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Protein

CCR4-NOT transcription complex subunit 8

Gene

CNOT8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT7. Catalytic component of the CCR4-NOT complex which is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity.4 Publications

Catalytic activityi

Exonucleolytic cleavage of poly(A) to 5'-AMP.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi40Divalent metal cation 1; catalyticBy similarity1
Metal bindingi40Divalent metal cation 2; catalyticBy similarity1
Metal bindingi42Divalent metal cation 2; catalyticBy similarity1
Metal bindingi161Divalent metal cation 1; catalyticBy similarity1
Metal bindingi230Divalent metal cation 2; catalyticBy similarity1

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • poly(A)-specific ribonuclease activity Source: UniProtKB
  • RNA binding Source: UniProtKB-KW
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Source: UniProtKB
  • gene silencing by miRNA Source: UniProtKB
  • negative regulation of cell proliferation Source: ProtInc
  • nuclear-transcribed mRNA poly(A) tail shortening Source: Reactome
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of mRNA catabolic process Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease, Repressor

Keywords - Biological processi

RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

Metal-binding, RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155508-MONOMER.
ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

Names & Taxonomyi

Protein namesi
Recommended name:
CCR4-NOT transcription complex subunit 8 (EC:3.1.13.4)
Alternative name(s):
CAF1-like protein
Short name:
CALIFp
CAF2
CCR4-associated factor 8
Caf1b
Gene namesi
Name:CNOT8
Synonyms:CALIF, POP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:9207. CNOT8.

Subcellular locationi

GO - Cellular componenti

  • CCR4-NOT complex Source: UniProtKB
  • cytosol Source: Reactome
  • intracellular Source: LIFEdb
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi40D → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated with A-42. 1 Publication1
Mutagenesisi42E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated with A-40. 1 Publication1

Organism-specific databases

DisGeNETi9337.
OpenTargetsiENSG00000155508.
PharmGKBiPA26679.

Polymorphism and mutation databases

BioMutaiCNOT8.
DMDMi15213949.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002128461 – 292CCR4-NOT transcription complex subunit 8Add BLAST292

Proteomic databases

EPDiQ9UFF9.
PaxDbiQ9UFF9.
PeptideAtlasiQ9UFF9.
PRIDEiQ9UFF9.

PTM databases

iPTMnetiQ9UFF9.
PhosphoSitePlusiQ9UFF9.

Expressioni

Gene expression databases

BgeeiENSG00000155508.
CleanExiHS_CNOT8.
ExpressionAtlasiQ9UFF9. baseline and differential.
GenevisibleiQ9UFF9. HS.

Organism-specific databases

HPAiHPA051398.

Interactioni

Subunit structurei

Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8. In the complex interacts directly with CNOT1. Interacts with BTG1, BTG2 and TOB1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BTG1P623244EBI-742299,EBI-742279
BTG1Q6IBC83EBI-742299,EBI-10250021
BTG2P785435EBI-742299,EBI-1047576
CNOT1A5YKK66EBI-742299,EBI-1222758
CNOT2Q9NZN83EBI-742299,EBI-743033
CNOT3O751753EBI-742299,EBI-743073
CNOT6Q9ULM62EBI-742299,EBI-2104530
TOB2Q141063EBI-742299,EBI-2562000

Protein-protein interaction databases

BioGridi114744. 36 interactors.
DIPiDIP-29084N.
IntActiQ9UFF9. 21 interactors.
MINTiMINT-155732.
STRINGi9606.ENSP00000285896.

