dbPTM

PER1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	PER1_HUMAN
UniProt AC	O15534
Protein Name	Period circadian protein homolog 1
Gene Name	PER1
Organism	Homo sapiens (Human).
Sequence Length	1290
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	MSGPLEGADGGGDPRPGESFCPGGVPSPGPPQHRPCPGPSLADDTDANSNGSSGNESNGHESRGASQRSSHSSSSGNGKDSALLETTESSKSTNSQSPSPPSSSIAYSLLSASSEQDNPSTSGCSSEQSARARTQKELMTALRELKLRLPPERRGKGRSGTLATLQYALACVKQVQANQEYYQQWSLEEGEPCSMDMSTYTLEELEHITSEYTLQNQDTFSVAVSFLTGRIVYISEQAAVLLRCKRDVFRGTRFSELLAPQDVGVFYGSTAPSRLPTWGTGASAGSGLRDFTQEKSVFCRIRGGPDRDPGPRYQPFRLTPYVTKIRVSDGAPAQPCCLLIAERIHSGYEAPRIPPDKRIFTTRHTPSCLFQDVDERAAPLLGYLPQDLLGAPVLLFLHPEDRPLMLAIHKKILQLAGQPFDHSPIRFCARNGEYVTMDTSWAGFVHPWSRKVAFVLGRHKVRTAPLNEDVFTPPAPSPAPSLDTDIQELSEQIHRLLLQPVHSPSPTGLCGVGAVTSPGPLHSPGSSSDSNGGDAEGPGPPAPVTFQQICKDVHLVKHQGQQLFIESRARPQSRPRLPATGTFKAKALPCQSPDPELEAGSAPVQAPLALVPEEAERKEASSCSYQQINCLDSILRYLESCNLPSTTKRKCASSSSYTTSSASDDDRQRTGPVSVGTKKDPPSAALSGEGATPRKEPVVGGTLSPLALANKAESVVSVTSQCSFSSTIVHVGDKKPPESDIIMMEDLPGLAPGPAPSPAPSPTVAPDPAPDAYRPVGLTKAVLSLHTQKEEQAFLSRFRDLGRLRGLDSSSTAPSALGERGCHHGPAPPSRRHHCRSKAKRSRHHQNPRAEAPCYVSHPSPVPPSTPWPTPPATTPFPAVVQPYPLPVFSPRGGPQPLPPAPTSVPPAAFPAPLVTPMVALVLPNYLFPTPSSYPYGALQTPAEGPPTPASHSPSPSLPALAPSPPHRPDSPLFNSRCSSPLQLNLLQLEELPRAEGAAVAGGPGSSAGPPPPSAEAAEPEARLAEVTESSNQDALSGSSDLLELLLQEDSRSGTGSAASGSLGSGLGSGSGSGSHEGGSTSASITRSSQSSHTSKYFGSIDSSEAEAGAARGGAEPGDQVIKYVLQDPIWLLMANADQRVMMTYQVPSRDMTSVLKQDRERLRAMQKQQPRFSEDQRRELGAVHSWVRKGQLPRALDVMACVDCGSSTQDPGHPDDPLFSELDGLGLEPMEEGGGEQGSSGGGSGEGEGCEEAQGGAKASSSQDLAMEEEEEGRSSSSPALPTAGNCTS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
19	Phosphorylation	GDPRPGESFCPGGVP CCCCCCCCCCCCCCC	37.76	26074081
27	Phosphorylation	FCPGGVPSPGPPQHR CCCCCCCCCCCCCCC	39.83	25850435
40	Phosphorylation	HRPCPGPSLADDTDA CCCCCCCCCCCCCCC	41.95	26074081
69	Phosphorylation	SRGASQRSSHSSSSG CCCCCCCCCCCCCCC	25.43	23401153
70	Phosphorylation	RGASQRSSHSSSSGN CCCCCCCCCCCCCCC	29.58	25954137
72	Phosphorylation	ASQRSSHSSSSGNGK CCCCCCCCCCCCCCC	33.59	23401153
73	Phosphorylation	SQRSSHSSSSGNGKD CCCCCCCCCCCCCCC	24.09	25954137
74	Phosphorylation	QRSSHSSSSGNGKDS CCCCCCCCCCCCCCC	45.33	23401153
75	Phosphorylation	RSSHSSSSGNGKDSA CCCCCCCCCCCCCCC	37.92	23401153
107	Phosphorylation	PPSSSIAYSLLSASS CCCHHHHHHHHHCCC	9.74	-
120	Ubiquitination	SSEQDNPSTSGCSSE CCCCCCCCCCCCCHH	41.27	-
121	Phosphorylation	SEQDNPSTSGCSSEQ CCCCCCCCCCCCHHH	30.32	-
122	Phosphorylation	EQDNPSTSGCSSEQS CCCCCCCCCCCHHHH	41.98	-
126	Phosphorylation	PSTSGCSSEQSARAR CCCCCCCHHHHHHHH	43.67	-
136	Ubiquitination	SARARTQKELMTALR HHHHHHHHHHHHHHH	52.80	29967540
159	Phosphorylation	ERRGKGRSGTLATLQ HHCCCCCCHHHHHHH	44.81	19835603
161	Phosphorylation	RGKGRSGTLATLQYA CCCCCCHHHHHHHHH	17.92	20068231
164	Phosphorylation	GRSGTLATLQYALAC CCCHHHHHHHHHHHH	19.94	20068231
