MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP000379

UniProt Annotations

Entry Information
Gene Namecalcium channel, voltage-dependent, P/Q type, alpha 1A subunit
Protein EntryCAC1A_HUMAN
UniProt IDO00555
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=8; Comment=Additional isoforms seem to exist.; Name=1; Synonyms=1A-1, BI-1-GGCAG; IsoId=O00555-1; Sequence=Displayed; Name=2; Synonyms=1A-2,BI-1; IsoId=O00555-2; Sequence=VSP_000875; Name=3; Synonyms=BI-1(V1); IsoId=O00555-3; Sequence=VSP_000871, VSP_000875; Name=4; Synonyms=BI-1(V1)-GGCAG; IsoId=O00555-4; Sequence=VSP_000871; Name=5; Synonyms=BI-1(V2); IsoId=O00555-5; Sequence=VSP_000872, VSP_000875; Name=6; Synonyms=BI-1(V2)-GGCAG; IsoId=O00555-6; Sequence=VSP_000872; Name=7; Synonyms=BI-1(V2,V3); IsoId=O00555-7; Sequence=VSP_000873, VSP_000874; Name=8; IsoId=O00555-8; Sequence=VSP_046165, VSP_046166;
DiseaseEpisodic ataxia 2 (EA2) [MIM:108500]: An autosomal dominant disorder characterized by acetozolamide-responsive attacks of ataxia, migraine-like symptoms, interictal nystagmus, and cerebellar atrophy. {ECO:0000269|PubMed:10987655, ECO:0000269|PubMed:11176968, ECO:0000269|PubMed:11723274, ECO:0000269|PubMed:12420090, ECO:0000269|PubMed:14718690, ECO:0000269|PubMed:15173248, ECO:0000269|PubMed:15293273, ECO:0000269|PubMed:18602318, ECO:0000269|PubMed:19232643, ECO:0000269|PubMed:20129625, ECO:0000269|PubMed:21696515, ECO:0000269|PubMed:8898206, ECO:0000269|PubMed:9302278}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseMigraine, familial hemiplegic, 1 (FHM1) [MIM:141500]: A subtype of migraine with aura associated with ictal hemiparesis and, in some families, cerebellar ataxia and atrophy. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking. {ECO:0000269|PubMed:10408532, ECO:0000269|PubMed:11409427, ECO:0000269|PubMed:11439943, ECO:0000269|PubMed:15032980, ECO:0000269|PubMed:18400034, ECO:0000269|PubMed:8898206}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseSpinocerebellar ataxia 6 (SCA6) [MIM:183086]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA6 is an autosomal dominant cerebellar ataxia (ADCA), mainly caused by expansion of a CAG repeat in the coding region of CACNA1A. There seems to be a correlation between the repeat number and earlier onset of the disorder. {ECO:0000269|PubMed:16325861, ECO:0000269|PubMed:20682717, ECO:0000269|PubMed:8988170, ECO:0000269|PubMed:9345107}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainEach of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
FunctionVoltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by the funnel toxin (Ftx) and by the omega-agatoxin- IVA (omega-Aga-IVA). They are however insensitive to dihydropyridines (DHP), and omega-conotoxin-GVIA (omega-CTx-GVIA).
InteractionQ8IZP0:ABI1; NbExp=2; IntAct=EBI-766279, EBI-375446; Q86SJ2:AMIGO2; NbExp=2; IntAct=EBI-766279, EBI-3866830; Q7Z5H3:ARHGAP22; NbExp=2; IntAct=EBI-766279, EBI-3866859; O95153:BZRAP1; NbExp=2; IntAct=EBI-766279, EBI-5915931; P67870:CSNK2B; NbExp=2; IntAct=EBI-766279, EBI-348169; O75953:DNAJB5; NbExp=2; IntAct=EBI-766279, EBI-5655937; P28799:GRN; NbExp=2; IntAct=EBI-766279, EBI-747754; P15822:HIVEP1; NbExp=2; IntAct=EBI-766279, EBI-722264; O94910:LPHN1; NbExp=2; IntAct=EBI-766279, EBI-3389315; Q8N2S1:LTBP4; NbExp=2; IntAct=EBI-766279, EBI-947718; O00339:MATN2; NbExp=2; IntAct=EBI-766279, EBI-949020; O75095:MEGF6; NbExp=2; IntAct=EBI-766279, EBI-947597; Q7Z7M0:MEGF8; NbExp=2; IntAct=EBI-766279, EBI-947617; Q9UHX1:PUF60; NbExp=2; IntAct=EBI-766279, EBI-1053259; Q8IXT5:RBM12B; NbExp=2; IntAct=EBI-766279, EBI-3044077; Q9BVA1:TUBB2B; NbExp=2; IntAct=EBI-766279, EBI-355665; P22695:UQCRC2; NbExp=2; IntAct=EBI-766279, EBI-1051424; P49750:YLPM1; NbExp=2; IntAct=EBI-766279, EBI-712871;
PolymorphismThe poly-Gln region of CACNA1A is polymorphic: 6 to 17 repeats in the normal population, expanded to about 21 to 30 repeats in SCA6. Repeat expansion has been reported also in a EA2 family.
SimilarityBelongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1A subfamily. {ECO:0000305}.
Subcellular LocationMembrane; Multi-pass membrane protein.
SubunitVoltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore- forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. Interact (via C-terminal CDB motif) with CABP1 in the pre- and postsynaptic membranes.
Tissue SpecificityBrain specific; mainly found in cerebellum, cerebral cortex, thalamus and hypothalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in heart, kidney, liver or muscle. Purkinje cells contain predominantly P- type VSCC, the Q-type being a prominent calcium current in cerebellar granule cells. {ECO:0000269|PubMed:1335101}.
Web ResourceName=Calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CACNA1A); Note=Leiden Open Variation Database (LOVD); URL="http://chromium.liacs.nl/LOVD2/home.php?select_db=CACNA1A";
Web ResourceName=Familial hemiplegic migraine (FHM) variation database, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit (CACNA1A); Note=Leiden Open Variation Database (LOVD); URL="http://grenada.lumc.nl/LOVD2/FHM/home.php?select_db=CACNA1A";
  logo