Structurei

3D structure databases

ProteinModelPortaliQ9UFF9.
SMRiQ9UFF9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the CAF1 family.Curated

Phylogenomic databases

eggNOGiKOG0304. Eukaryota.
COG5228. LUCA.
GeneTreeiENSGT00390000000080.
HOGENOMiHOG000173077.
HOVERGENiHBG051044.
InParanoidiQ9UFF9.
KOiK12581.
OMAiKSGIDFQ.
OrthoDBiEOG091G0M48.
PhylomeDBiQ9UFF9.
TreeFamiTF314185.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR027212. Cnot8.
IPR006941. RNase_CAF1.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERiPTHR10797:SF1. PTHR10797:SF1. 1 hit.
PfamiPF04857. CAF1. 2 hits.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UFF9-1) [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
MPAALVENSQ VICEVWASNL EEEMRKIREI VLSYSYIAMD TEFPGVVVRP
60 70 80 90 100
IGEFRSSIDY QYQLLRCNVD LLKIIQLGLT FTNEKGEYPS GINTWQFNFK
110 120 130 140 150
FNLTEDMYSQ DSIDLLANSG LQFQKHEEEG IDTLHFAELL MTSGVVLCDN
160 170 180 190 200
VKWLSFHSGY DFGYMVKLLT DSRLPEEEHE FFHILNLFFP SIYDVKYLMK
210 220 230 240 250
SCKNLKGGLQ EVADQLDLQR IGRQHQAGSD SLLTGMAFFR MKELFFEDSI
260 270 280 290
DDAKYCGRLY GLGTGVAQKQ NEDVDSAQEK MSILAIINNM QQ
Length:292
Mass (Da):33,540
Last modified:May 1, 2000 - v1
Checksum:i81027A966E51AFDB
GO
Isoform 2 (identifier: Q9UFF9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.

Note: No experimental confirmation available.
Show »
Length:186
Mass (Da):21,239
Checksum:i7704142451AE8485
GO
Isoform 3 (identifier: Q9UFF9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     105-158: Missing.

Note: No experimental confirmation available.
Show »
Length:238
Mass (Da):27,415
Checksum:i0EC415BBE87D19BF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti99 – 105FKFNLTE → CKLYLTV in AAP97157 (Ref. 3) Curated7
Sequence conflicti152K → R in BAB15119 (Ref. 5) Curated1
Sequence conflicti182F → L in AAD02685 (PubMed:10036195).Curated1
Sequence conflicti189F → S in AAD02685 (PubMed:10036195).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04875132L → P.1 PublicationCorresponds to variant rs1139980dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0555271 – 106Missing in isoform 2. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_055528105 – 158Missing in isoform 3. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF053318 mRNA. Translation: AAD02685.1.
AF180476 mRNA. Translation: AAF29830.1.
AF087844 mRNA. Translation: AAP97157.1.
AL122045 mRNA. Translation: CAB59181.1.
BT006857 mRNA. Translation: AAP35503.1.
AK025358 mRNA. Translation: BAB15119.1.
AK315864 mRNA. Translation: BAF98755.1.
AK297381 mRNA. Translation: BAH12567.1.
AK303775 mRNA. Translation: BAH14047.1.
AK314317 mRNA. Translation: BAG36965.1.
AK316221 mRNA. Translation: BAH14592.1.
AK316269 mRNA. Translation: BAH14640.1.
AC112169 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61625.1.
CH471062 Genomic DNA. Translation: EAW61626.1.
CH471062 Genomic DNA. Translation: EAW61627.1.
CH471062 Genomic DNA. Translation: EAW61628.1.
BC017366 mRNA. Translation: AAH17366.1.
CCDSiCCDS4329.1. [Q9UFF9-1]
CCDS75361.1. [Q9UFF9-3]
CCDS78074.1. [Q9UFF9-2]
PIRiT34529.
T52257.
RefSeqiNP_001288002.1. NM_001301073.1. [Q9UFF9-1]
NP_001288003.1. NM_001301074.1. [Q9UFF9-3]
NP_001288004.1. NM_001301075.1. [Q9UFF9-2]
NP_001288006.1. NM_001301077.1. [Q9UFF9-2]
NP_001288009.1. NM_001301080.1. [Q9UFF9-2]
NP_001288011.1. NM_001301082.1. [Q9UFF9-2]
NP_001288012.1. NM_001301083.1. [Q9UFF9-2]
NP_001288015.1. NM_001301086.1.
NP_004770.4. NM_004779.5. [Q9UFF9-1]
XP_005268584.1. XM_005268527.2. [Q9UFF9-3]
XP_011536008.1. XM_011537706.1. [Q9UFF9-2]
XP_011536010.1. XM_011537708.2. [Q9UFF9-2]
XP_016865537.1. XM_017010048.1. [Q9UFF9-1]
XP_016865538.1. XM_017010049.1. [Q9UFF9-1]
XP_016865539.1. XM_017010050.1. [Q9UFF9-1]
XP_016865540.1. XM_017010051.1. [Q9UFF9-1]
XP_016865541.1. XM_017010052.1. [Q9UFF9-3]
XP_016865542.1. XM_017010053.1. [Q9UFF9-3]
XP_016865543.1. XM_017010054.1. [Q9UFF9-3]
XP_016865544.1. XM_017010055.1. [Q9UFF9-3]
XP_016865545.1. XM_017010056.1. [Q9UFF9-3]
XP_016865546.1. XM_017010057.1. [Q9UFF9-2]
UniGeneiHs.26703.

