NCSTN (nicastrin)
- symbol:
- NCSTN
- locus group:
- protein-coding gene
- location:
- 1q23.2
- gene_family:
- alias symbol:
- KIAA0253|APH2
- alias name:
- None
- entrez id:
- 23385
- ensembl gene id:
- ENSG00000162736
- ucsc gene id:
- uc001fvx.4
- refseq accession:
- NM_015331
- hgnc_id:
- HGNC:17091
- approved reserved:
- 2005-02-08
NCSTN（Nicastrin）是γ-分泌酶复合体的核心组分之一，属于膜整合蛋白，主要位于细胞膜和高尔基体。它在阿尔茨海默病（AD）和多种癌症中发挥关键作用。NCSTN与早老素（PSEN1/PSEN2）、APH-1和PEN-2共同构成γ-分泌酶复合体，负责切割跨膜蛋白如淀粉样前体蛋白（APP）和Notch受体。APP被切割后产生β-淀粉样蛋白（Aβ），Aβ的异常沉积是AD的主要病理特征。Notch信号通路则调控细胞分化、增殖和存活，对胚胎发育和肿瘤发生至关重要。NCSTN的突变或表达异常会破坏γ-分泌酶功能，导致APP加工异常（如Aβ42增多）或Notch信号失调。例如，NCSTN突变可能引发早发性AD或某些皮肤疾病（如痤疮 inversa）。过表达NCSTN可能增强γ-分泌酶活性，促进Aβ生成或Notch依赖性肿瘤（如乳腺癌、T细胞白血病）；而表达降低可能导致Notch信号缺陷，影响发育或免疫功能。NCSTN属于γ-分泌酶复合体家族，该家族成员均参与跨膜蛋白的切割，依赖早老素催化活性。研究NCSTN有助于开发AD靶向药物（如γ-分泌酶抑制剂）或抗癌疗法，但需注意Notch通路抑制可能带来的副作用。
This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
这个基因编码I型跨膜糖蛋白，它是多聚γ分泌复合物的一个组成部分。所编码的蛋白质裂解完整的膜蛋白，包括Notch受体和β-淀粉状蛋白前体蛋白，并可以是用于γ-分泌复杂的组装所需要的稳定的辅助因子。 β-淀粉样蛋白前体蛋白的裂解产生淀粉样蛋白β肽的神经炎斑和在患有阿尔茨海默氏病的脑中的标志病变的主要成分;然而，所编码的蛋白质在阿尔茨海默氏症的作用的性质是不知道一定的。在这个基因的突变与家族性痤疮反常性有关。这个基因的假基因是存在于21号染色体此基因的备选剪接转录变体进行了说明，但其中的一些变体的全长性质尚未确定。 [由RefSeq的，2014年2月提供]
基因本体信息
NCSTN基因（以及对应的蛋白质）的细胞分布位置：
- 质膜
- 细胞质
- 细胞外
- 高尔基体
- 囊泡
- 细胞骨架
- 内质网
- 细胞核
- 内体
- 溶酶体
- 线粒体
NCSTN基因的本体（GO）信息：
| 名称 |
|---|
| 4330 Notch signaling pathway [PATH:hsa04330] |
| 5010 Alzheimer's disease [PATH:hsa05010] |
| 名称 |
|---|
| A third proteolytic cleavage releases NICD |
| Activated NOTCH1 Transmits Signal to the Nucleus |
| Axon guidance |
| Cell death signalling via NRAGE, NRIF and NADE |
| Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants |
| Constitutive Signaling by NOTCH1 PEST Domain Mutants |
| Degradation of the extracellular matrix |
| Developmental Biology |
| Disease |
| Diseases of signal transduction |
| EPH-ephrin mediated repulsion of cells |
| EPH-Ephrin signaling |
| Extracellular matrix organization |
| NOTCH2 Activation and Transmission of Signal to the Nucleus |
| NRIF signals cell death from the nucleus |
| Nuclear signaling by ERBB4 |
| p75 NTR receptor-mediated signalling |
| Regulated proteolysis of p75NTR |
| Signaling by ERBB4 |
| Signaling by NOTCH |
| Signaling by NOTCH1 |
| Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer |
| Signaling by NOTCH1 in Cancer |
| Signaling by NOTCH1 PEST Domain Mutants in Cancer |
| Signaling by NOTCH2 |
| Signaling by NOTCH3 |
| Signaling by NOTCH4 |
| Signalling by NGF |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Hidradenitis suppurativa, familial | 0.24 | 2 | 0 | CTD_human_UNIPROT |
| Alzheimer's Disease | 0.144841964 | 11 | 1 | BeFree_CTD_human_GAD_LHGDN |
| Memory impairment | 0.002367032 | 1 | 0 | GAD |
| Breast Carcinoma | 0.001357209 | 5 | 0 | BeFree |
| Malignant neoplasm of breast | 0.001357209 | 5 | 0 | BeFree |
| Hidradenitis Suppurativa | 0.000814326 | 3 | 0 | BeFree |
| Invasive breast carcinoma | 0.000542884 | 2 | 0 | BeFree |
| Central neuroblastoma | 0.000542884 | 2 | 0 | BeFree |
| Alzheimer Disease, Early Onset | 0.000542884 | 2 | 0 | BeFree |
| Neuroblastoma | 0.000542884 | 2 | 0 | BeFree |
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