WNT3是WNT基因家族的重要成员,该家族编码一组分泌型糖蛋白,通过调控WNT信号通路参与胚胎发育、细胞增殖、分化及组织稳态等关键生物学过程。WNT3蛋白作为典型的WNT配体,其核心功能是激活经典的β-catenin依赖型WNT通路(即WNT/β-catenin通路):当WNT3与细胞膜上的Frizzled受体和LRP5/6共受体结合后,会抑制β-catenin的降解复合体,导致β-catenin在细胞质中积累并转入细胞核,进而激活TCF/LEF转录因子调控靶基因表达。这一通路对中胚层形成、神经管闭合和肢体发育至关重要,尤其在胚胎早期背腹轴模式建立中发挥决定性作用。WNT3基因突变可导致严重发育缺陷,例如人类WNT3功能丧失性突变与罕见的畸形综合征"四肢-乳腺综合征"(Limb-Mammary Syndrome)相关,表现为肢体缺失、乳腺发育不全等;而小鼠Wnt3敲除则引发胚胎致死,伴随神经管和体节发育异常。WNT3过表达与多种癌症(如结直肠癌、乳腺癌)的发生发展密切相关,因其持续激活β-catenin通路会促进细胞异常增殖和转移。相反,WNT3表达不足可能影响组织再生能力,例如在骨骼修复中减弱成骨细胞分化。WNT家族包含19个成员(如WNT1、WNT5A等),其共性是通过自分泌/旁分泌方式传递信号,但根据激活通路类型分为两类:一类(如WNT3)主要启动β-catenin依赖的经典通路,另一类(如WNT5A)触发非经典通路(如平面细胞极性通路或钙离子通路)。WNT蛋白均具有高度保守的脂质修饰(棕榈酰化),这种修饰对其分泌和膜结合特性至关重要。需要注意的是,WNT3与同家族的WNT3A(Wnt3a)功能高度相似但表达模式不同,WNT3A在小鼠中更常用于实验研究。
The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]
Wnt信号基因家族由结构相关基因,其编码分泌信号蛋白。这些蛋白质有牵连肿瘤发生并在几个发育过程,包括胚胎发育过程中细胞命运和图案化的调节。此基因是WNT基因家族的一个成员。它编码表示98%的氨基酸同一性的小鼠WNT3蛋白和84%至人Wnt3a蛋白质,另一WNT基因产物的蛋白质。鼠标研究表明WNT3的在小鼠初级轴形成的要求。基因表达的研究表明,这种基因可通过WNT-β-连环蛋白的TCF信号转导通路的激活在人类乳腺癌,直肠癌,肺癌和胃癌的某些情况下,一个重要的角色。该基因簇与WNT15,其他家庭成员,在染色体17q21上的区域。 [由RefSeq的,2008年7月提供]
WNT3基因(以及对应的蛋白质)的细胞分布位置:
WNT3基因的本体(GO)信息:
名称 |
---|
4310 Wnt signaling pathway [PATH:hsa04310] |
4340 Hedgehog signaling pathway [PATH:hsa04340] |
4390 Hippo signaling pathway [PATH:hsa04390] |
4550 Signaling pathways regulating pluripotency of stem cells [PATH:hsa04550] |
4916 Melanogenesis [PATH:hsa04916] |
5200 Pathways in cancer [PATH:hsa05200] |
5206 MicroRNAs in cancer [PATH:hsa05206] |
5205 Proteoglycans in cancer [PATH:hsa05205] |
5217 Basal cell carcinoma [PATH:hsa05217] |
5166 HTLV-I infection [PATH:hsa05166] |
名称 |
---|
Class B/2 (Secretin family receptors) |
GPCR ligand binding |
Signaling by Wnt |
TCF dependent signaling in response to WNT |
WNT ligand biogenesis and trafficking |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Parkinson Disease | 0.127101096 | 3 | 3 | GAD_GWASCAT |
Malignant lymphoma, lymphocytic, intermediate differentiation, diffuse | 0.123267234 | 2 | 0 | BeFree_CTD_human_LHGDN |
Celiac Disease | 0.122367032 | 1 | 1 | GAD_GWASCAT |
Tetra-amelia autosomal recessive | 0.120542884 | 2 | 0 | BeFree_CTD_human |
Tetraamelia multiple malformations | 0.12 | 0 | 0 | ORPHANET |
Bladder Exstrophy and Epispadias Complex | 0.12 | 0 | 1 | CLINVAR |
Cleft Lip | 0.007101096 | 3 | 0 | GAD |
Cleft Palate | 0.007101096 | 3 | 0 | GAD |
melanoma | 0.002995792 | 2 | 0 | BeFree_LHGDN |
Progressive supranuclear palsy | 0.002367032 | 1 | 0 | GAD |
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