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UniProtKB - O08785 (CLOCK_MOUSE)

Entry version 198 (22 Apr 2020)
Sequence version 1 (01 Jul 1997)
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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

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. 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. 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. The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (By similarity). CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTL binds to the half-site 5'-GTGA-3' (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. 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. The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner (By similarity). Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (PubMed:30012868).By similarity32 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei84Important for interaction with ARNTL/BMAL1By similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, Acyltransferase, DNA-binding, Transferase
Biological processBiological rhythms, DNA damage, Transcription, Transcription regulation

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Circadian locomoter output cycles protein kaput (EC:2.3.1.48)
Short name:
mCLOCK
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Clock
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...MGIi		MGI:99698 Clock

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001271641 – 855Circadian locomoter output cycles protein kaputAdd BLAST855

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei38Phosphoserine1 Publication1
Modified residuei42Phosphoserine1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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
Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.1 Publication

Keywords - PTMi

Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQB - The MaxQuant DataBase

More...MaxQBi		O08785

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O08785

PeptideAtlas

More...PeptideAtlasi		O08785

PRoteomics IDEntifications database

More...PRIDEi		O08785

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O08785

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O08785

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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.4 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSMUSG00000029238 Expressed in pigmented layer of retina and 289 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O08785 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O08785 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 (PubMed:11779462).

Forms a heterodimer with ARNTL/BMAL1 (PubMed:9616112, PubMed:12897057, PubMed:16717091, PubMed:16980631, PubMed:18662546, PubMed:19946213, PubMed:22653727). The CLOCK-ARNTL/BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and for phosphorylation of both CLOCK and ARNTL/BMAL1 (PubMed:12897057).

Interacts with NR3C1 in a ligand-dependent fashion (PubMed:19141540).

Interacts with ESR1 and estrogen stimulates this interaction (By similarity).

Interacts with the complex p35/CDK5 (PubMed:24235147).

Interacts with RELA/p65 (PubMed:22895791).

Interacts with KAT2B, CREBBP and EP300 (By similarity).

Interacts with ID1 and ID3 (PubMed:20861012).

Interacts with ID2 (PubMed:20861012).

Interacts with MTA1 (PubMed:24089055).

Interacts with OGA (PubMed:23395175).

Interacts with SIRT1 (PubMed:18662546, PubMed:18662547).

Interacts with CIPC (PubMed:17310242).

Interacts with EZH2 (PubMed:16717091).

Interacts with EIF4E, PIWIL1 and DDX4 (PubMed:22900038).

Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (PubMed:16717091, PubMed:18430226, PubMed:18662546). 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 (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B (PubMed:19946213).

Interacts with KDM5A (PubMed:21960634).

Interacts with KMT2A; in a circadian manner (PubMed:21113167).

Interacts with MYBBP1A (PubMed:19129230).

Interacts with THRAP3 (PubMed:24043798).

Interacts with MED1; this interaction requires the presence of THRAP3 (PubMed:24043798).

Interacts with NCOA2 (PubMed:24529706). The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1.

Interacts with NDUFA9.

Interacts with IMPDH2; in a circadian manner (By similarity).

Interacts with ASS1; in a circadian manner (PubMed:28985504).

Interacts with PIWIL2 (via PIWI domain) (PubMed:28903391).

Interacts with HNF4A (By similarity).

By similarity27 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei39Interaction with E-box DNABy similarity1
Sitei43Interaction with E-box DNABy similarity1
Sitei47Interaction with E-box DNABy similarity1

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

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GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		198756, 17 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-3225 CLOCK-BMAL1 transcription complex
CPX-3228 CLOCK-BMAL2 transcription complex

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O08785

Database of interacting proteins

More...DIPi		DIP-30958N

Protein interaction database and analysis system

More...IntActi		O08785, 34 interactors

Molecular INTeraction database

More...MINTi		O08785

STRING: functional protein association networks

More...STRINGi		10090.ENSMUSP00000074656

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O08785 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1855
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O08785

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>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
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>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
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi32 – 47Nuclear localization signal1 PublicationAdd BLAST16

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi484 – 855Gln-richAdd BLAST372
Compositional biasi740 – 745Poly-Gln6
Compositional biasi751 – 759Poly-Gln9
Compositional biasi762 – 769Poly-Gln8
Compositional biasi828 – 837Poly-Gln10

