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Protein

Exosome complex exonuclease RRP44

Gene

DIS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Putative 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. DIS3 has both 3'-5' exonuclease and endonuclease activities.2 Publications

Miscellaneous

The association of DIS3 with the RNA exosome complex appears to be weak explaining its absence in some complex purifications.

Cofactori

Mg2+1 Publication, Mn2+1 Publication

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • endonuclease activity Source: UniProtKB
  • guanyl-nucleotide exchange factor activity Source: UniProtKB
  • RNA binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionEndonuclease, Exonuclease, Hydrolase, Nuclease, RNA-binding
Biological processrRNA processing
LigandMagnesium, Manganese

Enzyme and pathway databases

ReactomeiR-HSA-380994 ATF4 activates genes
R-HSA-429958 mRNA decay by 3' to 5' exoribonuclease
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol

Names & Taxonomyi

Protein namesi
Recommended name:
Exosome complex exonuclease RRP44 (EC:3.1.13.-, EC:3.1.26.-)
Alternative name(s):
Protein DIS3 homolog
Ribosomal RNA-processing protein 44
Gene namesi
Name:DIS3
Synonyms:KIAA1008, RRP44
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000083520.14
HGNCiHGNC:20604 DIS3
MIMi607533 gene
neXtProtiNX_Q9Y2L1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Exosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi146D → N: Loss of endonuclease activity; when associated with N-487. 1 Publication1
Mutagenesisi487D → N: Loss of exonuclease activity. Loss of endonuclease activity; when associated with N-146. 1 Publication1

Organism-specific databases

DisGeNETi22894
OpenTargetsiENSG00000083520
PharmGKBiPA162383628

Polymorphism and mutation databases

BioMutaiDIS3
DMDMi73620993

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001664191 – 958Exosome complex exonuclease RRP44Add BLAST958

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei18N6-acetyllysineCombined sources1
Modified residuei215PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y2L1
PaxDbiQ9Y2L1
PeptideAtlasiQ9Y2L1
PRIDEiQ9Y2L1
ProteomicsDBi85832
85833 [Q9Y2L1-2]

2D gel databases

SWISS-2DPAGEiQ9Y2L1

PTM databases

iPTMnetiQ9Y2L1
PhosphoSitePlusiQ9Y2L1
SwissPalmiQ9Y2L1

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000083520 Expressed in 211 organ(s), highest expression level in sperm
CleanExiHS_DIS3
ExpressionAtlasiQ9Y2L1 baseline and differential
GenevisibleiQ9Y2L1 HS

Organism-specific databases

HPAiHPA039281
HPA058762

Interactioni

Subunit structurei

Component of the RNA exosome complex. The catalytically inactive RNA exosome core (Exo-9) complex is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms.

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116559, 66 interactors
ComplexPortaliCPX-476 Nuclear exosome complex, DIS3-EXOSC10 variant
CPX-593 Exosome complex, DIS3 variant
CORUMiQ9Y2L1
IntActiQ9Y2L1, 21 interactors
MINTiQ9Y2L1
STRINGi9606.ENSP00000366997

Structurei

Secondary structure

1958
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y2L1
SMRiQ9Y2L1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 182PINcAdd BLAST119

Sequence similaritiesi

Belongs to the RNR ribonuclease family.Curated

Phylogenomic databases

eggNOGiKOG2102 Eukaryota
COG0557 LUCA
GeneTreeiENSGT00530000063106
HOVERGENiHBG059397
InParanoidiQ9Y2L1
KOiK12585
OMAiYVFVNEH
OrthoDBiEOG091G06EJ
PhylomeDBiQ9Y2L1
TreeFamiTF105755

