CLCN1
CLCN porodica gena hloridnih kanala ovisnih o naponu sastoji se od devet članova (CLCN1-7, Ka i Kb) koji pokazuju prilično različite funkcionalne karakteristike, dok dijele značajnu homologiju sekvence. Protein kodiran ovim genom reguliše električnu ekscitabilnost membrane skeletnih mišića. Kod ljudi, gen CLCN nalazi se na hromosomu 7. Mutacije ovog gena uzrokuju dva oblika nasljednih poremećaja ljudskih mišića: recesivnu generaliziranu miotonia congenita (Becker) i dominantnu miotoniju (Thomsen).).[5]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 988 aminokiselina, a molekulska težina 108.626 Da.[5]
| 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
[uredi | uredi izvor]Protein hloridnog kanala skeletnih mišića (CLCN1) je protein koji je kod ljudi kodiran genom CLCN1.[6] Mutacije u ovom proteinu uzrokuju poremećaj zvani myotonia congenita.
CLCN1 je kritičan za normalnu funkciju ćelija skeletnih 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 protokom iona u i iz mišićnih ćelija. CLCN1 formira ionski kanal koji kontrolira protok negativno nabijenih hloridnih iona u ove ćelije. Glavna funkcija ovog kanala je da stabilizuje električni naboj ćelija, omogućavajući mišićima da se normalno kontrahuju.
Kod ljudi s kongenitalnom miotonijom, zbog mutacije u CLCN1, ionski kanal propušta premalo kloridnih iona u ćeliju. Ovaj nedostatak hloridnih iona uzrokuje produžene kontrakcije mišića, koje su obilježje miotonija.
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000188037 - Ensembl, maj 2017
- ^ a b c GRCm38: 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
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- 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. PMC 394869. 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. PMC 1016598. 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. PMC 1801423. 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. PMC 1914535. 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. PMC 20158. PMID 9122265.
Vanjski linkovi
[uredi | uredi izvor]- GeneReviews/NCBI/NIH/UW entry on Myotonia Congenita
- CLCN1 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)
- Lokacija ljudskog genoma CLCN1 i stranica sa detaljima o genu CLCN1 u UCSC Genome Browseru.
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.