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Q9UFF9 (CNOT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:CNOT8
Synonyms:CALIF, POP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length292 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.13 Ref.14 Ref.16

Catalytic activity

Exonucleolytic cleavage of poly(A) to 5'-AMP. Ref.11

Subunit structure

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. Ref.2 Ref.9 Ref.10 Ref.12 Ref.16

Subcellular location

Cytoplasm. Nucleus Ref.10.

Sequence similarities

Belongs to the CAF1 family.

Ontologies

Keywords
   Biological processRNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   LigandMetal-binding
RNA-binding
   Molecular functionExonuclease
Hydrolase
Nuclease
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA metabolic process

Traceable author statement. Source: Reactome

RNA phosphodiester bond hydrolysis, exonucleolytic

Inferred from direct assay Ref.11. Source: GOC

exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay

Inferred from direct assay Ref.14. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

gene silencing by miRNA

Traceable author statement Ref.14. Source: UniProtKB

mRNA metabolic process

Traceable author statement. Source: Reactome

negative regulation of cell proliferation

Traceable author statement PubMed 9820826. Source: ProtInc

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Traceable author statement. Source: Reactome

nuclear-transcribed mRNA poly(A) tail shortening

Traceable author statement. Source: Reactome

positive regulation of cell proliferation

Inferred from mutant phenotype Ref.13. Source: UniProtKB

regulation of transcription, DNA-templated

Non-traceable author statement Ref.1. Source: UniProtKB

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentCCR4-NOT complex

Inferred from direct assay Ref.12. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

intracellular

Inferred from direct assay. Source: LIFEdb

nucleus

Non-traceable author statement Ref.1. Source: UniProtKB

   Molecular_function3'-5'-exoribonuclease activity

Inferred from direct assay Ref.11. Source: UniProtKB

RNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

poly(A)-specific ribonuclease activity

Inferred from direct assay Ref.11. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.2Ref.9PubMed 11747467PubMed 16189514PubMed 16778766PubMed 17452450PubMed 21900206PubMed 22977175. Source: IntAct

sequence-specific DNA binding transcription factor activity

Non-traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 292292CCR4-NOT transcription complex subunit 8
PRO_0000212846

Sites

Metal binding401Divalent metal cation 1; catalytic By similarity
Metal binding401Divalent metal cation 2; catalytic By similarity
Metal binding421Divalent metal cation 2; catalytic By similarity
Metal binding1611Divalent metal cation 1; catalytic By similarity
Metal binding2301Divalent metal cation 2; catalytic By similarity

Natural variations

Natural variant321L → P. Ref.1
Corresponds to variant rs1139980 [ dbSNP | Ensembl ].
VAR_048751

Experimental info

Mutagenesis401D → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated wit A-42. Ref.14
Mutagenesis421E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated wit A-40. Ref.14
Sequence conflict99 – 1057FKFNLTE → CKLYLTV in AAP97157. Ref.3
Sequence conflict1521K → R in BAB15119. Ref.5
Sequence conflict1821F → L in AAD02685. Ref.1
Sequence conflict1891F → S in AAD02685. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9UFF9 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 81027A966E51AFDB

FASTA29233,540
        10         20         30         40         50         60 
MPAALVENSQ VICEVWASNL EEEMRKIREI VLSYSYIAMD TEFPGVVVRP IGEFRSSIDY 

        70         80         90        100        110        120 
QYQLLRCNVD LLKIIQLGLT FTNEKGEYPS GINTWQFNFK FNLTEDMYSQ DSIDLLANSG 

       130        140        150        160        170        180 
LQFQKHEEEG IDTLHFAELL MTSGVVLCDN VKWLSFHSGY DFGYMVKLLT DSRLPEEEHE 

       190        200        210        220        230        240 
FFHILNLFFP SIYDVKYLMK SCKNLKGGLQ EVADQLDLQR IGRQHQAGSD SLLTGMAFFR 

