dbPTM

PER2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PER2_MOUSE
UniProt AC	O54943
Protein Name	Period circadian protein homolog 2
Gene Name	Per2
Organism	Mus musculus (Mouse).
Sequence Length	1257
Subcellular Localization	Nucleus . Cytoplasm . Cytoplasm, perinuclear region. Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Translocate to the nucleus after phosphorylation by CSNK1D or CSNK1E.
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 syndrome 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. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-ARTNL/BMAL1 interactions. Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. May propagate clock information to metabolic pathways via the interaction with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like ARNTL or G6PC. Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby transcriptional activation. Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels. Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas. Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression. May also be involved in the regulation of inflammatory processes. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1..
Protein Sequence	MNGYVDFSPSPTSPTKEPGAPQPTQAVLQEDVDMSSGSSGNENCSTGRDSQGSDCDDNGKELRMLVESSNTHPSPDDAFRLMMTEAEHNPSTSGCSSEQSAKADAHKELIRTLKELKVHLPADKKAKGKASTLATLKYALRSVKQVKANEEYYQLLMSSESQPCSVDVPSYSMEQVEGITSEYIVKNADMFAVAVSLVSGKILYISNQVASIFHCKKDAFSDAKFVEFLAPHDVSVFHSYTTPYKLPPWSVCSGLDSFTQECMEEKSFFCRVSVGKHHENEIRYQPFRMTPYLVKVQEQQGAESQLCCLLLAERVHSGYEAPRIPPEKRIFTTTHTPNCLFQAVDERAVPLLGYLPQDLIETPVLVQLHPSDRPLMLAIHKKILQAGGQPFDYSPIRFRTRNGEYITLDTSWSSFINPWSRKISFIIGRHKVRVGPLNEDVFAAPPCPEEKTPHPSVQELTEQIHRLLMQPVPHSGSSGYGSLGSNGSHEHLMSQTSSSDSNGQEESHRRRSGIFKTSGKIQTKSHVSHESGGQKEASVAEMQSSPPAQVKAVTTIERDSSGASLPKASFPEELAYKNQPPCSYQQISCLDSVIRYLESCSEAATLKRKCEFPANIPSRKATVSPGLHSGEAARPSKVTSHTEVSAHLSSLTLPGKAESVVSLTSQCSYSSTIVHVGDKKPQPELETVEDMASGPESLDGAAGGLSQEKGPLQKLGLTKEVLAAHTQKEEQGFLQRFREVSRLSALQAHCQNYLQERSRAQASDRGLRNTSGLESSWKKTGKNRKLKSKRVKTRDSSESTGSGGPVSHRPPLMGLNATAWSPSDTSQSSCPSAPFPTAVPAYPLPVFQAPGIVSTPGTVVAPPAATHTGFTMPVVPMGTQPEFAVQPLPFAAPLAPVMAFMLPSYPFPPATPNLPQAFLPSQPHFPAHPTLASEITPASQAEFPSRTSTLRQPCACPVTPPAGTVALGRASPPLFQSRGSSPLQLNLLQLEEAPEGSTGAAGTLGTTGTAASGLDCTSGTSRDRQPKAPPTCNEPSDTQNSDAISTSSDLLNLLLGEDLCSATGSALSRSGASATSDSLGSSSLGFGTSQSGAGSSDTSHTSKYFGSIDSSENNHKAKMIPDTEESEQFIKYVLQDPIWLLMANTDDSIMMTYQLPSRDLQAVLKEDQEKLKLLQRSQPRFTEGQRRELREVHPWVHTGGLPTAIDVTGCVYCESEEKGNICLPYEEDSPSPGLCDTSEAKEEEGEQLTGPRIEAQT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
8	Phosphorylation	MNGYVDFSPSPTSPT CCCCCCCCCCCCCCC	21.72	22817900
10	Phosphorylation	GYVDFSPSPTSPTKE CCCCCCCCCCCCCCC	39.34	22817900
12	Phosphorylation	VDFSPSPTSPTKEPG CCCCCCCCCCCCCCC	52.23	22817900
13	Phosphorylation	DFSPSPTSPTKEPGA CCCCCCCCCCCCCCC	33.68	22817900
15	Phosphorylation	SPSPTSPTKEPGAPQ CCCCCCCCCCCCCCC	48.05	22817900
53	Phosphorylation	TGRDSQGSDCDDNGK CCCCCCCCCCCCCCC	27.68	22817900
69	Phosphorylation	LRMLVESSNTHPSPD EEHHHHCCCCCCCHH	32.04	22817900
71	Phosphorylation	MLVESSNTHPSPDDA HHHHCCCCCCCHHHH	36.79	22817900
74	Phosphorylation	ESSNTHPSPDDAFRL HCCCCCCCHHHHHHH	33.10	22817900
84	Phosphorylation	DAFRLMMTEAEHNPS HHHHHHHHHCCCCCC	20.34	22817900
91	Phosphorylation	TEAEHNPSTSGCSSE HHCCCCCCCCCCCHH	40.29	22817900
92	Phosphorylation	EAEHNPSTSGCSSEQ HCCCCCCCCCCCHHH	30.32	22817900
478	Phosphorylation	PVPHSGSSGYGSLGS CCCCCCCCCCCCCCC	39.29	-
523	Phosphorylation	KTSGKIQTKSHVSHE ECCCCEEEECCCCCC	37.68	22817900
