KCNQ4

KCNQ4
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2OVC, 4GOW
Identifikatori
Aliasi	KCNQ4
Vanjski ID-jevi	OMIM: 603537 MGI: 1926803 HomoloGene: 78107 GeneCards: KCNQ4
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	40,840,452 bp
Lokacija gena (miš)
Hrom.	Hromosom 4 (miš)
Kraj	120,605,809 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• potassium channel activity; • voltage-gated ion channel activity; • ion channel activity; • GO:0001948, GO:0016582 vezivanje za proteine; • voltage-gated potassium channel activity; • delayed rectifier potassium channel activity; • calmodulin binding;
Ćelijska komponenta	• integral component of membrane; • membrana; • voltage-gated potassium channel complex; • ćelijska membrana; • basal plasma membrane;
Biološki proces	• regulation of ion transmembrane transport; • ion transport; • sluh; • potassium ion transport; • transmembrane transport; • potassium ion transmembrane transport; • inner ear morphogenesis;
	Izvori:Amigo / QuickGO
Ortolozi
	9132
	60613
	ENSG00000117013
	ENSMUSG00000028631
	P56696
	Q9JK97
	NM_004700; NM_172163
	NM_001081142
	NP_004691; NP_751895
	NP_001074611
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Član 4 potporodice KQT kalijskog naponskog kanala, poznat i kao naponski K_v7.4 jest protein koji je kod ljudi kodiran genom KCNQ4 sa hromosoma 1.^[5]^[6]^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 695 aminokiselina, a molekulska težina 77.101 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
MAEAPPRRLG	LGPPPGDAPR	AELVALTAVQ	SEQGEAGGGG	SPRRLGLLGS
PLPPGAPLPG	PGSGSGSACG	QRSSAAHKRY	RRLQNWVYNV	LERPRGWAFV
YHVFIFLLVF	SCLVLSVLST	IQEHQELANE	CLLILEFVMI	VVFGLEYIVR
VWSAGCCCRY	RGWQGRFRFA	RKPFCVIDFI	VFVASVAVIA	AGTQGNIFAT
SALRSMRFLQ	ILRMVRMDRR	GGTWKLLGSV	VYAHSKELIT	AWYIGFLVLI
FASFLVYLAE	KDANSDFSSY	ADSLWWGTIT	LTTIGYGDKT	PHTWLGRVLA
AGFALLGISF	FALPAGILGS	GFALKVQEQH	RQKHFEKRRM	PAANLIQAAW
RLYSTDMSRA	YLTATWYYYD	SILPSFRELA	LLFEHVQRAR	NGGLRPLEVR
RAPVPDGAPS	RYPPVATCHR	PGSTSFCPGE	SSRMGIKDRI	RMGSSQRRTG
PSKQHLAPPT	MPTSPSSEQV	GEATSPTKVQ	KSWSFNDRTR	FRASLRLKPR
TSAEDAPSEE	VAEEKSYQCE	LTVDDIMPAV	KTVIRSIRIL	KFLVAKRKFK
ETLRPYDVKD	VIEQYSAGHL	DMLGRIKSLQ	TRVDQIVGRG	PGDRKAREKG
DKGPSDAEVV	DEISMMGRVV	KVEKQVQSIE	HKLDLLLGFY	SRCLRSGTSA
SLGAVQVPLF	DPDITSDYHS	PVDHEDISVS	AQTLSISRSV	STNMD

Funkcija

Protein kodiran ovim genom formira kalijski kanal za koji se smatra da ima ključnu ulogu u regulaciji neuronske ekscitabilnosti, posebno u senzornim ćelijama kohleje. Kodirani protein može formirati homomultimerni kalijski kanal ili eventualno heteromultimerni kanal u vezi sa proteinom kodiranim genom KCNQ3.^[7]

Ligandi

ML213: KCNQ2/Q4 kanalski otvarač.^[9]

Klinički značaj

Struja koju generira ovaj ionski kanal inhibira muskarinski acetilkolinski receptor M1 i aktivira retigabin, novi lijek protiv konvulzija. Defekti ovog gena su uzrok nesindromske senzorinervne gluhoće tipa 2 (DFNA2), autosomno dominantnog oblika progresivnog gubitka sluha. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju različite izoforme.^[7]

Također pogledajte

Naponski kalijski kanal

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000117013 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000028631 - 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.
^ Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (Mar 1999). "KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness". Cell. 96 (3): 437–46. doi:10.1016/S0092-8674(00)80556-5. PMID 10025409.
^ Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.
^ ^a ^b ^c "Entrez Gene: KCNQ4 potassium voltage-gated channel, KQT-like subfamily, member 4".
^ "UniProt, P56696" (jezik: eng.). Pristupljeno 29. 11. 2021.CS1 održavanje: nepoznati jezik (link)
^ Yu H, Wu M, Townsend SD, et al. (2011). "Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener". ACS Chem Neurosci. 2 (10): 572–577. doi:10.1021/cn200065b. PMC 3223964. PMID 22125664.

