PER3_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PER3_MOUSE
• UniProt AC: O70361
• Protein Name: Period circadian protein homolog 3
• Gene Name: Per3
• Organism: Mus musculus (Mouse).
• Sequence Length: 1113
• Subcellular Localization: Cytoplasm . Nucleus . Mainly cytoplasmic. Translocates to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not TIMELESS.
• Protein Description: Originally described as 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, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme..
• Protein Sequence: MDPCGDPAVPGGDCPQTRGPGLQGASGQEGPLQGTCVDSSHSEHEDRNRMSEELIMVVQEMKKYFPAERHTKPSTLDALNYALRCVHSVQANSDFFQSLGPRGAHQADVTVYSLEDLTALASEHTSKNTDTFAAVFSFLSGRLVHISEQAALILNSKRGFLKSVHFVDLLAPQDVRAFYAHTAPTQLPFWNNWTQRASQYECAPAKPFFCRICGGGDREKRHYSPFRILPYLVHVHSSAQPEPEPCCLTLVEKIHSGYEAPRIPVDKRIFTTTHTPGCVFLEVDERAVPLLGYLPQDLIGTSILTYLHPEDRPLMVAIHQKVLKYAGHPPFEHSPVRFCTQNGEYVILDSSWSSFVNPWSRKVSFIIGRHKVRTSPLNEDVFATRIKKAASNDKDIAELQEQIHKLLLQPVHASASSGYGSLGSSGSQEQHVSITSSSESSGHCPEEGQHEQMTLQQVYASVNKIKNVGQQLYIESMARSSVKPVAETCVEPQGGDEQKDFSSSQTLKNKSTTDTGSGGNLQQEQPSSSYQQMNCIDSVIRYLTSYSLPALKRKCISCTNTSSSSEEAKPIPEVDSSQRDTEQLLDIRKQETTGPSTDIEGGAARTLSTAALSVASGISQCSCSSTSGHAPPLQSESVAVACKPWALRTKASHLAAGGFKHVGLTAAVLSAHTQKEEQNYVDRFREKILTSPYGCYLQQESRNRAQYSCVQAGSTAKHSRCAGSERQKHKRKKLPAPVDTSSPGAHLCPHVTGLLPDEQHWGPSASPSPLGAGLAFPSALVVPSQTPYLLPSFPLQDMASQGVGVSAAWGAAAGCPPLSAGPQAVAAFPSAYVDTLMTIFLHNAPLFPLWPPSFSPYPSLGAAGSSELAPLVPAMAPNPEPTTSGHSQRRVEENWEAHSEELPFISSRSSSPLQLNLLQEEMPAPSESADAVRRGAGPDAKHHCVTGPSGSRSRHCTSGELATATAQQESAAASGSSASSIYFSSTDYASEVSENRQRPQDRQRDEALPGAAEESIWRMIERTPECVLMTYQVPERGREEVLKQDLEKLQSMEQQQPLFSPAQREELAKVRSWIHSHTAPQEGHLQSCVACEDRGSVGDTAEVLEQHPAEDTS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
391	Phosphorylation	TRIKKAASNDKDIAE HHHHHHHHCCHHHHH	50.88	-
542	Phosphorylation	CIDSVIRYLTSYSLP HHHHHHHHHHHCCCH	11.83	20139300
547	Phosphorylation	IRYLTSYSLPALKRK HHHHHHCCCHHHHHH	27.87	20139300
714	Phosphorylation	YSCVQAGSTAKHSRC HHHHHCCCHHHCCCC	28.36	23684622
719	Phosphorylation	AGSTAKHSRCAGSER CCCHHHCCCCCCCHH	28.48	23684622
899	Phosphorylation	EENWEAHSEELPFIS HHHHHHHHHCCCCCC	39.55	25338131
906	Phosphorylation	SEELPFISSRSSSPL HHCCCCCCCCCCCHH	21.78	25338131
907	Phosphorylation	EELPFISSRSSSPLQ HCCCCCCCCCCCHHH	31.22	-
909	Phosphorylation	LPFISSRSSSPLQLN CCCCCCCCCCHHHHH	36.80	25338131
910	Phosphorylation	PFISSRSSSPLQLNL CCCCCCCCCHHHHHH	34.56	25338131
911	Phosphorylation	FISSRSSSPLQLNLL CCCCCCCCHHHHHHH	30.76	25338131

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of PER3_MOUSE !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of PER3_MOUSE !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PER3_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of PER3_MOUSE !!

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.