Q08162 (RRP44_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Exosome complex exonuclease DIS3
EC=3.1.13.-
EC=3.1.26.-

Alternative name(s):
Chromosome disjunction protein 3
Ribosomal RNA-processing protein 44

Gene names

Name:	DIS3
Synonyms:	RRP44
Ordered Locus Names:	YOL021C
ORF Names:	O2197

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	1001 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 cryptic unstable transcripts (CUTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and in RNA surveillance pathways, preventing translation of aberrant mRNAs. 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. DIS3 has both 3'-5' exonuclease and endonuclease activities. The exonuclease activity of DIS3 is down-regulated upon association with Exo-9 possibly involving a conformational change in the catalytic domain and threading of the RNA substrate through the complex central channel. Structured substrates can be degraded if they have a 3' single-stranded extension sufficiently long (such as 35 nt poly(A)) to span the proposed complex inner RNA-binding path and to reach the exonuclease site provided by DIS3. Plays a role in mitotic control. Ref.1 Ref.4 Ref.11
Cofactor	Mg2+. Ref.11
Subunit structure	Component of the RNA exosome complex. The catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits DIS3 and RRP6 in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits and peripheral S1 domain-containing components CSL4, RRP4 and RRP40 located on the top of the ring structure. DIS3 associates at the respective bottom side with Exo-9. Interacts with GSP1. Ref.1 Ref.4 Ref.9 Ref.11
Subcellular location	Cytoplasm. Mitochondrion. Nucleus › nucleolus Ref.6 Ref.8 Ref.10.
Miscellaneous	Present with 606 molecules/cell in log phase SD medium. Ref.7 Mn2+ doesn't support the hydrolytic activity. Activity is KCl or NaCl dependent and activity is slightly increased in the presence of reducing agents such as DTT or beta-mercaptoethanol and doesn't vary notably between pH 6.8 and 8.8.
Sequence similarities	Belongs to the RNR ribonuclease family. Contains 1 S1 motif domain.
Caution	It was originally thought (Ref.4) that there are multiple subunits in the exosome that have exonuclease activity but it was later shown (Ref.11 and Ref.9) that only this DIS3/RRP44 subunit of the exosome core has this activity.

Ontologies

Keywords
Biological process	rRNA processing
Cellular component	Cytoplasm Exosome Mitochondrion Nucleus
Ligand	RNA-binding
Molecular function	Endonuclease Exonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) Inferred from mutant phenotype Ref.4. Source: SGD nonfunctional rRNA decay Inferred from mutant phenotype. Source: SGD nuclear mRNA surveillance Inferred from mutant phenotype. Source: SGD nuclear polyadenylation-dependent CUT catabolic process Inferred from mutant phenotype. Source: SGD nuclear polyadenylation-dependent mRNA catabolic process Inferred by curator Ref.5. Source: SGD nuclear polyadenylation-dependent rRNA catabolic process Inferred from mutant phenotype. Source: SGD nuclear polyadenylation-dependent tRNA catabolic process Inferred from direct assay. Source: SGD nuclear-transcribed mRNA catabolic process, 3'-5' exonucleolytic nonsense-mediated decay Inferred by curator Ref.5. Source: SGD nuclear-transcribed mRNA catabolic process, non-stop decay Inferred by curator Ref.5. Source: SGD polyadenylation-dependent snoRNA 3'-end processing Inferred by curator Ref.5. Source: SGD
Cellular component	cytoplasmic exosome (RNase complex) Inferred from direct assay Ref.5. Source: SGD mitochondrion Inferred from direct assay Ref.8Ref.10. Source: SGD nuclear exosome (RNase complex) Inferred from direct assay Ref.5. Source: SGD nucleolus Inferred from direct assay. Source: SGD
Molecular function	3'-5'-exoribonuclease activity Inferred from direct assay Ref.11. Source: SGD endoribonuclease activity Inferred from direct assay Ref.12. Source: SGD protein binding Inferred from physical interaction. Source: IntAct tRNA binding Inferred from direct assay. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SKI6	P46948	9	EBI-1740,EBI-1788

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1001

1001

Exosome complex exonuclease DIS3

PRO_0000166423

Regions

Domain

904 – 1001

98

S1 motif

Region

1 – 235

235

Endoribonuclease

Experimental info

Mutagenesis

47

1

C → S: Slow growth; when associated with S-52 and S-55. Ref.12

Mutagenesis

52

1

C → S: Slow growth; when associated with S-47 and S-55. Ref.12

Mutagenesis

55

1

C → S: Slow growth; when associated with S-47 and S-52. Ref.12

Mutagenesis

171

1

D → A: Abolishes endoribonucleolytic activity; no effect on growth. No growth; when associated with N-551. Ref.12

Mutagenesis

198

1

D → A: Abolishes endoribonucleolytic activity; no effect on growth. No growth; when associated with N-551. Ref.12

Mutagenesis

551

1

D → N: Exoribonucleolytic activity abolished. Accumulation of partially processed 5.8S rRNA and partially degraded 5' ETS. No growth; when associated with A-171. No growth; when associated with A-198. Ref.11 Ref.12 Ref.13

Secondary structure

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1001

Helix Strand Turn

Details...