Family and domain databases

InterProiView protein in InterPro
IPR012340 NA-bd_OB-fold
IPR029060 PIN-like_dom_sf
IPR002716 PIN_dom
IPR001900 RNase_II/R
IPR022966 RNase_II/R_CS
IPR033771 Rrp44_CSD1
IPR033770 RRP44_S1
PfamiView protein in Pfam
PF13638 PIN_4, 1 hit
PF00773 RNB, 1 hit
PF17216 Rrp44_CSD1, 1 hit
PF17215 Rrp44_S1, 1 hit
SMARTiView protein in SMART
SM00670 PINc, 1 hit
SM00955 RNB, 1 hit
SUPFAMiSSF50249 SSF50249, 3 hits
SSF88723 SSF88723, 1 hit
PROSITEiView protein in PROSITE
PS01175 RIBONUCLEASE_II, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y2L1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLKSKTFLKK TRAGGVMKIV REHYLRDDIG CGAPGCAACG GAHEGPALEP
60 70 80 90 100
QPQDPASSVC PQPHYLLPDT NVLLHQIDVL EDPAIRNVIV LQTVLQEVRN
110 120 130 140 150
RSAPVYKRIR DVTNNQEKHF YTFTNEHHRE TYVEQEQGEN ANDRNDRAIR
160 170 180 190 200
VAAKWYNEHL KKMSADNQLQ VIFITNDRRN KEKAIEEGIP AFTCEEYVKS
210 220 230 240 250
LTANPELIDR LACLSEEGNE IESGKIIFSE HLPLSKLQQG IKSGTYLQGT
260 270 280 290 300
FRASRENYLE ATVWIHGDNE ENKEIILQGL KHLNRAVHED IVAVELLPKS
310 320 330 340 350
QWVAPSSVVL HDEGQNEEDV EKEEETERML KTAVSEKMLK PTGRVVGIIK
360 370 380 390 400
RNWRPYCGML SKSDIKESRR HLFTPADKRI PRIRIETRQA STLEGRRIIV
410 420 430 440 450
AIDGWPRNSR YPNGHFVRNL GDVGEKETET EVLLLEHDVP HQPFSQAVLS
460 470 480 490 500
FLPKMPWSIT EKDMKNREDL RHLCICSVDP PGCTDIDDAL HCRELENGNL
510 520 530 540 550
EVGVHIADVS HFIRPGNALD QESARRGTTV YLCEKRIDMV PELLSSNLCS
560 570 580 590 600
LKCDVDRLAF SCIWEMNHNA EILKTKFTKS VINSKASLTY AEAQLRIDSA
610 620 630 640 650
NMNDDITTSL RGLNKLAKIL KKRRIEKGAL TLSSPEVRFH MDSETHDPID
660 670 680 690 700
LQTKELRETN SMVEEFMLLA NISVAKKIHE EFSEHALLRK HPAPPPSNYE
710 720 730 740 750
ILVKAARSRN LEIKTDTAKS LAESLDQAES PTFPYLNTLL RILATRCMMQ
760 770 780 790 800
AVYFCSGMDN DFHHYGLASP IYTHFTSPIR RYADVIVHRL LAVAIGADCT
810 820 830 840 850
YPELTDKHKL ADICKNLNFR HKMAQYAQRA SVAFHTQLFF KSKGIVSEEA
860 870 880 890 900
YILFVRKNAI VVLIPKYGLE GTVFFEEKDK PNPQLIYDDE IPSLKIEDTV
910 920 930 940 950
FHVFDKVKVK IMLDSSNLQH QKIRMSLVEP QIPGISIPTD TSNMDLNGPK

KKKMKLGK
Length:958
Mass (Da):109,003
Last modified:August 16, 2005 - v2
Checksum:i92336BA0D06247FE
GO
Isoform 2 (identifier: Q9Y2L1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     78-129: DVLEDPAIRNVIVLQTVLQEVRNRSAPVYKRIRDVTNNQEKHFYTFTNEHHR → VSAWRPGTWASVASSLRLPGSL

Show »
Length:928
Mass (Da):105,040
Checksum:iEDE527578627579A
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G3V1J5G3V1J5_HUMAN
Exosome complex exonuclease RRP44
DIS3 KIAA1008, hCG_32200
796Annotation score:
F2Z2C0F2Z2C0_HUMAN
Exosome complex exonuclease RRP44
DIS3
559Annotation score:

Sequence cautioni

The sequence BAA76852 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti635P → S in CAH56266 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023099269N → S3 PublicationsCorresponds to variant dbSNP:rs4883918Ensembl.1
Natural variantiVAR_023100326T → R2 PublicationsCorresponds to variant dbSNP:rs7332388Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01497178 – 129DVLED…NEHHR → VSAWRPGTWASVASSLRLPG SL in isoform 2. 1 PublicationAdd BLAST52

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330044 mRNA Translation: AAL37479.1
AB023225 mRNA Translation: BAA76852.2 Different initiation.
AL832266 mRNA Translation: CAH56266.1
AK314715 mRNA Translation: BAG37259.1
AL080158 mRNA Translation: CAB45749.1
AL138695 Genomic DNA No translation available.
AL391384 Genomic DNA No translation available.
CH471093 Genomic DNA Translation: EAW80517.1
BC056143 mRNA Translation: AAH56143.1
CCDSiCCDS45057.1 [Q9Y2L1-2]
CCDS9447.1 [Q9Y2L1-1]
PIRiJE0110
RefSeqiNP_001121698.1, NM_001128226.2 [Q9Y2L1-2]
NP_055768.3, NM_014953.4 [Q9Y2L1-1]
UniGeneiHs.744104