167	Phosphorylation	GTLATLQYALACVKQ HHHHHHHHHHHHHHH	13.49	19835603
279	Ubiquitination	PSRLPTWGTGASAGS CCCCCCCCCCCCCCC	19.42	-
280	Phosphorylation	SRLPTWGTGASAGSG CCCCCCCCCCCCCCC	22.57	24114839
295	Ubiquitination	LRDFTQEKSVFCRIR CCCCCCCCCEEEEEC	41.94	23000965
308	Ubiquitination	IRGGPDRDPGPRYQP ECCCCCCCCCCCCCC	60.94	-
324	Ubiquitination	RLTPYVTKIRVSDGA CCCCCEEEEEECCCC	20.62	-
328	Phosphorylation	YVTKIRVSDGAPAQP CEEEEEECCCCCCCC	22.07	29083192
361	Phosphorylation	PPDKRIFTTRHTPSC CCCCCCEECCCCCCC	22.13	23927012
362	Phosphorylation	PDKRIFTTRHTPSCL CCCCCEECCCCCCCC	15.09	23927012
395	Ubiquitination	LLGAPVLLFLHPEDR HHCCCEEEEECCCCC	4.34	-
411	Ubiquitination	LMLAIHKKILQLAGQ HHHHHHHHHHHHHCC	34.19	-
434	Phosphorylation	FCARNGEYVTMDTSW EEEECCCEEEEECCC	11.56	-
576	Methylation	ARPQSRPRLPATGTF CCCCCCCCCCCCCCE	52.79	54557957
592	Phosphorylation	AKALPCQSPDPELEA EEECCCCCCCCCCCC	37.68	25159151
601	Phosphorylation	DPELEAGSAPVQAPL CCCCCCCCCCCCCCE	36.13	30576142
618	Ubiquitination	VPEEAERKEASSCSY CCHHHHHHHHHCCCH	49.49	29967540
632	Ubiquitination	YQQINCLDSILRYLE HHHHHHHHHHHHHHH	35.51	-
633	Phosphorylation	QQINCLDSILRYLES HHHHHHHHHHHHHHH	15.58	24719451
640	Phosphorylation	SILRYLESCNLPSTT HHHHHHHHCCCCCCC	13.00	20873877
645	Phosphorylation	LESCNLPSTTKRKCA HHHCCCCCCCCCCCC	52.45	20873877
646	Phosphorylation	ESCNLPSTTKRKCAS HHCCCCCCCCCCCCC	34.10	20873877
647	Phosphorylation	SCNLPSTTKRKCASS HCCCCCCCCCCCCCC	32.94	20873877
648	Ubiquitination	CNLPSTTKRKCASSS CCCCCCCCCCCCCCC	50.37	29967540
654	Phosphorylation	TKRKCASSSSYTTSS CCCCCCCCCCCCCCC	12.55	-
656	Phosphorylation	RKCASSSSYTTSSAS CCCCCCCCCCCCCCC	28.57	-
657	Phosphorylation	KCASSSSYTTSSASD CCCCCCCCCCCCCCC	18.91	-
661	Phosphorylation	SSSYTTSSASDDDRQ CCCCCCCCCCCCCCC	29.69	-
663	Phosphorylation	SYTTSSASDDDRQRT CCCCCCCCCCCCCCC	43.45	28985074
678	Ubiquitination	GPVSVGTKKDPPSAA CCCCEECCCCCCHHH	49.61	29967540
687	Phosphorylation	DPPSAALSGEGATPR CCCHHHCCCCCCCCC	30.03	21815630
692	Phosphorylation	ALSGEGATPRKEPVV HCCCCCCCCCCCCCC	34.19	21815630
695	Ubiquitination	GEGATPRKEPVVGGT CCCCCCCCCCCCCCC	68.52	29967540
702	Phosphorylation	KEPVVGGTLSPLALA CCCCCCCCCCHHHHC	20.38	19276368
704	Phosphorylation	PVVGGTLSPLALANK CCCCCCCCHHHHCCC	20.08	25159151
714	Phosphorylation	ALANKAESVVSVTSQ HHCCCCCCCEEECCC	32.45	-
717	Phosphorylation	NKAESVVSVTSQCSF CCCCCCEEECCCCCC	19.95	23663014
719	Phosphorylation	AESVVSVTSQCSFSS CCCCEEECCCCCCCE	12.94	23663014
720	Phosphorylation	ESVVSVTSQCSFSST CCCEEECCCCCCCEE	27.34	23663014
723	Phosphorylation	VSVTSQCSFSSTIVH EEECCCCCCCEEEEE	22.11	23663014
725	Phosphorylation	VTSQCSFSSTIVHVG ECCCCCCCEEEEECC	15.41	23663014
726	Phosphorylation	TSQCSFSSTIVHVGD CCCCCCCEEEEECCC	21.83	23663014
727	Phosphorylation	SQCSFSSTIVHVGDK CCCCCCEEEEECCCC	26.31	23663014