Helix

261 – 269

9

Beta strand

272 – 280

9

Beta strand

282 – 284

3

Beta strand

287 – 290

4

Beta strand

293 – 297

5

Beta strand

299 – 303

5

Helix

304 – 307

4

Beta strand

315 – 320

6

Helix

323 – 325

3

Turn

336 – 338

3

Beta strand

389 – 397

9

Beta strand

402 – 407

6

Helix

409 – 411

3

Beta strand

420 – 428

9

Beta strand

434 – 438

5

Helix

441 – 444

4

Beta strand

447 – 455

9

Beta strand

464 – 475

12

Helix

478 – 487

10

Helix

497 – 500

4

Helix

507 – 509

3

Helix

519 – 524

6

Helix

526 – 530

5

Beta strand

531 – 533

3

Beta strand

540 – 546

7

Beta strand

552 – 558

7

Beta strand

564 – 571

8

Helix

573 – 576

4

Helix

582 – 590

9

Helix

606 – 609

4

Turn

610 – 612

3

Beta strand

619 – 630

12

Beta strand

636 – 653

18

Helix

654 – 662

9

Helix

669 – 690

22

Beta strand

701 – 705

5

Beta strand

707 – 710

4

Beta strand

712 – 717

6

Helix

722 – 745

24

Turn

747 – 749

3

Beta strand

751 – 755

5

Helix

760 – 763

4

Helix

764 – 774

11

Helix

783 – 791

9

Helix

801 – 810

10

Beta strand

817 – 820

4

Helix

821 – 823

3

Helix

826 – 829

4

Turn

832 – 835

4

Turn

845 – 847

3

Helix

849 – 861

13

Helix

869 – 872

4

Helix

874 – 908

35

Beta strand

912 – 922

11

Beta strand

925 – 929

5

Turn

931 – 933

3

Beta strand

936 – 940

5

Helix

941 – 944

4

Helix

948 – 950

3

Beta strand

952 – 954

3

Turn

955 – 958

4

Beta strand

959 – 962

4

Beta strand

971 – 974

4

Beta strand

978 – 983

6

Beta strand

995 – 997

3

Sequences

	Sequence		Length	Mass (Da)
	Q08162 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 00DD31BD2D6904F4	FASTA	1,001	113,707
	10 20 30 40 50 60 MSVPAIAPRR KRLADGLSVT QKVFVRSRNG GATKIVREHY LRSDIPCLSR SCTKCPQIVV 70 80 90 100 110 120 PDAQNELPKF ILSDSPLELS APIGKHYVVL DTNVVLQAID LLENPNCFFD VIVPQIVLDE 130 140 150 160 170 180 VRNKSYPVYT RLRTLCRDSD DHKRFIVFHN EFSEHTFVER LPNETINDRN DRAIRKTCQW 190 200 210 220 230 240 YSEHLKPYDI NVVLVTNDRL NREAATKEVE SNIITKSLVQ YIELLPNADD IRDSIPQMDS 250 260 270 280 290 300 FDKDLERDTF SDFTFPEYYS TARVMGGLKN GVLYQGNIQI SEYNFLEGSV SLPRFSKPVL 310 320 330 340 350 360 IVGQKNLNRA FNGDQVIVEL LPQSEWKAPS SIVLDSEHFD VNDNPDIEAG DDDDNNESSS 370 380 390 400 410 420 NTTVISDKQR RLLAKDAMIA QRSKKIQPTA KVVYIQRRSW RQYVGQLAPS SVDPQSSSTQ 430 440 450 460 470 480 NVFVILMDKC LPKVRIRTRR AAELLDKRIV ISIDSWPTTH KYPLGHFVRD LGTIESAQAE 490 500 510 520 530 540 TEALLLEHDV EYRPFSKKVL ECLPAEGHDW KAPTKLDDPE AVSKDPLLTK RKDLRDKLIC 550 560 570 580 590 600 SIDPPGCVDI DDALHAKKLP NGNWEVGVHI ADVTHFVKPG TALDAEGAAR GTSVYLVDKR 610 620 630 640 650 660 IDMLPMLLGT DLCSLKPYVD RFAFSVIWEL DDSANIVNVN FMKSVIRSRE AFSYEQAQLR 670 680 690 700 710 720 IDDKTQNDEL TMGMRALLKL SVKLKQKRLE AGALNLASPE VKVHMDSETS DPNEVEIKKL 730 740 750 760 770 780 LATNSLVEEF MLLANISVAR KIYDAFPQTA MLRRHAAPPS TNFEILNEML NTRKNMSISL 790 800 810 820 830 840 ESSKALADSL DRCVDPEDPY FNTLVRIMST RCMMAAQYFY SGAYSYPDFR HYGLAVDIYT 850 860 870 880 890 900 HFTSPIRRYC DVVAHRQLAG AIGYEPLSLT HRDKNKMDMI CRNINRKHRN AQFAGRASIE 910 920 930 940 950 960 YYVGQVMRNN ESTETGYVIK VFNNGIVVLV PKFGVEGLIR LDNLTEDPNS AAFDEVEYKL 970 980 990 1000 TFVPTNSDKP RDVYVFDKVE VQVRSVMDPI TSKRKAELLL K

