CACNA1A
Cav2.1, znan i kao P/Q, je naponski ovisni kalcijev kanal, koji se uglavnom nalazi u mozgu.[5] Konkretno, nalazi se na predsinapsnim terminalima neurona u mozgu i cerebelumu.[5] Cav2.1 ima važnu ulogu u kontroli oslobađanja neurotransmitera između neurona.[5] Sastoji se od više podjedinica, uključujući alfa-1, beta, alfa-2 / delta i gama podjedinice.[6] Podjedinica alfa-1 je podjedinica koja formira pore, što znači da kroz nju prolaze joni kalcija.[5] Različiti tipovi kalcijevih kanala imaju različite verzije izoformi alfa-1 podjedinice. Cav 2.1 ima alfa-1A podjedinicu,[6] koj je kodirana genom CACNA1A. [a][5] Mutacije u CACNA1A povezane su s različitim neurvnim poremećajima, uključujući porodičnu hemiplegijsku migrenu, epizodnu ataksiju tip 2 i spinocerebelarnu ataksiju tip 6.[5]
Aminokiselinski sastav
uredi| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MARFGDEMPA | RYGGGGSGAA | AGVVVGSGGG | RGAGGSRQGG | QPGAQRMYKQ | ||||
| SMAQRARTMA | LYNPIPVRQN | CLTVNRSLFL | FSEDNVVRKY | AKKITEWPPF | ||||
| EYMILATIIA | NCIVLALEQH | LPDDDKTPMS | ERLDDTEPYF | IGIFCFEAGI | ||||
| KIIALGFAFH | KGSYLRNGWN | VMDFVVVLTG | ILATVGTEFD | LRTLRAVRVL | ||||
| RPLKLVSGIP | SLQVVLKSIM | KAMIPLLQIG | LLLFFAILIF | AIIGLEFYMG | ||||
| KFHTTCFEEG | TDDIQGESPA | PCGTEEPART | CPNGTKCQPY | WEGPNNGITQ | ||||
| FDNILFAVLT | VFQCITMEGW | TDLLYNSNDA | SGNTWNWLYF | IPLIIIGSFF | ||||
| MLNLVLGVLS | GEFAKERERV | ENRRAFLKLR | RQQQIERELN | GYMEWISKAE | ||||
| EVILAEDETD | GEQRHPFDGA | LRRTTIKKSK | TDLLNPEEAE | DQLADIASVG | ||||
| SPFARASIKS | AKLENSTFFH | KKERRMRFYI | RRMVKTQAFY | WTVLSLVALN | ||||
| TLCVAIVHYN | QPEWLSDFLY | YAEFIFLGLF | MSEMFIKMYG | LGTRPYFHSS | ||||
| FNCFDCGVII | GSIFEVIWAV | IKPGTSFGIS | VLRALRLLRI | FKVTKYWASL | ||||
| RNLVVSLLNS | MKSIISLLFL | LFLFIVVFAL | LGMQLFGGQF | NFDEGTPPTN | ||||
| FDTFPAAIMT | VFQILTGEDW | NEVMYDGIKS | QGGVQGGMVF | SIYFIVLTLF | ||||
| GNYTLLNVFL | AIAVDNLANA | QELTKDEQEE | EEAANQKLAL | QKAKEVAEVS | ||||
| PLSAANMSIA | VKEQQKNQKP | AKSVWEQRTS | EMRKQNLLAS | REALYNEMDP | ||||
| DERWKAAYTR | HLRPDMKTHL | DRPLVVDPQE | NRNNNTNKSR | AAEPTVDQRL | ||||
| GQQRAEDFLR | KQARYHDRAR | DPSGSAGLDA | RRPWAGSQEA | ELSREGPYGR | ||||
| ESDHHAREGS | LEQPGFWEGE | AERGKAGDPH | RRHVHRQGGS | RESRSGSPRT | ||||
| GADGEHRRHR | AHRRPGEEGP | EDKAERRARH | REGSRPARGG | EGEGEGPDGG | ||||
| ERRRRHRHGA | PATYEGDARR | EDKERRHRRR | KENQGSGVPV | SGPNLSTTRP | ||||
| IQQDLGRQDP | PLAEDIDNMK | NNKLATAESA | APHGSLGHAG | LPQSPAKMGN | ||||
| STDPGPMLAI | PAMATNPQNA | ASRRTPNNPG | NPSNPGPPKT | PENSLIVTNP | ||||
| SGTQTNSAKT | ARKPDHTTVD | IPPACPPPLN | HTVVQVNKNA | NPDPLPKKEE | ||||
| EKKEEEEDDR | GEDGPKPMPP | YSSMFILSTT | NPLRRLCHYI | LNLRYFEMCI | ||||
| LMVIAMSSIA | LAAEDPVQPN | APRNNVLRYF | DYVFTGVFTF | EMVIKMIDLG | ||||
| LVLHQGAYFR | DLWNILDFIV | VSGALVAFAF | TGNSKGKDIN | TIKSLRVLRV | ||||
| LRPLKTIKRL | PKLKAVFDCV | VNSLKNVFNI | LIVYMLFMFI | FAVVAVQLFK | ||||
| GKFFHCTDES | KEFEKDCRGK | YLLYEKNEVK | ARDREWKKYE | FHYDNVLWAL | ||||