Genome annotation databases

EnsembliENST00000285896; ENSP00000285896; ENSG00000155508. [Q9UFF9-1]
ENST00000403027; ENSP00000384747; ENSG00000155508. [Q9UFF9-1]
ENST00000517876; ENSP00000430493; ENSG00000155508. [Q9UFF9-1]
ENST00000519404; ENSP00000430833; ENSG00000155508. [Q9UFF9-3]
ENST00000520671; ENSP00000428305; ENSG00000155508. [Q9UFF9-2]
ENST00000521450; ENSP00000431034; ENSG00000155508. [Q9UFF9-2]
ENST00000521583; ENSP00000429882; ENSG00000155508. [Q9UFF9-2]
ENST00000523698; ENSP00000428565; ENSG00000155508. [Q9UFF9-2]
GeneIDi9337.
KEGGihsa:9337.
UCSCiuc003lvu.4. human. [Q9UFF9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF053318 mRNA. Translation: AAD02685.1.
AF180476 mRNA. Translation: AAF29830.1.
AF087844 mRNA. Translation: AAP97157.1.
AL122045 mRNA. Translation: CAB59181.1.
BT006857 mRNA. Translation: AAP35503.1.
AK025358 mRNA. Translation: BAB15119.1.
AK315864 mRNA. Translation: BAF98755.1.
AK297381 mRNA. Translation: BAH12567.1.
AK303775 mRNA. Translation: BAH14047.1.
AK314317 mRNA. Translation: BAG36965.1.
AK316221 mRNA. Translation: BAH14592.1.
AK316269 mRNA. Translation: BAH14640.1.
AC112169 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61625.1.
CH471062 Genomic DNA. Translation: EAW61626.1.
CH471062 Genomic DNA. Translation: EAW61627.1.
CH471062 Genomic DNA. Translation: EAW61628.1.
BC017366 mRNA. Translation: AAH17366.1.
CCDSiCCDS4329.1. [Q9UFF9-1]
CCDS75361.1. [Q9UFF9-3]
CCDS78074.1. [Q9UFF9-2]
PIRiT34529.
T52257.
RefSeqiNP_001288002.1. NM_001301073.1. [Q9UFF9-1]
NP_001288003.1. NM_001301074.1. [Q9UFF9-3]
NP_001288004.1. NM_001301075.1. [Q9UFF9-2]
NP_001288006.1. NM_001301077.1. [Q9UFF9-2]
NP_001288009.1. NM_001301080.1. [Q9UFF9-2]
NP_001288011.1. NM_001301082.1. [Q9UFF9-2]
NP_001288012.1. NM_001301083.1. [Q9UFF9-2]
NP_001288015.1. NM_001301086.1.
NP_004770.4. NM_004779.5. [Q9UFF9-1]
XP_005268584.1. XM_005268527.2. [Q9UFF9-3]
XP_011536008.1. XM_011537706.1. [Q9UFF9-2]
XP_011536010.1. XM_011537708.2. [Q9UFF9-2]
XP_016865537.1. XM_017010048.1. [Q9UFF9-1]
XP_016865538.1. XM_017010049.1. [Q9UFF9-1]
XP_016865539.1. XM_017010050.1. [Q9UFF9-1]
XP_016865540.1. XM_017010051.1. [Q9UFF9-1]
XP_016865541.1. XM_017010052.1. [Q9UFF9-3]
XP_016865542.1. XM_017010053.1. [Q9UFF9-3]
XP_016865543.1. XM_017010054.1. [Q9UFF9-3]
XP_016865544.1. XM_017010055.1. [Q9UFF9-3]
XP_016865545.1. XM_017010056.1. [Q9UFF9-3]
XP_016865546.1. XM_017010057.1. [Q9UFF9-2]
UniGeneiHs.26703.

