Marriotts Ridge High School, Baltimore, Maryland, USA.
Departments of Medicine (Cardiology) and Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Physiol Rep. 2023 Nov;11(21):e15844. doi: 10.14814/phy2.15844.
Smoothelins are cytoskeletal proteins with a single C-terminal calponin homology domain type 2 (CHD2). Little is known about the significance of variation in SMTN CHD2 domains, addressed here through analysis of public databases. A conserved 152 nt penultimate constitutive exon present in all SMTNs encodes helices II-IV of CHD2 with high identity (nt/aa 63/65%). Variable CHD2s of SMTN (helices IV-VI) are generated by alternative splicing of 165 nt exon E20. E20 and the CHD2 it encodes have high homology with the terminal constitutive exon of SMTNL1 (E8; nt/aa 72/75% identity). Unique to these CHD2 variants are a conserved extended nine amino acid C-terminal tail containing KTKK ubiquitination motifs. When E20 of SMTN is skipped (SMTN E20-), constitutive terminal E21 codes for helices IV-VI of CHD2. SMTN E21 has high identity with the terminal exon of SMTNL2 (E8; nt/aa 75/81% identity of aligned sequences) except for coding for a unique extended C-terminus (24 nt; 8aa) conserved only in mammals. SMTN isoform expression is tissue-specific: SMTNE20- and SMTNE20+ are highly expressed in SMC and non-muscle cells, respectively, while SMTNL1 + 2 are highly expressed in skeletal muscle cells. Tissue-specific expression of SMTN CHD2s with unique helices IV-VI suggest tissue-specific functions that require further study.
平滑肌肌球蛋白重链结合蛋白是一种含有单个 C 端钙调蛋白同源结构域 2 型（CHD2）的细胞骨架蛋白。关于 SMTN CHD2 结构域变异的意义知之甚少，本文通过对公共数据库的分析对此进行了研究。所有 SMTN 中都存在一个保守的 152nt 倒数第二个组成型外显子，该外显子编码 CHD2 的螺旋 II-IV，具有高度的同一性（nt/aa63/65%）。SMTN 的可变 CHD2（螺旋 IV-VI）是通过 165nt 外显子 E20 的选择性剪接产生的。E20 和它编码的 CHD2 与 SMTNL1 的末端组成型外显子 E8 具有高度同源性（nt/aa72/75%同一性）。这些 CHD2 变体所特有的是一个保守的扩展的九氨基酸 C 末端尾部，包含 KTKK 泛素化基序。当 SMTN 的 E20 被跳过（SMTN E20-）时，组成性末端 E21 编码 CHD2 的螺旋 IV-VI。SMTN E21 与 SMTNL2 的末端外显子高度同源（E8；对齐序列的 nt/aa75/81%同一性），除了编码一个独特的扩展 C 末端（24nt；8aa），该末端仅在哺乳动物中保守。SMTN 异构体的表达具有组织特异性：SMTNE20-和 SMTNE20+分别在 SMC 和非肌肉细胞中高度表达，而 SMTNL1+2 在骨骼肌细胞中高度表达。具有独特螺旋 IV-VI 的 SMTN CHD2 的组织特异性表达表明存在需要进一步研究的组织特异性功能。
