1.A.1.11.27
Voltage-dependent P/Q-type Ca2+ channel subunit α1A, CACNA1A (CACH4; CACN3; CACNL1A4) of 2,505 aas. The CACNA1A gene is widely expressed throughout the CNS. The encoding protein is 90% identical to 1.A.1.11.8. Associated with four neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), spinocerebellar ataxia type 6 (SCA6) and epileptic encephalopathy with nerve atrophy (Reinson et al. 2016). A gain of function mutation gave symptoms of congenital ataxia, abnormal eye movements and developmental delay with severe attacks of hemiplegic migraine (García Segarra et al. 2014). Mutations can cause F/SHM with high penitrance (Prontera et al. 2018). CACNA1A variants lead to a wide spectrum of neurological disorders including epileptic or non-epileptic paroxysmal events, cerebellar ataxia, and developmental delay. The variants are either gain of function GOF) or loss of function (LOF) mutations (Zhang et al. 2020). CACNA1A pathogenic variants have been linked to several neurological disorders including severe early onset developmental encephalopathies and cerebellar atrophy. Y1384 variants exhibit differential splice variant-specific effects on recovery from inactivation (Gandini et al. 2021). Patients with CACNA1A mutational variants located in the transmembrane region may be at high risk of status epilepticus (Niu et al. 2022).
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| Accession Number: | O00555 |
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| Protein Name: | Voltage-dependent P/Q-type calcium channel subunit alpha-1A |
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| Length: | 2505 |
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| Molecular Weight: | 282365.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 18 |
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| Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
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| Substrate |
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1: MARFGDEMPA RYGGGGSGAA AGVVVGSGGG RGAGGSRQGG QPGAQRMYKQ SMAQRARTMA
61: LYNPIPVRQN CLTVNRSLFL FSEDNVVRKY AKKITEWPPF EYMILATIIA NCIVLALEQH
121: LPDDDKTPMS ERLDDTEPYF IGIFCFEAGI KIIALGFAFH KGSYLRNGWN VMDFVVVLTG
181: ILATVGTEFD LRTLRAVRVL RPLKLVSGIP SLQVVLKSIM KAMIPLLQIG LLLFFAILIF
241: AIIGLEFYMG KFHTTCFEEG TDDIQGESPA PCGTEEPART CPNGTKCQPY WEGPNNGITQ
301: FDNILFAVLT VFQCITMEGW TDLLYNSNDA SGNTWNWLYF IPLIIIGSFF MLNLVLGVLS
361: GEFAKERERV ENRRAFLKLR RQQQIERELN GYMEWISKAE EVILAEDETD GEQRHPFDGA