       250        260        270        280        290 
MKELFFEDSI DDAKYCGRLY GLGTGVAQKQ NEDVDSAQEK MSILAIINNM QQ 

« Hide

References

« Hide 'large scale' references
[1]"The human POP2 gene: identification, sequencing, and mapping to the critical region of the 5q- syndrome."
Fidler C., Wainscoat J.S., Boultwood J.
Genomics 56:134-136(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-32.
[2]"Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits."
Albert T.K., Lemaire M., van Berkum N.L., Gentz R., Collart M.A., Timmers H.T.M.
Nucleic Acids Res. 28:809-817(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH CNOT1 AND CNOT3.
[3]"Cloning and characterization of a new human cDNA homologous to murine mCAF1 mRNA."
Jiang C.L., Yu L., Ding J.B., Ge H.P., He H., Zhao S.Y.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon and Tongue.
[6]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[9]"Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway."
Prevot D., Morel A.P., Voeltzel T., Rostan M.C., Rimokh R., Magaud J.P., Corbo L.
J. Biol. Chem. 276:9640-9648(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BTG1 AND BTG2.
[10]"BTG2 antiproliferative protein interacts with the human CCR4 complex existing in vivo in three cell-cycle-regulated forms."
Morel A.-P., Sentis S., Bianchin C., Le Romancer M., Jonard L., Rostan M.-C., Rimokh R., Corbo L.
J. Cell Sci. 116:2929-2936(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BTG2.
[11]"Conservation of the deadenylase activity of proteins of the Caf1 family in human."
Bianchin C., Mauxion F., Sentis S., Seraphin B., Corbo L.
RNA 11:487-494(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[12]"Human Ccr4-Not complexes contain variable deadenylase subunits."
Lau N.C., Kolkman A., van Schaik F.M., Mulder K.W., Pijnappel W.W., Heck A.J., Timmers H.T.
Biochem. J. 422:443-453(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE CCR4-NOT COMPLEX, COMPOSITION OF THE CCR4-NOT COMPLEX.
[13]"The Ccr4-NOT deadenylase subunits CNOT7 and CNOT8 have overlapping roles and modulate cell proliferation."
Aslam A., Mittal S., Koch F., Andrau J.C., Winkler G.S.
Mol. Biol. Cell 20:3840-3850(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"CCR4-NOT deadenylates mRNA associated with complexes in human cells."
Piao X., Zhang X., Wu L., Belasco J.G.
Mol. Cell. Biol. 30:1486-1494(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ASP-40 AND GLU-42.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex."
Doidge R., Mittal S., Aslam A., Winkler G.S.
PLoS ONE 7:E51331-E51331(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TOB1 AND BTG2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF053318 mRNA. Translation: AAD02685.1.
AF180476 mRNA. Translation: AAF29830.1.
AF087844 mRNA. Translation: AAP97157.1.
AL122045 mRNA. Translation: CAB59181.1.
AK025358 mRNA. Translation: BAB15119.1.
AK314317 mRNA. Translation: BAG36965.1.
BT006857 mRNA. Translation: AAP35503.1.
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.
CCDSCCDS4329.1.
PIRT34529.
T52257.
RefSeqNP_004770.4. NM_004779.4.
XP_005268583.1. XM_005268526.2.
UniGeneHs.26703.

3D structure databases

ProteinModelPortalQ9UFF9.
SMRQ9UFF9. Positions 12-262.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114744. 13 interactions.
DIPDIP-29084N.
IntActQ9UFF9. 17 interactions.
MINTMINT-155732.
STRING9606.ENSP00000285896.

PTM databases

PhosphoSiteQ9UFF9.

Polymorphism databases

DMDM15213949.

Proteomic databases

MaxQBQ9UFF9.
PaxDbQ9UFF9.
PRIDEQ9UFF9.

Protocols and materials databases

DNASU9337.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000285896; ENSP00000285896; ENSG00000155508.
ENST00000403027; ENSP00000384747; ENSG00000155508.
ENST00000517876; ENSP00000430493; ENSG00000155508.
GeneID9337.
KEGGhsa:9337.
UCSCuc003lvu.3. human.

Organism-specific databases

CTD9337.
GeneCardsGC05P154218.
HGNCHGNC:9207. CNOT8.
HPAHPA051398.
MIM603731. gene.
neXtProtNX_Q9UFF9.
PharmGKBPA26679.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5228.
HOGENOMHOG000173077.
HOVERGENHBG051044.
InParanoidQ9UFF9.
KOK12581.
OMAHDFFQIL.
OrthoDBEOG74BJSP.
PhylomeDBQ9UFF9.
TreeFamTF314185.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UFF9.
BgeeQ9UFF9.
CleanExHS_CNOT8.
GenevestigatorQ9UFF9.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
InterProIPR027212. Cnot8.
IPR006941. RNase_CAF1.
IPR012337. RNaseH-like_dom.
[Graphical view]
PANTHERPTHR10797:SF1. PTHR10797:SF1. 1 hit.
PfamPF04857. CAF1. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCNOT8. human.
GeneWikiCNOT8.
GenomeRNAi9337.
NextBio34971.
PROQ9UFF9.
SOURCESearch...

Entry information

Entry nameCNOT8_HUMAN
AccessionPrimary (citable) accession number: Q9UFF9
Secondary accession number(s): B2RAR8 expand/collapse secondary AC list , D3DQI8, O95709, Q7Z521, Q9H6Y1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 14, 2001
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM