透明质酸代谢
中文名称
通路描述
透明质酸（透明质酸、透明质酸或 HA）是一种阴离子糖胺聚糖（GAG），广泛分布于结缔组织、上皮组织和神经组织中，并在细胞外基质和皮肤中含量最高。HA 是 GAG 中独特的，因为它不被硫酸化，也不以蛋白聚糖的形式共价连接在蛋白质上。HA 聚合物非常大（分子量可达 1000 万 Da），能排出大量水分，使其成为优秀的润滑剂和减震器。HA 的另一个独特特征是它在细胞膜上合成，而其他 GAG 是在高尔基体中形成的。HA 是由 D-葡萄糖醛酸和 D-乙酰葡萄糖胺组成的二糖单元交替通过β-1,4和β-1,3糖苷键连接而成的聚合物。
英文描述
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes After translocation into the nucleus, the phosphorylated BMAL1:CLOCK heterodimer and, by inference, the BMAL1:NPAS2 heterodimer activate transcription by binding E-box elements (consensus: CANNTG) in the promoters of more than 2000 target genes (inferred from mouse homologs in Hatanaka et al. 2010, Guillaume et al. 2011) and recruiting coactivators such as CREB-binding protein (CREBBP) (inferred from mouse homologs in Garg et al. 2019), the histone methylase KMT2A (MLL1) and, presumably, components of the MLL1 complex (inferred from mouse homologs in Katada and Sassone-Corsi 2010). Transcriptional activation by BMAL1:CLOCK occurs during the day, thus genes regulated by BMAL1:CLOCK are diurnally expressed.
Among the thousands of genes activated by BMAL1:CLOCK are the Cryptochrome genes (CRY1, CRY2) and the Period genes (PER1, PER2, PER3) that encode proteins that repress BMAL1:CLOCK activity, forming the primary loop of the circadian clock (reviewed in Cox and Takahashi 2019). BMAL1:CLOCK also activates the expression of Retinoid-related orphan receptor genes RORA, RORB, and RORC and the heme-binding nuclear receptor gene NR1D1 (REV-ERBA) that bind the same ROR responsive elements (RRE, RORE) in the promoters of the BMAL1, CLOCK, and NPAS2 genes. RORA, RORB, RORC activate expression; NR1D1 represses expression. The reciprocal regulation of BMAL1:CLOCK and RORA, RORB, RORC, NR1D1 forms the secondary loop of the circadian clock.
Among the thousands of genes activated by BMAL1:CLOCK are the Cryptochrome genes (CRY1, CRY2) and the Period genes (PER1, PER2, PER3) that encode proteins that repress BMAL1:CLOCK activity, forming the primary loop of the circadian clock (reviewed in Cox and Takahashi 2019). BMAL1:CLOCK also activates the expression of Retinoid-related orphan receptor genes RORA, RORB, and RORC and the heme-binding nuclear receptor gene NR1D1 (REV-ERBA) that bind the same ROR responsive elements (RRE, RORE) in the promoters of the BMAL1, CLOCK, and NPAS2 genes. RORA, RORB, RORC activate expression; NR1D1 represses expression. The reciprocal regulation of BMAL1:CLOCK and RORA, RORB, RORC, NR1D1 forms the secondary loop of the circadian clock.
所含基因
21 个基因