Q9UFF9 (CNOT8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CNOT8
Synonyms:	CALIF, POP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	292 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	RNA-mediated gene silencing Transcription Transcription regulation Translation regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	Metal-binding RNA-binding
Molecular function	Exonuclease Hydrolase Nuclease Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay Inferred from direct assay Ref.14. Source: UniProtKB gene silencing by miRNA Traceable author statement Ref.14. Source: UniProtKB negative regulation of cell proliferation Traceable author statement PubMed 9820826. Source: ProtInc 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 transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	CCR4-NOT complex Inferred from direct assay Ref.12. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Non-traceable author statement Ref.1. Source: UniProtKB
Molecular_function	nucleic acid binding Inferred from electronic annotation. Source: InterPro poly(A)-specific ribonuclease activity Inferred from direct assay Ref.11. Source: UniProtKB sequence-specific DNA binding transcription factor activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BTG1	P62324	3	EBI-742299,EBI-742279
BTG2	P78543	2	EBI-742299,EBI-1047576
CNOT1	A5YKK6	3	EBI-742299,EBI-1222758
CNOT3	O75175	2	EBI-742299,EBI-743073
CNOT6	Q9ULM6	2	EBI-742299,EBI-2104530

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 292	292	CCR4-NOT transcription complex subunit 8		PRO_0000212846
Sites
	Metal binding	40	1	Divalent metal cation 1; catalytic By similarity
	Metal binding	40	1	Divalent metal cation 2; catalytic By similarity
	Metal binding	42	1	Divalent metal cation 2; catalytic By similarity
	Metal binding	161	1	Divalent metal cation 1; catalytic By similarity
	Metal binding	230	1	Divalent metal cation 2; catalytic By similarity
Natural variations
	Natural variant	32	1	L → P. Ref.1 Corresponds to variant rs1139980 [ dbSNP | Ensembl ].		VAR_048751
Experimental info
	Mutagenesis	40	1	D → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated wit A-42. Ref.14
	Mutagenesis	42	1	E → A: Impairs deadenylation and decay of mRNAi-targeted mRNA; when associated wit A-40. Ref.14
	Sequence conflict	99 – 105	7	FKFNLTE → CKLYLTV in AAP97157. Ref.3
	Sequence conflict	152	1	K → R in BAB15119. Ref.5
	Sequence conflict	182	1	F → L in AAD02685. Ref.1
	Sequence conflict	189	1	F → S in AAD02685. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UFF9 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 81027A966E51AFDB	FASTA	292	33,540
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00295501.
PIR	T34529. T52257.
RefSeq	NP_004770.4. NM_004779.4.
UniGene	Hs.26703.
3D structure databases
ProteinModelPortal	Q9UFF9.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29084N.
IntAct	Q9UFF9. 13 interactions.
MINT	MINT-155732.
STRING	9606.ENSP00000285896.
PTM databases
PhosphoSite	Q9UFF9.
Polymorphism databases
DMDM	15213949.
Proteomic databases
PaxDb	Q9UFF9.
PRIDE	Q9UFF9.
Protocols and materials databases
DNASU	9337.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000285896; ENSP00000285896; ENSG00000155508. ENST00000403027; ENSP00000384747; ENSG00000155508. ENST00000517876; ENSP00000430493; ENSG00000155508.
GeneID	9337.
KEGG	hsa:9337.
UCSC	uc003lvu.3. human.
Organism-specific databases
CTD	9337.
GeneCards	GC05P154218.
HGNC	HGNC:9207. CNOT8.
HPA	HPA051398.
MIM	603731. gene.
neXtProt	NX_Q9UFF9.
PharmGKB	PA26679.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5228.
HOGENOM	HOG000173077.
HOVERGEN	HBG051044.
InParanoid	Q9UFF9.
KO	K12581.
OMA	QPQNGLS.
OrthoDB	EOG4MKNGS.
PhylomeDB	Q9UFF9.
Enzyme and pathway databases
Reactome	REACT_21257. Metabolism of RNA. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9UFF9.
Bgee	Q9UFF9.
CleanEx	HS_CNOT8.
Genevestigator	Q9UFF9.
GermOnline	ENSG00000155508. Homo sapiens.
Family and domain databases
InterPro	IPR027212. Cnot8. IPR006941. RNase_CAF1. IPR012337. RNaseH-like_dom. [Graphical view]
PANTHER	PTHR10797:SF1. PTHR10797:SF1. 1 hit.
Pfam	PF04857. CAF1. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	CNOT8. human.
GenomeRNAi	9337.
NextBio	34971.
SOURCE	Search...

Entry information

Entry name

CNOT8_HUMAN

Accession

Primary (citable) accession number: Q9UFF9
Secondary accession number(s): B2RAR8 , D3DQI8, O95709, Q7Z521, Q9H6Y1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 14, 2001
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.