Format

Send to:

Choose Destination

Links from PubMed

    • Showing Current items.

    CLOCK clock circadian regulator [ Homo sapiens (human) ]

    Gene ID: 9575, updated on 8-May-2017
    Official Symbol
    CLOCKprovided by HGNC
    Official Full Name
    clock circadian regulatorprovided by HGNC
    Primary source
    HGNC:HGNC:2082
    See related
    Ensembl:ENSG00000134852 MIM:601851; Vega:OTTHUMG00000102141
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    KAT13D; bHLHe8
    Summary
    The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
    Orthologs
    Location:
    4q12
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 4 NC_000004.12 (55427901..55547138, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (56294068..56413076, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene steroid 5 alpha-reductase 3 Neighboring gene SRD5A3 antisense RNA 1 Neighboring gene FCF1 pseudogene 8 Neighboring gene uncharacterized LOC105377659 Neighboring gene transmembrane protein 165 Neighboring gene RNA, 7SK small nuclear pseudogene 30 Neighboring gene phosducin like 2 Neighboring gene neuromedin U

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Replication interactions

    Interaction Pubs
    Knockdown of clock homolog (mouse, CLOCK) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Go to the HIV-1, Human Interaction Database

    • BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystem (from REACTOME)
      BMAL1:CLOCK,NPAS2 activates circadian gene expression, organism-specific biosystemAs inferred from mouse, BMAL1:CLOCK (ARNTL:CLOCK) and BMAL1:NPAS2 (ARNTL:NPAS2) heterodimers bind to sequence elements (E boxes) in the promoters of target genes and enhance transcription (Gekakis et...
    • Chromatin modifying enzymes, organism-specific biosystem (from REACTOME)
      Chromatin modifying enzymes, organism-specific biosystemEukaryotic DNA is associated with histone proteins and organized into a complex nucleoprotein structure called chromatin. This structure decreases the accessibility of DNA but also helps to protect i...
    • Chromatin organization, organism-specific biosystem (from REACTOME)
      Chromatin organization, organism-specific biosystemChromatin organization refers to the composition and conformation of complexes between DNA, protein and RNA. It is determined by processes that result in the specification, formation or maintenance o...
    • Circadian Clock, organism-specific biosystem (from REACTOME)
      Circadian Clock, organism-specific biosystemAt the center of the mammalian circadian clock is a negative transcription/translation-based feedback loop: The BMAL1:CLOCK/NPAS2 (ARNTL:CLOCK/NPAS2) heterodimer transactivates CRY and PER genes by b...
    • Circadian rhythm, organism-specific biosystem (from KEGG)
      Circadian rhythm, organism-specific biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
    • Circadian rhythm, conserved biosystem (from KEGG)
      Circadian rhythm, conserved biosystemCircadian rhythm is an internal biological clock, which enables to sustain an approximately 24-hour rhythm in the absence of environmental cues. In mammals, the circadian clock mechanism consists of ...
    • Circadian rhythm pathway, organism-specific biosystem (from Pathway Interaction Database)
      Circadian rhythm pathway, organism-specific biosystem
      Circadian rhythm pathway
    • Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
      Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
    • Diurnally Regulated Genes with Circadian Orthologs, organism-specific biosystem (from WikiPathways)
      Diurnally Regulated Genes with Circadian Orthologs, organism-specific biosystemHuman genes regulated in the diurnal comparison with orthologues that display circadian regulation in mouse heart and liver (Panda 2002, Storch 2002), and SCN (Panda 2002). The 608 significantly regu...
    • Dopaminergic synapse, organism-specific biosystem (from KEGG)
      Dopaminergic synapse, organism-specific biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
    • Dopaminergic synapse, conserved biosystem (from KEGG)
      Dopaminergic synapse, conserved biosystemDopamine (DA) is an important and prototypical slow neurotransmitter in the mammalian brain, where it controls a variety of functions including locomotor activity, motivation and reward, learning an...
    • Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
      Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
    • HATs acetylate histones, organism-specific biosystem (from REACTOME)
      HATs acetylate histones, organism-specific biosystemHistone acetyltransferases (HATs) involved in histone modifications are referred to as A-type or nuclear HATs. They can be grouped into at least four families based on sequence conservation within th...
    • Herpes simplex infection, organism-specific biosystem (from KEGG)
      Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
    • Herpes simplex infection, conserved biosystem (from KEGG)
      Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
    • Melatonin metabolism and effects, organism-specific biosystem (from WikiPathways)
      Melatonin metabolism and effects, organism-specific biosystemMelatonin is an important regulator of circadian rythmus and influences also insulin secretion, immune function, retinal function and neuroprotection. The synthesis starts with the amino acid tryptop...
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • PPARA activates gene expression, organism-specific biosystem (from REACTOME)
      PPARA activates gene expression, organism-specific biosystemThe set of genes regulated by PPAR-alpha is not fully known in humans, however many examples have been found in mice. Genes directly activated by PPAR-alpha contain peroxisome proliferator receptor e...
    • RORA activates gene expression, organism-specific biosystem (from REACTOME)
      RORA activates gene expression, organism-specific biosystemAs inferred from mouse, RORA binds ROR elements (ROREs) in DNA and recruits the coactivators PPARGC1A (PGC-1alpha) and p300 (EP300, a histone acetylase) to activate transcription.
    • Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystem (from REACTOME)
      Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha), organism-specific biosystemPeroxisome proliferator-activated receptor alpha (PPAR-alpha) is the major regulator of fatty acid oxidation in the liver. PPARalpha is also the target of fibrate drugs used to treat abnormal plasma ...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • FLJ39000, FLJ42446, KIAA0334, DKFZp686I23208

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    E-box binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    RNA polymerase II core promoter proximal region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromatin DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    core promoter binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    core promoter sequence-specific DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    histone acetyltransferase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein dimerization activity IEA
    Inferred from Electronic Annotation
    more info
     
    sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transcription factor activity, sequence-specific DNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transcriptional activator activity, RNA polymerase II transcription factor binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    DNA damage checkpoint IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to ionizing radiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    circadian regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    PubMed 
    circadian regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    circadian regulation of gene expression ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    circadian rhythm TAS
    Traceable Author Statement
    more info
     
    histone acetylation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of glucocorticoid receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    photoperiodism TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of transcription from RNA polymerase II promoter IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    proteasome-mediated ubiquitin-dependent protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    regulation of hair cycle IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of insulin secretion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    regulation of transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    regulation of type B pancreatic cell development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    response to redox state IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    spermatogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    chromatoid body ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    chromosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Preferred Names
    circadian locomoter output cycles protein kaput
    Names
    circadian locomoter output cycles kaput protein
    class E basic helix-loop-helix protein 8
    clock homolog
    NP_001254772.1
    NP_004889.1
    XP_005265844.1
    XP_011532711.1
    XP_011532712.1
    XP_011532713.1
    XP_016864343.1
    XP_016864344.1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001267843.1NP_001254772.1  circadian locomoter output cycles protein kaput

      See identical proteins and their annotated locations for NP_001254772.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC069200, BC041878
      Consensus CDS
      CCDS3500.1
      UniProtKB/Swiss-Prot
      O15516
      UniProtKB/TrEMBL
      Q3ZCT4
      Related
      ENSP00000370723.1, OTTHUMP00000128334, ENST00000381322.5, OTTHUMT00000219982
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    2. NM_004898.3NP_004889.1  circadian locomoter output cycles protein kaput

      See identical proteins and their annotated locations for NP_004889.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC069200, AK223549, DA658950
      Consensus CDS
      CCDS3500.1
      UniProtKB/Swiss-Prot
      O15516
      UniProtKB/TrEMBL
      Q53EU0
      Related
      ENSP00000426983.1, OTTHUMP00000196798, ENST00000513440.5, OTTHUMT00000317146
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p7 Primary Assembly

      Range
      55427901..55547138 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017008854.1XP_016864343.1  circadian locomoter output cycles protein kaput isoform X1

      UniProtKB/Swiss-Prot
      O15516
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    2. XM_011534410.2XP_011532712.1  circadian locomoter output cycles protein kaput isoform X1

      See identical proteins and their annotated locations for XP_011532712.1

      UniProtKB/Swiss-Prot
      O15516
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    3. XM_005265787.2XP_005265844.1  circadian locomoter output cycles protein kaput isoform X1

      See identical proteins and their annotated locations for XP_005265844.1

      UniProtKB/Swiss-Prot
      O15516
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    4. XM_011534411.2XP_011532713.1  circadian locomoter output cycles protein kaput isoform X1

      See identical proteins and their annotated locations for XP_011532713.1

      UniProtKB/Swiss-Prot
      O15516
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    5. XM_011534409.2XP_011532711.1  circadian locomoter output cycles protein kaput isoform X1

      See identical proteins and their annotated locations for XP_011532711.1

      UniProtKB/Swiss-Prot
      O15516
      Conserved Domains (4) summary
      cd00083
      Location:3286
      HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
      cd00130
      Location:275373
      PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
      pfam13426
      Location:119220
      PAS_9; PAS domain
      pfam14598
      Location:274377
      PAS_11; PAS domain
    6. XM_017008855.1XP_016864344.1  circadian locomoter output cycles protein kaput isoform X2

    Alternate CHM1_1.1

    Genomic

    1. NC_018915.2 Alternate CHM1_1.1

      Range
      56329197..56448202 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Support Center