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TRPC5 Membrane Protein Introduction

Introduction of TRPC5

Short transient receptor potential channel 5 (TRPC5), encoded by the gene TRPC5,is a member of the transient receptor family. TRPC5 is a nonselective cation channel composed of subunits that probably have intracellular N and C termini, six transmembrane domains (TM1-TM6), and a pore-forming re-entrant loop between the TM5 and TM6. TRPC5 is mainly expressed in the brain with higher levels in fetal brain, and is also found in occipital pole, cerebellum, and liver. No alternatively spliced transcript variant has been reported for this gene.

Basic Information of TRPC5
Protein Name Short transient receptor potential channel 5
Gene Name TRPC5
Aliases Transient receptor protein 5
Organism Homo sapiens (Human)
UniProt ID Q9UL62
Transmembrane Times 6
Length (aa) 973
Sequence MAQLYYKKVNYSPYRDRIPLQIVRAETELSAEEKAFLNAVEKGDYATVKQALQEAEIYYNVNINCMDPLGRSALLIAIENENLEIMELLLNHSVYVGDALLYAIRKEVVGAVELLLSYRRPSGEKQVPTLMMDTQFSEFTPDITPIMLAAHTNNYEIIKLLVQKRVTIPRPHQIRCNCVECVSSSEVDSLRHSRSRLNIYKALASPSLIALSSEDPILTAFRLGWELKELSKVENEFKAEYEELSQQCKLFAKDLLDQARSSRELEIILNHRDDHSEELDPQKYHDLAKLKVAIKYHQKEFVAQPNCQQLLATLWYDGFPGWRRKHWVVKLLTCMTIGFLFPMLSIAYLISPRSNLGLFIKKPFIKFICHTASYLTFLFMLLLASQHIVRTDLHVQGPPPTVVEWMILPWVLGFIWGEIKEMWDGGFTEYIHDWWNLMDFAMNSLYLATISLKIVAYVKYNGSRPREEWEMWHPTLIAEALFAISNILSSLRLISLFTANSHLGPLQISLGRMLLDILKFLFIYCLVLLAFANGLNQLYFYYETRAIDEPNNCKGIRCEKQNNAFSTLFETLQSLFWSVFGLLNLYVTNVKARHEFTEFVGATMFGTYNVISLVVLLNMLIAMMNNSYQLIADHADIEWKFARTKLWMSYFDEGGTLPPPFNIIPSPKSFLYLGNWFNNTFCPKRDPDGRRRRRNLRSFTERNADSLIQNQHYQEVIRNLVKRYVAAMIRNSKTHEGLTEENFKELKQDISSFRYEVLDLLGNRKHPRSFSTSSTELSQRDDNNDGSGGARAKSKSVSFNLGCKKKTCHGPPLIRTMPRSSGAQGKSKAESSSKRSFMGPSLKKLGLLFSKFNGHMSEPSSEPMYTISDGIVQQHCMWQDIRYSQMEKGKAEACSQSEINLSEVELGEVQGAAQSSECPLACSSSLHCASSICSSNSKLLDSSEDVFETWGEACDLLMHKWGDGQEEQVTTRL

Function of TRPC5 Membrane Protein

TRPC5 is a type of multi-pass membrane protein and can form a non-specific Ca²⁺-activated cation channel that is functionally coupled to Ca²⁺-selective ion channels through local Ca²⁺ increases beneath the plasma membrane. TRPC5 is activated as a hetero-multimeric assembly with several other mammalian transient receptor potential channel proteins: TRPC1, TRPC3, and TRPC4. As a cation channel, TRPC5 is thought to be operated by a phosphatidylinositol second messenger system activated by G-protein coupled receptors or receptor tyrosine kinases. The canonical function of TRPC5 is to control the calcium ion transmembrane transport. Besides, TRPC5 is also shown to play roles in manganese ion transport, nervous system development, neuron differentiation, fear-related behaviors, control of neurite extension and growth cone morphology, regulation of cell proliferation, regulation of axon extension, regulation of membrane hyperpolarization, and so on.

Schematic representation of TRPC5 signaling. Fig.1 Schematic representation of TRPC5 signaling. (Patat, 2016)

Application of TRPC5 Membrane Protein in Literature

  1. Park S.E., et al. Contribution of Zinc-Dependent Delayed Calcium Influx via TRPC5 in Oxidative Neuronal Death and its Prevention by Novel TRPC Antagonist. Mol Neurobiol. 2018. PubMed ID: 30062674

    This article demonstrates that TRPC5 may be a novel potential therapeutic target against oxidative neuronal injury in prolonged seizures, and it also demonstrates that NU6027 is an effective inhibitor of TRPC5.

  2. Just S., et al. Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PLoS One. 2018, 13(1):e0191225. PubMed ID: 29385160

    This article introduces a novel small molecule antagonist of TRPC4 and TRPC5 containing ion channels and supports that the targeting of TRPC4 and TRPC5 channels may be a new mechanism of action for the therapy of psychiatric symptoms.

  3. Zhou Y., et al. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models. Science. 2017, 358(6368):1332-1336. PubMed ID: 29217578

    This article indicates that TRPC5 activity can drive disease and that inhibitors targeting TRPC5 may be potent for the treatment of progressive kidney diseases.

  4. Wang X., et al. TRPC5 Does Not Cause or Aggravate Glomerular Disease. J Am Soc Nephrol. 2018, 29(2):409-415. PubMed ID: 29061651

    This article suggests that the activation or overexpression of the TRPC5 ion channel actually does not cause injury of kidney barrier or aggravate such injury under pathologic conditions.

  5. Maddox J.W., et al. TRPC5 is required for the NO-dependent increase in dendritic Ca2+ and GABA release from chick retinal amacrine cells. J Neurophysiol. 2018, 119(1):262-273. PubMed ID: 28978766

    This article demonstrates that nitric oxide can activate TRPC5-mediated Ca²⁺ influx, which is enough to promote vesicular GABA release from retinal amacrine cells.

TRPC5 Preparation Options

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Reference

  1. Patat, et al. (2016). Truncating mutations in the adhesion G protein-coupled receptor G2 gene TRPC5 cause an X-linked congenital bilateral absence of vas deferens. The American Journal of Human Genetics. 99(2): 437-442.

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