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Protein Page:
CLOCK (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
CLOCK ARNTL/2-CLOCK heterodimers activate E-box element (3'- CACGTG-5') 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. Acetylates primarily histones H3 and H4. Acetylates also a non-histone substrate: ARNTL. Plays a role in DNA damage response (DDR) signaling during the S phase. Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL or ARNTL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerization with ARNTL is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and ARNTL. Interaction with PER and CRY proteins requires translocation to the nucleus. Interaction of the CLOCK-ARNTL heterodimer with PER or CRY inhibits transcription activation. Binds weakly ARNTL and ARNTL2 to form heterodimers which bind poorly to the E-box motif. 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. Highest levels in testis and skeletal muscle. Low levels in thymus, lung and liver. Expressed in all brain regions with highest levels in cerebellum. Highly expressed in the suprachiasmatic nucleus (SCN). Note: This description may include information from UniProtKB.
Protein type: EC 2.3.1.48; Transcription factor; DNA binding protein; Acetyltransferase
Cellular Component: transcription factor complex; intracellular membrane-bound organelle; nucleolus; chromosome; nucleus; cytosol
Molecular Function: protein dimerization activity; protein binding; signal transducer activity; histone acetyltransferase activity; DNA binding; sequence-specific DNA binding; chromatin DNA binding; transcription factor activity
Biological Process: circadian rhythm; transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; establishment and/or maintenance of chromatin architecture; positive regulation of transcription, DNA-dependent; response to redox state; signal transduction; activation of NF-kappaB transcription factor; regulation of transcription from RNA polymerase II promoter; regulation of transcription, DNA-dependent; photoperiodism; DNA damage checkpoint; spermatogenesis; positive regulation of transcription from RNA polymerase II promoter; circadian regulation of gene expression; histone acetylation; negative regulation of transcription, DNA-dependent; regulation of insulin secretion; regulation of hair cycle
Reference #:  O15516 (UniProtKB)
Alt. Names/Synonyms: BHLHE8; circadian locomoter output cycles kaput protein; Circadian locomoter output cycles protein kaput; Class E basic helix-loop-helix protein 8; CLOCK; clock homolog (mouse); hCLOCK; KAT13D; KIAA0334
Gene Symbols: CLOCK
Molecular weight: 95,304 Da
Basal Isoelectric point: 6.51  Predict pI for various phosphorylation states
CST Pathways:  Crosstalk between PTMs
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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CLOCK

Protein Structure Not Found.


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Sites Implicated In
transcription, altered: S427‑p, S431‑p
transcription, induced: T451‑p, T461‑p
intracellular localization: T451‑p, T461‑p
phosphorylation: S431‑p
protein degradation: S427‑p, S431‑p, S434‑p, S437‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 K31-ac GLVEEDDkDKAKRVS
1 1 S38 kDKAKRVSRNkSEKK
0 1 K41-ac AKRVSRNkSEKKRRD
1 1 S42 KRVSRNkSEKKRRDQ
0 1 S59-p VLIKELGsMLPGNAR
1 0 K67-sm MLPGNARkMDKSTVL
0 1 K85-ub IDFLRKHkEITAQSD
0 2 S164-p FIPEGEHsEVYKILS
0 1 S177-p LSTHLLEsDSLTPEY
0 2 K186-ub SLTPEYLkSKNQLEF
0 12 Y331-p CHEHLMQyGKGKSCY
0 1 K402-ub LPETAADkSQDsGSD
0 1 S406-p AADkSQDsGSDNRIN
0 1 S408 DkSQDsGSDNRINTV
0 1 T414 GSDNRINTVSLkEAL
0 1 S416 DNRINTVSLkEALER
0 1 K418-ub RINTVSLkEALERFD
2 2 S427-p ALERFDHsPtPsASs
0 2 T429-p ERFDHsPtPsASsRS
1 1 S431-p FDHsPtPsASsRSsR
0 1 S433 HsPtPsASsRSsRKS
1 0 S434-p sPtPsASsRSsRKSS
1 0 S437-p PsASsRSsRKSSHTA
1 0 T451-p AVSDPSStPTKIPTD
1 2 T461-p KIPTDTStPPRQHLP
0 2 R702-m2 FTQDRQIrFSQGQQL
0 1 S836-p LSRHRTDsLPDPSkV
1 0 K842-sm DsLPDPSkVQPQ___
  mouse

 
K31 GLVEEDDKDKAKRVs
S38-p KDKAKRVsRNKsEKK
K41 AKRVsRNKsEKKRRD
S42-p KRVsRNKsEKKRRDQ
S59 VLIKELGSMLPGNAR
K67 MLPGNARKMDKSTVL
K85 IDFLRKHKETTAQSD
S164 FIPEGEHSEVYKILS
S177 LSTHLLESDSLTPEY
K186-ub SLTPEYLkSKNQLEF
Y331-p CHEHLMQyGKGKSCY
K402 LPETAADKSQDsGsD
S406-p AADKSQDsGsDNRIN
S408-p DKSQDsGsDNRINTV
T414 GsDNRINTVSLKEAL
S416 DNRINTVSLKEALER
K418 RINTVSLKEALERFD
S427-p ALERFDHsPTPSASS
T429 ERFDHsPTPSASSRS
S431 FDHsPTPSASSRSSR
S433 HsPTPSASSRSSRKS
S434 sPTPSASSRSSRKSS
S437 PSASSRSSRKSSHTA
T451 AVSDPSSTPTKIPTD
T461 KIPTDTSTPPRQHLP
R698-m2 FTQDRQIrFSQGQQL
S845 LPRHRTDSLTDPSKV
K851 DSLTDPSKVQPQ___
  rat

 
K31 GLVEEDDKDKAKRVS
S38 KDKAKRVSRNKSEKK
K41 AKRVSRNKSEKKRRD
S42 KRVSRNKSEKKRRDQ
S59 VLIKELGSMLPGNAR
K67 MLPGNARKMDKSTVL
K85 IDFLRKHKEITAQSD
S164 FIPEGEHSEVYKILS
S177 LSTHLLESDSLTPED
K186 SLTPEDLKSKNQLEF
Y331 CHEHLMQYGKGKSCY
K402 LPETAADKSQDSGSD
S406 AADKSQDSGSDNRIN
S408 DKSQDSGSDNRINtV
T414-p GSDNRINtVsLKEAL
S416-p DNRINtVsLKEALER
K418 RINtVsLKEALERFD
S427 ALERFDHSPtPsAsS
T429-p ERFDHSPtPsAsSRS
S431-p FDHSPtPsAsSRSSR
S433-p HSPtPsAsSRSSRKS
S434 SPtPsAsSRSSRKSS
S437 PsAsSRSSRKSSHTA
T451 AVSDPSSTPTKIPTD
T461 KIPTDTSTPPRPHLP
R701 FTQDRQIRFSQGQQL
S852 LHRHRTDSLTDPSKV
K858 DSLTDPSKVQPQ___
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