| LTLFTVSTGE | GWPQVLKHSV | DATFENQGPS | PGYRMEMSIF | YVVYFVVFPF | ||||
| FFVNIFVALI | IITFQEQGDK | MMEEYSLEKN | ERACIDFAIS | AKPLTRHMPQ | ||||
| NKQSFQYRMW | QFVVSPPFEY | TIMAMIALNT | IVLMMKFYGA | SVAYENALRV | ||||
| FNIVFTSLFS | LECVLKVMAF | GILNYFRDAW | NIFDFVTVLG | SITDILVTEF | ||||
| GNNFINLSFL | RLFRAARLIK | LLRQGYTIRI | LLWTFVQSFK | ALPYVCLLIA | ||||
| MLFFIYAIIG | MQVFGNIGID | VEDEDSDEDE | FQITEHNNFR | TFFQALMLLF | ||||
| RSATGEAWHN | IMLSCLSGKP | CDKNSGILTR | ECGNEFAYFY | FVSFIFLCSF | ||||
| LMLNLFVAVI | MDNFEYLTRD | SSILGPHHLD | EYVRVWAEYD | PAAWGRMPYL | ||||
| DMYQMLRHMS | PPLGLGKKCP | ARVAYKRLLR | MDLPVADDNT | VHFNSTLMAL | ||||
| IRTALDIKIA | KGGADKQQMD | AELRKEMMAI | WPNLSQKTLD | LLVTPHKSTD | ||||
| LTVGKIYAAM | MIMEYYRQSK | AKKLQAMREE | QDRTPLMFQR | MEPPSPTQEG | ||||
| GPGQNALPST | QLDPGGALMA | HESGLKESPS | WVTQRAQEMF | QKTGTWSPEQ | ||||
| GPPTDMPNSQ | PNSQSVEMRE | MGRDGYSDSE | HYLPMEGQGR | AASMPRLPAE | ||||
| NQRRRGRPRG | NNLSTISDTS | PMKRSASVLG | PKARRLDDYS | LERVPPEENQ | ||||
| RHHQRRRDRS | HRASERSLGR | YTDVDTGLGT | DLSMTTQSGD | LPSKERDQER | ||||
| GRPKDRKHRQ | HHHHHHHHHH | PPPPDKDRYA | QERPDHGRAR | ARDQRWSRSP | ||||
| SEGREHMAHR | QGSSSVSGSP | APSTSGTSTP | RRGRRQLPQT | PSTPRPHVSY | ||||
| SPVIRKAGGS | GPPQQQQQQQ | QQQQAVARPG | RAATSGPRRY | PGPTAEPLAG | ||||
| DRPPTGGHSS | GRSPRMERRV | PGPARSESPR | ACRHGGARWP | ASGPHVSEGP | ||||
| PGPRHHGYYR | GSDYDEADGP | GSGGGEEAMA | GAYDAPPPVR | HASSGATGRS | ||||
| PRTPRASGPA | CASPSRHGRR | LPNGYYPAHG | LARPRGPGSR | KGLHEPYSES | ||||
| DDDWC |
- Simboli
Funkcija
urediKalcijski kanali koji zavise od napona posreduju ulasku iona kalcija u pobuđene ćelije, a također su uključeni u razne procese koji zavise od kalcija, uključujući kontrakciju mišića, oslobađanje hormona ili neurotransmitera i ekspresiju gena. Kalcijski kanali su višepodjedinstveni kompleksi sastavljeni od alfa-1, beta, alfa-2/delta i gama podjedinice. Aktivnošću kanala upravlja alfa-1 podjedinica koja formira pore, dok ostale djeluju kao pomoćne podjedinice koje reguliraju ovu aktivnost. Obilježavajuća svojstva tipova kalcijevih kanala povezana su prvenstveno s ekspresijom različitih alfa-1 izoformi, alfa-1A, B, C, D, E i S. Ovaj gen kodira alfa-1A podjedinicu, koja je pretežno eksprimirana u neuronskom tkivu.[6]
Klinički značaj
urediMutacije u genu CACNA1A povezane su s višestrukim nervim poremećajima, od kojih su mnogi epizodni, kao što su porodična hemiplegijska migrena, poremećaji pokreta kao što je epizodna ataksija i epilepsija sa više tipova napada.[8]
Ovaj gen također ima polimorfne varijacije zbog (CAG) n-ponavljanja. Za ovaj gen pronađeno je više varijanti transkripta koji kodiraju različite izoformi. U jednom skupu varijanti transkripta, n-ponavljanja (CAG) javljaju se u 3 'UTR i nisu povezane sa bilo kojom bolešću. Međutim, u drugom skupu varijanti, insercija proširuje područje kodiranja tako da uključuje (CAG) n-ponavljanje koje kodira poliglutaminov trakt. Širenje (CAG) n-ponavljanja sa normalnih 4-16 na 21-28 u kodnom području povezano je sa spinocerebelarnom ataksijom 6.[6]
