CAC1F_HUMAN
ID CAC1F_HUMAN Reviewed; 1977 AA.
AC O60840; A6NI29; F5CIQ9; O43901; O95226; Q9UHB1;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1F {ECO:0000305};
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.4;
GN Name=CACNA1F {ECO:0000312|HGNC:HGNC:1393}; Synonyms=CACNAF1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), AND VARIANTS CSNB2A
RP ASP-369; GLN-519; TRP-1060 AND HIS-1375.
RC TISSUE=Retina;
RX PubMed=9662399; DOI=10.1038/940;
RA Strom T.M., Nyakatura G., Apfelstedt-Sylla E., Hellebrand H., Lorenz B.,
RA Weber B.H.F., Wutz K., Gutwillinger N., Ruether K., Drescher B., Sauer C.,
RA Zrenner E., Meitinger T., Rosenthal A., Meindl A.;
RT "An L-type calcium-channel gene mutated in incomplete X-linked congenital
RT stationary night blindness.";
RL Nat. Genet. 19:260-263(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND INVOLVEMENT IN CSNB2A.
RX PubMed=9662400; DOI=10.1038/947;
RA Bech-Hansen N.T., Naylor M.J., Maybaum T.A., Pearce W.G., Koop B.,
RA Fishman G.A., Mets M., Musarella M.A., Boycott K.M.;
RT "Loss-of-function mutations in a calcium-channel alpha1-subunit gene in
RT Xp11.23 cause incomplete X-linked congenital stationary night blindness.";
RL Nat. Genet. 19:264-267(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10873387; DOI=10.1006/geno.2000.6204;
RA Naylor M.J., Rancourt D.E., Bech-Hansen N.T.;
RT "Isolation and characterization of a calcium channel gene, cacna1f, the
RT murine orthologue of the gene for incomplete X-linked congenital stationary
RT night blindness.";
RL Genomics 66:324-327(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Retina;
RX PubMed=19029287; DOI=10.1124/mol.108.049981;
RA Sinnegger-Brauns M.J., Huber I.G., Koschak A., Wild C., Obermair G.J.,
RA Einzinger U., Hoda J.C., Sartori S.B., Striessnig J.;
RT "Expression and 1,4-dihydropyridine-binding properties of brain L-type
RT calcium channel isoforms.";
RL Mol. Pharmacol. 75:407-414(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1211-1977.
RX PubMed=9344658; DOI=10.1006/geno.1997.4941;
RA Fisher S.E., Ciccodicola A., Tanaka K., Curci A., Desicato S., D'Urso M.,
RA Craig I.W.;
RT "Sequence-based exon prediction around the synaptophysin locus reveals a
RT gene-rich area containing novel genes in human proximal Xp.";
RL Genomics 45:340-347(1997).
RN [7]
RP ALTERNATIVE SPLICING (ISOFORM 4; ISOFORM 5 AND ISOFORM 6), TISSUE
RP SPECIFICITY, INTERACTION WITH CABP4, AND FUNCTION.
RX PubMed=27226626; DOI=10.1074/jbc.m116.731737;
RA Haeseleer F., Williams B., Lee A.;
RT "Characterization of C-terminal Splice Variants of Cav1.4 Ca2+ Channels in
RT Human Retina.";
RL J. Biol. Chem. 291:15663-15673(2016).
RN [8]
RP VARIANTS CSNB2A ASP-369; ASP-674 AND ASP-928.
RX PubMed=11281458; DOI=10.1007/s004390100461;
RA Boycott K.M., Maybaum T.A., Naylor M.J., Weleber R.G., Robitaille J.,
RA Miyake Y., Bergen A.A.B., Pierpont M.E., Pearce W.G., Bech-Hansen N.T.;
RT "A summary of 20 CACNA1F mutations identified in 36 families with
RT incomplete X-linked congenital stationary night blindness, and
RT characterization of splice variants.";
RL Hum. Genet. 108:91-97(2001).
RN [9]
RP VARIANTS CSNB2A ARG-74; PRO-229; ARG-261; ASP-369; CYS-753; PRO-860;
RP ARG-1018; TRP-1060; PRO-1079; ARG-1499; ARG-1500 AND PRO-1508.
RX PubMed=12111638; DOI=10.1038/sj.ejhg.5200828;
RA Wutz K., Sauer C., Zrenner E., Lorenz B., Alitalo T., Broghammer M.,
RA Hergersberg M., de la Chapelle A., Weber B.H.F., Wissinger B., Meindl A.,
RA Pusch C.M.;
RT "Thirty distinct CACNA1F mutations in 33 families with incomplete type of
RT XLCSNB and Cacna1f expression profiling in mouse retina.";
RL Eur. J. Hum. Genet. 10:449-456(2002).
RN [10]
RP VARIANTS CSNB2A ARG-150 AND ILE-635.
RX PubMed=12187427; DOI=10.1076/opge.23.2.71.2214;
RA Weleber R.G.;
RT "Infantile and childhood retinal blindness: a molecular perspective (The
RT Franceschetti Lecture).";
RL Ophthalmic Genet. 23:71-97(2002).
RN [11]
RP VARIANT CSNB2A THR-756, AND CHARACTERIZATION OF VARIANT CSNB2A THR-756.
