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FLASH GENE

Symbol

CACNA1C

contributors: mct/npt/pgu - updated : 20-11-2015

HGNC name	calcium channel, voltage-dependent, L type, alpha 1C subunit
HGNC id	1390

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	BRGS3 Brugada syndrome 3 TMTS Timothy syndrome
Location	12p13.33      Physical location : 2.162.415 - 2.807.115
Synonym name	voltage-gated calcium channel alpha subunit Cav1.2
	calcium channel, cardiac dihydropyridine-sensitive, alpha-1 subunit
	DHPR, alpha-1 subunit
	voltage-gated L-type calcium channel Cav1.2 alpha 1 subunit, splice
	variant 10*
Synonym symbol(s)	CACNL1A1, CCHL1A1, DHPCA1, L-VDCC, CaV1.2, CACH2, CACN2, TS, LTCC

DNA

TYPE	functioning gene
STRUCTURE	727.16 kb     47 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
text structure	DNA methylation status on the CpG island shore of Cacna1c may have an important role in transcript regulation

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	pter - D12S100 - D12S1117 - D12S1094 - D12S1113 - D12S1689 - D12S381E - D12S1694 - D12S2051 - (D12S2052 , D12S1108 ) - D12S1116 - D12S1096 - D12S2044 - D12S2049 - (D12S1615 , D12S1443 , CACNA1C ) - D12S1664 - (D12S1626 , D12S1403 ) - (D12S372 , D12S1062 ) - (D12S1866 , D12S1077 , D12S1315 )- D12S1467 - D12S1050 - cen
Authors	4st Workshop chrom.12 (97)

RNA

TRANSCRIPTS	type	messenger

text	many alternate transcriptional splice variants

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000719 47 - 13480 NP_000710 239.51 2138 - 2008 19065143 variant 18 or HLCC70 NM_001129827 49 - 13624 NP_001123299 245 2186 - 2008 19065143 HLCC90 NM_001129829 47 - 13603 NP_001123301 243.6 2179 - 2008 19065143 variant 3 or HLCC126 NM_001129830 48 - 13585 NP_001123302 - 2173 - 2008 19065143 variant 4 or HLCC85 NM_001129831 48 - 13564 NP_001123303 - 2166 - 2008 19065143 variant 5 or HLCC88 NM_001129832 48 - 13540 NP_001123304 - 2158 - 2008 19065143 variant 6 or HLCC87 NM_001129833 47 - 13537 NP_001123305 - 2157 - 2008 19065143 NM_001129834 47 - 13537 NP_001123306 - 2157 - 2008 19065143 variant 8 or HLCC71 NM_001129835 47 - 13537 NP_001123307 - 2157 - 2008 19065143 variant 9or HLCC72 NM_001129836 47 - 13531 NP_001123308 - 2155 - 2008 19065143 variant 10 or HLCC89 NM_001129837 46 - 13504 NP_001123309 - 2146 - 2008 19065143 variant 11 or HLCC73 NM_001129838 46 - 13504 NP_001123310 - 2146 - 2008 19065143 variant 12 or HLCC74 NM_001129839 46 - 13498 NP_001123311 - 2144 - 2008 19065143 variant 13 or HLCC125 NM_001129840 47 - 13480 NP_001123312 - 2138 - 2008 19065143 NM_001129841 47 - 13480 NP_001123313 - 2138 - 2008 19065143 variant 15 or HLCC69 NM_001129842 47 - 13480 NP_001123314 - 2138 - 2008 19065143 variant 16 or HLCC78 NM_001129843 47 - 13480 NP_001123315 - 2138 - 2008 19065143 variant 17 or HLCC77 NM_001129844 47 - 13471 NP_001123316 239 2135 - 2008 19065143 NM_001129846 46 - 13447 NP_001123318 238 2127 - 2008 19065143 variant 20 or HLCC76 NM_199460 50 - 13729 NP_955630 249 2221 - 2008 19065143 NM_001167624 48 - 13585 NP_001161096 - 2173 - 2008 19065143 NM_001167623 47 - 13480 NP_001161095 - 2138 - 2008 19065143 NM_001167625 47 - 13660 NP_001161097 - 2198 - 2008 19065143

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Endocrine pancreas         Lymphoid/Immune spleen       highly Nervous brain         Reproductive female system uterus     highly   male system testis     highly   male system prostate       Skin/Tegument skin appendages hair follicle     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum cardiac

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...)

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminus is important for the regulation of voltage-dependent inactivation (VDI)by CABP1
	four domains of homology
	a PDZ-binding motif at its cytosolic tail
	six alpha helical membrane spanning segments (24 transmembrane segments)
	distal C-terminus (approximately residues 1650-1950) with an important, predominantly inhibitory domain, specific for the heart channel, and containing sites for the SH2 and SH3 binding of Src kinase

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to rattus cacna1c
	ortholog to murine Cacna1c

Homologene

FAMILY	calcium channel alpha-1 subunit family
	Enigma subfamily of the PDZ-LIM domain protein family

CATEGORY

transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm
text	colocalized with CABP1 in somatodendritic areas of neurons in the brain

basic FUNCTION	calcium voltage-gated channel (VDCC), L type
	playing an important role in excitation-contraction coupling in the heart
	in iron transport into cardiomyocytes under iron-overloaded conditions
	role of voltage-gated Ca2+ channels in nonexcitable cells during development (PMID;

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Ca2+

protein	CACNA1C targeting to BIN1 is functionally important to cardiac calcium signaling
	AKAP7 interacts with neuronal CACNA1C via their C terminus
	serine 1884 is essential for the regulation of CACNA1C by PRKD1
	interaction between LDB3 and CACNA1C, that facilitated PRKA-mediated phosphorylation of the CACNA1C at Ser1928
	ADRA1B contraction of vascular smooth muscle involves activation of PLD1, which controls a portion of the ADRA1B-induced CACNA1C channel activity
	expression of CACNA1C mRNA was rhythmic (peaking during the late night) and regulated by the circadian clock component NR1D1
	HAP1 is important for insulin secretion of pancreatic beta-cells via regulating the intracellular trafficking and plasma membrane localization of CACNA1C, providing new insight into the mechanisms that regulate insulin release from pancreatic beta cells

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

TMTS , BRGS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in esophageal squamous cell carcinoma (ESCC)

Susceptibility

to bipolar disorder, and schizophrenia

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular     testosterone binding to CACNA1C, thereby supporting its beneficial role as an endogenous Ca2+ channel antagonist in the treatment of cardiovascular disease

ANIMAL & CELL MODELS

mice expressing CACNA1C channels with the distal C terminus deleted (DCT-/-) develop cardiac hypertrophy and die prematurely after E15