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Protein

Exosome complex component RRP41

Gene

EXOSC4

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

Functioni

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.5 Publications

Caution

The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.Curated

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • AU-rich element binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processrRNA processing

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

Protein family/group databases

MoonDBiQ9NPD3 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Exosome complex component RRP41
Alternative name(s):
Exosome component 4
Ribosomal RNA-processing protein 41
p12A
Gene namesi
Name:EXOSC4
Synonyms:RRP41, SKI6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000178896.6
HGNCiHGNC:18189 EXOSC4
MIMi606491 gene
neXtProtiNX_Q9NPD3

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

Organism-specific databases

OpenTargetsiENSG00000178896
PharmGKBiPA134867931

Polymorphism and mutation databases

BioMutaiEXOSC4
DMDMi14285756

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001399582 – 245Exosome complex component RRP41Add BLAST244

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9NPD3
MaxQBiQ9NPD3
PaxDbiQ9NPD3
PeptideAtlasiQ9NPD3
PRIDEiQ9NPD3
ProteomicsDBi81973

2D gel databases

SWISS-2DPAGEiQ9NPD3

PTM databases

iPTMnetiQ9NPD3
PhosphoSitePlusiQ9NPD3

Expressioni

Gene expression databases

BgeeiENSG00000178896 Expressed in 148 organ(s), highest expression level in left testis
CleanExiHS_EXOSC4
ExpressionAtlasiQ9NPD3 baseline and differential
GenevisibleiQ9NPD3 HS

Organism-specific databases

HPAiHPA024792

Interactioni

Subunit structurei

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 DDX60.3 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi120007, 114 interactors
ComplexPortaliCPX-476 Nuclear exosome complex, DIS3-EXOSC10 variant
CPX-591 Nucleolar exosome complex, EXOSC10 variant
CPX-592 Cytoplasmic exosome complex, DIS3L variant
CPX-593 Exosome complex, DIS3 variant
CPX-600 Cytoplasmic exosome complex, DIS3L-EXOSC10 variant
CORUMiQ9NPD3
DIPiDIP-31165N
IntActiQ9NPD3, 64 interactors
MINTiQ9NPD3
STRINGi9606.ENSP00000315476

Structurei

Secondary structure

1245
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9NPD3
SMRiQ9NPD3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9NPD3

Family & Domainsi

Sequence similaritiesi

Belongs to the RNase PH family.Curated

Phylogenomic databases

eggNOGiKOG1068 Eukaryota
COG0689 LUCA
GeneTreeiENSGT00550000074804
HOGENOMiHOG000229515
HOVERGENiHBG051519
InParanoidiQ9NPD3
KOiK11600
OMAiVINCQYS
PhylomeDBiQ9NPD3
TreeFamiTF313915

Family and domain databases

Gene3Di3.30.230.70, 1 hit
InterProiView protein in InterPro
IPR001247 ExoRNase_PH_dom1
IPR015847 ExoRNase_PH_dom2
IPR036345 ExoRNase_PH_dom2_sf
IPR027408 PNPase/RNase_PH_dom_sf
IPR020568 Ribosomal_S5_D2-typ_fold
PfamiView protein in Pfam
PF01138 RNase_PH, 1 hit
PF03725 RNase_PH_C, 1 hit
SUPFAMiSSF54211 SSF54211, 1 hit
SSF55666 SSF55666, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9NPD3-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGLELLSDQ GYRVDGRRAG ELRKIQARMG VFAQADGSAY IEQGNTKALA
60 70 80 90 100
VVYGPHEIRG SRARALPDRA LVNCQYSSAT FSTGERKRRP HGDRKSCEMG
110 120 130 140 150
LQLRQTFEAA ILTQLHPRSQ IDIYVQVLQA DGGTYAACVN AATLAVLDAG
160 170 180 190 200
IPMRDFVCAC SAGFVDGTAL ADLSHVEEAA GGPQLALALL PASGQIALLE
210 220 230 240
MDARLHEDHL ERVLEAAAQA ARDVHTLLDR VVRQHVREAS ILLGD
Length:245
Mass (Da):26,383
Last modified:January 23, 2007 - v3
Checksum:i7A24E97897DAF313
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PI41E9PI41_HUMAN
Exosome complex component RRP41
EXOSC4
261Annotation score:
E9PPI9E9PPI9_HUMAN
Exosome complex component RRP41
EXOSC4
156Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281133 mRNA Translation: AAF82134.1
AK000598 mRNA Translation: BAA91279.1
AC109322 Genomic DNA No translation available.
BC002777 mRNA Translation: AAH02777.1
CCDSiCCDS6414.1
RefSeqiNP_061910.1, NM_019037.2
UniGeneiHs.632041