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG3561 Eukaryota
ENOG410Y7Z8 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000157580

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O08785

KEGG Orthology (KO)

More...KOi		K02223

Identification of Orthologs from Complete Genome Data

More...OMAi		DNLAKCH

Database of Orthologous Groups

More...OrthoDBi		205871at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O08785

TreeFam database of animal gene trees

More...TreeFami		TF324568

Family and domain databases

Conserved Domains Database

More...CDDi		cd00083 HLH, 1 hit
cd00130 PAS, 2 hits

Database of protein disorder

More...DisProti		DP00734

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		4.10.280.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00010 HLH, 1 hit
PF00989 PAS, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00785 NCTRNSLOCATR

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00353 HLH, 1 hit
SM00086 PAC, 1 hit
SM00091 PAS, 2 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0J9YU61A0A0J9YU61_MOUSE
Circadian locomoter output cycles p...
Clock
854Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>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
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_002103484 – 513Missing in isoform Short. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF000998 mRNA Translation: AAC53200.1
AF146793 Genomic DNA Translation: AAD30565.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS19360.1 [O08785-1]

NCBI Reference Sequences

More...RefSeqi		NP_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]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENSMUST00000075159; ENSMUSP00000074656; ENSMUSG00000029238 [O08785-1]
ENSMUST00000202651; ENSMUSP00000143939; ENSMUSG00000029238 [O08785-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		12753

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		mmu:12753

UCSC genome browser

More...UCSCi		uc008xuq.3 mouse [O08785-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4F3LX-ray2.27A26-384[»]
5VJIX-ray1.86A/B/D/E516-560[»]
5VJXX-ray2.69B/C/E/F/H/I/K/L/N/O/S/T/V/W/Y/Z/b/c/e/f515-560[»]
SMRiO08785
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi198756, 17 interactors
ComplexPortaliCPX-3225 CLOCK-BMAL1 transcription complex
CPX-3228 CLOCK-BMAL2 transcription complex
CORUMiO08785
DIPiDIP-30958N
IntActiO08785, 34 interactors
MINTiO08785
STRINGi10090.ENSMUSP00000074656

PTM databases

iPTMnetiO08785
PhosphoSitePlusiO08785

Proteomic databases

MaxQBiO08785
PaxDbiO08785
PeptideAtlasiO08785
PRIDEiO08785

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		909 492 antibodies

The DNASU plasmid repository

More...DNASUi		12753

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		9575
MGIiMGI:99698 Clock

Phylogenomic databases

eggNOGiKOG3561 Eukaryota
ENOG410Y7Z8 LUCA
GeneTreeiENSGT00940000157580
InParanoidiO08785
KOiK02223
OMAiDNLAKCH
OrthoDBi205871at2759
PhylomeDBiO08785
TreeFamiTF324568

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		Clock mouse

Protein Ontology

More...PROi		PR:O08785
RNActiO08785 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSMUSG00000029238 Expressed in pigmented layer of retina and 289 other tissues
ExpressionAtlasiO08785 baseline and differential
GenevisibleiO08785 MM

Family and domain databases

CDDicd00083 HLH, 1 hit
cd00130 PAS, 2 hits
DisProtiDP00734
Gene3Di4.10.280.10, 1 hit
InterProiView protein in InterPro
IPR011598 bHLH_dom
IPR036638 HLH_DNA-bd_sf
IPR001067 Nuc_translocat
IPR001610 PAC
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR013767 PAS_fold
PfamiView protein in Pfam
PF00010 HLH, 1 hit
PF00989 PAS, 1 hit
PRINTSiPR00785 NCTRNSLOCATR
SMARTiView protein in SMART
SM00353 HLH, 1 hit
SM00086 PAC, 1 hit
SM00091 PAS, 2 hits
SUPFAMiSSF47459 SSF47459, 1 hit
SSF55785 SSF55785, 2 hits
PROSITEiView protein in PROSITE
PS50888 BHLH, 1 hit
PS50112 PAS, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCLOCK_MOUSE
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O08785
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 1, 1997
Last modified: April 22, 2020
This is version 198 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, 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
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