Q9NQT4 (EXOS5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	235 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.7 Ref.12
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. Ref.8 Ref.13
Subcellular location	Nucleus › nucleolus. 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 process	rRNA processing
Cellular component	Cytoplasm Exosome Nucleus
Coding sequence diversity	Polymorphism
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA deamination Inferred from direct assay Ref.12. Source: UniProtKB exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Inferred from mutant phenotype Ref.7. Source: UniProtKB rRNA processing Non-traceable author statement Ref.1. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome exosome (RNase complex) Inferred from direct assay Ref.10. Source: UniProtKB nucleolus Non-traceable author statement Ref.1. Source: UniProtKB transcriptionally active chromatin Inferred from mutant phenotype. Source: UniProtKB
Molecular function	3'-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.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXOSC1	Q9Y3B2	10	EBI-371876,EBI-371892
EXOSC3	Q9NQT5	7	EBI-371876,EBI-371866
EXOSC8	Q96B26	4	EBI-371876,EBI-371922

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 235

235

Exosome complex component RRP46

PRO_0000139975

Amino acid modifications

Modified residue

20

1

Phosphoserine Ref.9

Modified residue

27

1

Phosphoserine By similarity

Natural variations

Natural variant

5

1

T → M. Ref.4
Corresponds to variant rs10853751 [ dbSNP | Ensembl ].

VAR_030788

Natural variant

33

1

C → W.
Corresponds to variant rs34500671 [ dbSNP | Ensembl ].

VAR_051868

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

235

Helix Strand Turn

Details...

Beta strand

31 – 36

6

Beta strand

45 – 48

4

Beta strand

53 – 56

4

Beta strand

61 – 63

3

Beta strand

74 – 81

8

Helix

90 – 105

16

Beta strand

111 – 124

14

Helix

129 – 143

15

Beta strand

155 – 159

5

Beta strand

165 – 168

4

Helix

171 – 176

6

Beta strand

178 – 186

9

Turn

187 – 189

3

Beta strand

194 – 198

5

Helix

204 – 231

28

Sequences

	Sequence		Length	Mass (Da)
	Q9NQT4 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: C3C1FCB39D85B1EE	FASTA	235	25,249
	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

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: 11110791] [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: 12359762] [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. , 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: 15057824] [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: 15489334] [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: 10465791] [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: 11719186] [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: 11782436] [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: 11812149] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH EXOSC1.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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]	"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.
[13]	"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: 21515746] [Abstract] Cited for: INTERACTION WITH GTPBP1.
[14]	"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.
[15]	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.

IPI

IPI00644775.

RefSeq

NP_064543.3. NM_020158.3.

UniGene

Hs.283741.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NN6	X-ray	3.35	D	1-235	[»]

ProteinModelPortal

Q9NQT4.

SMR

Q9NQT4. Positions 25-234.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29846N.

IntAct

Q9NQT4. 17 interactions.

MINT

MINT-1479651.

STRING

Q9NQT4.

PTM databases

PhosphoSite

Q9NQT4.

Polymorphism databases

DMDM

14285757.

Proteomic databases

PRIDE

Q9NQT4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000221233; ENSP00000221233; ENSG00000077348.

GeneID

56915.

KEGG

hsa:56915.

UCSC

uc002oqo.1. human.

Organism-specific databases

CTD

56915.

GeneCards

GC19M041892.

H-InvDB

HIX0015155.

HGNC

HGNC:24662. EXOSC5.

MIM

606492. gene.

neXtProt

NX_Q9NQT4.

PharmGKB

PA134890468.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16080.

GeneTree

ENSGT00550000075002.

HOGENOM

HBG737187.

HOVERGEN

HBG051520.

InParanoid

Q9NQT4.

OMA

GSYLECN.

OrthoDB

EOG4PZJ7M.

PhylomeDB

Q9NQT4.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9NQT4.

Bgee

Q9NQT4.

CleanEx

HS_EXOSC5.

Genevestigator

Q9NQT4.

GermOnline

ENSG00000077348. Homo sapiens.

Family and domain databases

InterPro

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

KO

K12590.

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

62403.

SOURCE

Search...

Entry information

Entry name

EXOS5_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 103 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.