525	Phosphorylation	SGKIQTKSHVSHESG CCCEEEECCCCCCCC	32.29	22817900
528	Phosphorylation	IQTKSHVSHESGGQK EEEECCCCCCCCCCE	19.00	22817900
531	Phosphorylation	KSHVSHESGGQKEAS ECCCCCCCCCCEEEC	42.68	22817900
538	Phosphorylation	SGGQKEASVAEMQSS CCCCEEECHHHHHCC	23.97	22817900
544	Phosphorylation	ASVAEMQSSPPAQVK ECHHHHHCCCCCCEE	43.43	22817900
545	Phosphorylation	SVAEMQSSPPAQVKA CHHHHHCCCCCCEEE	20.29	22817900
554	Phosphorylation	PAQVKAVTTIERDSS CCCEEEEEEEEECCC	27.24	22817900
618	Phosphorylation	EFPANIPSRKATVSP CCCCCCCCCCEECCC	42.49	22817900
622	Phosphorylation	NIPSRKATVSPGLHS CCCCCCEECCCCCCC	25.26	22817900
624	Phosphorylation	PSRKATVSPGLHSGE CCCCEECCCCCCCCC	14.64	22817900
659	Phosphorylation	TLPGKAESVVSLTSQ CCCCCCEEEEEECCC	32.45	22817900
662	Phosphorylation	GKAESVVSLTSQCSY CCCEEEEEECCCCCC	24.63	22817900
691	Oxidation	ELETVEDMASGPESL CCCCHHHHHCCCCCC	1.70	17242355
693	Phosphorylation	ETVEDMASGPESLDG CCHHHHHCCCCCCCC	48.52	16983144
697	Phosphorylation	DMASGPESLDGAAGG HHHCCCCCCCCCCCC	34.59	16983144
706	Phosphorylation	DGAAGGLSQEKGPLQ CCCCCCCCCCCCHHH	39.30	16097765
758	Phosphorylation	QNYLQERSRAQASDR HHHHHHHHHHHHHHH	31.08	22817900
763	Phosphorylation	ERSRAQASDRGLRNT HHHHHHHHHHCCCCC	18.76	22817900
770	Phosphorylation	SDRGLRNTSGLESSW HHHCCCCCCCCHHHH	20.10	22817900
775	Phosphorylation	RNTSGLESSWKKTGK CCCCCCHHHHHHHCC	46.68	25338131
776	Phosphorylation	NTSGLESSWKKTGKN CCCCCHHHHHHHCCC	33.27	22817900
793	Phosphorylation	LKSKRVKTRDSSEST CCCCCCCCCCCCCCC	36.53	22817900
796	Phosphorylation	KRVKTRDSSESTGSG CCCCCCCCCCCCCCC	32.49	22817900
797	Phosphorylation	RVKTRDSSESTGSGG CCCCCCCCCCCCCCC	39.60	22817900
799	Phosphorylation	KTRDSSESTGSGGPV CCCCCCCCCCCCCCC	39.76	22817900
800	Phosphorylation	TRDSSESTGSGGPVS CCCCCCCCCCCCCCC	31.17	22817900
802	Phosphorylation	DSSESTGSGGPVSHR CCCCCCCCCCCCCCC	40.44	22817900
807	Phosphorylation	TGSGGPVSHRPPLMG CCCCCCCCCCCCCCC	19.53	22817900
858	Phosphorylation	GIVSTPGTVVAPPAA CEECCCCEEECCCCC	17.01	22817900
866	Phosphorylation	VVAPPAATHTGFTMP EECCCCCCCCCCCCC	23.29	22817900
868	Phosphorylation	APPAATHTGFTMPVV CCCCCCCCCCCCCEE	29.63	22817900
933	Phosphorylation	PAHPTLASEITPASQ CCCCCHHHCCCHHHH	32.42	22817900
939	Phosphorylation	ASEITPASQAEFPSR HHCCCHHHHCCCCCC	31.00	22817900
959	Phosphorylation	QPCACPVTPPAGTVA CCCCCCCCCCCCCEE	14.54	22817900
964	Phosphorylation	PVTPPAGTVALGRAS CCCCCCCCEECCCCC	12.52	22817900
971	Phosphorylation	TVALGRASPPLFQSR CEECCCCCCCCHHCC	26.20	27180971
977	Phosphorylation	ASPPLFQSRGSSPLQ CCCCCHHCCCCCCCE	31.13	24899341
980	Phosphorylation	PLFQSRGSSPLQLNL CCHHCCCCCCCEEEE	27.89	22817900
981	Phosphorylation	LFQSRGSSPLQLNLL CHHCCCCCCCEEEEE	32.24	22817900
997	Phosphorylation	LEEAPEGSTGAAGTL EECCCCCCCCCCCCC	23.23	22817900
998	Phosphorylation	EEAPEGSTGAAGTLG ECCCCCCCCCCCCCC	41.52	22817900
1126	Phosphorylation	MIPDTEESEQFIKYV ECCCCHHHHHHHHHH	30.39	20159955
1132	Phosphorylation	ESEQFIKYVLQDPIW HHHHHHHHHHCCCEE	11.11	25293948
1145	Phosphorylation	IWLLMANTDDSIMMT EEEEECCCCCCEEEE	31.48	25293948
1148	Phosphorylation	LMANTDDSIMMTYQL EECCCCCCEEEEEEC	18.39	25293948
1152	Phosphorylation	TDDSIMMTYQLPSRD CCCCEEEEEECCCHH	7.25	25293948
1153	Phosphorylation	DDSIMMTYQLPSRDL CCCEEEEEECCCHHH	7.08	25293948
1157	Phosphorylation	MMTYQLPSRDLQAVL EEEEECCCHHHHHHH	47.20	25293948
1231	Phosphorylation	PYEEDSPSPGLCDTS CCCCCCCCCCCCCCH	35.24	22817900
1237	Phosphorylation	PSPGLCDTSEAKEEE CCCCCCCCHHHHHHH	27.72	22817900
1238	Phosphorylation	SPGLCDTSEAKEEEG CCCCCCCHHHHHHHC	23.47	22817900

