Clock

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).By similarity31 Publications

Catalytic activityⁱ

Acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N₆-acetyl-L-lysine.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	84	Important for interaction with ARNTL/BMAL1By similarity		1

GO - Molecular functionⁱ

chromatin DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 24610784
DNA binding Source: UniProtKB
DNA-binding transcription activator activity, RNA polymerase II-specific
Source: BHF-UCL
Inferred from direct assayⁱ
- 15560782
DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- 22653727
DNA-binding transcription factor activity, RNA polymerase II-specific
Source: BHF-UCL
Inferred from direct assayⁱ
- 15147242
E-box binding
Source: UniProtKB
Inferred from direct assayⁱ
histone acetyltransferase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 19141540
protein dimerization activity Source: InterPro
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific
Source: BHF-UCL
Inferred by curatorⁱ
- 14672706
RNA polymerase II distal enhancer sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
RNA polymerase II proximal promoter sequence-specific DNA binding
Source: BHF-UCL
Inferred from direct assayⁱ
- 15147242
sequence-specific DNA binding
Source: UniProtKB
Inferred from direct assayⁱ
- 21613214
transcription factor binding
Source: MGI
Inferred from sequence alignmentⁱ
- 11707566

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cellular response to ionizing radiation Source: MGI
circadian regulation of gene expression
Source: UniProtKB
Inferred from mutant phenotypeⁱ
circadian rhythm
Source: MGI
Inferred from direct assayⁱ
- 12897057
DNA damage checkpoint Source: MGI
negative regulation of glucocorticoid receptor signaling pathway
Source: UniProtKB
Inferred from direct assayⁱ
- 24378737
negative regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 24378737
positive regulation of inflammatory response
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22894897
positive regulation of NF-kappaB transcription factor activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22895791
positive regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
positive regulation of transcription by RNA polymerase II
Source: BHF-UCL
Inferred from direct assayⁱ
proteasome-mediated ubiquitin-dependent protein catabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 23395176
protein acetylation
Source: UniProtKB
Inferred from direct assayⁱ
- 28985504
regulation of hair cycle Source: UniProtKB
regulation of insulin secretion
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20562852
regulation of transcription, DNA-templated
Source: UniProtKB
Inferred from direct assayⁱ
- 22653727
regulation of type B pancreatic cell development
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 20562852
response to redox state Source: UniProtKB
spermatogenesis
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 22900038

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Activator, Acyltransferase, DNA-binding, Transferase
Biological process	Biological rhythms, DNA damage, Transcription, Transcription regulation

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Circadian locomoter output cycles protein kaput (EC:2.3.1.48) Short name: mCLOCK
Gene namesⁱ	Name:Clock
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 5

Organism-specific databases

MGIⁱ	MGI:99698 Clock

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	38	S → 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 Publication	1
Mutagenesisⁱ	42	S → 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 Publication	1
Mutagenesisⁱ	57	L → E: Reduced ARNTL/BMAL1 binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. Abolishes regulation of circadian clock. 1 Publication	1
Mutagenesisⁱ	67	K → 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 Publication	1
Mutagenesisⁱ	74	L → E: Reduced ARNTL/BMAL1 binding. Abolishes transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. 1 Publication	1
Mutagenesisⁱ	284	W → A: Reduced ARNTL/BMAL1 binding. Slightly reduced transcriptional activation by the CLOCK-ARNTL/BMAL1 heterodimer. 1 Publication	1
Mutagenesisⁱ	427	S → A: Significant loss of phosphorylation. 2 Publications	1
Mutagenesisⁱ	431	S → A: Significant loss of phosphorylation. 1 Publication	1
Mutagenesisⁱ	656	P → A: Reduces histone acetyltransferase activity; when associated with A-658 and A-659. 1 Publication	1
Mutagenesisⁱ	658	Y → A: Reduces histone acetyltransferase activity; when associated with A-656 and A-659. 1 Publication	1
Mutagenesisⁱ	659	N → A: Reduces histone acetyltransferase activity; when associated with A-656 and A-658. 1 Publication	1
Mutagenesisⁱ	669	G → A: Reduces histone acetyltransferase activity; when associated with A-670 and A-672. 1 Publication	1
Mutagenesisⁱ	670	S → A: Reduces histone acetyltransferase activity; when associated with A-669 and A-672. 1 Publication	1
Mutagenesisⁱ	672	V → A: Reduces histone acetyltransferase activity; when associated with A-669 and A-670. 1 Publication	1
Mutagenesisⁱ	851	K → 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 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000127164	1 – 855	Circadian locomoter output cycles protein kaputAdd BLAST		855

