Endometriosis Knowledgebase

Search Result

Gene id

9575

Gene Summary Protein Summary Gene ontology KEGG pathways Diseases PubMed references

Gene Summary

Gene Symbol

CLOCK Gene UCSC Ensembl

Aliases

KAT13D, bHLHe8

Gene name

clock circadian regulator

Alternate names

circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput protein, class E basic helix-loop-helix protein 8, clock homolog,

Gene location

4q12 (55547137: 55427900) Exons: 28 NC_000004.12

Gene summary(Entrez)

The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

OMIM

601851

Protein Summary

Protein general information

O15516

Name: Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix loop helix protein 8) (bHLHe8)

Length: 846 Mass: 95,304

Tissue specificity: Hair follicles (at protein level). Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. High

Sequence

MLFTVSCSKMSSIVDRDDSSIFDGLVEEDDKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQ
KSIDFLRKHKEITAQSDASEIRQDWKPTFLSNEEFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLV
DQSIFNFIPEGEHSEVYKILSTHLLESDSLTPEYLKSKNQLEFCCHMLRGTIDPKEPSTYEYVKFIGNFKSLNSV
SSSAHNGFEGTIQRTHRPSYEDRVCFVATVRLATPQFIKEMCTVEEPNEEFTSRHSLEWKFLFLDHRAPPIIGYL
PFEVLGTSGYDYYHVDDLENLAKCHEHLMQYGKGKSCYYRFLTKGQQWIWLQTHYYITYHQWNSRPEFIVCTHTV
VSYAEVRAERRRELGIEESLPETAADKSQDSGSDNRINTVSLKEALERFDHSPTPSASSRSSRKSSHTAVSDPSS
TPTKIPTDTSTPPRQHLPAHEKMVQRRSSFSSQSINSQSVGSSLTQPVMSQATNLPIPQGMSQFQFSAQLGAMQH
LKDQLEQRTRMIEANIHRQQEELRKIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQ
VVPTNQIQSGMNTGHIGTTQHMIQQQTLQSTSTQSQQNVLSGHSQQTSLPSQTQSTLTAPLYNTMVISQPAAGSM
VQIPSSMPQNSTQSAAVTTFTQDRQIRFSQGQQLVTKLVTAPVACGAVMVPSTMLMGQVVTAYPTFATQQQQSQT
LSVTQQQQQQSSQEQQLTSVQQPSQAQLTQPPQQFLQTSRLLHGNPSTQLILSAAFPLQQSTFPQSHHQQHQSQQ
QQQLSRHRTDSLPDPSKVQPQ

Structural information

Protein Domains	bHLH. (34-84) PAS (107-177) PAS (262-332) PAC. (336-379)
Motifs	Nuclear localization(32-47)
Interpro:	IPR011598 IPR001067 IPR001610 IPR000014 IPR013767
Prosite:	PS50888 PS50112
Pfam:	PF00010 PF00989
CDD:	cd00083 cd00130
PDB:	4H10
PDBsum:	4H10
DIP:	46009
STRING:	ENSP00000308741;

Other Databases

GeneCards: CLOCK; Malacards: CLOCK

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000077	DNA damage checkpoint	IMP	biological_process
GO:0000978	RNA polymerase II core pr omoter proximal region se quence-specific DNA bindi ng	IDA	molecular_function
GO:0000982	transcription factor acti vity, RNA polymerase II c ore promoter proximal reg ion sequence-specific bin ding	ISS	molecular_function
GO:0001046	core promoter sequence-sp ecific DNA binding	IEA	molecular_function
GO:0001047	core promoter binding	ISS	molecular_function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular_function
GO:0003677	DNA binding	IDA	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	ISS	molecular_function
GO:0004402	histone acetyltransferase activity	IMP	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005634	nucleus	IDA	cellular_component
GO:0005654	nucleoplasm	IDA	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005667	transcription factor comp lex	IPI	cellular_component
GO:0005694	chromosome	IDA	cellular_component
GO:0006355	regulation of transcripti on, DNA-templated	ISS	biological_process
GO:0006357	regulation of transcripti on from RNA polymerase II promoter	TAS	biological_process
GO:0006366	transcription from RNA po lymerase II promoter	IEA	biological_process
GO:0007165	signal transduction	TAS	biological_process
GO:0007283	spermatogenesis	ISS	biological_process
GO:0007623	circadian rhythm	TAS	biological_process
GO:0009648	photoperiodism	TAS	biological_process
GO:0009649	entrainment of circadian clock	IEA	biological_process
GO:0016573	histone acetylation	IEA	biological_process
GO:0031490	chromatin DNA binding	ISS	molecular_function
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	IMP	biological_process
GO:0032922	circadian regulation of g ene expression	IDA	biological_process
GO:0033391	chromatoid body	ISS	cellular_component
GO:0042634	regulation of hair cycle	IMP	biological_process
GO:0043161	proteasome-mediated ubiqu itin-dependent protein ca tabolic process	ISS	biological_process
GO:0043231	intracellular membrane-bo unded organelle	IDA	cellular_component
GO:0043565	sequence-specific DNA bin ding	ISS	molecular_function
GO:0045892	negative regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	IDA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	IGI	biological_process
GO:0046983	protein dimerization acti vity	IEA	molecular_function
GO:0050729	positive regulation of in flammatory response	IEA	biological_process
GO:0050796	regulation of insulin sec retion	ISS	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	ISS	biological_process
GO:0051775	response to redox state	IDA	biological_process
GO:0070888	E-box binding	IDA	molecular_function
GO:0070888	E-box binding	IDA	molecular_function
GO:0071479	cellular response to ioni zing radiation	IDA	biological_process
GO:2000074	regulation of type B panc reatic cell development	ISS	biological_process
GO:2000323	negative regulation of gl ucocorticoid receptor sig naling pathway	ISS	biological_process
GO:0000077	DNA damage checkpoint	IMP	biological_process
GO:0000978	RNA polymerase II core pr omoter proximal region se quence-specific DNA bindi ng	IDA	molecular_function
GO:0000982	transcription factor acti vity, RNA polymerase II c ore promoter proximal reg ion sequence-specific bin ding	IEA	molecular_function
GO:0000982	transcription factor acti vity, RNA polymerase II c ore promoter proximal reg ion sequence-specific bin ding	ISS	molecular_function
GO:0001046	core promoter sequence-sp ecific DNA binding	IEA	molecular_function
GO:0001047	core promoter binding	IEA	molecular_function
GO:0001047	core promoter binding	ISS	molecular_function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	IEA	molecular_function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular_function
GO:0003677	DNA binding	IEA	molecular_function
GO:0003677	DNA binding	IDA	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	IEA	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	IEA	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	ISS	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	TAS	molecular_function
GO:0004402	histone acetyltransferase activity	IEA	molecular_function
GO:0004402	histone acetyltransferase activity	IEA	molecular_function
GO:0004402	histone acetyltransferase activity	IMP	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005634	nucleus	IEA	cellular_component
GO:0005634	nucleus	IEA	cellular_component
GO:0005634	nucleus	IEA	cellular_component
GO:0005634	nucleus	IEA	cellular_component
GO:0005634	nucleus	IDA	cellular_component
GO:0005654	nucleoplasm	IDA	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005667	transcription factor comp lex	IEA	cellular_component
GO:0005667	transcription factor comp lex	IEA	cellular_component
GO:0005667	transcription factor comp lex	IPI	cellular_component
GO:0005694	chromosome	IDA	cellular_component
GO:0005737	cytoplasm	IEA	cellular_component
GO:0005737	cytoplasm	IEA	cellular_component
GO:0005737	cytoplasm	IEA	cellular_component
GO:0005737	cytoplasm	IEA	cellular_component
GO:0006351	transcription, DNA-templa ted	IEA	biological_process
GO:0006355	regulation of transcripti on, DNA-templated	IEA	biological_process
GO:0006355	regulation of transcripti on, DNA-templated	IEA	biological_process
GO:0006355	regulation of transcripti on, DNA-templated	ISS	biological_process
GO:0006355	regulation of transcripti on, DNA-templated	IEA	biological_process
GO:0006357	regulation of transcripti on from RNA polymerase II promoter	TAS	biological_process
GO:0006366	transcription from RNA po lymerase II promoter	IEA	biological_process
GO:0006974	cellular response to DNA damage stimulus	IEA	biological_process
GO:0007165	signal transduction	TAS	biological_process
GO:0007283	spermatogenesis	IEA	biological_process
GO:0007283	spermatogenesis	ISS	biological_process
GO:0007623	circadian rhythm	IEA	biological_process
GO:0007623	circadian rhythm	TAS	biological_process
GO:0007623	circadian rhythm	TAS	biological_process
GO:0009416	response to light stimulu s	IEA	biological_process
GO:0009648	photoperiodism	TAS	biological_process
GO:0009649	entrainment of circadian clock	IEA	biological_process
GO:0016573	histone acetylation	IEA	biological_process
GO:0016740	transferase activity	IEA	molecular_function
GO:0016746	transferase activity, tra nsferring acyl groups	IEA	molecular_function
GO:0031490	chromatin DNA binding	IEA	molecular_function
GO:0031490	chromatin DNA binding	ISS	molecular_function
GO:0032922	circadian regulation of g ene expression	IEA	biological_process
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	IMP	biological_process
GO:0032922	circadian regulation of g ene expression	IDA	biological_process
GO:0033391	chromatoid body	IEA	cellular_component
GO:0033391	chromatoid body	ISS	cellular_component
GO:0042634	regulation of hair cycle	IMP	biological_process
GO:0043161	proteasome-mediated ubiqu itin-dependent protein ca tabolic process	IEA	biological_process
GO:0043161	proteasome-mediated ubiqu itin-dependent protein ca tabolic process	ISS	biological_process
GO:0043231	intracellular membrane-bo unded organelle	IDA	cellular_component
GO:0043565	sequence-specific DNA bin ding	IEA	molecular_function
GO:0043565	sequence-specific DNA bin ding	ISS	molecular_function
GO:0045892	negative regulation of tr anscription, DNA-template d	IEA	biological_process
GO:0045892	negative regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	IEA	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	IDA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	IEA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	IGI	biological_process
GO:0046983	protein dimerization acti vity	IEA	molecular_function
GO:0048511	rhythmic process	IEA	biological_process
GO:0050729	positive regulation of in flammatory response	IEA	biological_process
GO:0050796	regulation of insulin sec retion	IEA	biological_process
GO:0050796	regulation of insulin sec retion	ISS	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	IEA	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	ISS	biological_process
GO:0051775	response to redox state	IDA	biological_process
GO:0070888	E-box binding	IEA	molecular_function
GO:0070888	E-box binding	IDA	molecular_function
GO:0070888	E-box binding	IDA	molecular_function
GO:0071479	cellular response to ioni zing radiation	IDA	biological_process
GO:2000074	regulation of type B panc reatic cell development	IEA	biological_process
GO:2000074	regulation of type B panc reatic cell development	ISS	biological_process
GO:2000323	negative regulation of gl ucocorticoid receptor sig naling pathway	IEA	biological_process
GO:2000323	negative regulation of gl ucocorticoid receptor sig naling pathway	ISS	biological_process
GO:0000077	DNA damage checkpoint	IMP	biological_process
GO:0000978	RNA polymerase II core pr omoter proximal region se quence-specific DNA bindi ng	IDA	molecular_function
GO:0000982	transcription factor acti vity, RNA polymerase II c ore promoter proximal reg ion sequence-specific bin ding	ISS	molecular_function
GO:0001047	core promoter binding	ISS	molecular_function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular_function
GO:0003677	DNA binding	IDA	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	ISS	molecular_function
GO:0003700	transcription factor acti vity, sequence-specific D NA binding	TAS	molecular_function
GO:0004402	histone acetyltransferase activity	IMP	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005515	protein binding	IPI	molecular_function
GO:0005634	nucleus	IDA	cellular_component
GO:0005654	nucleoplasm	IDA	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005654	nucleoplasm	TAS	cellular_component
GO:0005667	transcription factor comp lex	IPI	cellular_component
GO:0005694	chromosome	IDA	cellular_component
GO:0006355	regulation of transcripti on, DNA-templated	ISS	biological_process
GO:0006357	regulation of transcripti on from RNA polymerase II promoter	TAS	biological_process
GO:0007165	signal transduction	TAS	biological_process
GO:0007283	spermatogenesis	ISS	biological_process
GO:0007623	circadian rhythm	TAS	biological_process
GO:0007623	circadian rhythm	TAS	biological_process
GO:0009648	photoperiodism	TAS	biological_process
GO:0031490	chromatin DNA binding	ISS	molecular_function
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	ISS	biological_process
GO:0032922	circadian regulation of g ene expression	IMP	biological_process
GO:0032922	circadian regulation of g ene expression	IDA	biological_process
GO:0033391	chromatoid body	ISS	cellular_component
GO:0042634	regulation of hair cycle	IMP	biological_process
GO:0043161	proteasome-mediated ubiqu itin-dependent protein ca tabolic process	ISS	biological_process
GO:0043231	intracellular membrane-bo unded organelle	IDA	cellular_component
GO:0043565	sequence-specific DNA bin ding	ISS	molecular_function
GO:0045892	negative regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	ISS	biological_process
GO:0045893	positive regulation of tr anscription, DNA-template d	IDA	biological_process
GO:0045944	positive regulation of tr anscription from RNA poly merase II promoter	IGI	biological_process
GO:0050796	regulation of insulin sec retion	ISS	biological_process
GO:0051092	positive regulation of NF -kappaB transcription fac tor activity	ISS	biological_process
GO:0051775	response to redox state	IDA	biological_process
GO:0070888	E-box binding	IDA	molecular_function
GO:0070888	E-box binding	IDA	molecular_function
GO:0071479	cellular response to ioni zing radiation	IDA	biological_process
GO:2000074	regulation of type B panc reatic cell development	ISS	biological_process
GO:2000323	negative regulation of gl ucocorticoid receptor sig naling pathway	ISS	biological_process

KEGG pathways

hsa05168  Herpes simplex infection
PTHR23042:SF2  Circadian clock system
hsa04728  Dopaminergic synapse
hsa04710  Circadian rhythm

Diseases

Associated diseases	References
Anorexia nervosa	PMID: 17516548
Autism	PMID: 17264841
Bipolar disorder	PMID: 14582141
Cancer	PMID: 19934327
Depression	PMID: 19693801
Endometriosis	PMID: 18379422
Insomnia	PMID: 12898572
Major depressive disorder	PMID: 19347611
Male infertility	PMID: 23527142
Metabolic syndrome	PMID: 18541547
Ovarian endometriosis	PMID: 23006437
Ovarian endometriosis	PMID: 23006437
Schizophrenia	PMID: 19839995
Ovarian endometriosis	INFBASE23006437

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes	Abstract
23006437	Endometrio sis (ovari an)			18 (8 moderate endometriosis, 10 severe endom etriosis)		CLOCK ESR1 and MYC	Show abstract