mRNA catabolic process

Inferred from mutant phenotype Ref.10. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

maturation of 5.8S rRNA

Inferred from mutant phenotype Ref.13. Source: UniProtKB

nuclear mRNA surveillance

Inferred from mutant phenotype Ref.9. Source: UniProtKB

nuclear-transcribed mRNA catabolic process

Inferred from mutant phenotype Ref.9. Source: UniProtKB

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Traceable author statement. Source: Reactome

positive regulation of cell growth

Inferred from mutant phenotype Ref.9. Source: UniProtKB

rRNA processing

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

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

exosome (RNase complex)

Inferred from direct assay Ref.12. Source: UniProtKB

nucleolus

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

nucleus

Inferred from direct assay Ref.9. 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

AU-rich element binding

Inferred from direct assay Ref.8. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 20531386Ref.16. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 245244Exosome complex component RRP41
PRO_0000139958

Amino acid modifications

Modified residue21N-acetylalanine Ref.5 Ref.11 Ref.17 Ref.18

Secondary structure

........................................ 245
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NPD3 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 7A24E97897DAF313

FASTA24526,383
        10         20         30         40         50         60 
MAGLELLSDQ GYRVDGRRAG ELRKIQARMG VFAQADGSAY IEQGNTKALA VVYGPHEIRG 

        70         80         90        100        110        120 
SRARALPDRA LVNCQYSSAT FSTGERKRRP HGDRKSCEMG LQLRQTFEAA ILTQLHPRSQ 

       130        140        150        160        170        180 
IDIYVQVLQA DGGTYAACVN AATLAVLDAG IPMRDFVCAC SAGFVDGTAL ADLSHVEEAA 

       190        200        210        220        230        240 
GGPQLALALL PASGQIALLE MDARLHEDHL ERVLEAAAQA ARDVHTLLDR VVRQHVREAS 


ILLGD 

« 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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [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].
Tissue: Skin.
[5]Bienvenut W.V.
Submitted (OCT-2004) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-13, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[6]"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.
[7]"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.
[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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MRNA DEGRADATION, SUBCELLULAR LOCATION.
[10]"Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'."
Mullen T.E., Marzluff W.F.
Genes Dev. 22:50-65(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HISTONE MRNA DEGRADATION ACTIVITY.
[11]"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] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"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.
[13]"Addition of poly(A) and poly(A)-rich tails during RNA degradation in the cytoplasm of human cells."
Slomovic S., Fremder E., Staals R.H., Pruijn G.J., Schuster G.
Proc. Natl. Acad. Sci. U.S.A. 107:7407-7412(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RRNA MATURATION.
[14]"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].
[15]"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.
[16]"DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling."
Miyashita M., Oshiumi H., Matsumoto M., Seya T.
Mol. Cell. Biol. 31:3802-3819(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDX60.
[17]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"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.
[20]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
AF281133 mRNA. Translation: AAF82134.1.
AK000598 mRNA. Translation: BAA91279.1.
AC109322 Genomic DNA. No translation available.
BC002777 mRNA. Translation: AAH02777.1.
CCDSCCDS6414.1.
RefSeqNP_061910.1. NM_019037.2.
UniGeneHs.632041.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2NN6X-ray3.35B2-245[»]
ProteinModelPortalQ9NPD3.
SMRQ9NPD3. Positions 7-241.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120007. 39 interactions.
IntActQ9NPD3. 29 interactions.
MINTMINT-2818708.
STRING9606.ENSP00000315476.

PTM databases

PhosphoSiteQ9NPD3.

Polymorphism databases

DMDM14285756.

2D gel databases

SWISS-2DPAGEQ9NPD3.

Proteomic databases

MaxQBQ9NPD3.
PaxDbQ9NPD3.
PRIDEQ9NPD3.

Protocols and materials databases

DNASU54512.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000316052; ENSP00000315476; ENSG00000178896.
ENST00000568113; ENSP00000455706; ENSG00000260189.
GeneID54512.
KEGGhsa:54512.
UCSCuc003zau.3. human.

Organism-specific databases

CTD54512.
GeneCardsGC08P145133.
HGNCHGNC:18189. EXOSC4.
HPAHPA024792.
MIM606491. gene.
neXtProtNX_Q9NPD3.
PharmGKBPA134867931.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0689.
HOGENOMHOG000229515.
HOVERGENHBG051519.
InParanoidQ9NPD3.
KOK11600.
OMADYVCACT.
PhylomeDBQ9NPD3.
TreeFamTF313915.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9NPD3.
BgeeQ9NPD3.
CleanExHS_EXOSC4.
GenevestigatorQ9NPD3.

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

EvolutionaryTraceQ9NPD3.
GeneWikiExosome_component_4.
GenomeRNAi54512.
NextBio56896.
PROQ9NPD3.
SOURCESearch...

Entry information

Entry nameEXOS4_HUMAN
AccessionPrimary (citable) accession number: Q9NPD3
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 132 of the entry and version 3 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 chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM