The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010] See more...

Aliases for CNOT4 Gene

Aliases for CNOT4 Gene

  • CCR4-NOT Transcription Complex Subunit 4 2 3 4 5
  • Potential Transcriptional Repressor NOT4Hp 3 4
  • RING-Type E3 Ubiquitin Transferase CNOT4 3 4
  • E3 Ubiquitin-Protein Ligase CNOT4 3 4
  • CCR4-Associated Factor 4 3 4
  • NOT4 3 4
  • NOT4 (Negative Regulator Of Transcription 4, Yeast) Homolog 3
  • CCR4-NOT Transcription Complex, Subunit 4 2
  • EC 2.3.2.27 4
  • CLONE243 3
  • NOT4H 3

External Ids for CNOT4 Gene

Previous HGNC Symbols for CNOT4 Gene

  • NOT4

Previous GeneCards Identifiers for CNOT4 Gene

  • GC07M133389
  • GC07M134448
  • GC07M134462
  • GC07M134503
  • GC07M134697
  • GC07M135046
  • GC07M129349

Summaries for CNOT4 Gene

Entrez Gene Summary for CNOT4 Gene

  • The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

GeneCards Summary for CNOT4 Gene

CNOT4 (CCR4-NOT Transcription Complex Subunit 4) is a Protein Coding gene. Diseases associated with CNOT4 include Adenoiditis. Among its related pathways are Gene Expression and TP53 Regulates Transcription of Cell Cycle Genes. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and nucleotide binding.

UniProtKB/Swiss-Prot Summary for CNOT4 Gene

  • Has E3 ubiquitin ligase activity, promoting ubiquitination and degradation of target proteins (PubMed:11823428, PubMed:22159038, PubMed:26575292). Involved in activation of the JAK/STAT pathway (PubMed:11823428, PubMed:22159038). Catalyzes ubiquitination of methylated RBM15 (PubMed:26575292).

Additional gene information for CNOT4 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CNOT4 Gene

Genomics for CNOT4 Gene

GeneHancer (GH) Regulatory Elements for CNOT4 Gene

Promoters and enhancers for CNOT4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J135507 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.8 826 4.2 ZNF217 ZSCAN5C SIN3A NRF1 USF1 POLR2G GTF2E2 PHF8 SIX5 TEAD4 CNOT4 lnc-SLC13A4-2 NUP205 STMP1 CALD1 piR-42694-155
GH07J134645 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 10.5 +863.3 863278 3.1 ZBTB40 ZNF217 CTCF SIN3A TCF12 POLR2G SP1 BCLAF1 GTF2E2 PHF8 BPGM lnc-AKR1B1-3 NUP205 CNOT4 ENSG00000231098 ENSG00000224375 RF00017-6652
GH07J135538 Enhancer 0.9 Ensembl ENCODE 12.3 -27.3 -27274 2.8 MYC RBM25 FOXA2 LEF1 IRF1 FOS CEBPG CEBPB SPI1 JUND CNOT4 STMP1 ENSG00000273219 RF00017-6656 NUP205
GH07J135972 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 4.2 -467.9 -467935 12.1 ZBTB40 ZNF217 ZSCAN5C SIN3A NRF1 POLR2G SP1 JUND PHF8 ZFX MTPN LUZP6 NUP205 RNU6-1154P CNOT4 lnc-STMP1-2
GH07J135146 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 4.3 +360.6 360576 6.6 FOXK2 ZBTB40 SIN3A USF1 POLR2G SP1 GTF2E2 ZNF639 EP300 KDM6A TMEM140 lnc-AGBL3-1 CYREN AGBL3 NUP205 WDR91 CNOT4 lnc-WDR91-1 lnc-C7orf49-2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CNOT4 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CNOT4

Top Transcription factor binding sites by QIAGEN in the CNOT4 gene promoter:
  • AREB6
  • GATA-1
  • GATA-2
  • GATA-3
  • HOXA9
  • HOXA9B
  • HSF2
  • Meis-1
  • Meis-1b
  • Pax-4a

Genomic Locations for CNOT4 Gene

Genomic Locations for CNOT4 Gene
chr7:135,361,795-135,510,127
(GRCh38/hg38)
Size:
148,333 bases
Orientation:
Minus strand
chr7:135,046,547-135,194,875
(GRCh37/hg19)
Size:
148,329 bases
Orientation:
Minus strand

Genomic View for CNOT4 Gene

Genes around CNOT4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CNOT4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CNOT4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CNOT4 Gene

Proteins for CNOT4 Gene

  • Protein details for CNOT4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95628-CNOT4_HUMAN
    Recommended name:
    CCR4-NOT transcription complex subunit 4
    Protein Accession:
    O95628
    Secondary Accessions:
    • B7Z6I4
    • E7ET38
    • F8VQP3
    • O95339
    • O95627
    • Q8IYM7
    • Q8NCL0
    • Q9NPQ1
    • Q9NZN6

    Protein attributes for CNOT4 Gene

    Size:
    575 amino acids
    Molecular mass:
    63510 Da
    Quaternary structure:
    • Interacts with CNOT1 via its C-terminus but does not stably associate with the CCR4-NOT complex. Binds E2 ubiquitin ligases via its RING domain. Interacts (via RING domain) with UBE2D2.
    SequenceCaution:
    • Sequence=AAC72963.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAC72963.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305}; Sequence=AAD00180.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAC11125.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CNOT4 Gene

    Alternative splice isoforms for CNOT4 Gene

neXtProt entry for CNOT4 Gene

Post-translational modifications for CNOT4 Gene

Antibody Products

  • Boster Bio Antibodies for CNOT4

No data available for DME Specific Peptides for CNOT4 Gene

Domains & Families for CNOT4 Gene

Gene Families for CNOT4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for CNOT4 Gene

Blocks:
  • RNA-binding region RNP-1 (RNA recognition motif)
  • Zn-finger, RING
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CNOT4 Gene

GenScript: Design optimal peptide antigens:
  • Potential transcriptional repressor NOT4Hp (CNOT4_HUMAN)
genes like me logo Genes that share domains with CNOT4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for CNOT4 Gene

Function for CNOT4 Gene

Molecular function for CNOT4 Gene

UniProtKB/Swiss-Prot Function:
Has E3 ubiquitin ligase activity, promoting ubiquitination and degradation of target proteins (PubMed:11823428, PubMed:22159038, PubMed:26575292). Involved in activation of the JAK/STAT pathway (PubMed:11823428, PubMed:22159038). Catalyzes ubiquitination of methylated RBM15 (PubMed:26575292).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269 PubMed:11823428, ECO:0000269 PubMed:26575292};.

Enzyme Numbers (IUBMB) for CNOT4 Gene

Phenotypes From GWAS Catalog for CNOT4 Gene

Gene Ontology (GO) - Molecular Function for CNOT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003723 RNA binding IEA,HDA 22681889
GO:0004842 ubiquitin-protein transferase activity IDA,IBA 15001359
GO:0005515 protein binding IPI 15001359
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with CNOT4: view
genes like me logo Genes that share phenotypes with CNOT4: view

Animal Models for CNOT4 Gene

MGI Knock Outs for CNOT4:
  • Cnot4 Cnot4<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for CNOT4 Gene

miRTarBase miRNAs that target CNOT4

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CNOT4 Gene

Localization for CNOT4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CNOT4 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CNOT4 gene
Compartment Confidence
cytosol 5
nucleus 4
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for CNOT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0030014 colocalizes_with CCR4-NOT complex IBA,IDA 19558367
genes like me logo Genes that share ontologies with CNOT4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CNOT4 Gene

Pathways & Interactions for CNOT4 Gene

genes like me logo Genes that share pathways with CNOT4: view

UniProtKB/Swiss-Prot O95628-CNOT4_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CNOT4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000289 nuclear-transcribed mRNA poly(A) tail shortening TAS --
GO:0006511 ubiquitin-dependent protein catabolic process IDA 26575292
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS --
GO:0016567 protein ubiquitination IBA 21873635
GO:0045652 regulation of megakaryocyte differentiation IDA 26575292
genes like me logo Genes that share ontologies with CNOT4: view

No data available for SIGNOR curated interactions for CNOT4 Gene

Drugs & Compounds for CNOT4 Gene

(3) Drugs for CNOT4 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(1) Additional Compounds for CNOT4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
14000-31-8
genes like me logo Genes that share compounds with CNOT4: view

Transcripts for CNOT4 Gene

mRNA/cDNA for CNOT4 Gene

6 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CNOT4 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b · 17c
SP1: -
SP2:
SP3:
SP4: - -
SP5:
SP6: - -
SP7:
SP8: - - -
SP9: -
SP10:
SP11: - - -

Relevant External Links for CNOT4 Gene

GeneLoc Exon Structure for
CNOT4

Expression for CNOT4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CNOT4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CNOT4 Gene

This gene is overexpressed in Testis (41.9) and Frontal cortex (7.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CNOT4 Gene



Protein tissue co-expression partners for CNOT4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CNOT4

SOURCE GeneReport for Unigene cluster for CNOT4 Gene:

Hs.490224

Evidence on tissue expression from TISSUES for CNOT4 Gene

  • Nervous system(4.3)
  • Muscle(2.3)
genes like me logo Genes that share expression patterns with CNOT4: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CNOT4 Gene

Orthologs for CNOT4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for CNOT4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CNOT4 31 30
  • 99.76 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CNOT4 31 30
  • 97.05 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CNOT4 31
  • 97 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CNOT4 31
  • 96 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CNOT4 31 30
  • 95.48 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Cnot4 17 31 30
  • 94.65 (n)
rat
(Rattus norvegicus)
Mammalia Cnot4 30
  • 94.41 (n)
chicken
(Gallus gallus)
Aves CNOT4 31 30
  • 89.43 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CNOT4 31
  • 89 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cnot4 30
  • 80.57 (n)
African clawed frog
(Xenopus laevis)
Amphibia cnot4-prov 30
zebrafish
(Danio rerio)
Actinopterygii zgc:63566 30
  • 71.09 (n)
CNOT4 (1 of 2) 31
  • 69 (a)
OneToMany
CNOT4 (2 of 2) 31
  • 67 (a)
OneToMany
zgc63566 30
fruit fly
(Drosophila melanogaster)
Insecta Cnot4 31
  • 26 (a)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea C49H3.5a 32
  • 56 (a)
ntl-4 31
  • 30 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MOT2 33 31
  • 30 (a)
sea squirt
(Ciona savignyi)
Ascidiacea Cin.7897 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.7897 30
Species where no ortholog for CNOT4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CNOT4 Gene

ENSEMBL:
Gene Tree for CNOT4 (if available)
TreeFam:
Gene Tree for CNOT4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CNOT4: view image

Paralogs for CNOT4 Gene

Pseudogenes.org Pseudogenes for CNOT4 Gene

genes like me logo Genes that share paralogs with CNOT4: view

No data available for Paralogs for CNOT4 Gene

Variants for CNOT4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CNOT4 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
rs17480616 - p.Ala7Gly

Additional dbSNP identifiers (rs#s) for CNOT4 Gene

Structural Variations from Database of Genomic Variants (DGV) for CNOT4 Gene

Variant ID Type Subtype PubMed ID
dgv1135n67 CNV loss 20364138
dgv6637n100 CNV gain 25217958
esv2442045 CNV deletion 19546169
esv2657378 CNV deletion 23128226
esv2668392 CNV deletion 23128226
esv2678090 CNV deletion 23128226
esv2735188 CNV deletion 23290073
esv2735189 CNV deletion 23290073
esv2735190 CNV deletion 23290073
esv29990 CNV gain 17803354
esv3542471 CNV deletion 23714750
esv3542472 CNV deletion 23714750
esv3542473 CNV deletion 23714750
esv3615119 CNV loss 21293372
esv3615120 CNV gain 21293372
nsv1019101 CNV gain 25217958
nsv1075999 CNV deletion 25765185
nsv1121679 CNV deletion 24896259
nsv1124269 CNV deletion 24896259
nsv482983 CNV loss 15286789
nsv520786 CNV gain 19592680
nsv5961 CNV insertion 18451855
nsv608460 CNV gain 21841781
nsv608461 CNV loss 21841781
nsv831146 CNV loss 17160897
nsv955971 CNV deletion 24416366
nsv970944 CNV duplication 23825009

Variation tolerance for CNOT4 Gene

Residual Variation Intolerance Score: 24.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.29; 88.22% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CNOT4 Gene

Human Gene Mutation Database (HGMD)
CNOT4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CNOT4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CNOT4 Gene

Disorders for CNOT4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for CNOT4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
adenoiditis
  • chronic adenoiditis
- elite association - COSMIC cancer census association via MalaCards
Search CNOT4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CNOT4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CNOT4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CNOT4 Gene

Publications for CNOT4 Gene

  1. Isolation and characterization of human orthologs of yeast CCR4-NOT complex subunits. (PMID: 10637334) Albert TK … Timmers HT (Nucleic acids research 2000) 2 3 4 54
  2. Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing. (PMID: 26575292) Zhang L … Zhao X (eLife 2015) 3 4 54
  3. Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells. (PMID: 22159038) Grönholm J … Rämet M (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012) 3 4 54
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54
  5. RING domains functioning as E3 ligases reveal distinct structural features: a molecular dynamics simulation study. (PMID: 18533727) Zhao JH … Liu HL (Journal of biomolecular structure & dynamics 2008) 2 3 54

Products for CNOT4 Gene