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Protein

CCR4-NOT transcription complex subunit 8

Gene

CNOT8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • DNA binding transcription factor activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW
  • poly(A)-specific ribonuclease activity Source: UniProtKB
  • RNA binding Source: UniProtKB-KW

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

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease, Repressor, RNA-binding
Biological processRNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation
LigandMetal-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000155508.13
HGNCiHGNC:9207 CNOT8
MIMi603731 gene
neXtProtiNX_Q9UFF9

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, 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

Show more details

Protein-protein interaction databases

BioGridi114744, 41 interactors
DIPiDIP-29084N
IntActiQ9UFF9, 23 interactors
MINTiQ9UFF9
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
OMAiHDFFQIL
OrthoDBiEOG091G0M48
PhylomeDBiQ9UFF9
TreeFamiTF314185

Family and domain databases

Gene3Di3.30.420.10, 1 hit
InterProiView protein in InterPro
IPR027212 Cnot8
IPR006941 RNase_CAF1
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
PANTHERiPTHR10797:SF1 PTHR10797:SF1, 1 hit
PfamiView protein in Pfam
PF04857 CAF1, 2 hits
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 → P1 PublicationCorresponds to variant dbSNP:rs1139980Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCNOT8_HUMAN
AccessioniPrimary (citable) accession number: Q9UFF9
Secondary accession number(s): B0AZS3
, B2RAR8, B7Z8R1, D3DQI8, O95709, Q7Z521, Q9H6Y1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: May 1, 2000
Last modified: May 23, 2018
This is version 156 of the entry and version 1 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

Complete proteome, Reference proteome

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