SCN9A

SCN9A
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	5EK0
Identifikatori
Aliasi	SCN9A
Vanjski ID-jevi	OMIM: 603415 MGI: 107636 HomoloGene: 2237 GeneCards: SCN9A
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	166,376,001 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	66,465,306 bp
Ontologija gena
Molekularna funkcija	• sodium ion binding; • sodium channel activity; • voltage-gated ion channel activity; • ion channel activity; • voltage-gated sodium channel activity;
Ćelijska komponenta	• voltage-gated sodium channel complex; • integral component of membrane; • membrana; • integral component of plasma membrane; • projekcija ćelije; • ćelijska membrana; • Akson;
Biološki proces	• membrane depolarization during action potential; • sodium ion transport; • regulation of ion transmembrane transport; • post-embryonic development; • ion transport; • behavioral response to pain; • transmembrane transport; • Nocicepcija; • inflammatory response; • response to toxic substance; • neuronal action potential; • sodium ion transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	6335
	20274
	ENSG00000169432
	ENSMUSG00000075316
	Q15858
	Q62205
	NM_002977; NM_001365536
	NM_001290674; NM_001290675; NM_018852
	NP_002968; NP_001352465
	NP_001277603; NP_001277604
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Na_v1.7 jest natrijski kanal koji je kod ljudi kodiran genom SCN9A sa hromosoma 2.^[5]^[6]^[7] Obično se eksprimira na visokim nivoima u dva tipa neurona: nociceptivnim (bolnim) neuronima u ganglijskom dorzalnom korijenu (DRG), rigeninusnoj gangliji i neuronima simpatičkih ganglija , koji su dio autonomnog (nevoljnog) nervnog sistema.^[8]^[9]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.988 aminokiselina, a molekulska masa 226.372 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAMLPPPGPQ	SFVHFTKQSL	ALIEQRIAER	KSKEPKEEKK	DDDEEAPKPS
SDLEAGKQLP	FIYGDIPPGM	VSEPLEDLDP	YYADKKTFIV	LNKGKTIFRF
NATPALYMLS	PFSPLRRISI	KILVHSLFSM	LIMCTILTNC	IFMTMNNPPD