Dopunska literatura

Coucke PJ, Van Hauwe P, Kelley PM, et al. (1999). "Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families". Hum. Mol. Genet. 8 (7): 1321–8. doi:10.1093/hmg/8.7.1321. PMID 10369879.
Talebizadeh Z, Kelley PM, Askew JW, et al. (2000). "Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss". Hum. Mutat. 14 (6): 493–501. doi:10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P. PMID 10571947.
Selyanko AA, Hadley JK, Wood IC, et al. (2000). "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors". J. Physiol. 522 (3): 349–55. doi:10.1111/j.1469-7793.2000.t01-2-00349.x. PMC 2269765. PMID 10713961.
Van Hauwe P, Coucke PJ, Ensink RJ, et al. (2000). "Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region". Am. J. Med. Genet. 93 (3): 184–7. doi:10.1002/1096-8628(20000731)93:3<184::AID-AJMG4>3.0.CO;2-5. PMID 10925378.
Beisel KW, Nelson NC, Delimont DC, Fritzsch B (2001). "Longitudinal gradients of KCNQ4 expression in spiral ganglion and cochlear hair cells correlate with progressive hearing loss in DFNA2". Brain Res. Mol. Brain Res. 82 (1–2): 137–49. doi:10.1016/S0169-328X(00)00204-7. PMID 11042367.
Søgaard R, Ljungstrøm T, Pedersen KA, et al. (2001). "KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology". Am. J. Physiol., Cell Physiol. 280 (4): C859–66. doi:10.1152/ajpcell.2001.280.4.C859. PMID 11245603.
Van Camp G, Coucke PJ, Akita J, et al. (2002). "A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment". Hum. Mutat. 20 (1): 15–9. doi:10.1002/humu.10096. PMID 12112653. S2CID 22495155.
Stern RE, Lalwani AK (2003). "Audiologic evidence for further genetic heterogeneity at DFNA2". Acta Otolaryngol. 122 (7): 730–5. doi:10.1080/003655402/000028059. PMID 12484650.
Schwake M, Jentsch TJ, Friedrich T (2003). "A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly". EMBO Rep. 4 (1): 76–81. doi:10.1038/sj.embor.embor715. PMC 1315815. PMID 12524525.
Li Y, Langlais P, Gamper N, et al. (2004). "Dual phosphorylations underlie modulation of unitary KCNQ K(+) channels by Src tyrosine kinase". J. Biol. Chem. 279 (44): 45399–407. doi:10.1074/jbc.M408410200. PMID 15304482.
Chambard JM, Ashmore JF (2005). "Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway". Pflügers Arch. 450 (1): 34–44. doi:10.1007/s00424-004-1366-2. PMID 15660259. S2CID 21570482.
Van Laer L, Carlsson PI, Ottschytsch N, et al. (2006). "The contribution of genes involved in potassium-recycling in the inner ear to noise-induced hearing loss". Hum. Mutat. 27 (8): 786–95. doi:10.1002/humu.20360. PMID 16823764. S2CID 25357017.
Van Eyken E, Van Laer L, Fransen E, et al. (2006). "KCNQ4: a gene for age-related hearing impairment?". Hum. Mutat. 27 (10): 1007–16. doi:10.1002/humu.20375. PMID 16917933. S2CID 8912727.
Su CC, Yang JJ, Shieh JC, et al. (2007). "Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan". Audiol. Neurootol. 12 (1): 20–6. doi:10.1159/000096154. PMID 17033161. S2CID 25256223.
Jensen HS, Grunnet M, Olesen SP (2007). "Inactivation as a New Regulatory Mechanism for Neuronal Kv7 Channels". Biophys. J. 92 (8): 2747–56. Bibcode:2007BpJ....92.2747J. doi:10.1529/biophysj.106.101287. PMC 1831682. PMID 17237198.
Howard RJ, Clark KA, Holton JM, Minor DL (2007). "Structural Insight into KCNQ (Kv7) Channel Assembly and Channelopathy". Neuron. 53 (5): 663–75. doi:10.1016/j.neuron.2007.02.010. PMC 3011230. PMID 17329207.
Iannotti FA, Panza E, Barrese V, Viggiano D, Soldovieri MV, Taglialatela M (mart 2010). "Expression, localization, and pharmacological role of Kv7 potassium channels in skeletal muscle proliferation, differentiation, and survival after myotoxic insults". J. Pharmacol. Exp. Ther. 332 (3): 811–20. doi:10.1124/jpet.109.162800. PMID 20040580. S2CID 17248733.
Iannotti FA, Barrese V, Formisano L, Taglialatela M (Feb 2013). "Specification of skeletal muscle differentiation by repressor element-1 silencing transcription factor (REST)-regulated Kv7.4 potassium channels". Mol Biol Cell. 24 (3): 274–84. doi:10.1091/mbc.E11-12-1044. PMC 3564528. PMID 23242999.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Deafness and Hereditary Hearing Loss Overview
KCNQ4 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
GeneReviews/NCBI/NIH/UW entry on DFNA2 Nonsyndromic Hearing Loss

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000117013 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000028631 - 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.

[pmid10025409-5] Kubisch C, Schroeder BC, Friedrich T, Lutjohann B, El-Amraoui A, Marlin S, Petit C, Jentsch TJ (Mar 1999). "KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness". Cell. 96 (3): 437–46. doi:10.1016/S0092-8674(00)80556-5. PMID 10025409.

[pmid16382104-6] Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID 16382104. S2CID 219195192.

[entrez-7] "Entrez Gene: KCNQ4 potassium voltage-gated channel, KQT-like subfamily, member 4".

[UniProt-8] "UniProt, P56696" (jezik: eng.). Pristupljeno 29. 11. 2021.CS1 održavanje: nepoznati jezik (link)

[pmid22125664-9] Yu H, Wu M, Townsend SD, et al. (2011). "Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener". ACS Chem Neurosci. 2 (10): 572–577. doi:10.1021/cn200065b. PMC 3223964. PMID 22125664.

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