PER1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PER1_MOUSE
• UniProt AC: O35973
• Protein Name: Period circadian protein homolog 1
• Gene Name: Per1
• Organism: Mus musculus (Mouse).
• Sequence Length: 1291
• Subcellular Localization: Nucleus. Cytoplasm. Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation. Translocate to the
• Protein Description: Transcriptional repressor which forms 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 NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1..
• Protein Sequence: MSGPLEGADGGGDPRPGEPFCPGGVPSPGAPQHRPCPGPSLADDTDANSNGSSGNESNGPESRGASQRSSHSSSSGNGKDSALLETTESSKSTNSQSPSPPSSSIAYSLLSASSEQDNPSTSGCSSEQSARARTQKELMTALRELKLRLPPERRGKGRSGTLATLQYALACVKQVQANQEYYQQWSLEEGEPCAMDMSTYTLEELEHITSEYTLRNQDTFSVAVSFLTGRIVYISEQAGVLLRCKRDVFRGARFSELLAPQDVGVFYGSTTPSRLPTWGTGTSAGSGLKDFTQEKSVFCRIRGGPDRDPGPRYQPFRLTPYVTKIRVSDGAPAQPCCLLIAERIHSGYEAPRIPPDKRIFTTRHTPSCLFQDVDERAAPLLGYLPQDLLGAPVLLFLHPEDRPLMLAIHKKILQLAGQPFDHSPIRFCARNGEYVTMDTSWAGFVHPWSRKVAFVLGRHKVRTAPLNEDVFTPPAPSPAPSLDSDIQELSEQIHRLLLQPVHSSSPTGLCGVGPLMSPGPLHSPGSSSDSNGGDAEGPGPPAPVTFQQICKDVHLVKHQGQQLFIESRAKPPPRPRLLATGTFKAKVLPCQSPNPELEVAPVPDQASLALAPEEPERKETSGCSYQQINCLDSILRYLESCNIPSTTKRKCASSSSYTASSASDDDKQRAGPVPVGAKKDPSSAMLSGEGATPRKEPVVGGTLSPLALANKAESVVSVTSQCSFSSTIVHVGDKKPPESDIIMMEDLPGLAPGPAPSPAPSPTVAPDPTPDAYRPVGLTKAVLSLHTQKEEQAFLNRFRDLGRLRGLDTSSVAPSAPGCHHGPIPPGRRHHCRSKAKRSRHHHHQTPRPETPCYVSHPSPVPSSGPWPPPPATTPFPAMVQPYPLPVFSPRGGPQPLPPAPTSVSPATFPSPLVTPMVALVLPNYLFPTPPSYPYGVSQAPVEGPPTPASHSPSPSLPPPPLSPPHRPDSPLFNSRCSSPLQLNLLQLEESPRTEGGAAAGGPGSSAGPLPPSEETAEPEARLVEVTESSNQDALSGSSDLLELLLQEDSRSGTGSAASGSLGSGLGSGSGSGSHEGGSTSASITRSSQSSHTSKYFGSIDSSEAEAGAARARTEPGDQVIKCVLQDPIWLLMANADQRVMMTYQVPSRDAASVLKQDRERLRAMQKQQPRFSEDQRRELGAVHSWVRKGQLPRALDVTACVDCGSSVQDPGHSDDPLFSELDGLGLEPMEEGGGEGGGCGVGGGGGDGGEEAQTQIGAKGSSSQDSAMEEEEQGGGSSSPALPAEENSTS

