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Identification
HMDB Protein ID HMDBP11569
Secondary Accession Numbers
  • 21013
Name Circadian locomoter output cycles protein kaput
Synonyms
  1. Class E basic helix-loop-helix protein 8
  2. bHLHe8
  3. hCLOCK
Gene Name CLOCK
Protein Type Enzyme
Biological Properties
General Function Involved in transcription regulator activity
Specific Function ARNTL/2-CLOCK heterodimers activate E-box element (5'-CACGTG-3') transcription of a number of proteins of the circadian clock. Activates transcription of PER1 and PER2. This transcription is inhibited in a feedback loop by PER and CRY proteins. Has intrinsic histone acetyltransferase activity and this enzymatic function contributes to chromatin-remodeling events implicated in circadian control of gene expression (By similarity). Acetylates primarily histones H3 and H4 (By similarity). Acetylates also a non-histone substrate: ARNTL (By similarity). Plays a role in DNA damage response (DDR) signaling during the S phase.
Pathways
  • Circadian rhythm
  • Dopaminergic synapse
  • Herpes simplex infection
Reactions
Acetyl-CoA + [histone] → Coenzyme A + acetyl-[histone] details
GO Classification
Biological Process
signal transduction
histone acetylation
cellular response to ionizing radiation
circadian regulation of gene expression
DNA damage checkpoint
entrainment of circadian clock
photoperiodism
Cellular Component
cytosol
chromosome
transcription factor complex
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
molecular transducer activity
signal transducer activity
transcription regulator activity
sequence-specific dna binding transcription factor activity
Molecular Function
signal transducer activity
E-box binding
RNA polymerase II core promoter proximal region sequence-specific DNA binding
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity
RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription
histone acetyltransferase activity
Process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
regulation of gene expression
regulation of transcription
regulation of transcription, dna-dependent
regulation of cellular process
signal transduction
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 4
Locus 4q12
SNPs CLOCK
Gene Sequence
>2541 bp
ATGTTGTTTACCGTAAGCTGTAGTAAAATGAGCTCGATTGTTGACAGAGATGACAGTAGT
ATTTTTGATGGGTTGGTGGAAGAAGATGACAAGGACAAAGCGAAAAGAGTATCTAGAAAC
AAATCTGAAAAGAAACGTAGAGATCAATTTAATGTTCTCATTAAAGAACTGGGATCCATG
CTTCCTGGTAATGCTAGAAAGATGGACAAATCTACTGTTCTGCAGAAAAGCATTGATTTT
TTACGAAAACATAAAGAAATCACTGCACAGTCAGATGCTAGTGAAATTCGACAGGACTGG
AAACCTACATTCCTTAGTAATGAAGAGTTTACACAATTAATGTTAGAGGCTCTTGATGGT
TTTTTTTTAGCAATCATGACAGATGGAAGCATAATATATGTGTCTGAGAGTGTAACTTCA
TTACTTGAACATTTACCATCTGATCTTGTGGATCAAAGTATATTTAATTTTATCCCAGAA
GGGGAACATTCAGAGGTTTATAAAATACTCTCTACTCATCTGCTGGAAAGTGATTCATTA
ACCCCAGAATATTTAAAATCAAAAAATCAGTTAGAATTCTGTTGTCACATGCTGCGAGGA
ACAATAGACCCAAAGGAGCCATCTACCTATGAATATGTAAAATTTATAGGAAATTTCAAA
TCTTTAAACAGTGTATCCTCTTCAGCACACAATGGTTTTGAAGGAACTATACAACGCACA
CATAGGCCATCTTATGAAGATAGAGTTTGTTTTGTAGCTACTGTCAGGTTAGCTACACCT
CAGTTCATCAAGGAAATGTGCACTGTTGAAGAACCCAATGAAGAGTTTACATCTAGACAT
AGTTTAGAATGGAAGTTTCTGTTTCTAGATCACAGGGCACCACCCATAATAGGGTATTTG
CCATTTGAAGTTCTGGGAACATCAGGCTATGATTACTATCATGTGGATGACCTAGAAAAT
TTGGCAAAATGTCATGAGCACTTAATGCAATATGGGAAAGGCAAATCATGTTATTATAGG
TTCCTGACTAAGGGGCAACAGTGGATTTGGCTTCAGACTCATTATTATATCACTTACCAT