421: LRRTTIKKSK TDLLNPEEAE DQLADIASVG SPFARASIKS AKLENSTFFH KKERRMRFYI
481: RRMVKTQAFY WTVLSLVALN TLCVAIVHYN QPEWLSDFLY YAEFIFLGLF MSEMFIKMYG
541: LGTRPYFHSS FNCFDCGVII GSIFEVIWAV IKPGTSFGIS VLRALRLLRI FKVTKYWASL
601: RNLVVSLLNS MKSIISLLFL LFLFIVVFAL LGMQLFGGQF NFDEGTPPTN FDTFPAAIMT
661: VFQILTGEDW NEVMYDGIKS QGGVQGGMVF SIYFIVLTLF GNYTLLNVFL AIAVDNLANA
721: QELTKDEQEE EEAANQKLAL QKAKEVAEVS PLSAANMSIA VKEQQKNQKP AKSVWEQRTS
781: EMRKQNLLAS REALYNEMDP DERWKAAYTR HLRPDMKTHL DRPLVVDPQE NRNNNTNKSR
841: AAEPTVDQRL GQQRAEDFLR KQARYHDRAR DPSGSAGLDA RRPWAGSQEA ELSREGPYGR
901: ESDHHAREGS LEQPGFWEGE AERGKAGDPH RRHVHRQGGS RESRSGSPRT GADGEHRRHR
961: AHRRPGEEGP EDKAERRARH REGSRPARGG EGEGEGPDGG ERRRRHRHGA PATYEGDARR
1021: EDKERRHRRR KENQGSGVPV SGPNLSTTRP IQQDLGRQDP PLAEDIDNMK NNKLATAESA
1081: APHGSLGHAG LPQSPAKMGN STDPGPMLAI PAMATNPQNA ASRRTPNNPG NPSNPGPPKT
1141: PENSLIVTNP SGTQTNSAKT ARKPDHTTVD IPPACPPPLN HTVVQVNKNA NPDPLPKKEE
1201: EKKEEEEDDR GEDGPKPMPP YSSMFILSTT NPLRRLCHYI LNLRYFEMCI LMVIAMSSIA
1261: LAAEDPVQPN APRNNVLRYF DYVFTGVFTF EMVIKMIDLG LVLHQGAYFR DLWNILDFIV
1321: VSGALVAFAF TGNSKGKDIN TIKSLRVLRV LRPLKTIKRL PKLKAVFDCV VNSLKNVFNI
1381: LIVYMLFMFI FAVVAVQLFK GKFFHCTDES KEFEKDCRGK YLLYEKNEVK ARDREWKKYE
1441: FHYDNVLWAL LTLFTVSTGE GWPQVLKHSV DATFENQGPS PGYRMEMSIF YVVYFVVFPF
1501: FFVNIFVALI IITFQEQGDK MMEEYSLEKN ERACIDFAIS AKPLTRHMPQ NKQSFQYRMW
1561: QFVVSPPFEY TIMAMIALNT IVLMMKFYGA SVAYENALRV FNIVFTSLFS LECVLKVMAF
1621: GILNYFRDAW NIFDFVTVLG SITDILVTEF GNNFINLSFL RLFRAARLIK LLRQGYTIRI
1681: LLWTFVQSFK ALPYVCLLIA MLFFIYAIIG MQVFGNIGID VEDEDSDEDE FQITEHNNFR
1741: TFFQALMLLF RSATGEAWHN IMLSCLSGKP CDKNSGILTR ECGNEFAYFY FVSFIFLCSF
1801: LMLNLFVAVI MDNFEYLTRD SSILGPHHLD EYVRVWAEYD PAAWGRMPYL DMYQMLRHMS
1861: PPLGLGKKCP ARVAYKRLLR MDLPVADDNT VHFNSTLMAL IRTALDIKIA KGGADKQQMD
1921: AELRKEMMAI WPNLSQKTLD LLVTPHKSTD LTVGKIYAAM MIMEYYRQSK AKKLQAMREE
1981: QDRTPLMFQR MEPPSPTQEG GPGQNALPST QLDPGGALMA HESGLKESPS WVTQRAQEMF
2041: QKTGTWSPEQ GPPTDMPNSQ PNSQSVEMRE MGRDGYSDSE HYLPMEGQGR AASMPRLPAE
2101: NQRRRGRPRG NNLSTISDTS PMKRSASVLG PKARRLDDYS LERVPPEENQ RHHQRRRDRS
2161: HRASERSLGR YTDVDTGLGT DLSMTTQSGD LPSKERDQER GRPKDRKHRQ HHHHHHHHHH
2221: PPPPDKDRYA QERPDHGRAR ARDQRWSRSP SEGREHMAHR QGSSSVSGSP APSTSGTSTP
2281: RRGRRQLPQT PSTPRPHVSY SPVIRKAGGS GPPQQQQQQQ QQQQAVARPG RAATSGPRRY
2341: PGPTAEPLAG DRPPTGGHSS GRSPRMERRV PGPARSESPR ACRHGGARWP ASGPHVSEGP
2401: PGPRHHGYYR GSDYDEADGP GSGGGEEAMA GAYDAPPPVR HASSGATGRS PRTPRASGPA
2461: CASPSRHGRR LPNGYYPAHG LARPRGPGSR KGLHEPYSES DDDWC