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	38	Phosphoserine1 Publication	1
Modified residueⁱ	42	Phosphoserine1 Publication	1
Cross-linkⁱ	67	Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)1 Publication
Modified residueⁱ	408	PhosphoserineCombined sources	1
Modified residueⁱ	427	Phosphoserine; by GSK3-beta2 Publications	1
Modified residueⁱ	431	Phosphoserine1 Publication	1
Modified residueⁱ	451	Phosphothreonine; by CDK51 Publication	1
Modified residueⁱ	461	Phosphothreonine; by CDK51 Publication	1
Cross-linkⁱ	851	Glycyl 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

MaxQB - The MaxQuant DataBase More...MaxQBⁱ	O08785
PaxDbⁱ	O08785
PeptideAtlas More...PeptideAtlasⁱ	O08785
PRIDEⁱ	O08785

PTM databases

iPTMnetⁱ	O08785
PhosphoSitePlusⁱ	O08785

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

Bgeeⁱ	ENSMUSG00000029238 Expressed in 290 organ(s), highest expression level in pigmented layer of retina
CleanExⁱ	MM_CLOCK
ExpressionAtlasⁱ	O08785 baseline and differential
Genevisibleⁱ	O08785 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 (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).By similarity26 Publications

Sites

Feature key	Position(s)	DescriptionActions	Length
Siteⁱ	39	Interaction with E-box DNABy similarity	1
Siteⁱ	43	Interaction with E-box DNABy similarity	1
Siteⁱ	47	Interaction with E-box DNABy similarity	1

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
Arntl	Q9WTL8	33	EBI-79859,EBI-644534
Arntl	Q9WTL8-2	2	EBI-79859,EBI-644559
Cry1	P97784	10	EBI-79859,EBI-1266607
Csnk1e	Q9JMK2	2	EBI-79859,EBI-771709
CSNK2B	P67870	2	EBI-79859,EBI-348169	From Homo sapiens.
Ddb1	Q3U1J4	4	EBI-79859,EBI-2552275
KMT2A	Q03164	3	EBI-79859,EBI-591370	From Homo sapiens.
NR1D2	Q14995	2	EBI-79859,EBI-6144053	From Homo sapiens.
Per2	O54943	10	EBI-79859,EBI-1266779
PPP1CA	P62136	2	EBI-79859,EBI-357253	From Homo sapiens.
PPP1CB	P62140	2	EBI-79859,EBI-352350	From Homo sapiens.
PPP1CC	P36873	2	EBI-79859,EBI-356283	From Homo sapiens.
PPP2R1B	P30154	2	EBI-79859,EBI-357094	From Homo sapiens.
PPP2R5D	Q14738	2	EBI-79859,EBI-396563	From Homo sapiens.
Prkca	P20444	3	EBI-79859,EBI-6976815
RORB	Q92753	2	EBI-79859,EBI-6144615	From Homo sapiens.
RORC	P51449	2	EBI-79859,EBI-3908771	From Homo sapiens.
Sirt1	Q923E4	11	EBI-79859,EBI-1802585

GO - Molecular functionⁱ

protein dimerization activity Source: InterPro
transcription factor binding
Source: MGI
Inferred from sequence alignmentⁱ
- 11707566

