CLCN1

CLCN1
Identifikatori
Aliasi	CLCN1
Vanjski ID-jevi	OMIM:118425MGI:88417HomoloGene:63GeneCards:CLCN1
Lokacija gena (čovjek)
Hrom.	Hromosom 7 (čovjek)
Kraj	143,352,083bp
Lokacija gena (miš)
Hrom.	Hromosom 6 (miš)
Kraj	42,292,690bp
ObrazacRNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	•protein homodimerization activity; •voltage-gated ion channel activity; •GO:0001948, GO:0016582 vezivanje za proteine; •chloride channel activity; •voltage-gated chloride channel activity;
Ćelijska komponenta	•integral component of membrane; •membrana; •ćelijska membrana; •integral component of plasma membrane; •chloride channel complex; •Sarkolema;
Biološki proces	•Mišićna kontrakcija; •regulation of ion transmembrane transport; •chloride transmembrane transport; •ion transport; •ion transmembrane transport; •neuronal action potential propagation; •chloride transport; •transmembrane transport;
	Izvori:Amigo/QuickGO
Ortolozi
	1180
	12723
	ENSG00000188037
	ENSMUSG00000029862
	P35523
	Q64347
	NM_000083
	NM_013491; NM_001363712
	NP_000074
	NP_038519; NP_001350641
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

CLCNporodica genahloridnih kanalaovisnih o naponu sastoji se od devet članova (CLCN1-7, Ka i Kb) koji pokazuju prilično različite funkcionalne karakteristike, dok dijele značajnuhomologiju sekvence.Proteinkodiran ovim genom reguliše električnu ekscitabilnost membrane skeletnih mišića. Kodljudi,genCLCNnalazi se nahromosomu 7.Mutacije ovog gena uzrokuju dva oblika nasljednih poremećaja ljudskih mišića: recesivnu generaliziranumiotonia congenita(Becker) i dominantnu miotoniju (Thomsen).).^[5]

Aminokiselinska sekvenca

Dužinapolipeptidnoglanca je 988aminokiselina,amolekulska težina108.626Da.^[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
MEQSRSQQRG	GEQSWWGSDP	QYQYMPFEHC	TSYGLPSENG	GLQHRLRKDA
GPRHNVHPTQ	IYGHHKEQFS	DREQDIGMPK	KTGSSSTVDS	KDEDHYSKCQ
DCIHRLGQVV	RRKLGEDGIF	LVLLGLLMAL	VSWSMDYVSA	KSLQAYKWSY
AQMQPSLPLQ	FLVWVTFPLV	LILFSALFCH	LISPQAVGSG	IPEMKTILRG
VVLKEYLTMK	AFVAKVVALT	AGLGSGIPVG	KEGPFVHIAS	ICAAVLSKFM
SVFCGVYEQP	YYYSDILTVG	CAVGVGCCFG	TPLGGVLFSI	EVTSTYFAVR
NYWRGFFAAT	FSAFVFRVLA	VWNKDAVTIT	ALFRTNFRMD	FPFDLKELPA
FAAIGICCGL	LGAVFVYLHR	QVMLGVRKHK	ALSQFLAKHR	LLYPGIVTFV
IASFTFPPGM	GQFMAGELMP	REAISTLFDN	NTWVKHAGDP	ESLGQSAVWI
HPRVNVVIII	FLFFVMKFWM	SIVATTMPIP	CGGFMPVFVL	GAAFGRLVGE
IMAMLFPDGI	LFDDIIYKIL	PGGYAVIGAA	ALTGAVSHTV	STAVICFELT
GQIAHILPMM	VAVILANMVA	QSLQPSLYDS	IIQVKKLPYL	PDLGWNQLSK
YTIFVEDIMV	RDVKFVSASY	TYGELRTLLQ	TTTVKTLPLV	DSKDSMILLG
SVERSELQAL	LQRHLCPERR	LRAAQEMARK	LSELPYDGKA	RLAGEGLPGA
PPGRPESFAF	VDEDEDEDLS	GKSELPPSLA	LHPSTTAPLS	PEEPNGPLPG
HKQQPEAPEP	AGQRPSIFQS	LLHCLLGRAR	PTKKKTTQDS	TDLVDNMSPE
EIEAWEQEQL	SQPVCFDSCC	IDQSPFQLVE	QTTLHKTHTL	FSLLGLHLAY
VTSMGKLRGV	LALEELQKAI	EGHTKSGVQL	RPPLASFRNT	TSTRKSTGAP
PSSAENWNLP	EDRPGATGTG	DVIAASPETP	VPSPSPEPPL	SLAPGKVEGE
LEELELVESP	GLEEELADIL	QGPSLRSTDE	EDEDELIL

Funkcija

Protein hloridnog kanala skeletnih mišića(CLCN1) jeproteinkoji je kod ljudi kodirangenomCLCN1.^[6]Mutacije u ovom proteinu uzrokuju poremećaj zvanimyotonia congenita.

CLCN1 je kritičan za normalnu funkciju ćelijaskeletnih mišića.Da bi se tijelo moglo normalno kretati, skeletni mišići moraju se napregnuti (kontrahirati) i opustiti na koordiniran način. Kontrakcija i relaksacija mišića kontrolišu se protokomionau i iz mišićnih ćelija. CLCN1 formiraionski kanalkoji kontrolira protok negativno nabijenih hloridnih iona u ove ćelije. Glavna funkcija ovog kanala je da stabilizuje električni naboj ćelija, omogućavajući mišićima da se normalnokontrahuju.

Kod ljudi s kongenitalnom miotonijom, zbog mutacije u CLCN1,ionski kanalpropušta premalo kloridnih iona u ćeliju. Ovaj nedostatak hloridnih iona uzrokuje produžene kontrakcije mišića, koje su obilježjemiotonija.

Također pogledajte

Reference

^^a ^b ^cGRCh38: Ensembl release 89: ENSG00000188037-Ensembl,maj 2017
^^a ^b ^cGRCm38: Ensembl release 89: ENSMUSG00000029862-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: CLCN1 chloride channel 1, skeletal muscle (Thomsen disease, autosomal dominant)".
^Koch MC, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ (Sep 1992). "The skeletal muscle chloride channel in dominant and recessive human myotonia".Science.257(5071): 797–800.Bibcode:1992Sci...257..797K.doi:10.1126/science.1379744.PMID 1379744.

Dopunska literatura

Hudson AJ, Ebers GC, Bulman DE (1995). "The skeletal muscle sodium and chloride channel diseases".Brain.118(2): 547–63.doi:10.1093/brain/118.2.547.PMID 7735894.
Uchida S, Sasaki S, Marumo F (1996). "Chloride transport across kidney epithelia through CLC chloride channels".Nippon Jinzo Gakkai Shi.38(7): 285–9.PMID 8741388.
Fahlke C (2000)."Molecular mechanisms of ion conduction in ClC-type chloride channels: lessons from disease-causing mutations".Kidney Int.57(3): 780–6.doi:10.1046/j.1523-1755.2000.00915.x.PMID 10720929.
Pusch M (2002)."Myotonia caused by mutations in the muscle chloride channel gene CLCN1".Hum. Mutat.19(4): 423–34.doi:10.1002/humu.10063.PMID 11933197.S2CID 41727736.
Colding-Jørgensen E (2005)."Phenotypic variability in myotonia congenita".Muscle Nerve.32(1): 19–34.doi:10.1002/mus.20295.PMID 15786415.S2CID 8336138.
Isobe M, Erikson J, Emanuel BS, et al. (1985). "Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells".Science.228(4699): 580–2.Bibcode:1985Sci...228..580I.doi:10.1126/science.3983641.PMID 3983641.
Lehmann-Horn F, Mailänder V, Heine R, George AL (1995). "Myotonia levior is a chloride channel disorder".Hum. Mol. Genet.4(8): 1397–402.doi:10.1093/hmg/4.8.1397.PMID 7581380.
George AL, Sloan-Brown K, Fenichel GM, et al. (1995). "Nonsense and missense mutations of the muscle chloride channel gene in patients with myotonia congenita".Hum. Mol. Genet.3(11): 2071–2.PMID 7874130.
Lorenz C, Meyer-Kleine C, Steinmeyer K, et al. (1994). "Genomic organization of the human muscle chloride channel CIC-1 and analysis of novel mutations leading to Becker-type myotonia".Hum. Mol. Genet.3(6): 941–6.doi:10.1093/hmg/3.6.941.PMID 7951242.
Heine R, George AL, Pika U, et al. (1995). "Proof of a non-functional muscle chloride channel in recessive myotonia congenita (Becker) by detection of a 4 base pair deletion".Hum. Mol. Genet.3(7): 1123–8.doi:10.1093/hmg/3.7.1123.PMID 7981681.
George AL, Crackower MA, Abdalla JA, et al. (1995). "Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita)".Nat. Genet.3(4): 305–10.doi:10.1038/ng0493-305.PMID 7981750.S2CID 12286250.
Steinmeyer K, Lorenz C, Pusch M, et al. (1994)."Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen)".EMBO J.13(4): 737–43.doi:10.1002/j.1460-2075.1994.tb06315.x.PMC394869.PMID 8112288.
Koch MC, Ricker K, Otto M, et al. (1994)."Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker)".J. Med. Genet.30(11): 914–7.doi:10.1136/jmg.30.11.914.PMC1016598.PMID 8301644.
Meyer-Kleine C, Steinmeyer K, Ricker K, et al. (1996)."Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia".Am. J. Hum. Genet.57(6): 1325–34.PMC1801423.PMID 8533761.
Mailänder V, Heine R, Deymeer F, Lehmann-Horn F (1996)."Novel muscle chloride channel mutations and their effects on heterozygous carriers".Am. J. Hum. Genet.58(2): 317–24.PMC1914535.PMID 8571958.
Pusch M, Steinmeyer K, Koch MC, Jentsch TJ (1996)."Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel".Neuron.15(6): 1455–63.doi:10.1016/0896-6273(95)90023-3.PMID 8845168.S2CID 18808219.
Fahlke C, Beck CL, George AL (1997)."A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel".Proc. Natl. Acad. Sci. U.S.A.94(6): 2729–34.Bibcode:1997PNAS...94.2729F.doi:10.1073/pnas.94.6.2729.PMC20158.PMID 9122265.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Myotonia Congenita
CLCN1 protein, humannaUS National Library of MedicineMedical Subject Headings(MeSH)
Lokacija ljudskog genomaCLCN1i stranica sa detaljima o genuCLCN1uUCSC Genome Browseru.

Ovaj članak uključuje tekst izNacionalne medicinske biblioteke Sjedinjenih Država,koji je ujavnom vlasništvu.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000188037-Ensembl,maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029862-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: CLCN1 chloride channel 1, skeletal muscle (Thomsen disease, autosomal dominant)".

[pmid1379744-6] Koch MC, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ (Sep 1992). "The skeletal muscle chloride channel in dominant and recessive human myotonia".Science.257(5071): 797–800.Bibcode:1992Sci...257..797K.doi:10.1126/science.1379744.PMID 1379744.

[1]

[2]

[3]

[4]

[5]

[6]