BMAL2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: BMAL2_HUMAN
• UniProt AC: Q8WYA1
• Protein Name: Aryl hydrocarbon receptor nuclear translocator-like protein 2
• Gene Name: ARNTL2
• Organism: Homo sapiens (Human).
• Sequence Length: 636
• Subcellular Localization: Nucleus .
• Protein Description: Transcriptional activator 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. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1..
• Protein Sequence: MAAEEEAAAGGKVLREENQCIAPVVSSRVSPGTRPTAMGSFSSHMTEFPRKRKGSDSDPSQSGIMTEKVVEKLSQNPLTYLLSTRIEISASSGSRVEDGEHQVKMKAFREAHSQTEKRRRDKMNNLIEELSAMIPQCNPMARKLDKLTVLRMAVQHLRSLKGLTNSYVGSNYRPSFLQDNELRHLILKTAEGFLFVVGCERGKILFVSKSVSKILNYDQASLTGQSLFDFLHPKDVAKVKEQLSSFDISPREKLIDAKTGLQVHSNLHAGRTRVYSGSRRSFFCRIKSCKISVKEEHGCLPNSKKKEHRKFYTIHCTGYLRSWPPNIVGMEEERNSKKDNSNFTCLVAIGRLQPYIVPQNSGEINVKPTEFITRFAVNGKFVYVDQRATAILGYLPQELLGTSCYEYFHQDDHNNLTDKHKAVLQSKEKILTDSYKFRAKDGSFVTLKSQWFSFTNPWTKELEYIVSVNTLVLGHSEPGEASFLPCSSQSSEESSRQSCMSVPGMSTGTVLGAGSIGTDIANEILDLQRLQSSSYLDDSSPTGLMKDTHTVNCRSMSNKELFPPSPSEMGELEATRQNQSTVAVHSHEPLLSDGAQLDFDALCDNDDTAMAAFMNYLEAEGGLGDPGDFSDIQWTL

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
18 (in isoform 6)	Phosphorylation	-	36.95	25106551
20 (in isoform 6)	Phosphorylation	-	4.28	25394399
23 (in isoform 6)	Phosphorylation	-	13.71	20873877
28 (in isoform 6)	Phosphorylation	-	25.98	20873877
30	Phosphorylation	PVVSSRVSPGTRPTA CEECCCCCCCCCCCC	19.26	28348404
30 (in isoform 6)	Phosphorylation	-	19.26	20873877
55	Phosphorylation	FPRKRKGSDSDPSQS CCCCCCCCCCCHHHC	36.66	28985074
55 (in isoform 4)	Phosphorylation	-	36.66	25106551
57 (in isoform 4)	Phosphorylation	-	53.79	25394399
57	Phosphorylation	RKRKGSDSDPSQSGI CCCCCCCCCHHHCCC	53.79	25627689
60 (in isoform 4)	Phosphorylation	-	41.80	20873877
65 (in isoform 4)	Phosphorylation	-	4.52	20873877
66 (in isoform 3)	Phosphorylation	-	30.63	25106551
66 (in isoform 9)	Phosphorylation	-	30.63	25106551
67 (in isoform 4)	Phosphorylation	-	26.86	20873877
68 (in isoform 9)	Phosphorylation	-	42.27	25394399
68 (in isoform 3)	Phosphorylation	-	42.27	25394399
71 (in isoform 9)	Phosphorylation	-	51.79	20873877
71 (in isoform 3)	Phosphorylation	-	51.79	20873877
76 (in isoform 9)	Phosphorylation	-	30.12	20873877
76 (in isoform 3)	Phosphorylation	-	30.12	20873877
78 (in isoform 3)	Phosphorylation	-	6.88	20873877
78 (in isoform 9)	Phosphorylation	-	6.88	20873877
148	Phosphorylation	ARKLDKLTVLRMAVQ HHHHHHHHHHHHHHH	24.20	-
203	Acetylation	VVGCERGKILFVSKS EEECCCCEEEEEECC	42.32	7973211
208	Phosphorylation	RGKILFVSKSVSKIL CCEEEEEECCHHHHC	16.33	-
209	Acetylation	GKILFVSKSVSKILN CEEEEEECCHHHHCC	49.96	7973221
210	Phosphorylation	KILFVSKSVSKILNY EEEEEECCHHHHCCC	24.90	-
212	Phosphorylation	LFVSKSVSKILNYDQ EEEECCHHHHCCCCH	22.52	-
213	Acetylation	FVSKSVSKILNYDQA EEECCHHHHCCCCHH	49.40	7973231
245	Phosphorylation	KVKEQLSSFDISPRE HHHHHHHCCCCCHHH	35.21	-
294	Sumoylation	KSCKISVKEEHGCLP EECEEEEEHHHCCCC	51.06	28112733
304	Acetylation	HGCLPNSKKKEHRKF HCCCCCCCCCCCCCE	74.61	30587049
306	Acetylation	CLPNSKKKEHRKFYT CCCCCCCCCCCCEEE	63.59	30587055
532	Phosphorylation	LDLQRLQSSSYLDDS HHHHHHHCCCCCCCC	26.33	22199227
533	Phosphorylation	DLQRLQSSSYLDDSS HHHHHHCCCCCCCCC	15.27	22199227
534	Phosphorylation	LQRLQSSSYLDDSSP HHHHHCCCCCCCCCC	34.66	22199227
535	Phosphorylation	QRLQSSSYLDDSSPT HHHHCCCCCCCCCCC	18.99	22199227
539	Phosphorylation	SSSYLDDSSPTGLMK CCCCCCCCCCCCCCC	37.57	22199227
540	Phosphorylation	SSYLDDSSPTGLMKD CCCCCCCCCCCCCCC	33.21	22199227
542	Phosphorylation	YLDDSSPTGLMKDTH CCCCCCCCCCCCCCC	44.91	22199227
575	Phosphorylation	EMGELEATRQNQSTV HCCCCCHHCCCCCCE	24.34	28348404

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

Oops, there are no upstream regulatory protein records of BMAL2_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of BMAL2_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 BMAL2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RORG_HUMAN	RORC	physical	23555304
UBE3A_HUMAN	UBE3A	physical	25660546
CLOCK_HUMAN	CLOCK	physical	28514442
CIPC_HUMAN	CIPC	physical	28514442
DHTK1_HUMAN	DHTKD1	physical	28514442
NPAS2_HUMAN	NPAS2	physical	28514442
MTA70_HUMAN	METTL3	physical	28514442
NSE4A_HUMAN	NSMCE4A	physical	28514442
HAUS4_HUMAN	HAUS4	physical	28514442
NEMO_HUMAN	IKBKG	physical	28514442
SSRP1_HUMAN	SSRP1	physical	28514442
CLPP_HUMAN	CLPP	physical	28514442
PER1_HUMAN	PER1	physical	28514442
MSRA_HUMAN	MSRA	physical	28514442
MDM2_HUMAN	MDM2	physical	28514442
FREM2_HUMAN	FREM2	physical	28514442
HAUS1_HUMAN	HAUS1	physical	28514442

Drug and Disease Associations

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