DCLK1(Doublecortin-like kinase 1)是一种微管相关蛋白激酶,属于双皮质素(Doublecortin,DCX)基因家族。该基因家族的特点是成员均含有双皮质素结构域,能够结合微管并参与神经元迁移、轴突导向和神经发育等过程。DCLK1在神经系统中高度表达,尤其在发育中的大脑皮层、海马体和嗅球中,对神经元的形态发生和突触可塑性具有重要作用。DCLK1编码的蛋白具有激酶活性,能够磷酸化微管相关蛋白,从而调节微管的稳定性与动力学,影响细胞骨架的重排。此外,DCLK1还参与肠道干细胞的维持和肿瘤发生,尤其在结直肠癌中,其过表达与肿瘤干细胞的自我更新和侵袭性增强相关。DCLK1的突变可能导致神经发育障碍,如智力障碍或癫痫,而其异常表达(过高或过低)可能破坏微管功能,影响细胞分裂和迁移。在癌症中,DCLK1的过表达不仅促进肿瘤进展,还可能通过激活Wnt/β-catenin等信号通路增强干性特征。相反,降低DCLK1表达可抑制肿瘤生长并减弱转移潜能。DCLK1还与阿尔茨海默病等神经退行性疾病相关,可能通过影响tau蛋白的磷酸化参与病理过程。该基因家族的其他成员(如DCX和DCLK2)也参与神经发育,但DCLK1因其激酶活性和广泛的表达模式在疾病中的作用更为突出。研究DCLK1的功能有助于开发针对神经系统疾病和癌症的靶向治疗策略。
This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.[provided by RefSeq, Sep 2010]
该基因编码的蛋白激酶超家族和doublecortin家族的一个成员。由该基因编码的蛋白质包含两个N末端doublecortin域,其结合微管和调节微管聚合,C末端的丝氨酸/苏氨酸蛋白激酶结构域,其示出基本同源的Ca2 + /钙调蛋白依赖性蛋白激酶和丝氨酸/在doublecortin和蛋白激酶结构域,其介导多种蛋白质 - 蛋白质相互作用之间富含脯氨酸的结构域。所编码的蛋白质的微管聚合活性是独立的蛋白激酶活性。编码的蛋白参与多种不同的细胞过程,包括神经元迁移,逆行运输,神经元凋亡和神经。该基因是由脑源性神经营养因子上调和与记忆和一般认知能力相关联。由两个备选的启动子的使用情况和可变剪接产生的多个转录物变体已有报道,但一些变体的全长性质和生物有效性尚未确定。这些变体编码不同的亚型,这是差异表达,有不同的激酶活性[由RefSeq的,2010年9月提供]
DCLK1基因(以及对应的蛋白质)的细胞分布位置:
DCLK1基因的本体(GO)信息:
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
IGA Glomerulonephritis | 0.12 | 1 | 0 | CTD_human |
Colorectal Neoplasms | 0.12 | 1 | 0 | CTD_human |
Tobacco Use Disorder | 0.002367032 | 1 | 0 | GAD |
Colorectal Cancer | 0.001900093 | 7 | 0 | BeFree |
Colorectal Carcinoma | 0.001900093 | 7 | 0 | BeFree |
Carcinogenesis | 0.001085767 | 4 | 0 | BeFree |
Pancreatic carcinoma | 0.000814326 | 3 | 0 | BeFree |
Malignant neoplasm of pancreas | 0.000814326 | 3 | 0 | BeFree |
Pancreatic Ductal Adenocarcinoma | 0.000542884 | 2 | 0 | BeFree |
Liver neoplasms | 0.000542884 | 2 | 0 | BeFree |
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