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	198756, 17 interactors
ComplexPortalⁱ	CPX-3225 CLOCK-BMAL1 transcription complex CPX-3228 CLOCK-BMAL2 transcription complex
CORUMⁱ	O08785
Database of interacting proteins More...DIPⁱ	DIP-30958N
IntActⁱ	O08785, 33 interactors
Molecular INTeraction database More...MINTⁱ	O08785
STRINGⁱ	10090.ENSMUSP00000074656

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	43 – 59	Combined sources	17
Beta strandⁱ	63 – 65	Combined sources	3
Helixⁱ	70 – 88	Combined sources	19
Helixⁱ	94 – 96	Combined sources	3
Helixⁱ	107 – 117	Combined sources	11
Beta strandⁱ	120 – 126	Combined sources	7
Beta strandⁱ	129 – 134	Combined sources	6
Helixⁱ	138 – 142	Combined sources	5
Helixⁱ	146 – 149	Combined sources	4
Helixⁱ	154 – 157	Combined sources	4
Helixⁱ	160 – 162	Combined sources	3
Helixⁱ	163 – 172	Combined sources	10
Beta strandⁱ	179 – 181	Combined sources	3
Helixⁱ	183 – 185	Combined sources	3
Helixⁱ	187 – 189	Combined sources	3
Beta strandⁱ	190 – 198	Combined sources	9
Beta strandⁱ	204 – 206	Combined sources	3
Beta strandⁱ	210 – 221	Combined sources	12
Beta strandⁱ	249 – 259	Combined sources	11
Beta strandⁱ	262 – 266	Combined sources	5
Beta strandⁱ	270 – 272	Combined sources	3
Beta strandⁱ	275 – 280	Combined sources	6
Beta strandⁱ	284 – 289	Combined sources	6
Helixⁱ	294 – 297	Combined sources	4
Helixⁱ	301 – 304	Combined sources	4
Helixⁱ	309 – 312	Combined sources	4
Helixⁱ	315 – 331	Combined sources	17
Beta strandⁱ	332 – 335	Combined sources	4
Beta strandⁱ	339 – 342	Combined sources	4
Beta strandⁱ	346 – 359	Combined sources	14
Turnⁱ	361 – 363	Combined sources	3
Beta strandⁱ	366 – 375	Combined sources	10
Helixⁱ	378 – 383	Combined sources	6
Helixⁱ	516 – 555	Combined sources	40

Show more details

3D structure databases

Database of protein disorder More...DisProtⁱ	DP00734
ProteinModelPortalⁱ	O08785
SMRⁱ	O08785
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	34 – 84	bHLHPROSITE-ProRule annotationAdd BLAST	51
Domainⁱ	107 – 177	PAS 1PROSITE-ProRule annotationAdd BLAST	71
Domainⁱ	262 – 332	PAS 2PROSITE-ProRule annotationAdd BLAST	71
Domainⁱ	336 – 379	PACAdd BLAST	44

Region

Feature key	Position(s)	DescriptionActions	Length
Regionⁱ	371 – 854	Interaction with NR3C11 PublicationAdd BLAST	484
Regionⁱ	450 – 570	Interaction with SIRT11 PublicationAdd BLAST	121
Regionⁱ	514 – 564	Implicated in the circadian rhythmicityAdd BLAST	51

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	32 – 47	Nuclear localization signal1 PublicationAdd BLAST		16

Compositional bias

Feature key	Position(s)	DescriptionActions	Length
Compositional biasⁱ	484 – 855	Gln-richAdd BLAST	372
Compositional biasⁱ	740 – 745	Poly-Gln	6
Compositional biasⁱ	751 – 759	Poly-Gln	9
Compositional biasⁱ	762 – 769	Poly-Gln	8
Compositional biasⁱ	828 – 837	Poly-Gln	10

Domainⁱ

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

Keywords - Domainⁱ

Repeat

Phylogenomic databases

eggNOGⁱ	KOG3561 Eukaryota ENOG410Y7Z8 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000118788
HOGENOMⁱ	HOG000234382
HOVERGENⁱ	HBG050997
InParanoidⁱ	O08785
KEGG Orthology (KO) More...KOⁱ	K02223
OMAⁱ	VPSTMFM
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G11CV
PhylomeDBⁱ	O08785
TreeFamⁱ	TF324568

