Q9NPD3 (EXOS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exosome complex component RRP41

Alternative name(s):
Exosome component 4
Ribosomal RNA-processing protein 41
p12A

Gene names

Name:	EXOSC4
Synonyms:	RRP41, SKI6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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 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. Nucleus › nucleolus. 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 process	rRNA processing
Cellular component	Cytoplasm Exosome Nucleus
Ligand	RNA-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	DNA 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_component	cytoplasm 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_function	3'-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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXOSC1	Q9Y3B2	4	EBI-371823,EBI-371892
EXOSC10	Q01780	3	EBI-371823,EBI-358236
EXOSC2	Q13868	5	EBI-371823,EBI-301735
EXOSC3	Q9NQT5	4	EBI-371823,EBI-371866
EXOSC9	Q06265	3	EBI-371823,EBI-347966

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 245

244

Exosome complex component RRP41

PRO_0000139958

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.5 Ref.11 Ref.17 Ref.18

Secondary structure

1

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245

Helix Strand Turn

Details...

Beta strand

14 – 17

4

Beta strand

25 – 30

6

Beta strand

32 – 45

14

Beta strand

47 – 57

11

Beta strand

60 – 62

3

Beta strand

72 – 78

7

Turn

80 – 82

3

Beta strand

83 – 85

3

Turn

89 – 91

3

Helix

94 – 109

16

Helix

113 – 115

3

Beta strand

119 – 129

11

Helix

134 – 148

15

Beta strand

158 – 165

8

Beta strand

168 – 172

5

Helix

175 – 178

4

Beta strand

185 – 189

5

Turn

191 – 193

3

Beta strand

198 – 201

4

Helix

210 – 239

30

Sequences

	Sequence		Length	Mass (Da)
	Q9NPD3 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 7A24E97897DAF313	FASTA	245	26,383
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

CCDS

CCDS6414.1.

RefSeq

NP_061910.1. NM_019037.2.

UniGene

Hs.632041.

3D structure databases

PDBe
RCSB-PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NN6	X-ray	3.35	B	2-245	[»]

ProteinModelPortal

Q9NPD3.

SMR

Q9NPD3. Positions 7-241.

ModBase

Search...

MobiDB

Search...

Protein-protein interaction databases

BioGrid

120007. 39 interactions.

IntAct

Q9NPD3. 29 interactions.

MINT

MINT-2818708.

STRING

9606.ENSP00000315476.

PTM databases

PhosphoSite

Q9NPD3.

Polymorphism databases

DMDM

14285756.

2D gel databases

SWISS-2DPAGE

Q9NPD3.

Proteomic databases

MaxQB

Q9NPD3.

PaxDb

Q9NPD3.

PRIDE

Q9NPD3.

Protocols and materials databases

DNASU

54512.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000316052; ENSP00000315476; ENSG00000178896.
ENST00000568113; ENSP00000455706; ENSG00000260189.

GeneID

54512.

KEGG

hsa:54512.

UCSC

uc003zau.3. human.

Organism-specific databases

CTD

54512.

GeneCards

GC08P145133.

HGNC

HGNC:18189. EXOSC4.

HPA

HPA024792.

MIM

606491. gene.

neXtProt

NX_Q9NPD3.

PharmGKB

PA134867931.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0689.

HOGENOM

HOG000229515.

HOVERGEN

HBG051519.

InParanoid

Q9NPD3.

KO

K11600.

OMA

DYVCACT.

PhylomeDB

Q9NPD3.

TreeFam

TF313915.

Enzyme and pathway databases

Reactome

REACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9NPD3.

Bgee

Q9NPD3.

CleanEx

HS_EXOSC4.

Genevestigator

Q9NPD3.

Family and domain databases

Gene3D

3.30.230.70. 1 hit.

InterPro

IPR001247. ExoRNase_PH_dom1.
IPR015847. ExoRNase_PH_dom2.
IPR027408. PNPase/RNase_PH_dom.
IPR020568. Ribosomal_S5_D2-typ_fold.
[Graphical view]

Pfam

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

SUPFAM

SSF54211. SSF54211. 1 hit.
SSF55666. SSF55666. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q9NPD3.

GeneWiki

Exosome_component_4.

GenomeRNAi

54512.

NextBio

56896.

PRO

Q9NPD3.

SOURCE

Search...

Entry information

Entry name

EXOS4_HUMAN

Accession

Primary (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 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.