Ask about this productRelated genes to: TMC2 Blocking Peptide
- Gene:
- TMC2 NIH gene
- Name:
- transmembrane channel like 2
- Previous symbol:
- C20orf145
- Synonyms:
- dJ686C3.3
- Chromosome:
- 20p13
- Locus Type:
- gene with protein product
- Date approved:
- 2001-10-08
- Date modifiied:
- 2015-11-12
Related products to: TMC2 Blocking Peptide
Related articles to: TMC2 Blocking Peptide
- The transmembrane channel-like (TMC) gene family encodes membrane proteins required for hair cell mechanotransduction. While TMC1 and TMC2 are indispensable for mammalian hearing, the functions of other paralogs remain poorly defined. Using zebrafish, we examined nine TMC genes (tmc1, tmc2a, tmc2b, tmc3, tmc4, tmc5, tmc6a, tmc6b, and tmc8) through phylogenetic, transcriptomic, and spatiotemporal expression analyses. tmc1, tmc2a, and tmc2b were robustly expressed in hair cells of the otic vesicle and neuromasts, supporting their early roles in hair cell differentiation. tmc3 and tmc6a showed clear expression by in situ hybridization but were underrepresented in transcriptomic datasets. tmc4 and tmc5 were more broadly expressed, including vestibular hair cells and neuromasts from 72 to 96 h post-fertilization (hpf). Several TMC genes were also detected in non-sensory tissues, suggesting potential roles in other developmental processes. Together, this study provides the first comprehensive atlas of TMC gene expression during zebrafish embryogenesis and reveals divergent expression patterns among paralogs. - Source: PubMed
Publication date: 2026/04/22
Geng KaixiWang XunWang XinLiu DongQian Fuping - TMC1 and TMC2 are mechanosensory ion channels of the vertebrate inner ear that mediate hearing and balance. How these channels open in response to mechanical force remains unresolved. Through comparative analyses of TMCs across eukaryote species, we find that TMC1 and TMC2 arose in vertebrates by gene duplication and evolved elaborate extracellular loops. Structural models demonstrate that the loop between transmembrane domains 1 and 2 arches over the channel pore and lies near TMIE, an auxiliary protein essential for function. In mammals, this loop shows signatures of positive selection and contains multiple sites linked to hereditary deafness, consistent with TMC1's specialization for auditory function. Electrophysiological recordings from mouse Tmc1/Tmc2-null cochlear hair cells expressing TMC1 variants demonstrate that alterations within this loop affect channel activation, identifying it as a modulatory feature that has been refined through structural adaptation. - Source: PubMed
Publication date: 2026/03/25
Akyuz NurunisaScott Trey JLoeb CorenaPan BifengLi YaqiaoPhillips Charles BBellono Nicholas WCorey David P - Sensory hair cells convert sound-induced vibrations into electrical signals through a process called mechanoelectrical transduction (MET). While the protein components of the MET complex are well studied, increasing evidence indicates that MET channel properties are significantly modulated by the surrounding lipid bilayer. The asymmetric distribution of membrane lipids between the inner and outer membrane leaflets is well established to shape membrane mechanics. The recent discovery that the core MET components TMC1 and TMC2 also act as lipid scramblases suggests a direct role for membrane lipid asymmetry in the dynamic shaping of auditory transduction. Because scramblase activity of TMC1/2 disrupts lipid asymmetry, we hypothesized that an opposing flippase may be required to restore and maintain lipid asymmetry. Here, we identify the P4-ATPase ATP8B1 and its chaperone TMEM30B as selectively expressed in outer hair cells (OHCs), enriched in stereocilia, and upregulated following the onset of MET and hearing. Loss of either protein results in elevated auditory brainstem response (ABR) thresholds, phosphatidylserine (PS) externalization, and rapid hair-cell degeneration, demonstrating that lipid homeostasis is crucial for OHC survival. Together, these findings establish ATP8B1 and TMEM30B as key regulators of membrane lipid asymmetry in sensory hair cells and establish TMEM30B as a novel deafness gene. - Source: PubMed
Publication date: 2026/02/13
De Hoyos Henry NLi SihanIm Jun-SubLuz-Ricca AlyssaSzeto BetsyJonas RachelKim EmmaAmin NikhilShin Jung-Bum - The family of transmembrane channel-like (TMC) genes encodes at least 8 transmembrane proteins that are conserved across species. However, except for TMC1 and TMC2, their functional role is largely unexplored. To determine the extent to which each of these subtypes contributes to pain and itch processing, here we investigated the anatomical and behavioral consequences of deleting 3 members of the TMC family in mice. We report that selective ablation of the Tmc3, Tmc5 or Tmc7 genes leads to different, and in some cases, opposite behavioral effects. Specifically, mice deficient for Tmc3 or Tmc5 exhibited reduced nociception across pain modalities (mechanical, heat and cold), whereas Tmc7 deletion increased nociception. With respect to itch, pruritogen-evoked scratching was increased in Tmc5 and Tmc7, but not Tmc3 knock-out mice. Interestingly, although the expression of Tmc3, Tmc5 and Tmc7 was upregulated in sensory neurons of mice in the spared nerve injury (SNI) model of neuropathic pain, ablating these genes did not prevent the mechanical allodynia that develops following SNI. Responses also did not change in an inflammatory pain setting. Taken together, we conclude that TMC3, TMC5 and TMC7 channels differentially contribute to pain and itch processing. The mechanisms underlying these differences remain to be determined. PERSPECTIVE: Tmc3 and Tmc5 knock-out mice exhibit decreased nociception; Tmc7 knock-out mice exhibit increased nociception; Tmc5 and Tmc7, but not Tmc3, contribute to itch processing. - Source: PubMed
Publication date: 2025/11/07
Braz João MBhardwaj KarnikaRodriguez-Rosado SianJewell MadisonCraik VeronicaBasbaum Allan I - TMC4 is a member of the transmembrane channel-like (TMC) protein family. In this family, TMC1 and TMC2 are thought to form the mechano-electrical transduction (MET) channel in the inner ear. On the other hand, the intrinsic functions of the other TMC family members (TMC3-8) are largely unknown. KCNQ1 (Kv7.1) channel is a voltage-gated potassium channel and plays crucial physiological roles with its auxiliary subunits, KCNE proteins (e.g. KCNQ1/KCNE1 complex contributes to cardiac repolarization, and KCNQ1/KCNE3 complex participates in epithelial ion transport). Recently, it was reported that TMC1 and TMC2 interacted with KCNQ1 and suppressed its K currents. However, the relationships between KCNQ1 and the other TMC proteins have not been examined. Here, we show a novel interaction and a functional association between overexpressed TMC4 and KCNQ1. The Bead Halo assay and FRET analysis revealed the physical interaction between these two proteins. Whole-cell patch clamp recording demonstrated that co-expression of TMC4 reduced KCNQ1 current densities without altering their voltage dependence and activation kinetics. This effect was also observed in the KCNQ1/KCNE1 and KCNQ1/KCNE3 channel complexes. A structural prediction using AlphaFold-Multimer suggested possible interaction sites between TMC4 and KCNQ1. Mutageneses, followed by patch clamp recording, suggested that specific amino acid residues at these sites contribute to the inhibitory effect of TMC4. These results indicate that TMC4 could function as a negative regulator of the KCNQ1 channel. Our findings could enhance the understanding of KCNQ1 channel regulation and propose potential research directions on the function of TMC4 under various physiological and pathological conditions. - Source: PubMed
Publication date: 2025/10/02
Aoyagi HirotaKawaguchi KoyaYano-Nashimoto SaoriYamaguchi Soichiro