WTKNVEYTFT	GIYTFESLVK	ILARGFCVGE	FTFLRDPWNW	LDFVVIVFAY
LTEFVNLGNV	SALRTFRVLR	ALKTISVIPG	LKTIVGALIQ	SVKKLSDVMI
LTVFCLSVFA	LIGLQLFMGN	LKHKCFRNSL	ENNETLESIM	NTLESEEDFR
KYFYYLEGSK	DALLCGFSTD	SGQCPEGYTC	VKIGRNPDYG	YTSFDTFSWA
FLALFRLMTQ	DYWENLYQQT	LRAAGKTYMI	FFVVVIFLGS	FYLINLILAV
VAMAYEEQNQ	ANIEEAKQKE	LEFQQMLDRL	KKEQEEAEAI	AAAAAEYTSI
RRSRIMGLSE	SSSETSKLSS	KSAKERRNRR	KKKNQKKLSS	GEEKGDAEKL
SKSESEDSIR	RKSFHLGVEG	HRRAHEKRLS	TPNQSPLSIR	GSLFSARRSS
RTSLFSFKGR	GRDIGSETEF	ADDEHSIFGD	NESRRGSLFV	PHRPQERRSS
NISQASRSPP	MLPVNGKMHS	AVDCNGVVSL	VDGRSALMLP	NGQLLPEVII
DKATSDDSGT	TNQIHKKRRC	SSYLLSEDML	NDPNLRQRAM	SRASILTNTV
EELEESRQKC	PPWWYRFAHK	FLIWNCSPYW	IKFKKCIYFI	VMDPFVDLAI
TICIVLNTLF	MAMEHHPMTE	EFKNVLAIGN	LVFTGIFAAE	MVLKLIAMDP
YEYFQVGWNI	FDSLIVTLSL	VELFLADVEG	LSVLRSFRLL	RVFKLAKSWP
TLNMLIKIIG	NSVGALGNLT	LVLAIIVFIF	AVVGMQLFGK	SYKECVCKIN
DDCTLPRWHM	NDFFHSFLIV	FRVLCGEWIE	TMWDCMEVAG	QAMCLIVYMM
VMVIGNLVVL	NLFLALLLSS	FSSDNLTAIE	EDPDANNLQI	AVTRIKKGIN
YVKQTLREFI	LKAFSKKPKI	SREIRQAEDL	NTKKENYISN	HTLAEMSKGH
NFLKEKDKIS	GFGSSVDKHL	MEDSDGQSFI	HNPSLTVTVP	IAPGESDLEN
MNAEELSSDS	DSEYSKVRLN	RSSSSECSTV	DNPLPGEGEE	AEAEPMNSDE
PEACFTDGCV	WRFSCCQVNI	ESGKGKIWWN	IRKTCYKIVE	HSWFESFIVL
MILLSSGALA	FEDIYIERKK	TIKIILEYAD	KIFTYIFILE	MLLKWIAYGY
KTYFTNAWCW	LDFLIVDVSL	VTLVANTLGY	SDLGPIKSLR	TLRALRPLRA
LSRFEGMRVV	VNALIGAIPS	IMNVLLVCLI	FWLIFSIMGV	NLFAGKFYEC
INTTDGSRFP	ASQVPNRSEC	FALMNVSQNV	RWKNLKVNFD	NVGLGYLSLL
QVATFKGWTI	IMYAAVDSVN	VDKQPKYEYS	LYMYIYFVVF	IIFGSFFTLN
LFIGVIIDNF	NQQKKKLGGQ	DIFMTEEQKK	YYNAMKKLGS	KKPQKPIPRP
GNKIQGCIFD	LVTNQAFDIS	IMVLICLNMV	TMMVEKEGQS	QHMTEVLYWI
NVVFIILFTG	ECVLKLISLR	HYYFTVGWNI	FDFVVVIISI	VGMFLADLIE
TYFVSPTLFR	VIRLARIGRI	LRLVKGAKGI	RTLLFALMMS	LPALFNIGLL
LFLVMFIYAI	FGMSNFAYVK	KEDGINDMFN	FETFGNSMIC	LFQITTSAGW
DGLLAPILNS	KPPDCDPKKV	HPGSSVEGDC	GNPSVGIFYF	VSYIIISFLV
VVNMYIAVIL	ENFSVATEES	TEPLSEDDFE	MFYEVWEKFD	PDATQFIEFS
KLSDFAAALD	PPLLIAKPNK	VQLIAMDLPM	VSGDRIHCLD	ILFAFTKRVL
GESGEMDSLR	SQMEERFMSA	NPSKVSYEPI	TTTLKRKQED	VSATVIQRAY
RRYRLRQNVK	NISSIYIKDG	DRDDDLLNKK	DMAFDNVNEN	SSPEKTDATS
STTSPPSYDS	VTKPDKEKYE	QDRTEKEDKG	KDSKESKK