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
53	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
69	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
71	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
84	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
91	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
92	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
525	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
528	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
531	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
538	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
544	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
545	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
545	S	Phosphorylation	Kinase	GRK2	Q99MK8	PSP
554	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
618	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
622	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
624	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
659	S	Phosphorylation	Kinase	CK1E	Q9JMK2	PSP
659	S	Phosphorylation	Kinase	CK1D	Q9DC28	PSP
662	S	Phosphorylation	Kinase	CK1D	Q9DC28	PSP
693	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
697	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
758	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
763	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
770	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
776	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
793	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
796	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
797	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
799	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
800	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
802	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
807	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
858	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
866	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
868	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
933	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
939	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
964	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
971	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
980	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
981	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
997	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
998	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
1237	T	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS
1238	S	Phosphorylation	Kinase	CSNK1D	Q9DC28	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of PER2_MOUSE !!

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of PER2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CLOCK_MOUSE	Clock	physical	14701732
PER1_MOUSE	Per1	physical	14701732
PER3_MOUSE	Per3	physical	14701732
CRY1_MOUSE	Cry1	physical	14701732
CRY2_MOUSE	Cry2	physical	14701732
PER2_MOUSE	Per2	physical	20211142
TF2AA_MOUSE	Gtf2a1	physical	20211142
FOXP1_MOUSE	Foxp1	physical	20211142
MED16_MOUSE	Med16	physical	20211142
SFPQ_MOUSE	Sfpq	physical	21680841
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
FBW1A_MOUSE	Btrc	physical	15767683
KC1E_MOUSE	Csnk1e	physical	15767683
CRY1_MOUSE	Cry1	physical	25127877
CRY2_MOUSE	Cry2	physical	25127877
UBP2_MOUSE	Usp2	physical	23213472
PML_HUMAN	PML	physical	22274616
PML_MOUSE	Pml	physical	22274616
CLOCK_MOUSE	Clock	physical	22274616
BMAL1_MOUSE	Arntl	physical	22274616

Drug and Disease Associations

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

Regulatory Network of PER2_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-693 AND SER-697, ANDMASS SPECTROMETRY.	17242355 [Abstract]
"Mapping of phosphorylation sites by a multi-protease approach withspecific phosphopeptide enrichment and NanoLC-MS/MS analysis."; Schlosser A., Vanselow J.T., Kramer A.; Anal. Chem. 77:5243-5250(2005). Cited for: PHOSPHORYLATION AT SER-525; SER-528; SER-531; SER-538; SER-544;THR-554; SER-706; SER-758; SER-763; THR-858; SER-939; THR-964; SER-971AND SER-1126.	16097765 [Abstract]