757	Phosphorylation	LAPGPAPSPAPSPTV CCCCCCCCCCCCCCC	35.48	27251275
761	Phosphorylation	PAPSPAPSPTVAPDP CCCCCCCCCCCCCCC	35.00	27251275
779	Phosphorylation	AYRPVGLTKAVLSLH CCCCCCHHHHHHHHC	15.84	20068231
787	Phosphorylation	KAVLSLHTQKEEQAF HHHHHHCCHHHHHHH	46.78	20068231
803	Dimethylation	SRFRDLGRLRGLDSS HHHHHHHHHCCCCCC	28.63	-
803	Methylation	SRFRDLGRLRGLDSS HHHHHHHHHCCCCCC	28.63	24376673
805	Dimethylation	FRDLGRLRGLDSSST HHHHHHHCCCCCCCC	42.12	-
805	Methylation	FRDLGRLRGLDSSST HHHHHHHCCCCCCCC	42.12	24376681
809	Phosphorylation	GRLRGLDSSSTAPSA HHHCCCCCCCCCCHH	31.09	23403867
810	Phosphorylation	RLRGLDSSSTAPSAL HHCCCCCCCCCCHHH	31.23	23401153
811	Phosphorylation	LRGLDSSSTAPSALG HCCCCCCCCCCHHHC	32.32	21712546
812	Phosphorylation	RGLDSSSTAPSALGE CCCCCCCCCCHHHCC	44.53	21955146
815	Phosphorylation	DSSSTAPSALGERGC CCCCCCCHHHCCCCC	33.39	23401153
830	Phosphorylation	HHGPAPPSRRHHCRS CCCCCCCCHHHHHHH	40.67	23312004
837	Phosphorylation	SRRHHCRSKAKRSRH CHHHHHHHHHHHCCC	42.22	-
892	Methylation	PLPVFSPRGGPQPLP CCCCCCCCCCCCCCC	62.59	115383505
979	Phosphorylation	PLFNSRCSSPLQLNL CCCCCCCCCHHHCCC	33.60	17081983
980	Phosphorylation	LFNSRCSSPLQLNLL CCCCCCCCHHHCCCE	33.00	15917222
1006	Phosphorylation	AVAGGPGSSAGPPPP CCCCCCCCCCCCCCC	21.83	30175587
1007	Phosphorylation	VAGGPGSSAGPPPPS CCCCCCCCCCCCCCC	43.06	27251275
1028	Phosphorylation	EARLAEVTESSNQDA CHHHHHHHHHCCCHH	22.96	27732954
1030	Phosphorylation	RLAEVTESSNQDALS HHHHHHHHCCCHHHC	25.81	27732954
1031	Phosphorylation	LAEVTESSNQDALSG HHHHHHHCCCHHHCC	32.07	27732954
1037	Phosphorylation	SSNQDALSGSSDLLE HCCCHHHCCCHHHHH	38.05	27732954
1039	Phosphorylation	NQDALSGSSDLLELL CCHHHCCCHHHHHHH	19.80	27732954
1040	Phosphorylation	QDALSGSSDLLELLL CHHHCCCHHHHHHHH	35.48	27732954
1096	Acetylation	SQSSHTSKYFGSIDS CCCCCCHHCCCCCCH	45.84	88937
1097	Phosphorylation	QSSHTSKYFGSIDSS CCCCCHHCCCCCCHH	16.97	23090842
1100	Phosphorylation	HTSKYFGSIDSSEAE CCHHCCCCCCHHHHH	17.21	25159151
1103	Phosphorylation	KYFGSIDSSEAEAGA HCCCCCCHHHHHHHH	28.54	25159151
1104	Phosphorylation	YFGSIDSSEAEAGAA CCCCCCHHHHHHHHH	36.76	25159151
1145	Phosphorylation	DQRVMMTYQVPSRDM CCEEEEEEECCCCCH	6.93	27642862
1153	Phosphorylation	QVPSRDMTSVLKQDR ECCCCCHHHHHHHHH	21.70	29083192
1154	Phosphorylation	VPSRDMTSVLKQDRE CCCCCHHHHHHHHHH	20.86	29083192
1186	Phosphorylation	RELGAVHSWVRKGQL HHHHHHHHHHHCCCC	22.22	18491316
1261	Phosphorylation	AQGGAKASSSQDLAM CCCCCCCCCHHCCCH	29.80	29978859
1262	Phosphorylation	QGGAKASSSQDLAME CCCCCCCCHHCCCHH	36.56	17525332
1263	Phosphorylation	GGAKASSSQDLAMEE CCCCCCCHHCCCHHH	25.81	17525332
1276	Phosphorylation	EEEEEGRSSSSPALP HHHHCCCCCCCCCCC	45.49	24275569
1278	Phosphorylation	EEEGRSSSSPALPTA HHCCCCCCCCCCCCC	41.40	27251275
1279	Phosphorylation	EEGRSSSSPALPTAG HCCCCCCCCCCCCCC	19.01	19664995