CAGTGGAATTCAAGGCCAGAGTTTATTGTTTGTACTCACACTGTAGTAAGTTATGCAGAA
GTTAGGGCTGAAAGACGACGAGAACTTGGCATTGAAGAGTCTCTTCCTGAGACAGCTGCT
GACAAAAGCCAAGATTCTGGGTCAGATAATCGTATAAACACAGTCAGTCTCAAGGAAGCA
TTGGAAAGGTTTGATCACAGCCCAACCCCTTCTGCCTCTTCTCGGAGTTCAAGAAAATCA
TCTCACACGGCCGTCTCAGACCCTTCCTCAACACCAACCAAGATCCCGACGGATACGAGC
ACTCCACCCAGGCAGCATTTACCAGCTCATGAGAAGATGGTGCAAAGAAGGTCATCATTT
AGTAGTCAGTCCATAAATTCCCAGTCTGTTGGTTCATCATTAACACAGCCAGTGATGTCT
CAAGCTACAAATTTACCAATTCCACAAGGCATGTCCCAGTTTCAGTTTTCAGCTCAATTA
GGAGCCATGCAACATCTGAAAGACCAATTGGAACAACGGACACGCATGATAGAAGCAAAT
ATTCATCGGCAACAAGAAGAACTAAGAAAAATTCAAGAACAACTTCAGATGGTCCATGGT
CAGGGGCTGCAGATGTTTTTGCAACAATCAAATCCTGGGTTGAATTTTGGTTCCGTTCAA
CTTTCTTCTGGAAATTCATCTAACATCCAGCAACTTGCACCTATAAATATGCAAGGCCAA
GTTGTTCCTACTAACCAGATTCAAAGTGGAATGAATACTGGACACATTGGCACAACTCAG
CACATGATACAACAACAGACTTTACAGAGTACATCAACTCAGAGTCAACAAAATGTACTG
AGTGGGCACAGTCAGCAAACATCTCTACCCAGTCAGACACAGAGCACTCTTACAGCCCCA
CTGTATAACACTATGGTGATTTCTCAGCCTGCAGCCGGAAGCATGGTCCAGATTCCATCT
AGTATGCCACAAAACAGCACCCAGAGTGCTGCAGTAACTACATTCACTCAGGACAGGCAG
ATAAGATTTTCTCAAGGTCAACAACTTGTGACCAAATTAGTGACTGCTCCTGTAGCTTGT
GGGGCAGTCATGGTACCTAGTACTATGCTTATGGGCCAGGTGGTGACTGCATATCCTACT
TTTGCTACACAACAGCAACAGTCACAGACATTGTCAGTAACGCAGCAGCAGCAGCAGCAG
AGCTCCCAGGAGCAGCAGCTCACTTCAGTTCAGCAACCATCTCAGGCTCAGCTGACCCAG
CCACCGCAACAATTTTTACAGACTTCTAGGTTGCTCCATGGGAATCCCTCAACTCAACTC
ATTCTCTCTGCTGCATTTCCTCTACAACAGAGCACCTTCCCTCAGTCACATCACCAGCAA
CATCAGTCTCAGCAACAGCAGCAACTCAGCCGGCACAGGACTGACAGCTTGCCCGACCCT
TCCAAGGTTCAACCACAGTAG
Protein Properties
Number of Residues 846
Molecular Weight 95303.295
Theoretical pI 6.999
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Circadian locomoter output cycles protein kaput
MLFTVSCSKMSSIVDRDDSSIFDGLVEEDDKDKAKRVSRNKSEKKRRDQFNVLIKELGSM
LPGNARKMDKSTVLQKSIDFLRKHKEITAQSDASEIRQDWKPTFLSNEEFTQLMLEALDG
FFLAIMTDGSIIYVSESVTSLLEHLPSDLVDQSIFNFIPEGEHSEVYKILSTHLLESDSL
TPEYLKSKNQLEFCCHMLRGTIDPKEPSTYEYVKFIGNFKSLNSVSSSAHNGFEGTIQRT
HRPSYEDRVCFVATVRLATPQFIKEMCTVEEPNEEFTSRHSLEWKFLFLDHRAPPIIGYL
PFEVLGTSGYDYYHVDDLENLAKCHEHLMQYGKGKSCYYRFLTKGQQWIWLQTHYYITYH
QWNSRPEFIVCTHTVVSYAEVRAERRRELGIEESLPETAADKSQDSGSDNRINTVSLKEA
LERFDHSPTPSASSRSSRKSSHTAVSDPSSTPTKIPTDTSTPPRQHLPAHEKMVQRRSSF
SSQSINSQSVGSSLTQPVMSQATNLPIPQGMSQFQFSAQLGAMQHLKDQLEQRTRMIEAN
IHRQQEELRKIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQ
VVPTNQIQSGMNTGHIGTTQHMIQQQTLQSTSTQSQQNVLSGHSQQTSLPSQTQSTLTAP
LYNTMVISQPAAGSMVQIPSSMPQNSTQSAAVTTFTQDRQIRFSQGQQLVTKLVTAPVAC
GAVMVPSTMLMGQVVTAYPTFATQQQQSQTLSVTQQQQQQSSQEQQLTSVQQPSQAQLTQ
PPQQFLQTSRLLHGNPSTQLILSAAFPLQQSTFPQSHHQQHQSQQQQQLSRHRTDSLPDP
SKVQPQ
GenBank ID Protein 4758010
UniProtKB/Swiss-Prot ID O15516
UniProtKB/Swiss-Prot Entry Name CLOCK_HUMAN
PDB IDs
GenBank Gene ID NM_004898.2
GeneCard ID CLOCK
GenAtlas ID CLOCK
HGNC ID HGNC:2082
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  4. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 1997 Apr 28;4(2):141-50. [PubMed:9205841 ]
  5. Sato TK, Yamada RG, Ukai H, Baggs JE, Miraglia LJ, Kobayashi TJ, Welsh DK, Kay SA, Ueda HR, Hogenesch JB: Feedback repression is required for mammalian circadian clock function. Nat Genet. 2006 Mar;38(3):312-9. Epub 2006 Feb 12. [PubMed:16474406 ]
  6. Steeves TD, King DP, Zhao Y, Sangoram AM, Du F, Bowcock AM, Moore RY, Takahashi JS: Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei. Genomics. 1999 Apr 15;57(2):189-200. [PubMed:10198158 ]