ANO3 Membrane Protein Introduction

Introduction of ANO3

ANO3 is encoded by the ANO3 gene and is also known as transmembrane protein 16C (TMEM16C). It belongs to the transmembrane protein 16 (TMEM16) family which is highly conserved in different eukaryotic organisms from fungi to invertebrate to mammals. TMEM16 family has ten members (A, B, C, D, E, F, G, H, J and K) in mammals. Meanwhile, its structure reveals that TMEM16 contains two subunits, each of which has 8 transmembrane helices and both the N- and C-terminus are inside the cell.

Basic Information of ANO3
Protein Name	Anoctamin-3
Gene Name	ANO3
Aliases	Transmembrane protein 16C, TMEM16C
Organism	Homo sapiens (Human)
UniProt ID	Q9BYT9
Transmembrane Times	8
Length (aa)	981
Sequence	MVHHSGSIQSFKQQKGMNISKSEITKETSLKPSRRSLPCLAQSYAYSKSLSQSTSLFQSTESESQAPTSITLISTDKAEQVNTEENKNDSVLRCSFADLSDFCLALGKDKDYTDESEHATYDRSRLINDFVIKDKSEFKTKLSKNDMNYIASSGPLFKDGKKRIDYILVYRKTNIQYDKRNTFEKNLRAEGLMLEKEPAIASPDIMFIKIHIPWDTLCKYAERLNIRMPFRKKCYYTDGRSKSMGRMQTYFRRIKNWMAQNPMVLDKSAFPDLEESDCYTGPFSRARIHHFIINNKDTFFSNATRSRIVYHMLERTKYENGISKVGIRKLINNGSYIAAFPPHEGAYKSSQPIKTHGPQNNRHLLYERWARWGMWYKHQPLDLIRLYFGEKIGLYFAWLGWYTGMLIPAAIVGLCVFFYGLFTMNNSQVSQEICKATEVFMCPLCDKNCSLQRLNDSCIYAKVTYLFDNGGTVFFAIFMAIWATVFLEFWKRRRSILTYTWDLIEWEEEEETLRPQFEAKYYKMEIVNPITGKPEPHQPSSDKVTRLLVSVSGIFFMISLVITAVFGVVVYRLVVMEQFASFKWNFIKQYWQFATSAAAVCINFIIIMLLNLAYEKIAYLLTNLEYPRTESEWENSFALKMFLFQFVNLNSSIFYIAFFLGRFVGHPGKYNKLFDRWRLEECHPSGCLIDLCLQMGVIMFLKQIWNNFMELGYPLIQNWWSRHKIKRGIHDASIPQWENDWNLQPMNLHGLMDEYLEMVLQFGFTTIFVAAFPLAPLLALLNNIIEIRLDAYKFVTQWRRPLPARATDIGIWLGILEGIGILAVITNAFVIAITSDYIPRFVYEYKYGPCANHVEPSENCLKGYVNNSLSFFDLSELGMGKSGYCRYRDYRGPPWSSKPYEFTLQYWHILAARLAFIIVFEHLVFGIKSFIAYLIPDVPKGLHDRIRREKYLVQEMMYEAELEHLQQQRRKSGQPVHHEWP

Function of ANO3 Membrane Protein

ANO3 is expressed in caudate nucleus 12 brains according to the gene co-expression network analysis (WGCN) of microarray data from human and chimpanzee. The expression pattern of ANO3 suggests an association of ANO3 with late-onset Alzheimer's disease (LOAD). Moreover, a recent genetic study linked ANO3 mutations shows that the expression of ANO3 is high in human striatum, hippocampus and cortex14. The expression pattern suggests that ANO3 may be involved in the human autosomal-dominant craniocervical dystonia. Other study reports that ANO3 is mainly expressed in neuronal tissues from both the central and peripheral nervous system, especially in the IB4 positive, non-peptidergic nociceptors in dorsal root ganglia. More importantly, the ANO3 knockout rats exhibit thermal and mechanical sensitivity, which is associated with increased neuronal excitability and broadened action potential in their IB4 positive dorsal root ganglia neurons. Meanwhile, ANO3 is reported to enhance the K⁺ Na⁺ channel activity in dorsal root ganglia neurons and thus regulates the processing of pain messages.

Fig.1 Proposed structure of ANO3 membrane protein. (Hartzell, 2016)

Application of ANO3 Membrane Protein in Literature

Huang F., et al. TMEM16C facilitates sodium-activated potassium currents in rat primary sensory neurons and regulates pain processing. Nat. Neurosci. 2013, 16(9):1284-1290. PubMed ID: 23872594

This article reports that TMEM16C (ANO3) interacts with the K⁺ Na⁺ channel and is involved in modulating the activity and sensitivity of K⁺ Na⁺ channel in dorsal root ganglia neurons.
Hopfner F., et al. Rare variants in ANO3 are not a susceptibility factor in essential tremor. Parkinsonism & Related Disorders. 2014, 20(1):134-135. PubMed ID: 24094724

This article reveals that ANO3 mutations have identified as one of a cause of cranio-cervical segmental dystonia, tremor and myoclonic jerks.
Miltgen M., et al. Novel heterozygous mutation in ANO3 responsible for craniocervical dystonia. Movement Disorders. 2016, 31(8):1251-1252. PubMed ID: 27392807

Authors in this group apply exome sequencing to identify a novel 1969G>A mutation in the ANO3 gene, which is associated with the development of cervical dystonia and segmental dystonia.
Blackburn P.R., et al. A novel ANO3 variant identified in a 53-year-old woman presenting with hyperkinetic dysarthria, blepharospasm, hyperkinesias, and complex motor tics. BMC Medical Genetics. 2016, 17:93. PubMed ID: 27919237

This article focuses on a novel heterozygous missense variant identified found in a 53-year-old female patient in exon 7 in the ANO3 gene. The patient developed a mixed hyperkinetic disorder and suggests that ANO3 may take part in the development of hyperkinetic disorder.
Charlesworth G., et al. Mutations in ANO3 Cause Dominant Craniocervical Dystonia: Ion Channel Implicated in Pathogenesis. Am. J. Hum. Genet. 2012, 91(6):1041-1050. PubMed ID: 23200863

This article evaluates the importance of ANO3 in the pathogenesis of autosomal-dominant craniocervical dystonia, and the implication of ANO3 suggests an alternative mechanism in this field.

ANO3 Preparation Options

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Reference

Hartzell H.C. and Whitlock J.M. (2016) TMEM16 chloride channels are two-faced. The Journal of General Physiology. 148(5):367.

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