3D structure databases

ProteinModelPortaliQ9UFF9.
SMRiQ9UFF9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114744. 36 interactors.
DIPiDIP-29084N.
IntActiQ9UFF9. 21 interactors.
MINTiMINT-155732.
STRINGi9606.ENSP00000285896.

PTM databases

iPTMnetiQ9UFF9.
PhosphoSitePlusiQ9UFF9.

Polymorphism and mutation databases

BioMutaiCNOT8.
DMDMi15213949.

Proteomic databases

EPDiQ9UFF9.
PaxDbiQ9UFF9.
PeptideAtlasiQ9UFF9.
PRIDEiQ9UFF9.

Protocols and materials databases

DNASUi9337.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000285896; ENSP00000285896; ENSG00000155508. [Q9UFF9-1]
ENST00000403027; ENSP00000384747; ENSG00000155508. [Q9UFF9-1]
ENST00000517876; ENSP00000430493; ENSG00000155508. [Q9UFF9-1]
ENST00000519404; ENSP00000430833; ENSG00000155508. [Q9UFF9-3]
ENST00000520671; ENSP00000428305; ENSG00000155508. [Q9UFF9-2]
ENST00000521450; ENSP00000431034; ENSG00000155508. [Q9UFF9-2]
ENST00000521583; ENSP00000429882; ENSG00000155508. [Q9UFF9-2]
ENST00000523698; ENSP00000428565; ENSG00000155508. [Q9UFF9-2]
GeneIDi9337.
KEGGihsa:9337.
UCSCiuc003lvu.4. human. [Q9UFF9-1]

Organism-specific databases

CTDi9337.
DisGeNETi9337.
GeneCardsiCNOT8.
HGNCiHGNC:9207. CNOT8.
HPAiHPA051398.
MIMi603731. gene.
neXtProtiNX_Q9UFF9.
OpenTargetsiENSG00000155508.
PharmGKBiPA26679.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0304. Eukaryota.
COG5228. LUCA.
GeneTreeiENSGT00390000000080.
HOGENOMiHOG000173077.
HOVERGENiHBG051044.
InParanoidiQ9UFF9.
KOiK12581.
OMAiKSGIDFQ.
OrthoDBiEOG091G0M48.
PhylomeDBiQ9UFF9.
TreeFamiTF314185.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000155508-MONOMER.
ReactomeiR-HSA-429947. Deadenylation of mRNA.
R-HSA-6804115. TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.

Miscellaneous databases

ChiTaRSiCNOT8. human.
GeneWikiiCNOT8.
GenomeRNAii9337.
PROiQ9UFF9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155508.
CleanExiHS_CNOT8.
ExpressionAtlasiQ9UFF9. baseline and differential.
GenevisibleiQ9UFF9. HS.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR027212. Cnot8.
IPR006941. RNase_CAF1.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERiPTHR10797:SF1. PTHR10797:SF1. 1 hit.
PfamiPF04857. CAF1. 2 hits.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCNOT8_HUMAN
AccessioniPrimary (citable) accession number: Q9UFF9
Secondary accession number(s): B0AZS3
, B2RAR8, B7Z8R1, D3DQI8, O95709, Q7Z521, Q9H6Y1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 143 of the entry and version 1 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.