Seroatlas · Human Serome Atlas

CLOCK

Circadian locomoter output cycles protein kaput

Also known as: bHLHe8, CLOCK_HUMAN, KAT13D, KIAA0334

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O15516
Gene: CLOCK
Ensembl: ENSG00000134852
Chromosome: 4
Canonical length: 846 aa
Protein class: Enzymes, Metabolic proteins, Predicted intracellular proteins, Transcription factors
Subcellular location: Nucleoplasm,Vesicles

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

846 residues, UniProt reviewed canonical sequence.

>O15516|CLOCK
     1  MLFTVSCSKM SSIVDRDDSS IFDGLVEEDD KDKAKRVSRN KSEKKRRDQF NVLIKELGSM
    61  LPGNARKMDK STVLQKSIDF LRKHKEITAQ SDASEIRQDW KPTFLSNEEF TQLMLEALDG
   121  FFLAIMTDGS IIYVSESVTS LLEHLPSDLV DQSIFNFIPE GEHSEVYKIL STHLLESDSL
   181  TPEYLKSKNQ LEFCCHMLRG TIDPKEPSTY EYVKFIGNFK SLNSVSSSAH NGFEGTIQRT
   241  HRPSYEDRVC FVATVRLATP QFIKEMCTVE EPNEEFTSRH SLEWKFLFLD HRAPPIIGYL
   301  PFEVLGTSGY DYYHVDDLEN LAKCHEHLMQ YGKGKSCYYR FLTKGQQWIW LQTHYYITYH
   361  QWNSRPEFIV CTHTVVSYAE VRAERRRELG IEESLPETAA DKSQDSGSDN RINTVSLKEA
   421  LERFDHSPTP SASSRSSRKS SHTAVSDPSS TPTKIPTDTS TPPRQHLPAH EKMVQRRSSF
   481  SSQSINSQSV GSSLTQPVMS QATNLPIPQG MSQFQFSAQL GAMQHLKDQL EQRTRMIEAN
   541  IHRQQEELRK IQEQLQMVHG QGLQMFLQQS NPGLNFGSVQ LSSGNSSNIQ QLAPINMQGQ
   601  VVPTNQIQSG MNTGHIGTTQ HMIQQQTLQS TSTQSQQNVL SGHSQQTSLP SQTQSTLTAP
   661  LYNTMVISQP AAGSMVQIPS SMPQNSTQSA AVTTFTQDRQ IRFSQGQQLV TKLVTAPVAC
   721  GAVMVPSTML MGQVVTAYPT FATQQQQSQT LSVTQQQQQQ SSQEQQLTSV QQPSQAQLTQ
   781  PPQQFLQTSR LLHGNPSTQL ILSAAFPLQQ STFPQSHHQQ HQSQQQQQLS RHRTDSLPDP
   841  SKVQPQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CLOCK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.55
Highest tissue expression: 13 nTPM

Expression across tissuesHPA

Tissue

testis: 13 nTPM
retina: 11 nTPM
parathyroid gland: 9.7 nTPM
thyroid gland: 9.5 nTPM
skeletal muscle: 9 nTPM
esophagus: 8.7 nTPM

Single-cell type

epicardial cells: 514 nCPM
thyrotrophs: 224 nCPM
lactotrophs: 204 nCPM
corticotrophs: 179 nCPM
myonuclei: 160 nCPM
somatotrophs: 157 nCPM

Immune cell

MAIT T-cell: 1.3 nTPM
myeloid DC: 1.1 nTPM
memory CD4 T-cell: 0.9 nTPM
NK-cell: 0.9 nTPM
T-reg: 0.9 nTPM
memory CD8 T-cell: 0.8 nTPM

Brain region

cerebellum: 34 nTPM
choroid plexus: 27 nTPM
hypothalamus: 26 nTPM
cerebral cortex: 26 nTPM
white matter: 25 nTPM
basal ganglia: 24 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.25
gnomAD pLI: 1
gnomAD missense Z: 1.83
DepMap mean gene effect: 0.01
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of CLOCK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads CLOCK as an antibody target. Whether an autoantibody or antibody against CLOCK could matter depends on whether native CLOCK is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

CLOCK is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label CLOCK as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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