SCN11A Membrane Protein Introduction

Introduction of SCN11A

Sodium channel protein type 11 subunit alpha, also known as SCN11A or Nav1.9 is a voltage-gated sodium ion channel protein which is encoded by the SCN11A gene on chromosome 3 in humans. SCN11A encodes a 1765 amino acids protein that shows the least degree of homology to other members of the neuronal VGSC family. The protein consists of 4 domains joined by 3 intracellular loops; each domain consists of 6 transmembrane segments and intracellular and extracellular junctions. The 4th transmembrane segment of each domain is the voltage-sensing region of the channel. The protein is highly expressed in nociceptive neurons of dorsal root ganglia and trigeminal ganglia and is a major effector of peripheral inflammatory pain hypersensitivity.

Basic Information of SCN11A
Protein Name	Sodium channel protein type 11 subunit alpha
Gene Name	SCN11A
Aliases	Peripheral nerve sodium channel 5(PN5), Sensory neuron sodium channel 2, Sodium channel protein type XI subunit alpha, Voltage-gated sodium channel, subunit alpha Nav1.9, hNaN
Organism	Homo sapiens (Human)
UniProt ID	Q9UI33
Transmembrane Times	24
Length (aa)	1791
Sequence	MDDRCYPVIFPDERNFRPFTSDSLAAIEKRIAIQKEKKKSKDQTGEVPQPRPQLDLKASRKLPKLYGDIPRELIGKPLEDLDPFYRNHKTFMVLNRKRTIYRFSAKHALFIFGPFNSIRSLAIRVSVHSLFSMFIIGTVIINCVFMATGPAKNSNSNNTDIAECVFTGIYIFEALIKILARGFILDEFSFLRDPWNWLDSIVIGIAIVSYIPGITIKLLPLRTFRVFRALKAISVVSRLKVIVGALLRSVKKLVNVIILTFFCLSIFALVGQQLFMGSLNLKCISRDCKNISNPEAYDHCFEKKENSPEFKMCGIWMGNSACSIQYECKHTKINPDYNYTNFDNFGWSFLAMFRLMTQDSWEKLYQQTLRTTGLYSVFFFIVVIFLGSFYLINLTLAVVTMAYEEQNKNVAAEIEAKEKMFQEAQQLLKEEKEALVAMGIDRSSLTSLETSYFTPKKRKLFGNKKRKSFFLRESGKDQPPGSDSDEDCQKKPQLLEQTKRLSQNLSLDHFDEHGDPLQRQRALSAVSILTITMKEQEKSQEPCLPCGENLASKYLVWNCCPQWLCVKKVLRTVMTDPFTELAITICIIINTVFLAMEHHKMEASFEKMLNIGNLVFTSIFIAEMCLKIIALDPYHYFRRGWNIFDSIVALLSFADVMNCVLQKRSWPFLRSFRVLRVFKLAKSWPTLNTLIKIIGNSVGALGSLTVVLVIVIFIFSVVGMQLFGRSFNSQKSPKLCNPTGPTVSCLRHWHMGDFWHSFLVVFRILCGEWIENMWECMQEANASSSLCVIVFILITVIGKLVVLNLFIALLLNSFSNEERNGNLEGEARKTKVQLALDRFRRAFCFVRHTLEHFCHKWCRKQNLPQQKEVAGGCAAQSKDIIPLVMEMKRGSETQEELGILTSVPKTLGVRHDWTWLAPLAEEEDDVEFSGEDNAQRITQPEPEQQAYELHQENKKPTSQRVQSVEIDMFSEDEPHLTIQDPRKKSDVTSILSECSTIDLQDGFGWLPEMVPKKQPERCLPKGFGCCFPCCSVDKRKPPWVIWWNLRKTCYQIVKHSWFESFIIFVILLSSGALIFEDVHLENQPKIQELLNCTDIIFTHIFILEMVLKWVAFGFGKYFTSAWCCLDFIIVIVSVTTLINLMELKSFRTLRALRPLRALSQFEGMKVVVNALIGAIPAILNVLLVCLIFWLVFCILGVYFFSGKFGKCINGTDSVINYTIITNKSQCESGNFSWINQKVNFDNVGNAYLALLQVATFKGWMDIIYAAVDSTEKEQQPEFESNSLGYIYFVVFIIFGSFFTLNLFIGVIIDNFNQQQKKLGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKCQGLVFDIVTSQIFDIIIISLIILNMISMMAESYNQPKAMKSILDHLNWVFVVIFTLECLIKIFALRQYYFTNGWNLFDCVVVLLSIVSTMISTLENQEHIPFPPTLFRIVRLARIGRILRLVRAARGIRTLLFALMMSLPSLFNIGLLLFLIMFIYAILGMNWFSKVNPESGIDDIFNFKTFASSMLCLFQISTSAGWDSLLSPMLRSKESCNSSSENCHLPGIATSYFVSYIIISFLIVVNMYIAVILENFNTATEESEDPLGEDDFDIFYEVWEKFDPEATQFIKYSALSDFADALPEPLRVAKPNKYQFLVMDLPMVSEDRLHCMDILFAFTARVLGGSDGLDSMKAMMEEKFMEANPLKKLYEPIVTTTKRKEEERGAAIIQKAFRKYMMKVTKGDQGDQNDLENGPHSPLQTLCNGDLSSFGVAKGKVHCD

