KCNQ2

KCNQ2
Identifikatori
Aliasi	KCNQ2
Vanjski ID-jevi	OMIM: 602235 MGI: 1309503 HomoloGene: 26174 GeneCards: KCNQ2
Lokacija gena (čovjek)
Hrom.	Hromosom 20 (čovjek)
Kraj	63,472,677 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	180,777,093 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• ankyrin binding; • ion channel activity; • voltage-gated ion channel activity; • voltage-gated potassium channel activity; • potassium channel activity; • calmodulin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • delayed rectifier potassium channel activity;
Ćelijska komponenta	• axon initial segment; • Ranvijerov čvor; • membrana; • integral component of membrane; • integral component of plasma membrane; • voltage-gated potassium channel complex; • ćelijska membrana;
Biološki proces	• regulation of ion transmembrane transport; • ion transport; • transmembrane transport; • nervous system development; • chemical synaptic transmission; • potassium ion transport; • potassium ion transmembrane transport;
	Izvori:Amigo / QuickGO
Ortolozi
	3785
	16536
	ENSG00000075043; ENSG00000281151
	ENSMUSG00000016346
	O43526
	Q9Z351
NM_004518; NM_172106; NM_172107; NM_172108; NM_172109;
	NM_001382235
NM_001003824; NM_001003825; NM_001006668; NM_001006669; NM_001006674;
	NM_001006675; NM_001006676; NM_001006677; NM_001006678; NM_001006679; NM_001006680; NM_010611; NM_001302888
NP_004509; NP_742104; NP_742105; NP_742106; NP_742107;
	NP_001369164
NP_001003824; NP_001003825; NP_001006669; NP_001006670; NP_001006675;
	NP_001289817; NP_034741
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

K_v7.2 (KvLQT2) jest naponski i lipidno vođeni kalijski kanalski protein koji je kod ljudi kodiran genom KCNQ2 sa hromosoma 20.

Povezan je sa benignom porodičnom neonatusom epilepsijom.

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 872 aminokiseline, a molekulska težina 95.848 Da. ]].^[5]

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
MVQKSRNGGV	YPGPSGEKKL	KVGFVGLDPG	APDSTRDGAL	LIAGSEAPKR
GSILSKPRAG	GAGAGKPPKR	NAFYRKLQNF	LYNVLERPRG	WAFIYHAYVF
LLVFSCLVLS	VFSTIKEYEK	SSEGALYILE	IVTIVVFGVE	YFVRIWAAGC
CCRYRGWRGR	LKFARKPFCV	IDIMVLIASI	AVLAAGSQGN	VFATSALRSL
RFLQILRMIR	MDRRGGTWKL	LGSVVYAHSK	ELVTAWYIGF	LCLILASFLV
YLAEKGENDH	FDTYADALWW	GLITLTTIGY	GDKYPQTWNG	RLLAATFTLI
GVSFFALPAG	ILGSGFALKV	QEQHRQKHFE	KRRNPAAGLI	QSAWRFYATN
LSRTDLHSTW	QYYERTVTVP	MYSSQTQTYG	ASRLIPPLNQ	LELLRNLKSK
SGLAFRKDPP	PEPSPSKGSP	CRGPLCGCCP	GRSSQKVSLK	DRVFSSPRGV
AAKGKGSPQA	QTVRRSPSAD	QSLEDSPSKV	PKSWSFGDRS	RARQAFRIKG
AASRQNSEEA	SLPGEDIVDD	KSCPCEFVTE	DLTPGLKVSI	RAVCVMRFLV
SKRKFKESLR	PYDVMDVIEQ	YSAGHLDMLS	RIKSLQSRVD	QIVGRGPAIT
DKDRTKGPAE	AELPEDPSMM	GRLGKVEKQV	LSMEKKLDFL	VNIYMQRMGI
PPTETEAYFG	AKEPEPAPPY	HSPEDSREHV	DRHGCIVKIV	RSSSSTGQKN
FSAPPAAPPV	QCPPSTSWQP	QSHPRQGHGT	SPVGDHGSLV	RIPPPPAHER
SLSAYGGGNR	ASMEFLRQED	TPGCRPPEGN	LRDSDTSISI	PSVDHEELER
SFSGFSISQS	KENLDALNSC	YAAVAPCAKV	RPYIAEGESD	TDSDLCTPCG
PPPRSATGEG	PFGDVGWAGP	RK

Funkcija[uredi | uredi izvor]

M-kanal je sporo aktivirajući i deaktivirajući kalijski kanal koji ima ključnu ulogu u regulaciji neuronske ekscitabilnosti. Formiran je asocijacijom proteina kodiranog ovim genom i srodnog proteina kodiranog genom KCNQ3, oba integralna membranska proteina. Struje M-kanala inhibiraju M1 muskarinski acetilkolinski receptori i aktiviraju retigabin, novi antikonvulzivni lijek. Defekti ovog gena uzrok su benignih porodičnih neonatusih konvulzija tipa 1 (BFNC), takođe poznatih kao epilepsija, benigni neonatusni tip 1 (EBN1). Za ovaj gen je pronađeno najmanje pet varijanti transkripta koje kodiraju pet različitih izoformi.^[5]

Ligandi[uredi | uredi izvor]

ICA-069673: Otvarač kanala na KCNQ2/Q3, 20 puta selektivniji u odnosu na KCNQ3/Q5, nema mjerljive aktivnosti na panelu srčanih ionskih kanala (hERG, Nav1.5, kanali tipa L i KCNQ1) i nema aktivnosti na GABA_A kanalima na 10 μM. Niz srodnih benzamida je pokazao aktivnost, od kojih je ovdje prikazan spoj broj 40.^[6]
ML252: Kanalski inhibitor, IC₅₀ = 70nM.^[7] i
Fosfatidilinozitol 4,5-bisfosfat (PIP₂)

Reference[uredi | uredi izvor]

^ ^a ^b ^c ENSG00000281151 GRCh38: Ensembl release 89: ENSG00000075043, ENSG00000281151 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000016346 - 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.
^ ^a ^b "Entrez Gene: KCNQ2 potassium voltage-gated channel, KQT-like subfamily, member 2".
^ Amato G (2011). "N -Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy". ACS Medicinal Chemistry Letters. 2 (6): 481–484. doi:10.1021/ml200053x. PMC 4018159. PMID 24900334.
^ Cheung YY, Yu H, Xu K, Zou B, Wu M, McManus OB, Li M, Lindsley CW, Hopkins CR (august 2012). "Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor". Journal of Medicinal Chemistry. 55 (15): 6975–9. doi:10.1021/jm300700v. PMC 3530927. PMID 22793372.

Dopunska literatura[uredi | uredi izvor]

Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X (decembar 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacological Reviews. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
Yokoyama M, Nishi Y, Yoshii J, Okubo K, Matsubara K (oktobar 1996). "Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles". DNA Research. 3 (5): 311–20. doi:10.1093/dnares/3.5.311. PMID 9039501.
Singh NA, Charlier C, Stauffer D, DuPont BR, Leach RJ, Melis R, Ronen GM, Bjerre I, Quattlebaum T, Murphy JV, McHarg ML, Gagnon D, Rosales TO, Peiffer A, Anderson VE, Leppert M (januar 1998). "A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns". Nature Genetics. 18 (1): 25–9. doi:10.1038/ng0198-25. PMID 9425895. S2CID 30469895.
Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK (januar 1998). "A potassium channel mutation in neonatal human epilepsy". Science. 279 (5349): 403–6. Bibcode:1998Sci...279..403B. doi:10.1126/science.279.5349.403. PMID 9430594.
Yang WP, Levesque PC, Little WA, Conder ML, Ramakrishnan P, Neubauer MG, Blanar MA (juli 1998). "Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy". The Journal of Biological Chemistry. 273 (31): 19419–23. doi:10.1074/jbc.273.31.19419. PMID 9677360.
Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M (novembar 1998). "The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3". FEBS Letters. 438 (3): 171–6. doi:10.1016/S0014-5793(98)01296-4. PMID 9827540. S2CID 33708352.
Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D (decembar 1998). "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel". Science. 282 (5395): 1890–3. Bibcode:1998Sci...282.1890W. doi:10.1126/science.282.5395.1890. PMID 9836639.
Schroeder BC, Kubisch C, Stein V, Jentsch TJ (decembar 1998). "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy". Nature. 396 (6712): 687–90. Bibcode:1998Natur.396..687S. doi:10.1038/25367. PMID 9872318. S2CID 4417442.
Biervert C, Steinlein OK (mart 1999). "Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions". Human Genetics. 104 (3): 234–40. doi:10.1007/PL00008713. PMID 10323247. S2CID 30751027.
Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Delmas P, Buckley NJ, London B, Brown DA (septembar 1999). "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell" (PDF). The Journal of Neuroscience. 19 (18): 7742–56. doi:10.1523/jneurosci.19-18-07742.1999. PMC 6782456. PMID 10479678.
Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B (mart 2000). "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current". The Journal of Neuroscience. 20 (5): 1710–21. doi:10.1523/jneurosci.20-05-01710.2000. PMC 6772928. PMID 10684873.
Rundfeldt C, Netzer R (mart 2000). "The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits". Neuroscience Letters. 282 (1–2): 73–6. doi:10.1016/S0304-3940(00)00866-1. PMID 10713399. S2CID 28431577.
Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA (februar 2000). "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors". The Journal of Physiology. 522 (3): 349–55. doi:10.1111/j.1469-7793.2000.t01-2-00349.x. PMC 2269765. PMID 10713961.
Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY (april 2000). "Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy". Proceedings of the National Academy of Sciences of the United States of America. 97 (9): 4914–9. Bibcode:2000PNAS...97.4914C. doi:10.1073/pnas.090092797. PMC 18332. PMID 10781098.
Schwake M, Pusch M, Kharkovets T, Jentsch TJ (maj 2000). "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy". The Journal of Biological Chemistry. 275 (18): 13343–8. doi:10.1074/jbc.275.18.13343. PMID 10788442.
Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA (august 2000). "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine". Molecular Pharmacology. 58 (2): 253–62. doi:10.1124/mol.58.2.253. PMID 10908292. S2CID 11112809.
Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK (septembar 2000). "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels". Molecular Pharmacology. 58 (3): 591–600. doi:10.1124/mol.58.3.591. PMID 10953053.
Tinel N, Diochot S, Lauritzen I, Barhanin J, Lazdunski M, Borsotto M (septembar 2000). "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit". FEBS Letters. 480 (2–3): 137–41. doi:10.1016/S0014-5793(00)01918-9. PMID 11034315. S2CID 8386123.
Smith JS, Iannotti CA, Dargis P, Christian EP, Aiyar J (februar 2001). "Differential expression of kcnq2 splice variants: implications to m current function during neuronal development". The Journal of Neuroscience. 21 (4): 1096–103. doi:10.1523/jneurosci.21-04-01096.2001. PMC 6762257. PMID 11160379.
Miraglia del Giudice E, Coppola G, Scuccimarra G, Cirillo G, Bellini G, Pascotto A (decembar 2000). "Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor". European Journal of Human Genetics. 8 (12): 994–7. doi:10.1038/sj.ejhg.5200570. PMID 11175290.

Vanjski linkovi[uredi | uredi izvor]

KCNQ2 Potassium Channel na US National Library of Medicine Medical Subject Headings (MeSH)

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

[refGRCh38Ensembl-1] ENSG00000281151 GRCh38: Ensembl release 89: ENSG00000075043, ENSG00000281151 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000016346 - 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.

[entrez-5] "Entrez Gene: KCNQ2 potassium voltage-gated channel, KQT-like subfamily, member 2".

[6] Amato G (2011). "N -Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy". ACS Medicinal Chemistry Letters. 2 (6): 481–484. doi:10.1021/ml200053x. PMC 4018159. PMID 24900334.

[pmid22793372-7] Cheung YY, Yu H, Xu K, Zou B, Wu M, McManus OB, Li M, Lindsley CW, Hopkins CR (august 2012). "Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor". Journal of Medicinal Chemistry. 55 (15): 6975–9. doi:10.1021/jm300700v. PMC 3530927. PMID 22793372.

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