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CLOCK clock circadian regulator [ Homo sapiens (human) ]

Gene ID: 9575, updated on 17-Jun-2019

Summary

Official Symbol
CLOCKprovided by HGNC
Official Full Name
clock circadian regulatorprovided by HGNC
Primary source
HGNC:HGNC:2082
See related
Ensembl:ENSG00000134852 MIM:601851
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]
Expression
Ubiquitous expression in testis (RPKM 7.8), thyroid (RPKM 6.2) and 24 other tissues See more
Orthologs

Genomic context

See CLOCK in Genome Data Viewer
Location:
4q12
Exon count:
28
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 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 RN7SK pseudogene 30 Neighboring gene phosducin like 2 Neighboring gene neuromedin U

Genomic regions, transcripts, and products

Expression

  • 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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

Pathways from BioSystems

  • 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 ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
DNA-binding transcription activator activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific NAS
Non-traceable Author Statement
more info
PubMed 
E-box binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II distal enhancer sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
RNA polymerase II proximal promoter sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
chromatin DNA binding ISS
Inferred from Sequence or Structural Similarity
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
 
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 by RNA polymerase II 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
 
protein acetylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of circadian rhythm 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 by RNA polymerase II 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
 
Component Evidence Code Pubs
chromatoid body ISS
Inferred from Sequence or Structural Similarity
more info
 
chromosome IDA
Inferred from Direct Assay
more info
PubMed 
cytosol 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 

General protein information

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
XP_024310052.1

NCBI Reference Sequences (RefSeq)

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, ENST00000381322.5
    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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  2. NM_004898.4NP_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, ENST00000513440.6
    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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p13 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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  5. XM_024454284.1XP_024310052.1  circadian locomoter output cycles protein kaput isoform X1

    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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  6. 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, ...
    pfam00989
    Location:109175
    PAS; PAS fold
    pfam09606
    Location:496686
    Med15; ARC105 or Med15 subunit of Mediator complex non-fungal
    cl25986
    Location:274377
    PAS_3; PAS fold
  7. XM_017008855.1XP_016864344.1  circadian locomoter output cycles protein kaput isoform X2

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