Function of SCN11A Membrane Protein

The voltage-gated sodium channel is a membrane protein complex that plays a fundamental role in the rising phase of the action potential of most excitable cells. Alpha subunits, such as SCN11A, regulate voltage-dependent gating and conductance. However, the auxiliary beta subunit regulates the motion characteristics of the channel and facilitates complex membrane localization. Aberrant alpha subunits expression patterns or mutations of alpha subunits result in several disorders. SCN11A involves nociception, having been linked to the perception of inflammatory, neuropathic and cold-related pain. Moreover, SCN11A regulates resting membrane potentials and prolongs the depolarization response to subthreshold stimuli. Mutant SCN11A channels display excessive activity at resting voltages, causing sustained depolarization of nociceptors, impair generation of action potentials and aberrant synaptic transmission. The diseases include neuropathy, hereditary sensory and autonomic, 7 episodic pain syndrome, familial, 3 (FEPS3), which are caused by mutations affecting the SCN11A gene represented in this entry.

Fig.1 Schematic of a typical VGSC. (Kanellopoulos, 2016)

Application of SCN11A Membrane Protein in Literature

Zhang X.Y., et al. Gain-of-function mutations in SCN11A cause familial episodic pain. American Journal of Human Genetics. 2013, 93(5):957-66. PubMed ID: 24207120

This article finds that episodic pain disorder may result from gain-of-function mutations in SCN11A.
Leipold E., et al. A de novo gain-of-function mutation in SCN11A causes loss of pain perception. Nature Genetics. 2013, 45(11):1399-404. PubMed ID: 24036948

This article suggests that mutant SCN11A results in continuous depolarization of nociceptors, which may impair action potentials and abnormal synaptic transmission.
Phatarakijnirund V., et al. Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9. Bone. 2016, 84:289-298. PubMed ID: 26746779

This article shows that three patients have marked joint hypermobility found in genetic disorders of connective tissue, indicating a potential role of SCN11A in connective tissues should be investigated.
Goral R.O., et al. Heterologous expression of NaV1.9 chimeras in various cell systems. Pflugers Arch. 2015, 467(12):2423-35. PubMed ID: 25916202

This article explains the mechanism that mutation S360Y makes NaV1.9 channels sensitive to tetrodotoxin and saxitoxin.
Huang J., et al. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy. Brain. 2014, 137(Pt 6):1627-42. PubMed ID: 24776970

This article suggests that missense mutations of Nav1.9 could be a reason for painful peripheral neuropathy.

SCN11A Preparation Options

Membrane proteins have been used in many fields. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-SCN11A antibody development services.

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

Kanellopoulos A H and Matsuyama A. (2016). Voltage-gated sodium channels and pain-related disorders. Clinical Science. 130(24): 2257-2265.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

	USA: Europe: Germany:
	Call us at: USA: UK: Germany:
	Fax:
	Email: