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1.A.1.11.4
The voltage-dependent L-type Ca2+ channel α-subunit-1C (L-type Cav1.2), CACNA1C (CACH2, CACN2, CACNL1A1, CCHL1A1) of 2221 aa. Mutations cause Timothy's syndrome, a disorder associated with autism (Splawski et al., 2006). The C-terminus of Cav1.2 encodes a transcription factor (Gomez-Ospina et al., 2006). Cav1.2 associates with the α-2, δ-1, β and γ subunits (Yang et al., 2011). The CRAC channel activator STIM1 binds and inhibits L-type voltage-gated calcium channel, Cav1.2 (Park et al., 2010).  This channel appears to function as the molecular switch for synaptic transmission (Atlas 2013). Intramembrane signalling occurs with syntaxin 1A for catecholamine release in chromaffin cells (Bachnoff et al. 2013).  miR-153 intron RNA is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, suggesting that IA-2beta and miR-153 have opposite functional effects on the secretory pathway (Xu et al. 2015).   Co-localizes with Syntaxin-1A in nano clusters at the plasma membrane (Sajman et al. 2017). It is a high voltage-activated Ca2+ channel in contrast to Cav3.3 which is a low voltage-activated Ca2+ channel (Sanchez-Sandoval et al. 2018). Nifedipine blocks and potentiates this and other L-type VIC Ca2+ channels (Wang et al. 2018).  Cav1.2 is upregulated when STIM1 is deficient (Pascual-Caro et al. 2018). CaV1.2 regulates chondrogenesis during limb development (Atsuta et al. 2019). CACNA1C may be a prognostic predictor of survival in ovarian cancer (Chang and Dong 2021). Kinase and phosphatase modulation of T-type Ca2+ channel (TTCC) isoforms Cav3.1, Cav3.2, and Cav3.3, are mostly described for roles unrelated to cellular excitability (Sharma et al. 2023), and potential modulations that are yet to be explored are also discussed. Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes (Kuo et al. 2023).  A novel binding site between the voltage-dependent calcium channel CaV1.2 subunit and the CaVβ2 subunit has been discovered using a new analysis method for protein-protein interactions (Murakami et al. 2023). CACNA1C is one of the top risk genes for schizophrenia; A novel 17-variant block across introns 36-45 of CACNA1C was significantly associated with schizophrenia; a novel 17-variant block across introns 36-45 of CACNA1C was responsible (Guo et al. 2023). A novel binding site has been found between the voltage-dependent calcium channel CaV1.2 subunit and CaVβ2 subunit (Murakami et al. 2023). The CaV1.2 distal carboxy terminus functions in the regulation of L-type current (Arancibia et al. 2024).

Accession Number:Q13936
Protein Name:Cav1.2
Length:2221
Molecular Weight:248892.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:21
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate calcium(2+), calcium ion

Cross database links:

DIP: DIP-29589N
RefSeq: NP_000710.5    NP_001123299.1    NP_001123301.1    NP_001123302.1    NP_001123303.1    NP_001123304.1    NP_001123305.1    NP_001123306.1    NP_001123307.1    NP_001123308.1    NP_001123309.1    NP_001123310.1    NP_001123311.1    NP_001123312.1    NP_001123313.1    NP_001123314.1    NP_001123315.1    NP_001123316.1    NP_001123318.1    NP_001161095.1    NP_001161096.1    NP_001161097.1   
Entrez Gene ID: 775   
Pfam: PF08763    PF00520   
OMIM: 114205  gene
601005  phenotype
611875  phenotype
KEGG: hsa:775   

Gene Ontology

GO:0014069 C:postsynaptic density
GO:0005891 C:voltage-gated calcium channel complex
GO:0005516 F:calmodulin binding
GO:0015270 F:dihydropyridine-sensitive calcium channel a...
GO:0060402 P:calcium ion transport into cytosol
GO:0055085 P:transmembrane transport

References (23)

