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Protein

CCR4-NOT transcription complex subunit 6-like

Gene

CNOT6L

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

Exonucleolytic cleavage of poly(A) to 5'-AMP.1 Publication

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2401 Publication1
Metal bindingi240Magnesium 11 Publication1
Metal bindingi410Magnesium 21 Publication1
Metal bindingi412Magnesium 21 Publication1
Active sitei4891 Publication1
Active sitei5291 Publication1
Metal bindingi529Magnesium 21 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

mRNA processing, RNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138767-MONOMER.
BRENDAi3.1.13.4. 2681.
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 6-like (EC:3.1.13.4)
Alternative name(s):
Carbon catabolite repressor protein 4 homolog B
Gene namesi
Name:CNOT6L
Synonyms:CCR4B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:18042. CNOT6L.

Subcellular locationi

GO - Cellular componenti

  • CCR4-NOT complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi240E → A: No enzymatic activity. 1 Publication1
Mutagenesisi410D → A: Loss of deadenylase activity. 1 Publication1
Mutagenesisi489D → A: Loss of deadenylase activity. 2 Publications1
Mutagenesisi489D → A: No enzymatic activity. 2 Publications1
Mutagenesisi529H → A: Loss of deadenylase activity. 2 Publications1
Mutagenesisi529H → A: No enzymatic activity. 2 Publications1

Organism-specific databases

DisGeNETi246175.
OpenTargetsiENSG00000138767.
PharmGKBiPA38480.

Polymorphism and mutation databases

BioMutaiCNOT6L.
DMDMi166216089.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003145871 – 555CCR4-NOT transcription complex subunit 6-likeAdd BLAST555

Proteomic databases

EPDiQ96LI5.
MaxQBiQ96LI5.
PaxDbiQ96LI5.
PeptideAtlasiQ96LI5.
PRIDEiQ96LI5.

PTM databases

iPTMnetiQ96LI5.
PhosphoSitePlusiQ96LI5.

Expressioni

Tissue specificityi

Highly expressed in placenta, skeletal muscle, pancreas, testis and leukocytes. Weakly expressed in heart, spleen and thymus.1 Publication

Gene expression databases

BgeeiENSG00000138767.
CleanExiHS_CNOT6L.
ExpressionAtlasiQ96LI5. baseline and differential.
GenevisibleiQ96LI5. HS.

Organism-specific databases

HPAiHPA042688.

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 (PubMed:19558367). Interacts with CNOT1, CNOT3, CNOT7, CNOT8 and CNOT9 (PubMed:17452450). Interacts with TOB1 (PubMed:18377426). Interacts with NANOS2 (By similarity). Interacts with ZFP36 (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CNOT1A5YKK63EBI-1046635,EBI-1222758
CNOT2Q9NZN82EBI-1046635,EBI-743033
CNOT3O751752EBI-1046635,EBI-743073
CNOT7Q9UIV13EBI-1046635,EBI-2105113
TOB1P506163EBI-1046635,EBI-723281

Protein-protein interaction databases

BioGridi128873. 29 interactors.
DIPiDIP-46837N.
IntActiQ96LI5. 20 interactors.
STRINGi9606.ENSP00000264903.

