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Q96LI5 (CNO6L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
CCR4-NOT transcription complex subunit 6-like

EC=3.1.13.4
Alternative name(s):
Carbon catabolite repressor protein 4 homolog B
Gene names
Name:CNOT6L
Synonyms:CCR4B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length555 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. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in the deadenylation-dependent degradation of mRNAs through the 3'-UTR AU-rich element-mediated mechanism. Involved in deadenylation-dependent degradation of CDKN1B mRNA. Its mRNA deadenylase activity can be inhibited by TOB1. Mediates cell proliferation and cell survival and prevents cellular senescence. Ref.4 Ref.8

Catalytic activity

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

Cofactor

Magnesium. Ref.9

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. Interacts with NANOS2 By similarity. Ref.4 Ref.5 Ref.6

Subcellular location

Cytoplasm. Nucleus Ref.4 Ref.8.

Tissue specificity

Highly expressed in placenta, skeletal muscle, pancreas, testis and leukocytes. Weakly expressed in heart, spleen and thymus. Ref.4

Miscellaneous

Depletion of CNOT6L causes cell growth defect.

Sequence similarities

Belongs to the CCR4/nocturin family.

Contains 4 LRR (leucine-rich) repeats.

Ontologies

Keywords
   Biological processmRNA processing
RNA-mediated gene silencing
Transcription
Transcription regulation
Translation regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainLeucine-rich repeat
Repeat
   LigandMagnesium
Metal-binding
   Molecular functionExonuclease
Hydrolase
Nuclease
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRNA metabolic process

Traceable author statement. Source: Reactome

RNA phosphodiester bond hydrolysis, exonucleolytic

Traceable author statement. Source: GOC

gene expression

Traceable author statement. Source: Reactome

gene silencing by RNA

Inferred from electronic annotation. Source: UniProtKB-KW

mRNA destabilization

Inferred from electronic annotation. Source: Ensembl

mRNA metabolic process

Traceable author statement. Source: Reactome

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.8. Source: UniProtKB

positive regulation of cytoplasmic mRNA processing body assembly

Inferred from mutant phenotype Ref.8. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

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.6. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

poly(A)-specific ribonuclease activity

Traceable author statement. Source: Reactome

protein binding

Inferred from physical interaction Ref.4Ref.5PubMed 22977175. Source: IntAct

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96LI5-1)

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.
Isoform 2 (identifier: Q96LI5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     127-153: Missing.
     486-502: GVIDYIFYSKTHMNVLG → VSGSLWAGVEIISDTSM
     503-555: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 555555CCR4-NOT transcription complex subunit 6-like
PRO_0000314587

Regions

Repeat57 – 7822LRR 1
Repeat80 – 10122LRR 2
Repeat103 – 12523LRR 3
Repeat126 – 14823LRR 4
Region1 – 152152Required for interaction with CNOT1, CNOT3 and CNOT7
Region158 – 555398Nuclease domain

Sites

Active site2401 Probable
Active site4891 Probable
Active site5291 Probable
Metal binding2401Magnesium 1
Metal binding4101Magnesium 2
Metal binding4121Magnesium 2
Metal binding5291Magnesium 2

Natural variations

Alternative sequence127 – 15327Missing in isoform 2.
VSP_030321
Alternative sequence486 – 50217GVIDY…MNVLG → VSGSLWAGVEIISDTSM in isoform 2.
VSP_030322
Alternative sequence503 – 55553Missing in isoform 2.
VSP_030323

Experimental info

Mutagenesis2401E → A: No enzymatic activity. Ref.9
Mutagenesis4101D → A: Loss of deadenylase activity. Ref.4
Mutagenesis4891D → A: Loss of deadenylase activity. Ref.4 Ref.9
Mutagenesis4891D → A: No enzymatic activity. Ref.4 Ref.9
Mutagenesis5291H → A: Loss of deadenylase activity. Ref.4 Ref.9
Mutagenesis5291H → A: No enzymatic activity. Ref.4 Ref.9
Sequence conflict4391R → G in BAB71707. Ref.1

Secondary structure

....................................................................... 555
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: C6E94F1BAE222241

FASTA55563,001
        10         20         30         40         50         60 
MRLIGMPKEK YDPPDPRRIY TIMSAEEVAN GKKSHWAELE ISGRVRSLST SLWSLTHLTA 

        70         80         90        100        110        120 
LHLNDNYLSR IPPDIAKLHN LVYLDLSSNK LRSLPAELGN MVSLRELLLN NNLLRVLPYE 

       130        140        150        160        170        180 
LGRLFQLQTL GLKGNPLSQD ILNLYQDPDG TRKLLNFMLD NLAVHPEQLP PRPWITLKER 

       190        200        210        220        230        240 
DQILPSASFT VMCYNVLCDK YATRQLYGYC PSWALNWEYR KKGIMEEIVN CDADIISLQE 

       250        260        270        280        290        300 
VETEQYFTLF LPALKERGYD GFFSPKSRAK IMSEQERKHV DGCAIFFKTE KFTLVQKHTV 

       310        320        330        340        350        360 
EFNQVAMANS DGSEAMLNRV MTKDNIGVAV VLEVHKELFG AGMKPIHAAD KQLLIVANAH 

       370        380        390        400        410        420 
MHWDPEYSDV KLIQTMMFVS EVKNILEKAS SRPGSPTADP NSIPLVLCAD LNSLPDSGVV 

       430        440        450        460        470        480 
EYLSNGGVAD NHKDFKELRY NECLMNFSCN GKNGSSEGRI THGFQLKSAY ENNLMPYTNY 

       490        500        510        520        530        540 
TFDFKGVIDY IFYSKTHMNV LGVLGPLDPQ WLVENNITGC PHPHIPSDHF SLLTQLELHP 

       550 
PLLPLVNGVH LPNRR 

« Hide

Isoform 2 [UniParc].

