Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Circadian locomoter output cycles protein kaput

Gene

CLOCK

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

Functioni

Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1.7 Publications

Catalytic activityi

Acetyl-CoA + [histone] = CoA + acetyl-[histone].

Enzyme regulationi

The redox state of the cell can modulate the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer; NADH and NADPH enhance the DNA-binding activity of the heterodimer.1 Publication

GO - Molecular functioni

GO - Biological processi

  • cellular response to ionizing radiation Source: UniProtKB
  • circadian regulation of gene expression Source: UniProtKB
  • circadian rhythm Source: Reactome
  • DNA damage checkpoint Source: UniProtKB
  • negative regulation of glucocorticoid receptor signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • photoperiodism Source: ProtInc
  • positive regulation of inflammatory response Source: Ensembl
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of hair cycle Source: UniProtKB
  • regulation of insulin secretion Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • regulation of type B pancreatic cell development Source: UniProtKB
  • response to redox state Source: UniProtKB
  • signal transduction Source: ProtInc
  • spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator, Acyltransferase, Transferase

Keywords - Biological processi

Biological rhythms, DNA damage, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:HS05922-MONOMER.
ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-3214847. HATs acetylate histones.
R-HSA-400253. Circadian Clock.
SIGNORiO15516.

Names & Taxonomyi

Protein namesi
Recommended name:
Circadian locomoter output cycles protein kaput (EC:2.3.1.48)
Short name:
hCLOCK
Alternative name(s):
Class E basic helix-loop-helix protein 8
Short name:
bHLHe8
Gene namesi
Name:CLOCK
Synonyms:BHLHE8, KIAA0334
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:2082. CLOCK.

Subcellular locationi

GO - Cellular componenti

  • chromatoid body Source: UniProtKB
  • chromosome Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi116E → K: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition of CLOCK-ARNTL/BMAL1 transcriptional activity; when associated with K-367 and L-601. 1 Publication1
Mutagenesisi332G → E: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition of CLOCK-ARNTL/BMAL1 transcriptional activity; when associated with L-840. 1 Publication1
Mutagenesisi360H → Y: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition of CLOCK-ARNTL/BMAL1 transcriptional activity. 1 Publication1
Mutagenesisi367E → K: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition CLOCK-ARNTL/BMAL1 transcriptional activity; when associated with E-116 and L-601. 1 Publication1
Mutagenesisi451T → F: Significant loss in phosphorylation. 1 Publication1
Mutagenesisi461T → F: Significant loss in phosphorylation. 1 Publication1
Mutagenesisi601V → L: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition of CLOCK-ARNTL/BMAL1 transcriptional activity; when associated with K-116 and K-367. 1 Publication1
Mutagenesisi840P → L: 3-fold increase in PER1 reporter activity by CLOCK-ARNTL/BMAL1. Some reduction of CRY1 inhibition of CLOCK-ARNTL/BMAL1 transcriptional activity; when associated with E-332. 1 Publication1

Organism-specific databases

DisGeNETi9575.
OpenTargetsiENSG00000134852.
PharmGKBiPA26609.

Polymorphism and mutation databases

BioMutaiCLOCK.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271631 – 846Circadian locomoter output cycles protein kaputAdd BLAST846

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38PhosphoserineBy similarity1
Modified residuei42PhosphoserineBy similarity1
Cross-linki67Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei408PhosphoserineBy similarity1
Modified residuei427Phosphoserine; by GSK3-betaBy similarity1
Modified residuei431PhosphoserineBy similarity1
Modified residuei451Phosphothreonine; by CDK51 Publication1
Modified residuei461Phosphothreonine; by CDK51 Publication1
Cross-linki842Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Post-translational modificationi

Ubiquitinated, leading to its proteasomal degradation.By similarity
O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2/3 and CRY1/2.By similarity
Phosphorylation is dependent on the CLOCK-ARNTL/BMAL1 heterodimer formation. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver. May be phosphorylated by CSNK1D and CKSN1E.1 Publication
Sumoylation enhances its transcriptional activity and interaction with ESR1, resulting in up-regulation of ESR1 activity. Estrogen stimulates sumoylation. Desumoylation by SENP1 negatively regulates its transcriptional activity. Sumoylation stimulates cell proliferation and increases the proportion of S phase cells in breast cancer cell lines.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO15516.
PaxDbiO15516.
PeptideAtlasiO15516.
PRIDEiO15516.

PTM databases

iPTMnetiO15516.
PhosphoSitePlusiO15516.

Expressioni

Tissue specificityi

Hair follicles (at protein level). Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in testis and skeletal muscle. Low levels in thymus, lung and liver. Expressed in all brain regions with highest levels in cerebellum. Highly expressed in the suprachiasmatic nucleus (SCN).2 Publications

Gene expression databases

BgeeiENSG00000134852.
CleanExiHS_CLOCK.
ExpressionAtlasiO15516. baseline and differential.
GenevisibleiO15516. HS.

Organism-specific databases

HPAiHPA001867.
HPA027565.

Interactioni

Subunit structurei

Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts with ID1, ID3, MTA1, CIPC, RELA/p65, EIF4E, PIWIL1, DDX4, MGEA5, SIRT1, PER1, CRY2 and EZH2. Interacts with KMT2A in a circadian manner (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with ARNTL/BMAL1 and this heterodimerization is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and for phosphorylation of both CLOCK and ARNTL/BMAL1. Interacts with NR3C1 in a ligand-dependent fashion. Interacts with ESR1 and estrogen stimulates this interaction. Interacts with the complex p35/CDK5. Interacts with KAT2B, CREBBP, EP300 and ID2. Interacts with PER2 and CRY1 and the interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation. Interaction of the CLOCK-ARNTL/BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA. The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B. Interacts with KDM5A. Interacts with MYBBP1A (By similarity). Interacts with THRAP3 (By similarity). Interacts with MED1; this interaction requires the presence of THRAP3 (By similarity). Interacts with NCOA2 (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1 (PubMed:25936801).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARNTLO00327-84EBI-1794265,EBI-11991546

Protein-protein interaction databases

BioGridi114944. 34 interactors.
DIPiDIP-46009N.
IntActiO15516. 4 interactors.
STRINGi9606.ENSP00000308741.

Structurei

Secondary structure

1846
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi33 – 58Combined sources26
Beta strandi61 – 63Combined sources3
Helixi70 – 89Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H10X-ray2.40B29-89[»]
ProteinModelPortaliO15516.
SMRiO15516.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 84bHLHPROSITE-ProRule annotationAdd BLAST51
Domaini107 – 177PAS 1PROSITE-ProRule annotationAdd BLAST71
Domaini262 – 332PAS 2PROSITE-ProRule annotationAdd BLAST71
Domaini336 – 379PACAdd BLAST44

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni371 – 845Interaction with NR3C1By similarityAdd BLAST475
Regioni450 – 570Interaction with SIRT1By similarityAdd BLAST121
Regioni514 – 564Implicated in the circadian rhythmicityBy similarityAdd BLAST51

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 47Nuclear localization signalBy similarityAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi744 – 760Gln-richAdd BLAST17
Compositional biasi819 – 828Poly-Gln10

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation
Contains 2 PAS (PER-ARNT-SIM) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IQ5V. Eukaryota.
ENOG410Y7Z8. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234382.
HOVERGENiHBG050997.
InParanoidiO15516.
KOiK02223.
OMAiTPINMQG.
OrthoDBiEOG091G11CV.
PhylomeDBiO15516.
TreeFamiTF324568.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O15516-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLFTVSCSKM SSIVDRDDSS IFDGLVEEDD KDKAKRVSRN KSEKKRRDQF
60 70 80 90 100
NVLIKELGSM LPGNARKMDK STVLQKSIDF LRKHKEITAQ SDASEIRQDW
110 120 130 140 150
KPTFLSNEEF TQLMLEALDG FFLAIMTDGS IIYVSESVTS LLEHLPSDLV
160 170 180 190 200
DQSIFNFIPE GEHSEVYKIL STHLLESDSL TPEYLKSKNQ LEFCCHMLRG
210 220 230 240 250
TIDPKEPSTY EYVKFIGNFK SLNSVSSSAH NGFEGTIQRT HRPSYEDRVC
260 270 280 290 300
FVATVRLATP QFIKEMCTVE EPNEEFTSRH SLEWKFLFLD HRAPPIIGYL
310 320 330 340 350
PFEVLGTSGY DYYHVDDLEN LAKCHEHLMQ YGKGKSCYYR FLTKGQQWIW
360 370 380 390 400
LQTHYYITYH QWNSRPEFIV CTHTVVSYAE VRAERRRELG IEESLPETAA
410 420 430 440 450
DKSQDSGSDN RINTVSLKEA LERFDHSPTP SASSRSSRKS SHTAVSDPSS
460 470 480 490 500
TPTKIPTDTS TPPRQHLPAH EKMVQRRSSF SSQSINSQSV GSSLTQPVMS
510 520 530 540 550
QATNLPIPQG MSQFQFSAQL GAMQHLKDQL EQRTRMIEAN IHRQQEELRK
560 570 580 590 600
IQEQLQMVHG QGLQMFLQQS NPGLNFGSVQ LSSGNSSNIQ QLAPINMQGQ
610 620 630 640 650
VVPTNQIQSG MNTGHIGTTQ HMIQQQTLQS TSTQSQQNVL SGHSQQTSLP
660 670 680 690 700
SQTQSTLTAP LYNTMVISQP AAGSMVQIPS SMPQNSTQSA AVTTFTQDRQ
710 720 730 740 750
IRFSQGQQLV TKLVTAPVAC GAVMVPSTML MGQVVTAYPT FATQQQQSQT
760 770 780 790 800
LSVTQQQQQQ SSQEQQLTSV QQPSQAQLTQ PPQQFLQTSR LLHGNPSTQL
810 820 830 840
ILSAAFPLQQ STFPQSHHQQ HQSQQQQQLS RHRTDSLPDP SKVQPQ
Length:846
Mass (Da):95,304
Last modified:January 1, 1998 - v1
Checksum:iC292B451A33E4CBF
GO

Sequence cautioni

The sequence BAA20792 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti440S → P in AAF13733 (PubMed:10198158).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040061208S → C.Corresponds to variant rs34897046dbSNPEnsembl.1
Natural variantiVAR_040062380E → K.Corresponds to variant rs1056478dbSNPEnsembl.1
Natural variantiVAR_029076395L → I.Corresponds to variant rs6855837dbSNPEnsembl.1
Natural variantiVAR_029077542H → R.Corresponds to variant rs3762836dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF011568 mRNA. Translation: AAB83969.1.
AH008440 Genomic DNA. Translation: AAF13733.1.
EF015897 Genomic DNA. Translation: ABM64208.1.
AB002332 mRNA. Translation: BAA20792.2. Different initiation.
AK291708 mRNA. Translation: BAF84397.1.
BC126157 mRNA. Translation: AAI26158.1.
BC126159 mRNA. Translation: AAI26160.1.
AB005535 mRNA. Translation: BAA21774.1.
CCDSiCCDS3500.1.
RefSeqiNP_001254772.1. NM_001267843.1.
NP_004889.1. NM_004898.3.
XP_005265844.1. XM_005265787.2.
XP_011532711.1. XM_011534409.2.
XP_011532712.1. XM_011534410.2.
XP_011532713.1. XM_011534411.2.
XP_016864343.1. XM_017008854.1.
UniGeneiHs.436975.
Hs.689578.

Genome annotation databases

EnsembliENST00000309964; ENSP00000308741; ENSG00000134852.
ENST00000381322; ENSP00000370723; ENSG00000134852.
ENST00000513440; ENSP00000426983; ENSG00000134852.
GeneIDi9575.
KEGGihsa:9575.
UCSCiuc003haz.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF011568 mRNA. Translation: AAB83969.1.
AH008440 Genomic DNA. Translation: AAF13733.1.
EF015897 Genomic DNA. Translation: ABM64208.1.
AB002332 mRNA. Translation: BAA20792.2. Different initiation.
AK291708 mRNA. Translation: BAF84397.1.
BC126157 mRNA. Translation: AAI26158.1.
BC126159 mRNA. Translation: AAI26160.1.
AB005535 mRNA. Translation: BAA21774.1.
CCDSiCCDS3500.1.
RefSeqiNP_001254772.1. NM_001267843.1.
NP_004889.1. NM_004898.3.
XP_005265844.1. XM_005265787.2.
XP_011532711.1. XM_011534409.2.
XP_011532712.1. XM_011534410.2.
XP_011532713.1. XM_011534411.2.
XP_016864343.1. XM_017008854.1.
UniGeneiHs.436975.
Hs.689578.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H10X-ray2.40B29-89[»]
ProteinModelPortaliO15516.
SMRiO15516.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114944. 34 interactors.
DIPiDIP-46009N.
IntActiO15516. 4 interactors.
STRINGi9606.ENSP00000308741.

PTM databases

iPTMnetiO15516.
PhosphoSitePlusiO15516.

Polymorphism and mutation databases

BioMutaiCLOCK.

Proteomic databases

MaxQBiO15516.
PaxDbiO15516.
PeptideAtlasiO15516.
PRIDEiO15516.

Protocols and materials databases

DNASUi9575.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000309964; ENSP00000308741; ENSG00000134852.
ENST00000381322; ENSP00000370723; ENSG00000134852.
ENST00000513440; ENSP00000426983; ENSG00000134852.
GeneIDi9575.
KEGGihsa:9575.
UCSCiuc003haz.3. human.

Organism-specific databases

CTDi9575.
DisGeNETi9575.
GeneCardsiCLOCK.
HGNCiHGNC:2082. CLOCK.
HPAiHPA001867.
HPA027565.
MIMi601851. gene.
neXtProtiNX_O15516.
OpenTargetsiENSG00000134852.
PharmGKBiPA26609.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ5V. Eukaryota.
ENOG410Y7Z8. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234382.
HOVERGENiHBG050997.
InParanoidiO15516.
KOiK02223.
OMAiTPINMQG.
OrthoDBiEOG091G11CV.
PhylomeDBiO15516.
TreeFamiTF324568.

Enzyme and pathway databases

BioCyciZFISH:HS05922-MONOMER.
ReactomeiR-HSA-1368082. RORA activates gene expression.
R-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-3214847. HATs acetylate histones.
R-HSA-400253. Circadian Clock.
SIGNORiO15516.

Miscellaneous databases

ChiTaRSiCLOCK. human.
GeneWikiiCLOCK.
GenomeRNAii9575.
PROiO15516.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134852.
CleanExiHS_CLOCK.
ExpressionAtlasiO15516. baseline and differential.
GenevisibleiO15516. HS.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR001067. Nuc_translocat.
IPR001610. PAC.
IPR000014. PAS.
IPR013767. PAS_fold.
[Graphical view]
PfamiPF00010. HLH. 1 hit.
PF00989. PAS. 1 hit.
[Graphical view]
PRINTSiPR00785. NCTRNSLOCATR.
SMARTiSM00353. HLH. 1 hit.
SM00086. PAC. 1 hit.
SM00091. PAS. 2 hits.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
SSF55785. SSF55785. 2 hits.
PROSITEiPS50888. BHLH. 1 hit.
PS50112. PAS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLOCK_HUMAN
AccessioniPrimary (citable) accession number: O15516
Secondary accession number(s): A0AV01
, A2I2N9, O14516, Q9UIT8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 174 of the entry and version 1 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

CLOCK-ARNTL/BMAL1 double mutations within the PAS domains result in synergistic desensitization to high levels of CRY on repression of CLOCK-ARNTL/BMAl1 transcriptional activity of PER1 and disrupt circadian rhythmicity.

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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.