Girault J A, Labesse G, Mornon J P, Callebaut I
INSERM U114, Collège de France, Paris, France.
Mol Med. 1998 Dec;4(12):751-69.
The band 4.1 domain was first identified in the red blood cell protein band 4.1, and subsequently in ezrin, radixin, and moesin (ERM proteins) and other proteins, including tumor suppressor merlin/schwannomin, talin, unconventional myosins VIIa and X, and protein tyrosine phosphatases. Recently, the presence of a structurally related domain has been demonstrated in the N-terminal region of two groups of tyrosine kinases: the focal adhesion kinases (FAK) and the Janus kinases (JAK). Additional proteins containing the 4.1/JEF (JAK, ERM, FAK) domain include plant kinesin-like calmodulin-binding proteins (KCBP) and a number of uncharacterized open reading frames identified by systematic DNA sequencing. Phylogenetic analysis of amino acid sequences suggests that band 4.1/JEF domains can be grouped in several families that have probably diverged early during evolution. Hydrophobic cluster analysis indicates that the band 4.1/JEF domains might consist of a duplicated module of approximately 140 residues and a central hinge region. A conserved property of the domain is its capacity to bind to the membrane-proximal region of the C-terminal cytoplasmic tail of proteins with a single transmembrane segment. Many proteins with band 4.1/JEF domains undergo regulated intra- or intermolecular homotypic interactions. Additional properties common to band 4.1/JEF domains of several proteins are binding of phosphoinositides and regulation by GTPases of the Rho family. Many proteins with band 4. 1/JEF domains are associated with the actin-based cytoskeleton and are enriched at points of contact with other cells or the extracellular matrix, from which they can exert control over cell growth. Thus, proteins with band 4.1/JEF domain are at the crossroads between cytoskeletal organization and signal transduction in multicellular organisms. Their importance is underlined by the variety of diseases that can result from their mutations.
4.1结构域最初是在红细胞蛋白带4.1中被鉴定出来的，随后在埃兹蛋白、根蛋白和膜突蛋白（ERM蛋白）以及其他蛋白质中被发现，包括肿瘤抑制因子默林/施万宁、踝蛋白、非常规肌球蛋白VIIa和X，以及蛋白酪氨酸磷酸酶。最近，在两组酪氨酸激酶的N端区域也发现了结构相关的结构域：粘着斑激酶（FAK）和Janus激酶（JAK）。其他含有4.1/JEF（JAK、ERM、FAK）结构域的蛋白质包括植物类驱动蛋白钙调蛋白结合蛋白（KCBP）以及通过系统DNA测序鉴定出的一些未被表征的开放阅读框。氨基酸序列的系统发育分析表明，4.1/JEF结构域可以分为几个家族，这些家族可能在进化早期就已经分化。疏水簇分析表明，4.1/JEF结构域可能由一个约140个残基的重复模块和一个中央铰链区组成。该结构域的一个保守特性是它能够与具有单个跨膜段的蛋白质的C端细胞质尾巴的膜近端区域结合。许多含有4.1/JEF结构域的蛋白质会发生受调控的分子内或分子间同型相互作用。几种蛋白质的4.1/JEF结构域共有的其他特性是与磷酸肌醇结合以及受Rho家族GTP酶的调节。许多含有4.1/JEF结构域的蛋白质与基于肌动蛋白的细胞骨架相关，并富集于与其他细胞或细胞外基质的接触点，它们可以从这些点对细胞生长进行控制。因此，含有4.1/JEF结构域的蛋白质处于多细胞生物细胞骨架组织和信号转导的交叉点。它们的重要性体现在其突变可能导致的多种疾病上。