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
121	Phosphorylation	SEQDNPSTSGCSSEQ CCCCCCCCCCCCHHH	30.32	-
122	Phosphorylation	EQDNPSTSGCSSEQS CCCCCCCCCCCHHHH	41.98	-
126	Phosphorylation	PSTSGCSSEQSARAR CCCCCCCHHHHHHHH	43.67	-
134	Phosphorylation	EQSARARTQKELMTA HHHHHHHHHHHHHHH	42.90	26060331
140	Phosphorylation	RTQKELMTALRELKL HHHHHHHHHHHHHHH	34.85	26060331
269	Phosphorylation	DVGVFYGSTTPSRLP CEEEEECCCCCCCCC	20.09	24719451
592	Phosphorylation	AKVLPCQSPNPELEV EEEECCCCCCCCCEE	33.10	30352176
661	Phosphorylation	SSSYTASSASDDDKQ CCCCCCCCCCCCHHH	29.36	15148313
663	Phosphorylation	SYTASSASDDDKQRA CCCCCCCCCCHHHHC	43.45	15148313
683	Phosphorylation	GAKKDPSSAMLSGEG CCCCCHHHHCCCCCC	24.08	25338131
702	Phosphorylation	KEPVVGGTLSPLALA CCCCCCCCCCHHHHC	20.38	28833060
704	Phosphorylation	PVVGGTLSPLALANK CCCCCCCCHHHHCCC	20.08	25521595
714	Phosphorylation	ALANKAESVVSVTSQ HHCCCCCCCEEECCC	32.45	22817900
787	Phosphorylation	KAVLSLHTQKEEQAF HHHHHHCCHHHHHHH	46.78	23882026
815	Phosphorylation	DTSSVAPSAPGCHHG CCCCCCCCCCCCCCC	37.04	-
978	Phosphorylation	PLFNSRCSSPLQLNL CCCCCCCCCHHHCCE	33.60	21743459
979	Phosphorylation	LFNSRCSSPLQLNLL CCCCCCCCHHHCCEE	33.00	21743459
1096	Phosphorylation	QSSHTSKYFGSIDSS CCCCCCCCCCCCCHH	16.97	25293948
1099	Phosphorylation	HTSKYFGSIDSSEAE CCCCCCCCCCHHHHH	17.21	29472430
1102	Phosphorylation	KYFGSIDSSEAEAGA CCCCCCCHHHHHHHH	28.54	29472430
1103	Phosphorylation	YFGSIDSSEAEAGAA CCCCCCHHHHHHHHH	36.76	25293948

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
121	T	Phosphorylation	Kinase	CSNK1E	Q9JMK2	Uniprot
122	S	Phosphorylation	Kinase	CSNK1E	Q9JMK2	Uniprot
126	S	Phosphorylation	Kinase	CSNK1E	Q9JMK2	Uniprot
661	S	Phosphorylation	Kinase	CSNK1E	Q9JMK2	GPS
663	S	Phosphorylation	Kinase	CSNK1E	Q9JMK2	GPS
714	S	Phosphorylation	Kinase	CSNK1E	P49674	GPS
714	S	Phosphorylation	Kinase	KC1E	Q9JMK2	PhosphoELM

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of PER1_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 PER1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CLOCK_MOUSE	Clock	physical	14701732
PER2_MOUSE	Per2	physical	14701732
PER3_MOUSE	Per3	physical	14701732
CRY1_MOUSE	Cry1	physical	14701732
CRY2_MOUSE	Cry2	physical	14701732
CRY2_MOUSE	Cry2	genetic	12782655
HIF1A_HUMAN	HIF1A	physical	11726537
PER1_MOUSE	Per1	physical	20211142
TLX3_MOUSE	Tlx3	physical	20211142
FOXP1_MOUSE	Foxp1	physical	20211142
SIN3A_MOUSE	Sin3a	physical	21680841
CLOCK_MOUSE	Clock	physical	21680841
BMAL1_MOUSE	Arntl	physical	21680841
CRY1_MOUSE	Cry1	physical	21680841
KC1E_MOUSE	Csnk1e	physical	21680841
KC1D_MOUSE	Csnk1d	physical	21680841
NONO_MOUSE	Nono	physical	21680841
SFPQ_MOUSE	Sfpq	physical	21680841
PER1_MOUSE	Per1	physical	21966515
CRY1_MOUSE	Cry1	physical	21966515
BMAL1_MOUSE	Arntl	physical	21966515
KC1E_MOUSE	Csnk1e	physical	21966515
UBP2_MOUSE	Usp2	physical	21966515
UBP2_MOUSE	Usp2	physical	23213472

Drug and Disease Associations

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