LAMC1(层粘连蛋白γ1)是层粘连蛋白家族的重要成员,属于层粘连蛋白γ链亚家族。层粘连蛋白家族是一类细胞外基质糖蛋白,主要由α、β、γ三条链组成,共同形成十字形结构,在基底膜的形成和维持中发挥核心作用。LAMC1编码的γ1链是大多数层粘连蛋白异源三聚体的必需组分,与α和β链共同构成功能性层粘连蛋白(如laminin-111、laminin-332等)。该基因家族的主要共性是参与细胞黏附、迁移、分化及组织发育,尤其在胚胎发育、伤口愈合和神经突触形成中至关重要。LAMC1通过整合素等受体与细胞相互作用,影响细胞信号通路(如PI3K/AKT、MAPK),其表达产物主要分布于基底膜,如皮肤、肾脏、肌肉和神经组织。突变或表达异常会导致严重疾病:LAMC1功能缺失突变与交界型大疱性表皮松解症(JEB)相关,表现为皮肤脆性增加和水疱形成;还与肾脏发育异常、肌营养不良和神经退行性疾病有关。过表达LAMC1可能促进肿瘤侵袭和转移,因其能增强癌细胞与基质的黏附及迁移能力;而表达降低则导致基底膜结构缺陷,引发组织脆弱性和发育障碍。此外,LAMC1表达水平变化会影响其他基底膜成分(如胶原IV)的组装,并调控MMPs(基质金属蛋白酶)的活性,进一步改变微环境稳态。在癌症中,LAMC1高表达常预示不良预后,可能与血管生成和上皮-间质转化(EMT)相关。研究还发现LAMC1在干细胞微环境中维持干细胞特性具有重要作用。
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also suggested that it had diverged considerably from the beta chain genes. Embryos of transgenic mice in which both alleles of the gamma 1 chain gene were inactivated by homologous recombination, lacked basement membranes, indicating that laminin, gamma 1 chain is necessary for laminin heterotrimer assembly. It has been inferred by analogy with the strikingly similar 3' UTR sequence in mouse laminin gamma 1 cDNA, that multiple polyadenylation sites are utilized in human to generate the 2 different sized mRNAs (5.5 and 7.5 kb) seen on Northern analysis. [provided by RefSeq, Aug 2011]
层粘连蛋白,一个家庭的细胞外基质糖蛋白,是基底膜的主要非胶原成分。他们已牵涉在多种生物学过程,包括细胞粘着,分化,迁移,信令,神经突向外生长和转移。层粘连蛋白,3个非同一链组成的:层粘连蛋白α,β和γ(前身为A,B1和B2,分别),有一个十字形结构,其中包括3短臂,每个由不同的链形成,一个长臂组成所有的3链。每个层粘连蛋白链是由不同的基因编码的蛋白质的多域。每条链的几种同工型已被描述。不同的α,β和γ链异构体结合以引起其通过阿拉伯数字在其发现的顺序指定不同异源层粘连蛋白同种型,即alpha1beta1gamma1异源是层粘连蛋白1的不同链和三聚体分子的生物功能在很大程度上是未知,但一些链已显示对于不同其组织分布,推测反映出体内多种功能。该基因编码的γ链同种型层粘连蛋白,γ-1.伽玛1链,以前被认为是一个β链,包含类似于β链结构域,但是,缺乏短α区分离结构??域I和II。该基因的结构组织还建议,已经从β链基因显着分歧。其中伽玛1链基因的两个等位基因被同源重组失活的转基因小鼠的胚胎,缺乏基底膜,表明层粘连蛋白,γ-1链是必要的层粘连蛋白异源组件。据推断类比与层粘连蛋白的鼠标伽马1基因的惊人相似的3‘UTR序列,多个多聚腺苷酸化位点被利用在人类产生上看到北方的分析2不同大小的mRNA(5.5和7.5 kb的)。 [由RefSeq的,2011年8月提供]
LAMC1基因(以及对应的蛋白质)的细胞分布位置:
LAMC1基因的本体(GO)信息:
| 名称 |
|---|
| 4151 PI3K-Akt signaling pathway [PATH:hsa04151] |
| 4512 ECM-receptor interaction [PATH:hsa04512] |
| 4510 Focal adhesion [PATH:hsa04510] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5222 Small cell lung cancer [PATH:hsa05222] |
| 5020 Prion diseases [PATH:hsa05020] |
| 5146 Amoebiasis [PATH:hsa05146] |
| 5145 Toxoplasmosis [PATH:hsa05145] |
| 名称 |
|---|
| Axon guidance |
| Degradation of the extracellular matrix |
| Developmental Biology |
| ECM proteoglycans |
| Extracellular matrix organization |
| L1CAM interactions |
| Laminin interactions |
| Non-integrin membrane-ECM interactions |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| Prostatic Neoplasms | 0.12272435 | 2 | 0 | CTD_human_LHGDN |
| Pelvic Organ Prolapse | 0.120542884 | 2 | 0 | BeFree_CTD_human |
| Aortic Diseases | 0.12 | 1 | 0 | CTD_human |
| Marfan Syndrome | 0.12 | 1 | 0 | CTD_human |
| Colorectal Cancer | 0.12 | 1 | 1 | GWASCAT |
| Pierson syndrome | 0.002985861 | 11 | 0 | BeFree |
| Brain Neoplasms | 0.00272435 | 1 | 0 | LHGDN |
| Glioblastoma | 0.00272435 | 1 | 0 | LHGDN |
| Alzheimer's Disease | 0.00272435 | 1 | 0 | LHGDN |
| Amyotrophic Lateral Sclerosis | 0.00272435 | 1 | 0 | LHGDN |
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