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00083 HLH, 1 hit cd00130 PAS, 2 hits
Gene3Dⁱ	4.10.280.10, 1 hit
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
PRINTSⁱ	PR00785 NCTRNSLOCATR
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit SM00086 PAC, 1 hit SM00091 PAS, 2 hits
SUPFAMⁱ	SSF47459 SSF47459, 1 hit SSF55785 SSF55785, 2 hits
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit PS50112 PAS, 2 hits

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

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

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

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

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

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        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 SSQFQFSAQL GAMQHLKDQL 
       510        520        530        540        550
EQRTRMIEAN IHRQQEELRK IQEQLQMVHG QGLQMFLQQS NPGLNFGSVQ 
       560        570        580        590        600
LSSGNSNIQQ LTPVNMQGQV VPANQVQSGH ISTGQHMIQQ QTLQSTSTQQ 
       610        620        630        640        650
SQQSVMSGHS QQTSLPSQTP STLTAPLYNT MVISQPAAGS MVQIPSSMPQ 
       660        670        680        690        700
NSTQSATVTT FTQDRQIRFS QGQQLVTKLV TAPVACGAVM VPSTMLMGQV 
       710        720        730        740        750
VTAYPTFATQ QQQAQTLSVT QQQQQQQQQP PQQQQQQQQS SQEQQLPSVQ 
       760        770        780        790        800
QPAQAQLGQP PQQFLQTSRL LHGNPSTQLI LSAAFPLQQS TFPPSHHQQH 
       810        820 
QPQQQQQLPR HRTDSLTDPS KVQPQ

Show »

Length:825

Mass (Da):93,371

Checksum:ⁱFABAE927F765B680

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	A0A0J9YU61	A0A0J9YU61_MOUSE		Circadian locomoter output cycles p... Circadian locomoter output cycles protein kaput	Clock	854	Annotation score:

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 key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_002103	484 – 513	Missing in isoform Short. 1 PublicationAdd BLAST		30

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ 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]
UniGeneⁱ	Mm.3552 Mm.392894

Genome annotation databases

Ensemblⁱ	ENSMUST00000075159; ENSMUSP00000074656; ENSMUSG00000029238 [O08785-1] ENSMUST00000202651; ENSMUSP00000143939; ENSMUSG00000029238 [O08785-1]
GeneIDⁱ	12753
KEGGⁱ	mmu:12753
UCSC genome browser More...UCSCⁱ	uc008xuq.3 mouse [O08785-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
O08785	MKIAA0334 protein (Fragment)		MOUSE		857	UniRef100_O08785
Uncharacterized protein (Fragment)		MOUSE		272
UPI0003D7177E		MOUSE		730
O08785-2	CLOCK (Fragment)		MOUSE		222	UniRef100_O08785-2

Protein	Similar proteins		Species	Score	Length	Source
O08785	Circadian locomoter output cycles protein kaput		NANGA		865	UniRef90_O08785
Circadian locomoter output cycles protein kaput		SPACA		865
Circadian locomoter output cycles protein kaput		SPAJD		865
Circadian locomoter output cycles protein kaput		RAT		862
Circadian locomoter output cycles protein kaput	)	HUMAN		846
+187
O08785-2	CLOCK (Fragment)		MOUSE		222	UniRef90_O08785-2
Circadian locomoter output cycles protein kaput		RAT		833
Uncharacterized protein		PIG		827
Uncharacterized protein		MACNE		821
Uncharacterized protein		MACMU		820
+22

Protein	Similar proteins		Species	Score	Length	Source
O08785	Circadian locomoter output cycles protein kaput		SPACA		865	UniRef50_O08785
Circadian locomoter output cycles protein kaput		NANGA		865
Circadian locomoter output cycles protein kaput		SPAJD		865
Circadian locomoter output cycles protein kaput		RAT		862
Circadian locomoter output cycles protein kaput		PONAB		846
+325