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Dis3, implicated in mitotic control, binds directly to Ran and enhances the GEF activity of RCC1." Noguchi E., Hayashi N., Azuma Y., Seki T., Nakamura M., Nakashima N., Yanagida M., He X., Mueller U., Sazer S., Nishimoto T. EMBO J. 15:5595-5605(1996) [PubMed: 8896453] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INTERACTION WITH GSP1.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K. Nature 387:98-102(1997) [PubMed: 9169874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases." Mitchell P., Petfalski E., Shevchenko A., Mann M., Tollervey D. Cell 91:457-466(1997) [PubMed: 9390555] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT.
[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: IDENTIFICATION IN THE EXOSOME COMPLEX BY MASS SPECTROMETRY.
[6]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[7]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[8]	"The proteome of Saccharomyces cerevisiae mitochondria." Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed: 14576278] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Strain: ATCC 76625 / YPH499.
[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: EXOSOME EXONUCLEASE ACTIVITY, SUBUNIT.
[10]	"Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics." Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A. J. Proteome Res. 5:1543-1554(2006) [PubMed: 16823961] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"A single subunit, Dis3, is essentially responsible for yeast exosome core activity." Dziembowski A., Lorentzen E., Conti E., Seraphin B. Nat. Struct. Mol. Biol. 14:15-22(2007) [PubMed: 17173052] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, INTERACTION OF THE EXOSOME WITH RRP6 AND SKI7, SUBUNIT, MUTAGENESIS OF ASP-551.
[12]	"The exosome contains domains with specific endoribonuclease, exoribonuclease and cytoplasmic mRNA decay activities." Schaeffer D., Tsanova B., Barbas A., Reis F.P., Dastidar E.G., Sanchez-Rotunno M., Arraiano C.M., van Hoof A. Nat. Struct. Mol. Biol. 16:56-62(2009) [PubMed: 19060898] [Abstract] Cited for: CATALYTIC ACTIVITY AS ENDONUCLEASE, MUTAGENESIS OF CYS-47; CYS-52; CYS-55; ASP-171; ASP-198 AND ASP-551.
[13]	"Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family." Lorentzen E., Basquin J., Tomecki R., Dziembowski A., Conti E. Mol. Cell 29:717-728(2008) [PubMed: 18374646] [Abstract] Cited for: CATALYTIC ACTIVITY, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 242-1001 IN COMPLEX WITH SINGLE-STRANDED RNA AND MAGNESIUM ION, MUTAGENESIS OF ASP-551.
[14]	"The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation." Bonneau F., Basquin J., Ebert J., Lorentzen E., Conti E. Cell 139:547-559(2009) [PubMed: 19879841] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH SKI6 AND RRP45.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D76430 Genomic DNA. Translation: BAA11176.1.
Z74763 Genomic DNA. Translation: CAA99021.1.
BK006948 Genomic DNA. Translation: DAA10760.1.

PIR

S66704.

RefSeq

NP_014621.1. NM_001183275.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VNU	X-ray	2.30	D	242-1001	[»]
2WP8	X-ray	3.00	J	25-1001	[»]

ProteinModelPortal

Q08162.

SMR

Q08162. Positions 36-1001.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2355N.

IntAct

Q08162. 24 interactions.

MINT

MINT-614156.

STRING

Q08162.

Proteomic databases

PeptideAtlas

Q08162.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YOL021C; YOL021C; YOL021C.

GeneID

854138.

KEGG

sce:YOL021C.

NMPDR

fig|4932.3.peg.5714.

Organism-specific databases

CYGD

YOL021c.

SGD

S000005381. DIS3.

Phylogenomic databases

eggNOG

fuNOG04303.

GeneTree

EFGT00050000002831.

HOGENOM

HBG434190.

OMA

VDKRIDM.

OrthoDB

EOG4VHPFH.

Gene expression databases

ArrayExpress

Q08162.

Genevestigator

Q08162.

GermOnline

YOL021C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR006596. PINc_nuc-bd.
IPR003029. Rbsml_prot_S1_RNA-bd_dom.
IPR022967. RNA-binding_domain_S1.
IPR001900. RNase_II/R.
IPR022966. RNase_II/R_CS.
[Graphical view]

KO

K12585.

Pfam

PF00773. RNB. 1 hit.
[Graphical view]

SMART

SM00670. PINc. 1 hit.
SM00955. RNB. 1 hit.
SM00316. S1. 1 hit.
[Graphical view]

PROSITE

PS01175. RIBONUCLEASE_II. 1 hit.
PS50126. S1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

975871.

Entry information

Entry name

RRP44_YEAST

Accession

Primary (citable) accession number: Q08162
Secondary accession number(s): D6W244

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	December 14, 2011
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program