Genome annotation databases

EnsembliENST00000377767; ENSP00000366997; ENSG00000083520 [Q9Y2L1-1]
ENST00000377780; ENSP00000367011; ENSG00000083520 [Q9Y2L1-2]
GeneIDi22894
KEGGihsa:22894
UCSCiuc001vix.6 human [Q9Y2L1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330044 mRNA Translation: AAL37479.1
AB023225 mRNA Translation: BAA76852.2 Different initiation.
AL832266 mRNA Translation: CAH56266.1
AK314715 mRNA Translation: BAG37259.1
AL080158 mRNA Translation: CAB45749.1
AL138695 Genomic DNA No translation available.
AL391384 Genomic DNA No translation available.
CH471093 Genomic DNA Translation: EAW80517.1
BC056143 mRNA Translation: AAH56143.1
CCDSiCCDS45057.1 [Q9Y2L1-2]
CCDS9447.1 [Q9Y2L1-1]
PIRiJE0110
RefSeqiNP_001121698.1, NM_001128226.2 [Q9Y2L1-2]
NP_055768.3, NM_014953.4 [Q9Y2L1-1]
UniGeneiHs.744104

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6D6Qelectron microscopy3.45K1-958[»]
6D6Relectron microscopy3.45K1-958[»]
6H25electron microscopy3.80J1-958[»]
ProteinModelPortaliQ9Y2L1
SMRiQ9Y2L1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116559, 66 interactors
ComplexPortaliCPX-476 Nuclear exosome complex, DIS3-EXOSC10 variant
CPX-593 Exosome complex, DIS3 variant
CORUMiQ9Y2L1
IntActiQ9Y2L1, 21 interactors
MINTiQ9Y2L1
STRINGi9606.ENSP00000366997

PTM databases

iPTMnetiQ9Y2L1
PhosphoSitePlusiQ9Y2L1
SwissPalmiQ9Y2L1

Polymorphism and mutation databases

BioMutaiDIS3
DMDMi73620993

2D gel databases

SWISS-2DPAGEiQ9Y2L1

Proteomic databases

EPDiQ9Y2L1
PaxDbiQ9Y2L1
PeptideAtlasiQ9Y2L1
PRIDEiQ9Y2L1
ProteomicsDBi85832
85833 [Q9Y2L1-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377767; ENSP00000366997; ENSG00000083520 [Q9Y2L1-1]
ENST00000377780; ENSP00000367011; ENSG00000083520 [Q9Y2L1-2]
GeneIDi22894
KEGGihsa:22894
UCSCiuc001vix.6 human [Q9Y2L1-1]

Organism-specific databases

CTDi22894
DisGeNETi22894
EuPathDBiHostDB:ENSG00000083520.14
GeneCardsiDIS3
H-InvDBiHIX0011365
HGNCiHGNC:20604 DIS3
HPAiHPA039281
HPA058762
MIMi607533 gene
neXtProtiNX_Q9Y2L1
OpenTargetsiENSG00000083520
PharmGKBiPA162383628
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2102 Eukaryota
COG0557 LUCA
GeneTreeiENSGT00530000063106
HOVERGENiHBG059397
InParanoidiQ9Y2L1
KOiK12585
OMAiYVFVNEH
OrthoDBiEOG091G06EJ
PhylomeDBiQ9Y2L1
TreeFamiTF105755

Enzyme and pathway databases

ReactomeiR-HSA-380994 ATF4 activates genes
R-HSA-429958 mRNA decay by 3' to 5' exoribonuclease
R-HSA-450385 Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513 Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-450604 KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-6791226 Major pathway of rRNA processing in the nucleolus and cytosol

Miscellaneous databases

ChiTaRSiDIS3 human
GeneWikiiDIS3
GenomeRNAii22894
PROiPR:Q9Y2L1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000083520 Expressed in 211 organ(s), highest expression level in sperm
CleanExiHS_DIS3
ExpressionAtlasiQ9Y2L1 baseline and differential
GenevisibleiQ9Y2L1 HS

Family and domain databases

InterProiView protein in InterPro
IPR012340 NA-bd_OB-fold
IPR029060 PIN-like_dom_sf
IPR002716 PIN_dom
IPR001900 RNase_II/R
IPR022966 RNase_II/R_CS
IPR033771 Rrp44_CSD1
IPR033770 RRP44_S1
PfamiView protein in Pfam
PF13638 PIN_4, 1 hit
PF00773 RNB, 1 hit
PF17216 Rrp44_CSD1, 1 hit
PF17215 Rrp44_S1, 1 hit
SMARTiView protein in SMART
SM00670 PINc, 1 hit
SM00955 RNB, 1 hit
SUPFAMiSSF50249 SSF50249, 3 hits
SSF88723 SSF88723, 1 hit
PROSITEiView protein in PROSITE
PS01175 RIBONUCLEASE_II, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRRP44_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2L1
Secondary accession number(s): A6NI21
, B2RBL2, Q5W0P7, Q5W0P8, Q658Z7, Q7Z481, Q8WWI2, Q9UG36
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 16, 2005
Last modified: November 7, 2018
This is version 189 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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