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AF000998 mRNA Translation: AAC53200.1 AF146793 Genomic DNA Translation: AAD30565.1
CCDSⁱ	CCDS19360.1 [O08785-1]
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]
UniGeneⁱ	Mm.3552 Mm.392894

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 entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	4F3L	X-ray	2.27	A	26-384	[»]
	5VJI	X-ray	1.86	A/B/D/E	516-560	[»]
	5VJX	X-ray	2.69	B/C/E/F/H/I/K/L/N/O/S/T/V/W/Y/Z/b/c/e/f	515-560	[»]
DisProtⁱ	DP00734
ProteinModelPortalⁱ	O08785
SMRⁱ	O08785
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	198756, 17 interactors
ComplexPortalⁱ	CPX-3225 CLOCK-BMAL1 transcription complex CPX-3228 CLOCK-BMAL2 transcription complex
CORUMⁱ	O08785
DIPⁱ	DIP-30958N
IntActⁱ	O08785, 33 interactors
MINTⁱ	O08785
STRINGⁱ	10090.ENSMUSP00000074656

PTM databases

iPTMnetⁱ	O08785
PhosphoSitePlusⁱ	O08785

Proteomic databases

MaxQBⁱ	O08785
PaxDbⁱ	O08785
PeptideAtlasⁱ	O08785
PRIDEⁱ	O08785

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	12753
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000075159; ENSMUSP00000074656; ENSMUSG00000029238 [O08785-1] ENSMUST00000202651; ENSMUSP00000143939; ENSMUSG00000029238 [O08785-1]
GeneIDⁱ	12753
KEGGⁱ	mmu:12753
UCSCⁱ	uc008xuq.3 mouse [O08785-1]

Organism-specific databases

CTDⁱ	9575
MGIⁱ	MGI:99698 Clock

Phylogenomic databases

eggNOGⁱ	KOG3561 Eukaryota ENOG410Y7Z8 LUCA
GeneTreeⁱ	ENSGT00760000118788
HOGENOMⁱ	HOG000234382
HOVERGENⁱ	HBG050997
InParanoidⁱ	O08785
KOⁱ	K02223
OMAⁱ	VPSTMFM
OrthoDBⁱ	EOG091G11CV
PhylomeDBⁱ	O08785
TreeFamⁱ	TF324568

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:O08785
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000029238 Expressed in 290 organ(s), highest expression level in pigmented layer of retina
CleanExⁱ	MM_CLOCK
ExpressionAtlasⁱ	O08785 baseline and differential
Genevisibleⁱ	O08785 MM

Family and domain databases

CDDⁱ	cd00083 HLH, 1 hit cd00130 PAS, 2 hits
Gene3Dⁱ	4.10.280.10, 1 hit
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
Pfamⁱ	View protein in Pfam PF00010 HLH, 1 hit PF00989 PAS, 1 hit
PRINTSⁱ	PR00785 NCTRNSLOCATR
SMARTⁱ	View protein in SMART SM00353 HLH, 1 hit SM00086 PAC, 1 hit SM00091 PAS, 2 hits
SUPFAMⁱ	SSF47459 SSF47459, 1 hit SSF55785 SSF55785, 2 hits
PROSITEⁱ	View protein in PROSITE PS50888 BHLH, 1 hit PS50112 PAS, 2 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CLOCK_MOUSE
Accessionⁱ	O08785Primary (citable) accession number: O08785
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
	Last sequence update:	July 1, 1997
	Last modified:	November 7, 2018
	This is version 187 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

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

UniProtKB

UniParc

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UniRef

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Supporting data

UniProtKB - O08785 (CLOCK_MOUSE)

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Circadian locomoter output cycles protein kaput

Select a section on the left to see content.

<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

Sites

<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

GO - Biological processi

<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

Organism-specific databases

<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

Nucleus

Cytosol

Other locations

Cytosol

Endoplasmic reticulum

Nucleus

Other locations

Keywords - Cellular componenti

<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

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

<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

Sites

GO - Molecular functioni

Protein-protein interaction databases

<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

3D structure databases

<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

Region

Motif

Compositional bias

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<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 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

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