FNIP2 Q9P278

卵泡素相互作用蛋白2 (FNIP1样蛋白) (O6-甲基鸟嘌呤诱导凋亡蛋白1)

功能描述

GTPase激活蛋白FLCN的结合伴侣：通过调节控制MiT/TFE因子TFEB和TFE3的非经典mTORC1信号级联反应，参与细胞对氨基酸可用性的反应 (PubMed:18663353, PubMed:31672913, PubMed:36103527)。促进FLCN募集到溶酶体并与Rag GTPases相互作用，从而导致非经典mTORC1信号的激活所必需的 (By similarity)。在低氨基酸条件下，作为溶酶体膜上溶酶体folliculin复合物 (LFC) 的组分，该复合物抑制FLCN的GTPase激活活性，从而使mTORC1失活并促进TFEB和TFE3的核易位 (PubMed:31672913, PubMed:36103527)。在氨基酸再刺激后，LFC复合物的解离释放了FLCN的GTPase激活活性，导致mTORC1激活以及随后的TFEB和TFE3失活 (PubMed:31672913)。与FLCN一起调节自噬：经ULK1磷酸化后，与GABARAP相互作用并促进自噬 (PubMed:25126726)。除了在mTORC1信号传导中的作用外，还作为HSP90AA1/Hsp90的辅伴侣：抑制HSP90AA1/Hsp90的ATPase活性，导致激活HSP90AA1/Hsp90的激酶和非激酶客户蛋白 (PubMed:18403135)。作为支架将客户蛋白FLCN装载到HSP90AA1/Hsp90上 (PubMed:18403135)。与激活辅伴侣AHSA1竞争结合HSP90AA1，从而为客户蛋白的分子伴侣作用提供了一个相互调节机制 (PubMed:18403135)。可能在O6-甲基鸟嘌呤错配损伤诱导的细胞凋亡信号转导通路中发挥作用 (By similarity)。 {ECO:0000250|UniProtKB:Q80TD3, ECO:0000250|UniProtKB:Q8TF40, ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:36103527}。

组织特异性

Widely expressed with highest levels in muscle, nasal mucosa, salivary gland, uvula, fat, liver, heart, placenta and pancreas (PubMed:18403135, PubMed:18663353, PubMed:27353360). Moderately expressed in the lung, small intestine, kidney and brain. Lower levels detected in renal cell carcinoma than in normal kidney tissue (PubMed:18403135). Higher levels detected in oncocytoma tumors than in normal kidney. Higher levels detected in renal cell carcinoma tumors than in normal kidney tissue (PubMed:27353360).

亚细胞定位

Lysosome membrane