CACNA1A

CACNA1A
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3BXK
Identifikatori
Aliasi	CACNA1A
Vanjski ID-jevi	OMIM: 601011 MGI: 109482 HomoloGene: 56383 GeneCards: CACNA1A
Lokacija gena (čovjek)
Hrom.	Hromosom 19 (čovjek)
Kraj	13,633,025 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	85,366,875 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• vezivanje iona metala; • ion channel activity; • voltage-gated ion channel activity; • syntaxin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • voltage-gated calcium channel activity; • calcium channel activity; • high voltage-gated calcium channel activity; • amyloid-beta binding;
Ćelijska komponenta	• citoplazma; • Naponom kontrolirani kalcijev kanal; • projekcija ćelije; • jedro; • membrana; • integral component of membrane; • ćelijska membrana; • soma;
Biološki proces	• calcium ion transport; • Ćelijska smrt; • transmembrane transport; • membrane depolarization during action potential; • regulation of ion transmembrane transport; • ion transport; • GO:0015915 transport; • regulation of insulin secretion; • calcium ion transmembrane transport; • positive regulation of cytosolic calcium ion concentration; • membrane depolarization; • chemical synaptic transmission; • modulation of chemical synaptic transmission; • calcium ion import; • response to amyloid-beta; • cellular response to amyloid-beta;
	Izvori:Amigo / QuickGO
Ortolozi
	773
	12286
	ENSG00000141837
	ENSMUSG00000034656
	O00555
	P97445
	NM_023035; NM_000068; NM_001127221; NM_001127222; NM_001174080
	NM_001252059; NM_001252060; NM_001252061; NM_007578
	NP_000059; NP_001120693; NP_001120694; NP_001167551; NP_075461
	NP_001238988; NP_001238989; NP_001238990; NP_031604
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Ca_v2.1, 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] Ca_v2.1 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. Ca_v 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

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

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

Funkcija

Kalcijski 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

Mutacije 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

Pokazano je da Cav2.1 ima interakcije sa CACNB4.^[9]^[10]

Napomene

^ CACNA1A skraćenica je punog imena gena, CAlcium voltated gated ChaNnel subunit AIpha 1A, što je opis proteina koji je kodiran genom.^[7]

Reference

^ ^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

Terwindt G, Kors E, Haan J, Vermeulen F, Van den Maagdenberg A, Frants R, Ferrari M (juni 2002). "Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine". Archives of Neurology. 59 (6): 1016–8. doi:10.1001/archneur.59.6.1016. PMID 12056940.
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (decembar 2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacological Reviews. 57 (4): 411–25. doi:10.1124/pr.57.4.5. PMID 16382099. S2CID 10386627.
Perez-Reyes E, Castellano A, Kim HS, Bertrand P, Baggstrom E, Lacerda AE, et al. (januar 1992). "Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel". The Journal of Biological Chemistry. 267 (3): 1792–7. PMID 1370480.
Barry EL, Viglione MP, Kim YI, Froehner SC (januar 1995). "Expression and antibody inhibition of P-type calcium channels in human small-cell lung carcinoma cells". The Journal of Neuroscience. 15 (1 Pt 1): 274–83. doi:10.1523/JNEUROSCI.15-01-00274.1995. PMC 6578292. PMID 7823133.
Joutel A, Bousser MG, Biousse V, Labauge P, Chabriat H, Nibbio A, et al. (septembar 1993). "A gene for familial hemiplegic migraine maps to chromosome 19". Nature Genetics. 5 (1): 40–5. doi:10.1038/ng0993-40. PMID 8220421. S2CID 6493091.
Margolis RL, Breschel TS, Li SH, Kidwai AS, Antonarakis SE, McInnis MG, Ross CA (juli 1995). "Characterization of cDNA clones containing CCA trinucleotide repeats derived from human brain". Somatic Cell and Molecular Genetics. 21 (4): 279–84. doi:10.1007/BF02255782. PMID 8525433. S2CID 22174220.
Rettig J, Sheng ZH, Kim DK, Hodson CD, Snutch TP, Catterall WA (juli 1996). "Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25". Proceedings of the National Academy of Sciences of the United States of America. 93 (14): 7363–8. doi:10.1073/pnas.93.14.7363. PMC 38990. PMID 8692999.
Diriong S, Lory P, Williams ME, Ellis SB, Harpold MM, Taviaux S (decembar 1995). "Chromosomal localization of the human genes for alpha 1A, alpha 1B, and alpha 1E voltage-dependent Ca2+ channel subunits". Genomics. 30 (3): 605–9. doi:10.1006/geno.1995.1284. PMID 8825650.
Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, et al. (novembar 1996). "Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4". Cell. 87 (3): 543–52. doi:10.1016/S0092-8674(00)81373-2. hdl:1765/57576. PMID 8898206. S2CID 16840573.
Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, et al. (januar 1997). "Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel". Nature Genetics. 15 (1): 62–9. doi:10.1038/ng0197-62. PMID 8988170. S2CID 9116828.
De Waard M, Liu H, Walker D, Scott VE, Gurnett CA, Campbell KP (januar 1997). "Direct binding of G-protein betagamma complex to voltage-dependent calcium channels". Nature. 385 (6615): 446–50. doi:10.1038/385446a0. PMID 9009193. S2CID 4287544.
Qin N, Platano D, Olcese R, Stefani E, Birnbaumer L (august 1997). "Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors". Proceedings of the National Academy of Sciences of the United States of America. 94 (16): 8866–71. doi:10.1073/pnas.94.16.8866. PMC 23172. PMID 9238069.
Riess O, Schöls L, Bottger H, Nolte D, Vieira-Saecker AM, Schimming C, et al. (august 1997). "SCA6 is caused by moderate CAG expansion in the alpha1A-voltage-dependent calcium channel gene". Human Molecular Genetics. 6 (8): 1289–93. doi:10.1093/hmg/6.8.1289. PMID 9259275.
Jodice C, Mantuano E, Veneziano L, Trettel F, Sabbadini G, Calandriello L, et al. (oktobar 1997). "Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p". Human Molecular Genetics. 6 (11): 1973–8. doi:10.1093/hmg/6.11.1973. PMID 9302278.
Charvin N, L'evêque C, Walker D, Berton F, Raymond C, Kataoka M, et al. (august 1997). "Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel". The EMBO Journal. 16 (15): 4591–6. doi:10.1093/emboj/16.15.4591. PMC 1170085. PMID 9303303.
Ishikawa K, Tanaka H, Saito M, Ohkoshi N, Fujita T, Yoshizawa K, et al. (august 1997). "Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1". American Journal of Human Genetics. 61 (2): 336–46. doi:10.1086/514867. PMC 1715894. PMID 9311738.
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

CACNA1A protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

[8] CACNA1A skraćenica je punog imena gena, CAlcium voltated gated ChaNnel subunit AIpha 1A, što je opis proteina koji je kodiran genom.^[7]

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000141837 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000034656 - 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.

[Migraine_Genetics-5] ^ ^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.

[NCBI-6] "CACNA1A". Gene. National Center for Biotechnology Information. 16. 3. 2021. Pristupljeno 28. 3. 2021.

[7] "The Science of CACNA1A". CACNA1A Foundation. Pristupljeno 28. 3. 2021.

[9] 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.

[pmid9442082-10] 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.

[pmid10212211-11] 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.

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