Interakcije
urediPokazano je da Cav2.1 ima interakcije sa CACNB4.[9][10]
Napomene
urediReference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000141837 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034656 - 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 c d e f Sutherland HG, Albury CL, Griffiths LR (21. 6. 2019). "Advances in genetics of migraine". The Journal of Headache and Pain. 20 (1). doi:10.1186/s10194-019-1017-9. PMID 31226929.
- ^ a b c d "CACNA1A". Gene. National Center for Biotechnology Information. 16. 3. 2021. Pristupljeno 28. 3. 2021.
- ^ "The Science of CACNA1A". CACNA1A Foundation. Pristupljeno 28. 3. 2021.
- ^ Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (februar 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID 31784983. S2CID 208498567.
- ^ Walker D, Bichet D, Campbell KP, De Waard M (januar 1998). "A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit". The Journal of Biological Chemistry. 273 (4): 2361–7. doi:10.1074/jbc.273.4.2361. PMID 9442082.
- ^ Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, et al. (april 1999). "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation". The Journal of Biological Chemistry. 274 (18): 12383–90. doi:10.1074/jbc.274.18.12383. PMID 10212211.
Dopunska literatura
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- Walker D, Bichet D, Campbell KP, De Waard M (januar 1998). "A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit". The Journal of Biological Chemistry. 273 (4): 2361–7. doi:10.1074/jbc.273.4.2361. PMID 9442082.
- Yue Q, Jen JC, Thwe MM, Nelson SF, Baloh RW (maj 1998). "De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia". American Journal of Medical Genetics. 77 (4): 298–301. doi:10.1002/(SICI)1096-8628(19980526)77:4<298::AID-AJMG9>3.0.CO;2-J. PMID 9600739.
- Hans M, Urrutia A, Deal C, Brust PF, Stauderman K, Ellis SB, et al. (mart 1999). "Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels". Biophysical Journal. 76 (3): 1384–400. doi:10.1016/S0006-3495(99)77300-5. PMC 1300117. PMID 10049321.
- Walker D, Bichet D, Geib S, Mori E, Cornet V, Snutch TP, et al. (april 1999). "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation". The Journal of Biological Chemistry. 274 (18): 12383–90. doi:10.1074/jbc.274.18.12383. PMID 10212211.
- Jen JC (maj 2015). "Familial Hemiplegic Migraine". u Pagon RA, Bird TD, Dolan CR, et al. (ured.). GeneReviews [Internet]. Seattle WA: University of Washington, Seattle. NBK1388. Provjerite vrijednost datuma u parametru: parametri
|year=/|date=nisu u skladu (pomoć) - Spacey S (decembar 2011). Episodic Ataxia Type 2. NBK1501. In GeneReviews
- Gomez CM (juli 2013). Spinocerebellar Ataxia Type 6. NBK1140. In GeneReviews
Vanjski linkovi
uredi- CACNA1A protein, human na US National Library of Medicine Medical Subject Headings (MeSH)