PER3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PER3_HUMAN
• UniProt AC: P56645
• Protein Name: Period circadian protein homolog 3
• Gene Name: PER3
• Organism: Homo sapiens (Human).
• Sequence Length: 1201
• 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: MPRGEAPGPGRRGAKDEALGEESGERWSPEFHLQRKLADSSHSEQQDRNRVSEELIMVVQEMKKYFPSERRNKPSTLDALNYALRCVHSVQANSEFFQILSQNGAPQADVSMYSLEELATIASEHTSKNTDTFVAVFSFLSGRLVHISEQAALILNRKKDVLASSHFVDLLAPQDMRVFYAHTARAQLPFWNNWTQRAARYECAPVKPFFCRIRGGEDRKQEKCHSPFRIIPYLIHVHHPAQPELESEPCCLTVVEKIHSGYEAPRIPVNKRIFTTTHTPGCVFLEVDEKAVPLLGYLPQDLIGTSILSYLHPEDRSLMVAIHQKVLKYAGHPPFEHSPIRFCTQNGDYIILDSSWSSFVNPWSRKISFIIGRHKVRTSPLNEDVFATKIKKMNDNDKDITELQEQIYKLLLQPVHVSVSSGYGSLGSSGSQEQLVSIASSSEASGHRVEETKAEQMTLQQVYASVNKIKNLGQQLYIESMTKSSFKPVTGTRTEPNGGGECKTFTSFHQTLKNNSVYTEPCEDLRNDEHSPSYQQINCIDSVIRYLKSYNIPALKRKCISCTNTTSSSSEEDKQNHKADDVQALQAGLQIPAIPKSEMPTNGRSIDTGGGAPQILSTAMLSLGSGISQCGYSSTIVHVPPPETARDATLFCEPWTLNMQPAPLTSEEFKHVGLTAAVLSAHTQKEEQNYVDKFREKILSSPYSSYLQQESRSKAKYSYFQGDSTSKQTRSAGCRKGKHKRKKLPEPPDSSSSNTGSGPRRGAHQNAQPCCPSAASSPHTSSPTFPPAAMVPSQAPYLVPAFPLPAATSPGREYAAPGTAPEGLHGLPLSEGLQPYPAFPFPYLDTFMTVFLPDPPVCPLLSPSFLPCPFLGATASSAISPSMSSAMSPTLDPPPSVTSQRREEEKWEAQSEGHPFITSRSSSPLQLNLLQEEMPRPSESPDQMRRNTCPQTEYCVTGNNGSESSPATTGALSTGSPPRENPSHPTASALSTGSPPMKNPSHPTASALSTGSPPMKNPSHPTASTLSMGLPPSRTPSHPTATVLSTGSPPSESPSRTGSAASGSSDSSIYLTSSVYSSKISQNGQQSQDVQKKETFPNVAEEPIWRMIRQTPERILMTYQVPERVKEVVLKEDLEKLESMRQQQPQFSHGQKEELAKVYNWIQSQTVTQEIDIQACVTCENEDSADGAATSCGQVLVEDSC