Structurei

Secondary structure

1555
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi174 – 176Combined sources3
Beta strandi187 – 195Combined sources9
Helixi199 – 201Combined sources3
Turni204 – 206Combined sources3
Helixi212 – 215Combined sources4
Helixi217 – 231Combined sources15
Beta strandi234 – 242Combined sources9
Helixi243 – 248Combined sources6
Helixi250 – 256Combined sources7
Beta strandi259 – 266Combined sources8
Beta strandi268 – 270Combined sources3
Helixi274 – 278Combined sources5
Beta strandi281 – 288Combined sources8
Turni289 – 291Combined sources3
Beta strandi292 – 301Combined sources10
Helixi302 – 308Combined sources7
Helixi314 – 318Combined sources5
Turni319 – 322Combined sources4
Beta strandi326 – 334Combined sources9
Helixi336 – 338Combined sources3
Beta strandi353 – 360Combined sources8
Helixi365 – 367Combined sources3
Helixi368 – 386Combined sources19
Beta strandi405 – 410Combined sources6
Helixi418 – 425Combined sources8
Beta strandi427 – 429Combined sources3
Helixi433 – 435Combined sources3
Helixi443 – 447Combined sources5
Beta strandi459 – 461Combined sources3
Beta strandi466 – 468Combined sources3
Turni469 – 473Combined sources5
Beta strandi474 – 476Combined sources3
Beta strandi478 – 480Combined sources3
Beta strandi489 – 494Combined sources6
Turni495 – 497Combined sources3
Beta strandi498 – 504Combined sources7
Helixi509 – 514Combined sources6
Beta strandi519 – 522Combined sources4
Beta strandi527 – 529Combined sources3
Beta strandi532 – 538Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NGNX-ray2.40A158-555[»]
3NGOX-ray2.20A158-555[»]
3NGQX-ray1.80A158-555[»]
5DV2X-ray2.07A158-555[»]
ProteinModelPortaliQ96LI5.
SMRiQ96LI5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96LI5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati57 – 78LRR 1Add BLAST22
Repeati80 – 101LRR 2Add BLAST22
Repeati103 – 125LRR 3Add BLAST23
Repeati126 – 148LRR 4Add BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 152Required for interaction with CNOT1, CNOT3 and CNOT71 PublicationAdd BLAST152
Regioni158 – 555Nuclease domainAdd BLAST398

Sequence similaritiesi

Belongs to the CCR4/nocturin family.Curated
Contains 4 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG4886. LUCA.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000294222.
HOVERGENiHBG052641.
InParanoidiQ96LI5.
KOiK12603.
PhylomeDBiQ96LI5.
TreeFamiTF323175.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 3 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF56219. SSF56219. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96LI5-1) [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
MRLIGMPKEK YDPPDPRRIY TIMSAEEVAN GKKSHWAELE ISGRVRSLST
60 70 80 90 100
SLWSLTHLTA LHLNDNYLSR IPPDIAKLHN LVYLDLSSNK LRSLPAELGN
110 120 130 140 150
MVSLRELLLN NNLLRVLPYE LGRLFQLQTL GLKGNPLSQD ILNLYQDPDG
160 170 180 190 200
TRKLLNFMLD NLAVHPEQLP PRPWITLKER DQILPSASFT VMCYNVLCDK
210 220 230 240 250
YATRQLYGYC PSWALNWEYR KKGIMEEIVN CDADIISLQE VETEQYFTLF
260 270 280 290 300
LPALKERGYD GFFSPKSRAK IMSEQERKHV DGCAIFFKTE KFTLVQKHTV
310 320 330 340 350
EFNQVAMANS DGSEAMLNRV MTKDNIGVAV VLEVHKELFG AGMKPIHAAD
360 370 380 390 400
KQLLIVANAH MHWDPEYSDV KLIQTMMFVS EVKNILEKAS SRPGSPTADP
410 420 430 440 450
NSIPLVLCAD LNSLPDSGVV EYLSNGGVAD NHKDFKELRY NECLMNFSCN
460 470 480 490 500
GKNGSSEGRI THGFQLKSAY ENNLMPYTNY TFDFKGVIDY IFYSKTHMNV
510 520 530 540 550
LGVLGPLDPQ WLVENNITGC PHPHIPSDHF SLLTQLELHP PLLPLVNGVH