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	P49674	Uniprot
122	S	Phosphorylation	Kinase	CSNK1E	P49674	Uniprot
126	S	Phosphorylation	Kinase	CSNK1E	P49674	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW11	Q9UKB1	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:15767683

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of PER1_HUMAN !!

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 PER1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CRY1_HUMAN	CRY1	physical	10531061
KC1E_HUMAN	CSNK1E	physical	10848614
KC1D_HUMAN	CSNK1D	physical	11165242
PER3_HUMAN	PER3	physical	10837028
KC1E_HUMAN	CSNK1E	physical	15917222
KC1G2_HUMAN	CSNK1G2	physical	15917222
FBW1A_HUMAN	BTRC	physical	17463251
CCD57_HUMAN	CCDC57	physical	24722188
RBPMS_HUMAN	RBPMS	physical	24722188
RBPMS_HUMAN	RBPMS	physical	25416956
KAPCB_HUMAN	PRKACB	physical	26186194
CRY1_HUMAN	CRY1	physical	26186194
CRY1_HUMAN	CRY1	physical	28514442

Drug and Disease Associations

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

Regulatory Network of PER1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-815, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704, AND MASSSPECTROMETRY.	19413330 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-704 AND SER-815, ANDMASS SPECTROMETRY.	18669648 [Abstract]
"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage."; Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; Science 316:1160-1166(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1262 AND SER-1263, ANDMASS SPECTROMETRY.	17525332 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-979; SER-980; SER-1100;SER-1103 AND SER-1104, AND MASS SPECTROMETRY.	17081983 [Abstract]