CNO6L_MOUSE
ID CNO6L_MOUSE Reviewed; 555 AA.
AC Q8VEG6; Q3U9M0; Q8C0P4;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=CCR4-NOT transcription complex subunit 6-like;
DE EC=3.1.13.4 {ECO:0000250|UniProtKB:Q96LI5};
GN Name=Cnot6l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 269-277, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [5]
RP INTERACTION WITH NANOS2.
RX PubMed=20133598; DOI=10.1073/pnas.0908664107;
RA Suzuki A., Igarashi K., Aisaki K., Kanno J., Saga Y.;
RT "NANOS2 interacts with the CCR4-NOT deadenylation complex and leads to
RT suppression of specific RNAs.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:3594-3599(2010).
RN [6]
RP INTERACTION WITH ZFP36.
RX PubMed=21078877; DOI=10.1128/mcb.00717-10;
RA Clement S.L., Scheckel C., Stoecklin G., Lykke-Andersen J.;
RT "Phosphorylation of tristetraprolin by MK2 impairs AU-rich element mRNA
RT decay by preventing deadenylase recruitment.";
RL Mol. Cell. Biol. 31:256-266(2011).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=22367759; DOI=10.1002/stem.1070;
RA Zheng X., Dumitru R., Lackford B.L., Freudenberg J.M., Singh A.P.,
RA Archer T.K., Jothi R., Hu G.;
RT "Cnot1, Cnot2, and Cnot3 maintain mouse and human ESC identity and inhibit
RT extraembryonic differentiation.";
RL Stem Cells 30:910-922(2012).
CC -!- FUNCTION: Poly(A) nuclease with 3'-5' RNase activity. Catalytic
CC component of the CCR4-NOT complex which is one of the major cellular
CC mRNA deadenylases and is linked to various cellular processes including
CC bulk mRNA degradation, miRNA-mediated repression, translational
CC repression during translational initiation and general transcription
CC regulation. Additional complex functions may be a consequence of its
CC influence on mRNA expression. Involved in mRNA decay mediated by the
CC major-protein-coding determinant of instability (mCRD) of the FOS gene
CC in the cytoplasm. Involved in deadenylation-dependent degradation of
CC CDKN1B mRNA. Its mRNA deadenylase activity can be inhibited by TOB1.
CC Mediates cell proliferation and cell survival and prevents cellular
CC senescence (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage of poly(A) to 5'-AMP.; EC=3.1.13.4;
CC Evidence={ECO:0000250|UniProtKB:Q96LI5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q96LI5};
CC Note=Binds 2 magnesium ions, but the ions interact each with only 1 or
CC 2 residues. {ECO:0000250|UniProtKB:Q96LI5};
CC -!- SUBUNIT: Component of the CCR4-NOT complex; distinct complexes seem to
CC exist that differ in the participation of probably mutually exclusive
CC catalytic subunits; the complex contains two deadenylase subunits,
CC CNOT6 or CNOT6L, and CNOT7 or CNOT8 (By similarity). Interacts with
CC CNOT1, CNOT3, CNOT7, CNOT8 and CNOT9 (By similarity). Interacts with
CC TOB1 (By similarity). Interacts with NANOS2 (PubMed:20133598).
CC Interacts with ZFP36 (PubMed:21078877). {ECO:0000250|UniProtKB:Q96LI5,
CC ECO:0000269|PubMed:20133598, ECO:0000269|PubMed:21078877}.
CC -!- INTERACTION:
CC Q8VEG6; Q60809: Cnot7; NbExp=2; IntAct=EBI-2104661, EBI-2104739;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q96LI5}. Nucleus
CC {ECO:0000250|UniProtKB:Q96LI5}. Note=Predominantly cytoplasmic.
CC {ECO:0000250|UniProtKB:Q96LI5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8VEG6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VEG6-2; Sequence=VSP_030324;
CC Name=3;
CC IsoId=Q8VEG6-3; Sequence=VSP_030324, VSP_030325, VSP_030326;
CC -!- DEVELOPMENTAL STAGE: Expressed in embryonic stem (ES) cells.
CC {ECO:0000269|PubMed:22367759}.
CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC26790.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK030112; BAC26790.1; ALT_FRAME; mRNA.
DR EMBL; AK151728; BAE30646.1; -; mRNA.
DR EMBL; AC129600; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC149285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018506; AAH18506.1; -; mRNA.
DR CCDS; CCDS19448.1; -. [Q8VEG6-2]
DR CCDS; CCDS51566.1; -. [Q8VEG6-1]
DR RefSeq; NP_001272440.1; NM_001285511.1. [Q8VEG6-2]
DR RefSeq; NP_001272443.1; NM_001285514.1.
DR RefSeq; NP_659159.1; NM_144910.2. [Q8VEG6-2]
DR RefSeq; NP_849185.2; NM_178854.4. [Q8VEG6-1]
DR RefSeq; XP_006534933.1; XM_006534870.3. [Q8VEG6-2]
DR RefSeq; XP_006534934.1; XM_006534871.1. [Q8VEG6-2]
DR AlphaFoldDB; Q8VEG6; -.
DR SMR; Q8VEG6; -.
DR DIP; DIP-46842N; -.
DR IntAct; Q8VEG6; 5.
DR MINT; Q8VEG6; -.
DR STRING; 10090.ENSMUSP00000119415; -.
DR iPTMnet; Q8VEG6; -.
DR PhosphoSitePlus; Q8VEG6; -.
DR EPD; Q8VEG6; -.
DR MaxQB; Q8VEG6; -.
DR PaxDb; Q8VEG6; -.