[1] “Molecular diversity of L-type Ca2+ channel transcripts in human fibroblasts.”  Soldatov N.M.et.al.   1316612
[2] “Cloning, chromosomal localization, and functional expression of the alpha-1 subunit of the L-type voltage-dependent calcium channel from normal human heart.”  Schultz D.et.al.   8392192
[3] “Genomic structure of human L-type Ca2+ channel.”  Soldatov N.M.et.al.   7959794
[4] “Different voltage-dependent inhibition by dihydropyridines of human Ca2+ channel splice variants.”  Soldatov N.M.et.al.   7737988
[5] “Properties of three COOH-terminal splice variants of a human cardiac L-type Ca2+-channel alpha1-subunit.”  Kloeckner U.et.al.   9087614
[6] “Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation.”  Soldatov N.M.et.al.   9013606
[7] “Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene.”  Zuehlke R.D.et.al.   9607315
[8] “Alpha(1C) (Ca(V)1.2) L-type calcium channel mediates mechanosensitive calcium regulation.”  Lyford G.L.et.al.   12176756
[9] “Atherosclerosis-related molecular alteration of the human CaV1.2 calcium channel alpha1C subunit.”  Tiwari S.et.al.   17071743
[10] “The finished DNA sequence of human chromosome 12.”  Scherer S.E.et.al.   16541075
[11] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[12] “A novel long N-terminal isoform of human L-type Ca2+ channel is up-regulated by protein kinase C.”  Blumenstein Y.et.al.   11741969
[13] “Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes.”  Perez-Reyes E.et.al.   2173707
[14] “Assignment of the human gene for the alpha 1 subunit of the cardiac DHP-sensitive Ca2+ channel (CCHL1A1) to chromosome 12p12-pter.”  Powers P.A.et.al.   1653763
[15] “Mapping of a human brain voltage-gated calcium channel to human chromosome 12p13-pter.”  Sun W.et.al.   1335957
[16] “Molecular localization of ion selectivity sites within the pore of a human L-type cardiac calcium channel.”  Tang S.et.al.   8099908
[17] “Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit.”  Qin N.et.al.   12181424
[18] “Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with Cav1.2 (L-type) Ca2+ channels.”  Zhou H.et.al.   15140941
[19] “Molecular mechanism for divergent regulation of Cav1.2 Ca2+ channels by calmodulin and Ca2+-binding protein-1.”  Zhou H.et.al.   15980432
[20] “Structure of a complex between a voltage-gated calcium channel beta-subunit and an alpha-subunit domain.”  Van Petegem F.et.al.   15141227
[21] “Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.”  Splawski I.et.al.   15454078
[22] “Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.”  Splawski I.et.al.   15863612
[23] “Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.”  Antzelevitch C.et.al.   17224476
Structure:
1T0J   2BE6   2F3Y   2F3Z   3G43   2LQC   3OXQ   5V2P   5V2Q   6C0A   [...more]