Funkcija

Struktura ljudskog naponski vođenog natrijevog kanala Nav1.7 u kompleksu sa pomoćnim beta-podjedinicama, ProTx-II i tetrodotoksinom (Y1755 dolje), iz RCSB PDB (6J8J).

Na_v1.7 je naponski vođeni natrijski kanal i igra ključnu ulogu u stvaranju i provođenju akcijskih potencijala i stoga je važanza električnu signalizaciju većine ekscitabilnih ćelija. Na_v1.7 je prisutan na završecima nerava koji osjećaju bol, nociceptorima, blizu regije gdje je impuls pokrenut. Stimulacija nervnih završetaka nociceptora proizvodi "generatorske potencijale", koji su male promjene napona kroz neuronske membrane. Na_v1.7 kanal pojačava ove membranske depolarizacije, a kada razlika membranskog potencijala dostigne određeni prag, neuron se aktivira. U senzornim neuronima, višestruke natrijeve struje zavisne od napona mogu se razlikovati po njihovoj ovisnosti o naponu i po osjetljivosti na blokator natrijskih kanala ([tetrodotoksin]). Na_v1.7 kanal proizvodi brzo aktivirajuću i inaktivirajuću struju koja je osjetljiva na nivo tetrodotoksina.^[10] Na_v1.7 je važan u ranim fazama neuronske elektrogeneze. Aktivnost Na_v1.7 sastoji se od sporog prijelaza kanala u neaktivno stanje kada je depolariziran, čak i u manjem stepenu.^[11] Ovo svojstvo omogućava da ovi kanali ostanu dostupni za aktivaciju čak i sa malim ili sporo razvijajućim depolarizacijama. Stimulacija nervnih završetaka nociceptora proizvodi "generatorske potencijale", male promjene u naponu na neuronskim membranama.^[11] Ovo dovodi neurone do napona koji stimulira Na_v1,8, koji ima više depolarizovani prag aktivacije koji proizvodi većinu transmembranske struje, odgovorne za depolarizirajuću fazu akcijskih potencijala.^[12]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000169432 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000075316 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Klugbauer N, Lacinova L, Flockerzi V, Hofmann F (mart 1995). "Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells". The EMBO Journal. 14 (6): 1084–90. doi:10.1002/j.1460-2075.1995.tb07091.x. PMC 398185. PMID 7720699.
^ Plummer NW, Meisler MH (april 1999). "Evolution and diversity of mammalian sodium channel genes". Genomics. 57 (2): 323–31. doi:10.1006/geno.1998.5735. PMID 10198179.
^ Catterall WA, Goldin AL, Waxman SG (decembar 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. S2CID 7332624.
^ ^a ^b Raymond CK, Castle J, Garrett-Engele P, Armour CD, Kan Z, Tsinoremas N, Johnson JM (oktobar 2004). "Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia". The Journal of Biological Chemistry. 279 (44): 46234–41. doi:10.1074/jbc.M406387200. PMID 15302875.
^ Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG (maj 2006). "A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons". Proceedings of the National Academy of Sciences of the United States of America. 103 (21): 8245–50. Bibcode:2006PNAS..103.8245R. doi:10.1073/pnas.0602813103. PMC 1472458. PMID 16702558.
^ Catterall WA (2000). "Structure and regulation of voltage-gated Ca2+ channels". Annual Review of Cell and Developmental Biology. 16: 521–55. doi:10.1146/annurev.cellbio.16.1.521. PMID 11031246.
^ ^a ^b Cummins TR, Howe JR, Waxman SG (decembar 1998). "Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel". The Journal of Neuroscience. 18 (23): 9607–19. doi:10.1523/JNEUROSCI.18-23-09607.1998. PMC 6793269. PMID 9822722.
^ Renganathan M, Cummins TR, Waxman SG (august 2001). "Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons". Journal of Neurophysiology. 86 (2): 629–40. doi:10.1152/jn.2001.86.2.629. PMID 11495938. S2CID 11579149.

Dopunska literatura

Emery EC, Luiz AP, Wood JN (august 2016). "Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief". Expert Opinion on Therapeutic Targets. 20 (8): 975–83. doi:10.1517/14728222.2016.1162295. PMC 4950419. PMID 26941184.

Vanjski linkovi

SCN9A protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on SCN9A-Related Inherited Erythromelalgia
Q15858

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000169432 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000075316 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid7720699-5] Klugbauer N, Lacinova L, Flockerzi V, Hofmann F (mart 1995). "Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells". The EMBO Journal. 14 (6): 1084–90. doi:10.1002/j.1460-2075.1995.tb07091.x. PMC 398185. PMID 7720699.

[pmid10198179-6] Plummer NW, Meisler MH (april 1999). "Evolution and diversity of mammalian sodium channel genes". Genomics. 57 (2): 323–31. doi:10.1006/geno.1998.5735. PMID 10198179.

[pmid16382098-7] Catterall WA, Goldin AL, Waxman SG (decembar 2005). "International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels". Pharmacological Reviews. 57 (4): 397–409. doi:10.1124/pr.57.4.4. PMID 16382098. S2CID 7332624.

[pmid15302875-8] Raymond CK, Castle J, Garrett-Engele P, Armour CD, Kan Z, Tsinoremas N, Johnson JM (oktobar 2004). "Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia". The Journal of Biological Chemistry. 279 (44): 46234–41. doi:10.1074/jbc.M406387200. PMID 15302875.

[pmid16702558-9] Rush AM, Dib-Hajj SD, Liu S, Cummins TR, Black JA, Waxman SG (maj 2006). "A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons". Proceedings of the National Academy of Sciences of the United States of America. 103 (21): 8245–50. Bibcode:2006PNAS..103.8245R. doi:10.1073/pnas.0602813103. PMC 1472458. PMID 16702558.

[pmid11031246-10] Catterall WA (2000). "Structure and regulation of voltage-gated Ca2+ channels". Annual Review of Cell and Developmental Biology. 16: 521–55. doi:10.1146/annurev.cellbio.16.1.521. PMID 11031246.

[Cummins_1998-11] Cummins TR, Howe JR, Waxman SG (decembar 1998). "Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel". The Journal of Neuroscience. 18 (23): 9607–19. doi:10.1523/JNEUROSCI.18-23-09607.1998. PMC 6793269. PMID 9822722.

[12] Renganathan M, Cummins TR, Waxman SG (august 2001). "Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons". Journal of Neurophysiology. 86 (2): 629–40. doi:10.1152/jn.2001.86.2.629. PMID 11495938. S2CID 11579149.

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