DKK1(Dickkopf-1)是一种分泌型糖蛋白,属于Dickkopf(DKK)基因家族成员,该家族包括DKK1、DKK2、DKK3和DKK4等。DKK家族蛋白的共同特点是能够调控Wnt信号通路,尤其是通过结合LRP5/6共受体来抑制经典的Wnt/β-catenin通路。DKK1是Wnt信号通路的重要拮抗剂,主要通过与LRP5/6结合,阻止Wnt配体与受体复合物的形成,从而抑制β-catenin的稳定性和核转位,影响下游靶基因的表达。DKK1在胚胎发育、骨骼形成、细胞增殖和分化等过程中发挥关键作用,尤其在骨代谢中至关重要,它通过抑制成骨细胞活性促进骨吸收,与骨质疏松症等骨骼疾病密切相关。DKK1的突变或表达异常可能导致多种疾病,例如过表达与多发性骨髓瘤、类风湿性关节炎和某些癌症(如肝癌、肺癌)的进展相关,因其促进肿瘤微环境形成和转移;而降低表达则可能增强Wnt信号,导致骨密度增加或某些增生性疾病。此外,DKK1在神经系统中也有表达,其异常可能与神经退行性疾病有关。在基因家族中,DKK成员均含有两个保守的半胱氨酸富集结构域,但各成员对Wnt通路的调控效果不同,例如DKK2在某些条件下可激活而非抑制Wnt信号。DKK1的过表达会显著抑制组织再生和修复,而敲除或抑制DKK1可促进骨形成和损伤修复,因此在治疗骨质疏松或骨折时成为潜在靶点。研究还发现DKK1与炎症反应、血管生成等过程相关,进一步拓宽了其病理生理意义。
This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the WNT signaling pathway. Elevated levels of DKK1 in bone marrow plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma. [provided by RefSeq, Jul 2008]
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DKK1基因(以及对应的蛋白质)的细胞分布位置:
DKK1基因的本体(GO)信息:
| 名称 |
|---|
| 4310 Wnt signaling pathway [PATH:hsa04310] |
| 名称 |
|---|
| Developmental Biology |
| Disease |
| Diseases of signal transduction |
| misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling |
| negative regulation of TCF-dependent signaling by WNT ligand antagonists |
| POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation |
| Signal Transduction |
| Signaling by Wnt |
| Signaling by WNT in cancer |
| TCF dependent signaling in response to WNT |
| Transcriptional regulation of pluripotent stem cells |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Mammary Neoplasms | 0.134164635 | 7 | 0 | BeFree_CTD_human_LHGDN |
| Peripheral Neuropathy | 0.12 | 1 | 0 | CTD_human |
| Endometriosis | 0.12 | 1 | 0 | CTD_human |
| Metabolic Bone Disorder | 0.08 | 1 | 0 | RGD |
| Diabetic Nephropathy | 0.08 | 1 | 0 | RGD |
| Osteoarthritis, Knee | 0.08 | 1 | 0 | RGD |
| Seizures | 0.08 | 1 | 0 | RGD |
| Multiple Myeloma | 0.02041773 | 18 | 0 | BeFree_LHGDN |
| Bone Diseases | 0.011158911 | 12 | 0 | BeFree_LHGDN |
| Neoplasm Metastasis | 0.009248887 | 15 | 0 | BeFree_LHGDN |
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