Genome annotation databases

EnsembliENST00000316052; ENSP00000315476; ENSG00000178896
GeneIDi54512
KEGGihsa:54512
UCSCiuc003zau.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281133 mRNA Translation: AAF82134.1
AK000598 mRNA Translation: BAA91279.1
AC109322 Genomic DNA No translation available.
BC002777 mRNA Translation: AAH02777.1
CCDSiCCDS6414.1
RefSeqiNP_061910.1, NM_019037.2
UniGeneiHs.632041

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NN6X-ray3.35B2-245[»]
6D6Qelectron microscopy3.45B1-245[»]
6D6Relectron microscopy3.45B1-245[»]
6H25electron microscopy3.80B1-245[»]
ProteinModelPortaliQ9NPD3
SMRiQ9NPD3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120007, 114 interactors
ComplexPortaliCPX-476 Nuclear exosome complex, DIS3-EXOSC10 variant
CPX-591 Nucleolar exosome complex, EXOSC10 variant
CPX-592 Cytoplasmic exosome complex, DIS3L variant
CPX-593 Exosome complex, DIS3 variant
CPX-600 Cytoplasmic exosome complex, DIS3L-EXOSC10 variant
CORUMiQ9NPD3
DIPiDIP-31165N
IntActiQ9NPD3, 64 interactors
MINTiQ9NPD3
STRINGi9606.ENSP00000315476

Protein family/group databases

MoonDBiQ9NPD3 Predicted

PTM databases

iPTMnetiQ9NPD3
PhosphoSitePlusiQ9NPD3

Polymorphism and mutation databases

BioMutaiEXOSC4
DMDMi14285756

2D gel databases

SWISS-2DPAGEiQ9NPD3

Proteomic databases

EPDiQ9NPD3
MaxQBiQ9NPD3
PaxDbiQ9NPD3
PeptideAtlasiQ9NPD3
PRIDEiQ9NPD3
ProteomicsDBi81973

Protocols and materials databases

DNASUi54512
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316052; ENSP00000315476; ENSG00000178896
GeneIDi54512
KEGGihsa:54512
UCSCiuc003zau.4 human

Organism-specific databases

CTDi54512
EuPathDBiHostDB:ENSG00000178896.6
GeneCardsiEXOSC4
HGNCiHGNC:18189 EXOSC4
HPAiHPA024792
MIMi606491 gene
neXtProtiNX_Q9NPD3
OpenTargetsiENSG00000178896
PharmGKBiPA134867931
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1068 Eukaryota
COG0689 LUCA
GeneTreeiENSGT00550000074804
HOGENOMiHOG000229515
HOVERGENiHBG051519
InParanoidiQ9NPD3
KOiK11600
OMAiVINCQYS
PhylomeDBiQ9NPD3
TreeFamiTF313915

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

ChiTaRSiEXOSC4 human
EvolutionaryTraceiQ9NPD3
GeneWikiiExosome_component_4
GenomeRNAii54512
PROiPR:Q9NPD3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000178896 Expressed in 148 organ(s), highest expression level in left testis
CleanExiHS_EXOSC4
ExpressionAtlasiQ9NPD3 baseline and differential
GenevisibleiQ9NPD3 HS

Family and domain databases

Gene3Di3.30.230.70, 1 hit
InterProiView protein in InterPro
IPR001247 ExoRNase_PH_dom1
IPR015847 ExoRNase_PH_dom2
IPR036345 ExoRNase_PH_dom2_sf
IPR027408 PNPase/RNase_PH_dom_sf
IPR020568 Ribosomal_S5_D2-typ_fold
PfamiView protein in Pfam
PF01138 RNase_PH, 1 hit
PF03725 RNase_PH_C, 1 hit
SUPFAMiSSF54211 SSF54211, 1 hit
SSF55666 SSF55666, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEXOS4_HUMAN
AccessioniPrimary (citable) accession number: Q9NPD3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 171 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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