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
28	Phosphorylation	EESGERWSPEFHLQR CCCCCCCCHHHHHHH	22.29	29449344
75	Phosphorylation	SERRNKPSTLDALNY HHHCCCCCHHHHHHH	43.12	27732954
76	Phosphorylation	ERRNKPSTLDALNYA HHCCCCCHHHHHHHH	36.87	27732954
82	Phosphorylation	STLDALNYALRCVHS CHHHHHHHHHHHHHH	14.09	27732954
141	Phosphorylation	VAVFSFLSGRLVHIS HHHHHHHHCCEEEHH	21.62	24719451
328	Ubiquitination	AIHQKVLKYAGHPPF HHHHHHHHHCCCCCC	35.72	-
388	Phosphorylation	LNEDVFATKIKKMND CCHHHHHHHHHHCCC	23.10	-
389	Ubiquitination	NEDVFATKIKKMNDN CHHHHHHHHHHCCCC	49.45	-
408	Phosphorylation	TELQEQIYKLLLQPV HHHHHHHHHHHHCCE	8.69	-
458	Phosphorylation	ETKAEQMTLQQVYAS HHHHHHHHHHHHHHH	22.55	26074081
463	Phosphorylation	QMTLQQVYASVNKIK HHHHHHHHHHHHHHH	6.71	26074081
465	Phosphorylation	TLQQVYASVNKIKNL HHHHHHHHHHHHHHH	14.45	26074081
477	Phosphorylation	KNLGQQLYIESMTKS HHHCHHHEEEECCCC	9.78	26074081
480	Phosphorylation	GQQLYIESMTKSSFK CHHHEEEECCCCCCC	23.38	26074081
482	Phosphorylation	QLYIESMTKSSFKPV HHEEEECCCCCCCCC	36.73	26074081
605	Phosphorylation	EMPTNGRSIDTGGGA HCCCCCCCCCCCCCH	26.64	22210691
608	Phosphorylation	TNGRSIDTGGGAPQI CCCCCCCCCCCHHHH	35.74	22210691
622	Phosphorylation	ILSTAMLSLGSGISQ HHHHHHHHCCCCCHH	20.01	11865049
625	Phosphorylation	TAMLSLGSGISQCGY HHHHHCCCCCHHCCC	37.94	11865049
628	Phosphorylation	LSLGSGISQCGYSST HHCCCCCHHCCCCCE	23.97	11865049
633	Phosphorylation	GISQCGYSSTIVHVP CCHHCCCCCEEEECC	13.29	11865049
634	Phosphorylation	ISQCGYSSTIVHVPP CHHCCCCCEEEECCC	17.42	11865049
635	Phosphorylation	SQCGYSSTIVHVPPP HHCCCCCEEEECCCC	22.52	11865049
644	Phosphorylation	VHVPPPETARDATLF EECCCCCCCCCCEEE	32.54	22210691
718	Phosphorylation	SRSKAKYSYFQGDST HHHCCCCCCCCCCCC	20.82	-
753	Phosphorylation	EPPDSSSSNTGSGPR CCCCCCCCCCCCCCC	40.12	-
755	Phosphorylation	PDSSSSNTGSGPRRG CCCCCCCCCCCCCCC	34.37	-
757	Phosphorylation	SSSSNTGSGPRRGAH CCCCCCCCCCCCCCC	43.52	-
911	Phosphorylation	EEKWEAQSEGHPFIT HHHHHHHHCCCCCCC	53.22	23186163
918	Phosphorylation	SEGHPFITSRSSSPL HCCCCCCCCCCCCHH	20.61	23186163
919	Phosphorylation	EGHPFITSRSSSPLQ CCCCCCCCCCCCHHH	25.91	23917254
921	Phosphorylation	HPFITSRSSSPLQLN CCCCCCCCCCHHHHH	34.63	28450419
922	Phosphorylation	PFITSRSSSPLQLNL CCCCCCCCCHHHHHH	34.56	28450419
923	Phosphorylation	FITSRSSSPLQLNLL CCCCCCCCHHHHHHH	30.76	28450419
983	Phosphorylation	SPPRENPSHPTASAL CCCCCCCCCCCHHHH	54.39	27080861
986	Phosphorylation	RENPSHPTASALSTG CCCCCCCCHHHHCCC	28.02	27080861
988	Phosphorylation	NPSHPTASALSTGSP CCCCCCHHHHCCCCC	32.02	27080861
991	Phosphorylation	HPTASALSTGSPPMK CCCHHHHCCCCCCCC	30.36	27080861
992	Phosphorylation	PTASALSTGSPPMKN CCHHHHCCCCCCCCC	42.39	27080861
994	Phosphorylation	ASALSTGSPPMKNPS HHHHCCCCCCCCCCC	26.39	23917254
1012	Phosphorylation	ASALSTGSPPMKNPS CHHHCCCCCCCCCCC	26.39	23186163
1019	Phosphorylation	SPPMKNPSHPTASTL CCCCCCCCCCCCCCC	52.04	27050516
1035	Phosphorylation	MGLPPSRTPSHPTAT CCCCCCCCCCCCCEE	33.22	28450419
1037	Phosphorylation	LPPSRTPSHPTATVL CCCCCCCCCCCEEEE	41.30	28450419
1040	Phosphorylation	SRTPSHPTATVLSTG CCCCCCCCEEEECCC	29.54	28450419
1042	Phosphorylation	TPSHPTATVLSTGSP CCCCCCEEEECCCCC	25.18	28450419
1045	Phosphorylation	HPTATVLSTGSPPSE CCCEEEECCCCCCCC	26.79	28450419
1046	Phosphorylation	PTATVLSTGSPPSES CCEEEECCCCCCCCC	37.20	28450419
1048	Phosphorylation	ATVLSTGSPPSESPS EEEECCCCCCCCCCC	33.45	28450419
1051	Phosphorylation	LSTGSPPSESPSRTG ECCCCCCCCCCCCCC	54.83	26434776
1053	Phosphorylation	TGSPPSESPSRTGSA CCCCCCCCCCCCCCC	32.29	12655319
1055	Phosphorylation	SPPSESPSRTGSAAS CCCCCCCCCCCCCCC	52.32	26434776
1072	Phosphorylation	SDSSIYLTSSVYSSK CCCEEEEECCHHHCC	11.28	-
1073	Phosphorylation	DSSIYLTSSVYSSKI CCEEEEECCHHHCCC	18.40	-
1118	Phosphorylation	TPERILMTYQVPERV CCCCEEEEECCCHHH	13.83	29978859
1119	Phosphorylation	PERILMTYQVPERVK CCCEEEEECCCHHHH	8.11	29978859

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

Oops, there are no upstream regulatory protein records of PER3_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of PER3_HUMAN !!

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PER2_HUMAN	PER2	physical	10837028
ATM_HUMAN	ATM	physical	21070773
CHK2_HUMAN	CHEK2	physical	21070773
CRY2_HUMAN	CRY2	physical	26496610
AVL9_HUMAN	AVL9	physical	26496610
GRDN_HUMAN	CCDC88A	physical	26496610
MIB1_HUMAN	MIB1	physical	26496610
AN36A_HUMAN	ANKRD36	physical	26496610
FANCA_HUMAN	FANCA	physical	28215707

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.