Checksum: 6E2E2BB67749C501
Show »

FASTA47553,891

References

« Hide 'large scale' references
[1]"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] (ISOFORM 2).
Tissue: Testis.
[2]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 208-555 (ISOFORM 1).
Tissue: Testis.
[4]"Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth."
Morita M., Suzuki T., Nakamura T., Yokoyama K., Miyasaka T., Yamamoto T.
Mol. Cell. Biol. 27:4980-4990(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CNOT1; CNOT3; CNOT7; CNOT8 AND CNOT9, TISSUE SPECIFICITY, MUTAGENESIS OF ASP-410; ASP-489 AND HIS-529.
[5]"Interaction of antiproliferative protein Tob with the CCR4-NOT deadenylase complex."
Miyasaka T., Morita M., Ito K., Suzuki T., Fukuda H., Takeda S., Inoue J., Semba K., Yamamoto T.
Cancer Sci. 99:755-761(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, INTERACTION WITH TOB1.
[6]"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.
[7]"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].
[8]"The Ccr4a (CNOT6) and Ccr4b (CNOT6L) deadenylase subunits of the human Ccr4-Not complex contribute to the prevention of cell death and senescence."
Mittal S., Aslam A., Doidge R., Medica R., Winkler G.S.
Mol. Biol. Cell 22:748-758(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity."
Wang H., Morita M., Yang X., Suzuki T., Yang W., Wang J., Ito K., Wang Q., Zhao C., Bartlam M., Yamamoto T., Rao Z.
EMBO J. 29:2566-2576(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 158-555 ALONE AND IN COMPLEX WITH AMP ANALOG AND POLY-A DNA, MUTAGENESIS OF GLU-240; ASP-489 AND HIS-529, COFACTOR, ACTIVE SITE, MAGNESIUM-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK058188 mRNA. Translation: BAB71707.1.
AC104701 Genomic DNA. No translation available.
AL133112 mRNA. Translation: CAB61415.1.
CCDSCCDS47082.1. [Q96LI5-1]
CCDS68731.1. [Q96LI5-1]
PIRT42705.
RefSeqNP_001273719.1. NM_001286790.1. [Q96LI5-1]
NP_653172.2. NM_144571.2. [Q96LI5-1]
UniGeneHs.592519.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3NGNX-ray2.40A158-555[»]
3NGOX-ray2.20A158-555[»]
3NGQX-ray1.80A158-555[»]
ProteinModelPortalQ96LI5.
SMRQ96LI5. Positions 36-540.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128873. 12 interactions.
DIPDIP-46837N.
IntActQ96LI5. 19 interactions.
STRING9606.ENSP00000264903.

PTM databases

PhosphoSiteQ96LI5.

Polymorphism databases

DMDM166216089.

Proteomic databases

MaxQBQ96LI5.
PaxDbQ96LI5.
PRIDEQ96LI5.

Protocols and materials databases

DNASU246175.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264903; ENSP00000264903; ENSG00000138767. [Q96LI5-1]
ENST00000504123; ENSP00000424896; ENSG00000138767. [Q96LI5-1]
GeneID246175.
KEGGhsa:246175.
UCSCuc003hks.3. human. [Q96LI5-1]
uc003hkt.1. human. [Q96LI5-2]

Organism-specific databases

CTD246175.
GeneCardsGC04M078634.
HGNCHGNC:18042. CNOT6L.
HPAHPA042688.
neXtProtNX_Q96LI5.
PharmGKBPA38480.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4886.
HOGENOMHOG000294222.
HOVERGENHBG052641.
InParanoidQ96LI5.
KOK12603.
OrthoDBEOG7JX35D.
PhylomeDBQ96LI5.
TreeFamTF323175.

Enzyme and pathway databases

ReactomeREACT_21257. Metabolism of RNA.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ96LI5.
BgeeQ96LI5.
CleanExHS_CNOT6L.
GenevestigatorQ96LI5.

Family and domain databases

Gene3D3.60.10.10. 1 hit.
InterProIPR005135. Endo/exonuclease/phosphatase.
IPR001611. Leu-rich_rpt.
[Graphical view]
PfamPF03372. Exo_endo_phos. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
SUPFAMSSF56219. SSF56219. 1 hit.
PROSITEPS51450. LRR. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ96LI5.
GenomeRNAi246175.
NextBio91870.
PROQ96LI5.

Entry information

Entry nameCNO6L_HUMAN
AccessionPrimary (citable) accession number: Q96LI5
Secondary accession number(s): Q9UF92
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: July 9, 2014
This is version 101 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM