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Protein

Circadian locomoter output cycles protein kaput

Gene

Clock

Organism
Mus musculus (Mouse)
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. May play a role in spermatogenesis; contributes to the chromatoid body assembly and physiology. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1.30 Publications

Catalytic activityi

Acetyl-CoA + [histone] = CoA + acetyl-[histone].1 Publication

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.By similarity

GO - Molecular functioni

  • chromatin DNA binding Source: UniProtKB
  • core promoter binding Source: UniProtKB
  • core promoter sequence-specific DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • E-box binding Source: UniProtKB
  • histone acetyltransferase activity Source: UniProtKB
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  • sequence-specific DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: MGI

GO - Biological processi

  • cellular response to ionizing radiation Source: MGI
  • circadian regulation of gene expression Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • DNA damage checkpoint Source: MGI
  • negative regulation of glucocorticoid receptor signaling pathway Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of inflammatory response Source: UniProtKB
  • 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: BHF-UCL
  • 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 type B pancreatic cell development Source: UniProtKB
  • response to redox state Source: UniProtKB
  • 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

ReactomeiR-MMU-1368082. RORA activates gene expression.
R-MMU-1368092. Rora activates gene expression.
R-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-1989781. PPARA activates gene expression.
R-MMU-400253. Circadian Clock.
R-MMU-508751. Circadian Clock.

Names & Taxonomyi

Protein namesi
Recommended name:
Circadian locomoter output cycles protein kaput (EC:2.3.1.48)
Short name:
mCLOCK
Gene namesi
Name:Clock
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:99698. Clock.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38S → D: Significant decrease in transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Significant decrease in transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer, reduced nuclear localization and DNA-binding; when associated with D-42. 1 Publication1
Mutagenesisi42S → D: Significant decrease in transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Significant decrease in transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer, reduced nuclear localization and DNA-binding; when associated with D-38. 1 Publication1
Mutagenesisi57L → E: Reduced ARNTL/BMAL1 binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Abolishes regulation of circadian clock. 1 Publication1
Mutagenesisi67K → R: Decrease in sumoylation and its transcriptional activity. Abolishes sumoylation and interaction with ESR1 and decrease in its transcriptional activity; when associated with R-851. 1 Publication1
Mutagenesisi74L → E: Reduced ARNTL/BMAL1 binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. 1 Publication1
Mutagenesisi284W → A: Reduced ARNTL/BMAL1 binding. Slightly reduced transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. 1 Publication1
Mutagenesisi427S → A: Significant loss of phosphorylation. 2 Publications1
Mutagenesisi431S → A: Significant loss of phosphorylation. 1 Publication1
Mutagenesisi656P → A: Reduces histone acetyltransferase activity; when associated with A-658 and A-659. 1 Publication1
Mutagenesisi658Y → A: Reduces histone acetyltransferase activity; when associated with A-656 and A-659. 1 Publication1
Mutagenesisi659N → A: Reduces histone acetyltransferase activity; when associated with A-656 and A-658. 1 Publication1
Mutagenesisi669G → A: Reduces histone acetyltransferase activity; when associated with A-670 and A-672. 1 Publication1
Mutagenesisi670S → A: Reduces histone acetyltransferase activity; when associated with A-669 and A-672. 1 Publication1
Mutagenesisi672V → A: Reduces histone acetyltransferase activity; when associated with A-669 and A-670. 1 Publication1
Mutagenesisi851K → R: Decrease in sumoylation and its transcriptional activity. Abolishes sumoylation and interaction with ESR1 and decrease in its transcriptional activity; when associated with R-67. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001271641 – 855Circadian locomoter output cycles protein kaputAdd BLAST855

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38Phosphoserine1 Publication1
Modified residuei42Phosphoserine1 Publication1
Cross-linki67Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Modified residuei408PhosphoserineCombined sources1
Modified residuei427Phosphoserine; by GSK3-beta2 Publications1
Modified residuei431Phosphoserine1 Publication1
Modified residuei451Phosphothreonine; by CDK51 Publication1
Modified residuei461Phosphothreonine; by CDK51 Publication1
Cross-linki851Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication

Post-translational modificationi

Ubiquitinated, leading to its proteasomal degradation.1 Publication
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 CRY1/2.2 Publications
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: the hyperphosphorylated form peaks at midnight (CT18), while the hypophosphorylated form is abundant throughout the day. May be phosphorylated by CSNK1D and CKSN1E.6 Publications
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.1 Publication

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO08785.
PaxDbiO08785.
PeptideAtlasiO08785.
PRIDEiO08785.

PTM databases

iPTMnetiO08785.
PhosphoSitePlusiO08785.

Expressioni

Tissue specificityi

Expressed equally in brain, eye, testes, ovaries, liver, heart, lung, kidney. In the brain, expression is abundant in the suprachiasmatic nuclei (SCN), in the pyriform cortex, and in the hippocampus. Low expression throughout the rest of the brain. Expression does not appear to undergo circadian oscillations.3 Publications

Inductioni

In the SCN, nuclear expression is lowest between CT7 and CT13. Cytoplasmic expression is highest at these times. In liver, peak levels from CT21 to CT3. Expression of both phosphorylated and unphosphorylated forms of ARNTL/BMAL1 with other circadian clock proteins occurs between CT15 and CT18. Expression in the heart oscillates in a circadian manner.3 Publications

Gene expression databases

BgeeiENSMUSG00000029238.
CleanExiMM_CLOCK.
ExpressionAtlasiO08785. baseline and differential.
GenevisibleiO08785. MM.

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 KAT2B, CREBBP, EP300 (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 ID1, ID2, ID3, MTA1, CIPC, RELA/p65, EIF4E, PIWIL1, DDX4, MGEA5, SIRT1 and EZH2. Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a 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 KMT2A in a circadian manner. Interacts with MYBBP1A. Interacts with THRAP3. Interacts with MED1; this interaction requires the presence of THRAP3. Interacts with NCOA2. The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1 (By similarity).By similarity25 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ArntlQ9WTL824EBI-79859,EBI-644534
Cry1P977847EBI-79859,EBI-1266607
Csnk1eQ9JMK22EBI-79859,EBI-771709
CSNK2BP678702EBI-79859,EBI-348169From a different organism.
NR1D2Q149952EBI-79859,EBI-6144053From a different organism.
Per2O5494310EBI-79859,EBI-1266779
PPP1CAP621362EBI-79859,EBI-357253From a different organism.
PPP1CBP621402EBI-79859,EBI-352350From a different organism.
PPP1CCP368732EBI-79859,EBI-356283From a different organism.
PPP2R1BP301542EBI-79859,EBI-357094From a different organism.
PPP2R5DQ147382EBI-79859,EBI-396563From a different organism.
PrkcaP204443EBI-79859,EBI-6976815
RORBQ927532EBI-79859,EBI-6144615From a different organism.
RORCP514492EBI-79859,EBI-3908771From a different organism.
Sirt1Q923E411EBI-79859,EBI-1802585

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198756. 17 interactors.
DIPiDIP-30958N.
IntActiO08785. 28 interactors.
MINTiMINT-4654078.
STRINGi10090.ENSMUSP00000074656.

Structurei

Secondary structure

1855
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi43 – 59Combined sources17
Beta strandi63 – 65Combined sources3
Helixi70 – 88Combined sources19
Helixi94 – 96Combined sources3
Helixi107 – 117Combined sources11
Beta strandi120 – 126Combined sources7
Beta strandi129 – 134Combined sources6
Helixi138 – 142Combined sources5
Helixi146 – 149Combined sources4
Helixi154 – 157Combined sources4
Helixi160 – 162Combined sources3
Helixi163 – 172Combined sources10
Beta strandi179 – 181Combined sources3
Helixi183 – 185Combined sources3
Helixi187 – 189Combined sources3
Beta strandi190 – 198Combined sources9
Beta strandi204 – 206Combined sources3
Beta strandi210 – 221Combined sources12
Beta strandi249 – 259Combined sources11
Beta strandi262 – 266Combined sources5
Beta strandi270 – 272Combined sources3
Beta strandi275 – 280Combined sources6
Beta strandi284 – 289Combined sources6
Helixi294 – 297Combined sources4
Helixi301 – 304Combined sources4
Helixi309 – 312Combined sources4
Helixi315 – 331Combined sources17
Beta strandi332 – 335Combined sources4
Beta strandi339 – 342Combined sources4
Beta strandi346 – 359Combined sources14
Turni361 – 363Combined sources3
Beta strandi366 – 375Combined sources10
Helixi378 – 383Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4F3LX-ray2.27A26-384[»]
DisProtiDP00734.
ProteinModelPortaliO08785.
SMRiO08785.
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 – 854Interaction with NR3C11 PublicationAdd BLAST484
Regioni450 – 570Interaction with SIRT11 PublicationAdd BLAST121
Regioni514 – 564Implicated in the circadian rhythmicityAdd BLAST51

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 47Nuclear localization signal1 PublicationAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi484 – 855Gln-richAdd BLAST372
Compositional biasi740 – 745Poly-Gln6
Compositional biasi751 – 759Poly-Gln9
Compositional biasi762 – 769Poly-Gln8
Compositional biasi828 – 837Poly-Gln10

Domaini

Contains a Gln-rich C-terminal domain which could correspond to the transactivation domain.

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

eggNOGiKOG3561. Eukaryota.
ENOG410Y7Z8. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234382.
HOVERGENiHBG050997.
InParanoidiO08785.
KOiK02223.
OMAiTPINMQG.
OrthoDBiEOG091G11CV.
PhylomeDBiO08785.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: O08785-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVFTVSCSKM SSIVDRDDSS IFDGLVEEDD KDKAKRVSRN KSEKKRRDQF
60 70 80 90 100
NVLIKELGSM LPGNARKMDK STVLQKSIDF LRKHKETTAQ 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 EYVRFIGNFK SLTSVSTSTH 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 EKMTQRRSSF SSQSINSQSV GPSLTQPAMS
510 520 530 540 550
QAANLPIPQG MSQFQFSAQL GAMQHLKDQL EQRTRMIEAN IHRQQEELRK
560 570 580 590 600
IQEQLQMVHG QGLQMFLQQS NPGLNFGSVQ LSSGNSNIQQ LTPVNMQGQV
610 620 630 640 650
VPANQVQSGH ISTGQHMIQQ QTLQSTSTQQ SQQSVMSGHS QQTSLPSQTP
660 670 680 690 700
STLTAPLYNT MVISQPAAGS MVQIPSSMPQ NSTQSATVTT FTQDRQIRFS
710 720 730 740 750
QGQQLVTKLV TAPVACGAVM VPSTMLMGQV VTAYPTFATQ QQQAQTLSVT
760 770 780 790 800
QQQQQQQQQP PQQQQQQQQS SQEQQLPSVQ QPAQAQLGQP PQQFLQTSRL
810 820 830 840 850
LHGNPSTQLI LSAAFPLQQS TFPPSHHQQH QPQQQQQLPR HRTDSLTDPS

KVQPQ
Length:855
Mass (Da):96,393
Last modified:July 1, 1997 - v1
Checksum:i9864D947049742F4
GO
Isoform Short (identifier: O08785-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     484-513: Missing.

Show »
Length:825
Mass (Da):93,371
Checksum:iFABAE927F765B680
GO

Polymorphismi

The naturally-occurring CLOCK variant, missing exon 19 (deletion of AA 514-564) due to an A-->T nucleotide transversion in a splice donor site, forms a heterodimer with DNA, but fails to activate transcription. Homozygous CLOCK mutants have a circadian rhythm that is increased from 3 to 4 hours and usually the circadian rhythmicity is lost at constant darkness. Expression of CLOCK is also reduced. There also exists an alternative spliced CLOCK variant missing both exon 18 and exon 19 (AA 484-564).1 Publication

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_002103484 – 513Missing in isoform Short. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000998 mRNA. Translation: AAC53200.1.
AF146793 Genomic DNA. Translation: AAD30565.1.
CCDSiCCDS19360.1. [O08785-1]
RefSeqiNP_001276755.1. NM_001289826.1. [O08785-1]
NP_031741.1. NM_007715.6. [O08785-1]
XP_017176137.1. XM_017320648.1. [O08785-1]
XP_017176139.1. XM_017320650.1. [O08785-2]
UniGeneiMm.3552.
Mm.392894.

Genome annotation databases

EnsembliENSMUST00000075159; ENSMUSP00000074656; ENSMUSG00000029238. [O08785-1]
ENSMUST00000202651; ENSMUSP00000143939; ENSMUSG00000029238. [O08785-1]
GeneIDi12753.
KEGGimmu:12753.
UCSCiuc008xuq.3. mouse. [O08785-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000998 mRNA. Translation: AAC53200.1.
AF146793 Genomic DNA. Translation: AAD30565.1.
CCDSiCCDS19360.1. [O08785-1]
RefSeqiNP_001276755.1. NM_001289826.1. [O08785-1]
NP_031741.1. NM_007715.6. [O08785-1]
XP_017176137.1. XM_017320648.1. [O08785-1]
XP_017176139.1. XM_017320650.1. [O08785-2]
UniGeneiMm.3552.
Mm.392894.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4F3LX-ray2.27A26-384[»]
DisProtiDP00734.
ProteinModelPortaliO08785.
SMRiO08785.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198756. 17 interactors.
DIPiDIP-30958N.
IntActiO08785. 28 interactors.
MINTiMINT-4654078.
STRINGi10090.ENSMUSP00000074656.

PTM databases

iPTMnetiO08785.
PhosphoSitePlusiO08785.

Proteomic databases

MaxQBiO08785.
PaxDbiO08785.
PeptideAtlasiO08785.
PRIDEiO08785.

Protocols and materials databases

DNASUi12753.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075159; ENSMUSP00000074656; ENSMUSG00000029238. [O08785-1]
ENSMUST00000202651; ENSMUSP00000143939; ENSMUSG00000029238. [O08785-1]
GeneIDi12753.
KEGGimmu:12753.
UCSCiuc008xuq.3. mouse. [O08785-1]

Organism-specific databases

CTDi9575.
MGIiMGI:99698. Clock.

Phylogenomic databases

eggNOGiKOG3561. Eukaryota.
ENOG410Y7Z8. LUCA.
GeneTreeiENSGT00760000118788.
HOGENOMiHOG000234382.
HOVERGENiHBG050997.
InParanoidiO08785.
KOiK02223.
OMAiTPINMQG.
OrthoDBiEOG091G11CV.
PhylomeDBiO08785.
TreeFamiTF324568.

Enzyme and pathway databases

ReactomeiR-MMU-1368082. RORA activates gene expression.
R-MMU-1368092. Rora activates gene expression.
R-MMU-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-MMU-1368110. Bmal1:Clock,Npas2 activates circadian gene expression.
R-MMU-1989781. PPARA activates gene expression.
R-MMU-400253. Circadian Clock.
R-MMU-508751. Circadian Clock.

Miscellaneous databases

PROiO08785.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029238.
CleanExiMM_CLOCK.
ExpressionAtlasiO08785. baseline and differential.
GenevisibleiO08785. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: O08785
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 1, 1997
Last modified: November 2, 2016
This is version 170 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.