SET Q01105

SET蛋白 (HLA-DR相关蛋白II) (颗粒酶A活化DNase抑制剂) (IGAAD) (PHAPII) (磷酸酶2A抑制剂I2PP2A) (I-2PP2A) (模板活化因子I) (TAF-I)

功能描述

功能：多任务蛋白，参与细胞凋亡、转录、核小体组装和组蛋白伴侣活性。Isoform 2 的抗细胞凋亡活性通过抑制 GZMA 激活的 DNase NME1 介导。在细胞毒性 T 淋巴细胞 (CTL) 诱导的细胞凋亡过程中，GZMA 切割 SET，破坏其与 NME1 的结合并解除对 NME1 的抑制。Isoform 1 和 isoform 2 是蛋白磷酸酶 2A 的强效抑制剂。Isoform 1 和 isoform 2 抑制 EP300/CREBBP 和 PCAF 介导的组蛋白 (HAT) 和核小体乙酰化，最可能的机制是掩盖组蛋白的赖氨酸残基，使其不被乙酰转移酶接触。主要抑制靶点是组蛋白 H4。HAT 抑制导致 HAT 依赖性转录沉默并阻止 DNA 的主动去甲基化。两种 isoform 均刺激与病毒核心蛋白复合的腺病毒基因组的 DNA 复制；然而，isoform 2 的比活性更高。{ECO:0000269|PubMed:11555662, ECO:0000269|PubMed:12628186}。

组织特异性

Widely expressed. Low levels in quiescent cells during serum starvation, contact inhibition or differentiation. Highly expressed in Wilms' tumor.

亚细胞定位

Cytoplasm, cytosol. Endoplasmic reticulum. Nucleus, nucleoplasm. Note=In the cytoplasm, found both in the cytosol and associated with the endoplasmic reticulum. The SET complex is associated with the endoplasmic reticulum. Following CTL attack and cleavage by GZMA, moves rapidly to the nucleus, where it is found in the nucleoplasm, avoiding the nucleolus. Similar translocation to the nucleus is also observed for lymphocyte-activated killer cells after the addition of calcium.