Clk Clock [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Clkprovided by FlyBase
Official Full Name: Clockprovided by FlyBase
Primary source: FLYBASE:FBgn0023076
Locus tag: Dmel_CG7391
See related: AllianceGenome:FB:FBgn0023076
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: bHLHe10; CG7391; clk; CLK; clock; CLOCK; dClck; dclk; dClk; dCLK; dCLK/JRK; dClock; dCLOCK; Dmel\CG7391; Jerk; jrk; Jrk; PAS1
Summary: Enables DNA binding activity; chromatin binding activity; and protein heterodimerization activity. Contributes to RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including circadian regulation of heart rate; locomotor rhythm; and regulation of gene expression. Part of CLOCK-BMAL transcription complex. Is expressed in several structures, including Bolwig nerve; adult fat body; brain; intrinsic neurons; and pacemaker neurons. Human ortholog(s) of this gene implicated in Alzheimer's disease and alcohol use disorder. Orthologous to human CLOCK (clock circadian regulator) and NPAS2 (neuronal PAS domain protein 2). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 66A12-66A12; 3-21 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3L	NT_037436.4 (7763233..7775603, complement)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3L	NT_037436.3 (7756333..7768703, complement)

Chromosome 3L - NT_037436.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.
Title: CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.
Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms.
Title: Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms.
Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae.
Title: Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae.
Study finds that AMP-activated protein kinase (SNF4Agamma) regulates circadian rhythm by affecting CLOCK in drosophila. Study shows that the AMPKgamma subunit of AMPK, a central regulator of cellular metabolism, copurifies with the CLK/CYC complex in Drosophila S2 cells.
Title: AMP-Activated Protein Kinase Regulates Circadian Rhythm by Affecting CLOCK in Drosophila.
Data suggest that the clock genes PERIOD and TIMELESS in peripheral clocks show reduction in both expression level and rhythmicity with age.
Title: Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster.
Spliceosome factors target tim mRNA to control clock protein accumulation and circadian behavior in Drosophila.
Title: Spliceosome factors target timeless (tim) mRNA to control clock protein accumulation and circadian behavior in Drosophila.
In vivo functional characterization of PER O-GlcNAcylation sites indicates that O-GlcNAcylation at PER(S942) reduces interactions between PER and CLOCK (CLK), the key transcriptional activator of clock-controlled genes
Title: O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression.
experiments define the genetic architecture required to initiate circadian clock function in Drosophila, reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that Clk, cyc, and cry expression is sufficient to drive clock expression in naive cells
Title: CLOCK stabilizes CYCLE to initiate clock function in Drosophila.
propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions
Title: Pacemaker-neuron-dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation.
ClkAR mutants showed significantly faster age-related locomotor deficits. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the brain
Title: Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

Submit: New GeneRIF Correction See all GeneRIFs (36)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	NAS Non-traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
contributes_to RNA polymerase II transcription regulatory region sequence-specific DNA binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in behavioral response to cocaine	NAS Non-traceable Author Statement more info	PubMed
involved_in behavioral response to cocaine	TAS Traceable Author Statement more info	PubMed
involved_in circadian regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in circadian regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in circadian regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in circadian regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian regulation of heart rate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in circadian rhythm	NAS Non-traceable Author Statement more info	PubMed
involved_in circadian rhythm	TAS Traceable Author Statement more info	PubMed
involved_in eclosion rhythm	NAS Non-traceable Author Statement more info	PubMed
involved_in eclosion rhythm	TAS Traceable Author Statement more info	PubMed
involved_in entrainment of circadian clock	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotor rhythm	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotor rhythm	NAS Non-traceable Author Statement more info	PubMed
involved_in locomotor rhythm	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian sleep/wake cycle, sleep	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to light stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to temperature stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to temperature stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in rhythmic behavior	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of CLOCK-BMAL transcription complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CLOCK-BMAL transcription complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
part_of transcription regulator complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: clock

Names: CG7391-PA; CG7391-PD; CG7391-PF; CG7391-PG; CG7391-PH; CLOCK; Clk-PA; Clk-PD; Clk-PF; Clk-PG; Clk-PH; dClock

NCBI Reference Sequences (RefSeq)

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Genome Annotation

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

Reference assembly

Genomic

NT_037436.4 Reference assembly

Range

7763233..7775603 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_079240.3 → NP_523964.2 clock, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_523964.2

Status: REVIEWED

UniProtKB/Swiss-Prot

O61735

Related

FBpp0076500

Conserved Domains (4) summary

smart00091
Location:89 → 149

PAS; PAS domain

cd00083
Location:12 → 64

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:260 → 362

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 ...

pfam14598
Location:261 → 364

PAS_11; PAS domain
NM_206299.2 → NP_996021.2 clock, isoform H [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996021.2

Status: REVIEWED

UniProtKB/TrEMBL

G7H802

Conserved Domains (2) summary

cd00130
Location:132 → 234

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 ...

pfam14598
Location:133 → 236

PAS_11; PAS domain
NM_001014574.2 → NP_001014574.1 clock, isoform F [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001014574.1

Status: REVIEWED

UniProtKB/Swiss-Prot

O61735

Conserved Domains (3) summary

smart00091
Location:27 → 87

PAS; PAS domain

cd00130
Location:198 → 300

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 ...

pfam14598
Location:199 → 302

PAS_11; PAS domain
NM_001014576.2 → NP_001014576.1 clock, isoform D [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001014576.1

Status: REVIEWED

UniProtKB/Swiss-Prot

A4V1L9, A4V1M0, O61735, O76342, O77137, Q59E25, Q9VSB0

Conserved Domains (4) summary

smart00091
Location:93 → 153

PAS; PAS domain

cd00083
Location:16 → 68

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:264 → 366

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 ...

pfam14598
Location:265 → 368

PAS_11; PAS domain
NM_170628.2 → NP_729294.2 clock, isoform G [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_729294.2

Status: REVIEWED

UniProtKB/TrEMBL

G7H802

Conserved Domains (2) summary

cd00130
Location:132 → 234

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 ...

pfam14598
Location:133 → 236

PAS_11; PAS domain