DR PeptideAtlas; Q8VEG6; -.
DR PRIDE; Q8VEG6; -.
DR ProteomicsDB; 283457; -. [Q8VEG6-1]
DR ProteomicsDB; 283458; -. [Q8VEG6-2]
DR ProteomicsDB; 283459; -. [Q8VEG6-3]
DR Antibodypedia; 50898; 62 antibodies from 15 providers.
DR DNASU; 231464; -.
DR Ensembl; ENSMUST00000113005; ENSMUSP00000108629; ENSMUSG00000034724. [Q8VEG6-1]
DR Ensembl; ENSMUST00000122003; ENSMUSP00000113821; ENSMUSG00000034724. [Q8VEG6-3]
DR Ensembl; ENSMUST00000155901; ENSMUSP00000119415; ENSMUSG00000034724. [Q8VEG6-2]
DR GeneID; 231464; -.
DR KEGG; mmu:231464; -.
DR UCSC; uc008yfd.2; mouse. [Q8VEG6-3]
DR UCSC; uc008yfe.2; mouse. [Q8VEG6-1]
DR CTD; 246175; -.
DR MGI; MGI:2443154; Cnot6l.
DR VEuPathDB; HostDB:ENSMUSG00000034724; -.
DR eggNOG; KOG0620; Eukaryota.
DR GeneTree; ENSGT00940000157298; -.
DR HOGENOM; CLU_016428_4_2_1; -.
DR InParanoid; Q8VEG6; -.
DR OrthoDB; 724242at2759; -.
DR PhylomeDB; Q8VEG6; -.
DR TreeFam; TF323175; -.
DR Reactome; R-MMU-429947; Deadenylation of mRNA.
DR Reactome; R-MMU-6804115; TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain.
DR BioGRID-ORCS; 231464; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Cnot6l; mouse.
DR PRO; PR:Q8VEG6; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8VEG6; protein.
DR Bgee; ENSMUSG00000034724; Expressed in hair follicle and 261 other tissues.
DR ExpressionAtlas; Q8VEG6; baseline and differential.
DR Genevisible; Q8VEG6; MM.
DR GO; GO:0030014; C:CCR4-NOT complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004535; F:poly(A)-specific ribonuclease activity; IMP:MGI.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0061157; P:mRNA destabilization; IMP:MGI.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0000288; P:nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; IMP:MGI.
DR GO; GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0010606; P:positive regulation of cytoplasmic mRNA processing body assembly; ISS:UniProtKB.
DR CDD; cd10312; Deadenylase_CCR4b; 1.
DR Gene3D; 3.60.10.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR034967; Deadenylase_CCR4b.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF13855; LRR_8; 1.
DR SMART; SM00369; LRR_TYP; 3.
DR SUPFAM; SSF56219; SSF56219; 1.
DR PROSITE; PS51450; LRR; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; Exonuclease;
KW Hydrolase; Leucine-rich repeat; Magnesium; Metal-binding; mRNA processing;
KW Nuclease; Nucleus; Reference proteome; Repeat; RNA-mediated gene silencing;
KW Transcription; Transcription regulation; Translation regulation.
FT CHAIN 1..555
FT /note="CCR4-NOT transcription complex subunit 6-like"
FT /id="PRO_0000314588"
FT REPEAT 57..78
FT /note="LRR 1"
FT REPEAT 80..101
FT /note="LRR 2"
FT REPEAT 103..125
FT /note="LRR 3"
FT REPEAT 126..148
FT /note="LRR 4"
FT REGION 1..152
FT /note="Required for interaction with CNOT1, CNOT3 and
FT CNOT7"
FT /evidence="ECO:0000250"
FT REGION 158..555
FT /note="Nuclease domain"
FT /evidence="ECO:0000250"
FT ACT_SITE 410
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 240
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 240
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 276
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 360
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 365
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 410
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 412
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 479
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT BINDING 484
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LI5"
FT VAR_SEQ 1..6
FT /note="MRLIGM -> M (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_030324"
FT VAR_SEQ 440
FT /note="Y -> V (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030325"
FT VAR_SEQ 441..555
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030326"
FT CONFLICT 238
FT /note="L -> F (in Ref. 1; BAE30646)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 555 AA; 63023 MW; FDC180DB315919DB CRC64;
MRLIGMPKEK YDPPDPRRIY TIMSAEEVAN GKKSHWAELE ISGRVRSLST SLWSLTHLTA
LHLNDNNLAR IPPDIAKLHN LVYLDLSSNK LRSLPAELGN MVSLRELLLN DNYLRVLPYE
LGRLFQLQTL GLTGNPLSQD IMSLYQDPDG TRKLLNFMLD NLAVHPEQLP PRPWITLKER
DQILPSASFT VMCYNVLCDK YATRQLYGYC PSWALNWEYR KKGIMEEIVN WDADIISLQE
VETEQYFTLF LPALKDRGYD GFFSPKSRAK IMSEQERKHV DGCAIFFKTE KFTLVQKHTV
EFNQVAMANS DGSEAMLNRV MTKDNIGVAV VLEVHKELFG TGMKPIHAAD KQLLIVANAH
MHWDPEYSDV KLIQTMMFVS EVKNILEKAS SRPGSPTADP NSIPLVLCAD LNSLPDSGVV
EYLSNGGVAD NHKDFKELRY NECLMNFSCS GKNGSSEGRI THGFQLKSAY ENNLMPYTNY
TFDFKGVIDY IFYSKTHMNV LGVLGPLDPQ WLVENNITGC PHPHIPSDHF SLLTQLELHP
PLLPLVNGVH LPNRR
