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HCN3 Membrane Protein Introduction

Introduction of HCN3

Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3, also known as HCN3 channel, is a multi-pass membrane protein that functions as a voltage-gated cation channel. HCN3 in human is encoded by HCN3 gene. This channel protein is a member of the family of closely related cyclic adenosine monophosphate-binding channel proteins, which are referred to as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. HCN3 seems to be largely insensitive to cAMP.

Basic Information of HCN3
Protein Name Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
Gene Name HCN3
Aliases N/A
Organism Homo sapiens (Human)
UniProt ID Q9P1Z3
Transmembrane Times 6
Length (aa) 774
Sequence MEAEQRPAAGASEGATPGLEAVPPVAPPPATAASGPIPKSGPEPKRRHLGTLLQPTVNKFSLRVFGSHKAVEIEQERVKSAGAWIIHPYSDFRFYWDLIMLLLMVGNLIVLPVGITFFKEENSPPWIVFNVLSDTFFLLDLVLNFRTGIVVEEGAEILLAPRAIRTRYLRTWFLVDLISSIPVDYIFLVVELEPRLDAEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQWEEIFHMTYDLASAVVRIFNLIGMMLLLCHWDGCLQFLVPMLQDFPPDCWVSINHMVNHSWGRQYSHALFKAMSHMLCIGYGQQAPVGMPDVWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFHKLPADTRQRIHEYYEHRYQGKMFDEESILGELSEPLREEIINFTCRGLVAHMPLFAHADPSFVTAVLTKLRFEVFQPGDLVVREGSVGRKMYFIQHGLLSVLARGARDTRLTDGSYFGEICLLTRGRRTASVRADTYCRLYSLSVDHFNAVLEEFPMMRRAFETVAMDRLLRIGKKNSILQRKRSEPSPGSSGGIMEQHLVQHDRDMARGVRGRAPSTGAQLSGKPVLWEPLVHAPLQAAAVTSNVAIALTHQRGPLPLSPDSPATLLARSAWRSAGSPASPLVPVRAGPWASTSRLPAPPARTLHASLSRAGRSQVSLLGPPPGGGGRRLGPRGRPLSASQPSLPQRATGDGSPGRKGSGSERLPPSGLLAKPPRTAQPPRPPVPEPATPRGLQLSANM

Function of HCN3 Membrane Protein

Hyperpolarization-activated cyclic nucleotide-gated channels are a set of voltage-gated ion channels, and the threshold voltage in these channels is modulated by the metabolic state of the cell (levels of cyclic nucleotides, such as cAMP), thus enabling them to regulate cellular voltage in a context-specific manner. These channels are widely expressed in the brain and other parts of the central and peripheral nervous systems. They open upon hyperpolarized (negative) Vmem, producing large currents that are a mix of sodium and potassium fluxes. HCN channels particularly play a role in the spatial and working memory, thalamic control of vigilance states, cerebellum-dependent motor learning, and neuropathic pain. A study conducted in the mouse suggested that HCN3 channels might be involved in the regulation of the circadian system. HCN3 channels have been reported to be present in the intergeniculate leaflet (IGL) of the hypothalamus. And this nucleus is supposed to be critical for the integration and transmission of entrainment cues to the suprachiasmatic nucleus (SCN).

Structure of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3. Fig.1 Structure of potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3.

Application of HCN3 Membrane Protein in Literature

  1. Tang W., et al. MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways. Sci Rep. 2016, 6:36268. PubMed ID: 27824082

    Authors in this article suggested that the lincRNAs HCN3, linc01105, and MEG3 may be important in biological behaviors of neuroblastoma through mechanisms involving p53 pathway members such as HIF-1α, Noxa, and Bid.

  2. Leist M., et al. Two types of interneurons in the mouse lateral geniculate nucleus are characterized by different h-current density. Sci Rep. 2016, 6:24904. PubMed ID: 27121468

    This article attempted to elucidate functional aspects of HCN3 channels and reveals that Ih in IN was modulated by PIP2 probably based on the abundant expression of the HCN3 isoform.

  3. O'Donnell A.M., et al. Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung’s disease. World J Gastroenterol. 2015, 21(18):5635-40. PubMed ID: 25987789

    Findings of this article demonstrated that reduced HCN3 expression in aganglionic bowel indicated its potential role in HSCR pathophysiology.

  4. Kretschmannova K., et al. The expression and role of hyperpolarization-activated and cyclic nucleotide-gated channels in endocrine anterior pituitary cells. Mol Endocrinol. 2012, 26(1):153-64. PubMed ID: 22135067

    This article focused on the potential role of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in electrical activity of cultured rat anterior pituitary cells.

HCN3 Preparation Options

To obtain the soluble and functional target protein, we present robust reconstitution forms as well as multiple active formats for membrane proteins. Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-HCN3 antibody development services.


Creative Biolabs is a leading specialty CRO providing state-of-the-art platforms in membrane protein preparation to our worldwide clients. Our scientific team is able to deliver a full range of standard and custom professional membrane protein preparation services using our Magic™ Membrane Platform. Please feel free to contact us for more technical support.

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