LPNRR
Length:555
Mass (Da):63,001
Last modified:January 15, 2008 - v2
Checksum:iC6E94F1BAE222241
GO
Isoform 2 (identifier: Q96LI5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:475
Mass (Da):53,891
Checksum:i6E2E2BB67749C501
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti439R → G in BAB71707 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030321127 – 153Missing in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_030322486 – 502GVIDY…MNVLG → VSGSLWAGVEIISDTSM in isoform 2. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_030323503 – 555Missing in isoform 2. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK058188 mRNA. Translation: BAB71707.1.
AC104701 Genomic DNA. No translation available.
AL133112 mRNA. Translation: CAB61415.1.
CCDSiCCDS68731.1. [Q96LI5-1]
PIRiT42705.
RefSeqiNP_001273719.1. NM_001286790.1. [Q96LI5-1]
NP_653172.2. NM_144571.2. [Q96LI5-1]
UniGeneiHs.592519.

Genome annotation databases

EnsembliENST00000504123; ENSP00000424896; ENSG00000138767. [Q96LI5-1]
GeneIDi246175.
KEGGihsa:246175.
UCSCiuc011ccd.4. human. [Q96LI5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK058188 mRNA. Translation: BAB71707.1.
AC104701 Genomic DNA. No translation available.
AL133112 mRNA. Translation: CAB61415.1.
CCDSiCCDS68731.1. [Q96LI5-1]
PIRiT42705.
RefSeqiNP_001273719.1. NM_001286790.1. [Q96LI5-1]
NP_653172.2. NM_144571.2. [Q96LI5-1]
UniGeneiHs.592519.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3NGNX-ray2.40A158-555[»]
3NGOX-ray2.20A158-555[»]
3NGQX-ray1.80A158-555[»]
5DV2X-ray2.07A158-555[»]
ProteinModelPortaliQ96LI5.
SMRiQ96LI5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128873. 29 interactors.
DIPiDIP-46837N.
IntActiQ96LI5. 20 interactors.
STRINGi9606.ENSP00000264903.

PTM databases

iPTMnetiQ96LI5.
PhosphoSitePlusiQ96LI5.

Polymorphism and mutation databases

BioMutaiCNOT6L.
DMDMi166216089.

Proteomic databases

EPDiQ96LI5.
MaxQBiQ96LI5.
PaxDbiQ96LI5.
PeptideAtlasiQ96LI5.
PRIDEiQ96LI5.

Protocols and materials databases

DNASUi246175.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000504123; ENSP00000424896; ENSG00000138767. [Q96LI5-1]
GeneIDi246175.
KEGGihsa:246175.
UCSCiuc011ccd.4. human. [Q96LI5-1]

Organism-specific databases

CTDi246175.
DisGeNETi246175.
GeneCardsiCNOT6L.
HGNCiHGNC:18042. CNOT6L.
HPAiHPA042688.
neXtProtiNX_Q96LI5.
OpenTargetsiENSG00000138767.
PharmGKBiPA38480.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0620. Eukaryota.
COG4886. LUCA.
COG5239. LUCA.
GeneTreeiENSGT00550000074364.
HOGENOMiHOG000294222.
HOVERGENiHBG052641.
InParanoidiQ96LI5.
KOiK12603.
PhylomeDBiQ96LI5.
TreeFamiTF323175.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000138767-MONOMER.
BRENDAi3.1.13.4. 2681.
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.

Miscellaneous databases

ChiTaRSiCNOT6L. human.
EvolutionaryTraceiQ96LI5.
GenomeRNAii246175.
PROiQ96LI5.

Gene expression databases

BgeeiENSG00000138767.
CleanExiHS_CNOT6L.
ExpressionAtlasiQ96LI5. baseline and differential.
GenevisibleiQ96LI5. HS.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
PF13855. LRR_8. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 3 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
SSF56219. SSF56219. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCNO6L_HUMAN
AccessioniPrimary (citable) accession number: Q96LI5
Secondary accession number(s): Q9UF92
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: November 30, 2016
This is version 126 of the entry and version 2 of the sequence. [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

Miscellaneous

Depletion of CNOT6L causes cell growth defect.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.