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Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence 
1:	MVNENTRMYI PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR 
61:	QAKLMGSAGN ATISTVSSTQ RKRQQYGKPK KQGSTTATRP PRALLCLTLK NPIRRACISI 
121:	VEWKPFEIII LLTIFANCVA LAIYIPFPED DSNATNSNLE RVEYLFLIIF TVEAFLKVIA 
181:	YGLLFHPNAY LRNGWNLLDF IIVVVGLFSA ILEQATKADG ANALGGKGAG FDVKALRAFR 
241:	VLRPLRLVSG VPSLQVVLNS IIKAMVPLLH IALLVLFVII IYAIIGLELF MGKMHKTCYN 
301:	QEGIADVPAE DDPSPCALET GHGRQCQNGT VCKPGWDGPK HGITNFDNFA FAMLTVFQCI 
361:	TMEGWTDVLY WVNDAVGRDW PWIYFVTLII IGSFFVLNLV LGVLSGEFSK EREKAKARGD 
421:	FQKLREKQQL EEDLKGYLDW ITQAEDIDPE NEDEGMDEEK PRNMSMPTSE TESVNTENVA 
481:	GGDIEGENCG ARLAHRISKS KFSRYWRRWN RFCRRKCRAA VKSNVFYWLV IFLVFLNTLT 
541:	IASEHYNQPN WLTEVQDTAN KALLALFTAE MLLKMYSLGL QAYFVSLFNR FDCFVVCGGI 
601:	LETILVETKI MSPLGISVLR CVRLLRIFKI TRYWNSLSNL VASLLNSVRS IASLLLLLFL 
661:	FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD NFPQSLLTVF QILTGEDWNS VMYDGIMAYG 
721:	GPSFPGMLVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLTSAQKEEE EEKERKKLAR 
781:	TASPEKKQEL VEKPAVGESK EEKIELKSIT ADGESPPATK INMDDLQPNE NEDKSPYPNP 
841:	ETTGEEDEEE PEMPVGPRPR PLSELHLKEK AVPMPEASAF FIFSSNNRFR LQCHRIVNDT 
901:	IFTNLILFFI LLSSISLAAE DPVQHTSFRN HILFYFDIVF TTIFTIEIAL KILGNADYVF 
961:	TSIFTLEIIL KMTAYGAFLH KGSFCRNYFN ILDLLVVSVS LISFGIQSSA INVVKILRVL 
1021:	RVLRPLRAIN RAKGLKHVVQ CVFVAIRTIG NIVIVTTLLQ FMFACIGVQL FKGKLYTCSD 
1081:	SSKQTEAECK GNYITYKDGE VDHPIIQPRS WENSKFDFDN VLAAMMALFT VSTFEGWPEL 
1141:	LYRSIDSHTE DKGPIYNYRV EISIFFIIYI IIIAFFMMNI FVGFVIVTFQ EQGEQEYKNC 
1201:	ELDKNQRQCV EYALKARPLR RYIPKNQHQY KVWYVVNSTY FEYLMFVLIL LNTICLAMQH 
1261:	YGQSCLFKIA MNILNMLFTG LFTVEMILKL IAFKPKGYFS DPWNVFDFLI VIGSIIDVIL 
1321:	SETNHYFCDA WNTFDALIVV GSIVDIAITE VNPAEHTQCS PSMNAEENSR ISITFFRLFR 
1381:	VMRLVKLLSR GEGIRTLLWT FIKSFQALPY VALLIVMLFF IYAVIGMQVF GKIALNDTTE 
1441:	INRNNNFQTF PQAVLLLFRC ATGEAWQDIM LACMPGKKCA PESEPSNSTE GETPCGSSFA 
1501:	VFYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWA EYDPEAKGRI 
1561:	KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVSMNMPLNS DGTVMFNATL FALVRTALRI 
1621:	KTEGNLEQAN EELRAIIKKI WKRTSMKLLD QVVPPAGDDE VTVGKFYATF LIQEYFRKFK 
1681:	KRKEQGLVGK PSQRNALSLQ AGLRTLHDIG PEIRRAISGD LTAEEELDKA MKEAVSAASE 
1741:	DDIFRRAGGL FGNHVSYYQS DGRSAFPQTF TTQRPLHINK AGSSQGDTES PSHEKLVDST 
1801:	FTPSSYSSTG SNANINNANN TALGRLPRPA GYPSTVSTVE GHGPPLSPAI RVQEVAWKLS 
1861:	SNRERHVPMC EDLELRRDSG SAGTQAHCLL LRKANPSRCH SRESQAAMAG QEETSQDETY 
1921:	EVKMNHDTEA CSEPSLLSTE MLSYQDDENR QLTLPEEDKR DIRQSPKRGF LRSASLGRRA 
1981:	SFHLECLKRQ KDRGGDISQK TVLPLHLVHH QALAVAGLSP LLQRSHSPAS FPRPFATPPA 
2041:	TPGSRGWPPQ PVPTLRLEGV ESSEKLNSSF PSIHCGSWAE TTPGGGGSSA ARRVRPVSLM 
2101:	VPSQAGAPGR QFHGSASSLV EAVLISEGLG QFAQDPKFIE VTTQELADAC DMTIEEMESA 
2161:	ADNILSGGAP QSPNGALLPF VNCRDAGQDR AGGEEDAGCV RARGAPSEEE LQDSRVYVSS 
2221:	L