RX PubMed=15897456; DOI=10.1073/pnas.0501907102;
RA Hemara-Wahanui A., Berjukow S., Hope C.I., Dearden P.K., Wu S.-B.,
RA Wilson-Wheeler J., Sharp D.M., Lundon-Treweek P., Clover G.M., Hoda J.-C.,
RA Striessnig J., Marksteiner R., Hering S., Maw M.A.;
RT "A CACNA1F mutation identified in an X-linked retinal disorder shifts the
RT voltage dependence of Cav1.4 channel activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:7553-7558(2005).
RN [12]
RP VARIANT THR-746.
RX PubMed=16960802; DOI=10.1086/508067;
RA Zeitz C., Kloeckener-Gruissem B., Forster U., Kohl S., Magyar I.,
RA Wissinger B., Matyas G., Borruat F.-X., Schorderet D.F., Zrenner E.,
RA Munier F.L., Berger W.;
RT "Mutations in CABP4, the gene encoding the Ca2+-binding protein 4, cause
RT autosomal recessive night blindness.";
RL Am. J. Hum. Genet. 79:657-667(2006).
RN [13]
RP INVOLVEMENT IN CORDX3.
RX PubMed=16505158; DOI=10.1136/jmg.2006.040741;
RA Jalkanen R., Maentyjaervi M., Tobias R., Isosomppi J., Sankila E.-M.,
RA Alitalo T., Bech-Hansen N.T.;
RT "X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the
RT CACNA1F gene.";
RL J. Med. Genet. 43:699-704(2006).
RN [14]
RP INVOLVEMENT IN AIED.
RX PubMed=17525176; DOI=10.1167/iovs.06-1103;
RA Jalkanen R., Bech-Hansen N.T., Tobias R., Sankila E.-M., Maentyjaervi M.,
RA Forsius H., de la Chapelle A., Alitalo T.;
RT "A novel CACNA1F gene mutation causes Aland Island eye disease.";
RL Invest. Ophthalmol. Vis. Sci. 48:2498-2502(2007).
RN [15]
RP VARIANT CSNB2A ARG-603, AND VARIANT AIED ARG-603.
RX PubMed=22194652;
RA Vincent A., Wright T., Day M.A., Westall C.A., Heon E.;
RT "A novel p.Gly603Arg mutation in CACNA1F causes Aland island eye disease
RT and incomplete congenital stationary night blindness phenotypes in a
RT family.";
RL Mol. Vis. 17:3262-3270(2011).
CC -!- FUNCTION: [Isoform 1]: Voltage-sensitive calcium channels (VSCC)
CC mediate the entry of calcium ions into excitable cells and are also
CC involved in a variety of calcium-dependent processes, including muscle
CC contraction, hormone or neurotransmitter release, gene expression, cell
CC motility, cell division and cell death. The isoform alpha-1F gives rise
CC to L-type calcium currents. Long-lasting (L-type) calcium channels
CC belong to the 'high-voltage activated' (HVA) group. They are blocked by
CC dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.
CC Activates at more negative voltages and does not undergo calcium-
CC dependent inactivation (CDI), due to incoming calcium ions, during
CC depolarization. {ECO:0000269|PubMed:27226626}.
CC -!- FUNCTION: [Isoform 4]: Voltage-dependent L-type calcium channel
CC activates at more hyperpolarized voltages and exhibits a robust
CC calcium-dependent inactivation (CDI), due to incoming calcium ions,
CC during depolarizations. {ECO:0000269|PubMed:27226626}.
CC -!- FUNCTION: [Isoform 6]: Voltage-dependent L-type calcium channel
CC activates at more hyperpolarized voltages and exhibits a robust
CC calcium-dependent inactivation (CDI), due to incoming calcium ions,
CC during depolarizations. {ECO:0000269|PubMed:27226626}.
CC -!- SUBUNIT: Voltage-dependent calcium channels are multisubunit complexes,
CC consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1
CC ratio. The channel activity is directed by the pore-forming and
CC voltage-sensitive alpha-1 subunit. In many cases, this subunit is
CC sufficient to generate voltage-sensitive calcium channel activity. The
CC auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge
CC regulate the channel activity. Interacts (via IQ domain) with CABP4; in
CC a calcium independent manner (By similarity). {ECO:0000250,
CC ECO:0000305}.
CC -!- SUBUNIT: [Isoform 4]: Interacts with CABP4; suppresses robust calcium-
CC dependent inactivation of channel without enhancing the hyperpolarized
CC voltage-dependent activation (PubMed:27226626).
CC {ECO:0000269|PubMed:27226626}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=Cav1.4FL {ECO:0000303|PubMed:27226626};
CC IsoId=O60840-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60840-2; Sequence=VSP_036785;
CC Name=3;
CC IsoId=O60840-4; Sequence=VSP_045172;
CC Name=4; Synonyms=Cav1.4Deltaex p45,47 {ECO:0000303|PubMed:27226626};
CC IsoId=O60840-5; Sequence=VSP_058923, VSP_058924;
CC Name=5; Synonyms=Cav1.4Deltaex p45 {ECO:0000303|PubMed:27226626};
CC IsoId=O60840-6; Sequence=VSP_058923;
CC Name=6; Synonyms=Cav1.4Deltaex 47 {ECO:0000303|PubMed:27226626};
CC IsoId=O60840-7; Sequence=VSP_058924;
CC -!- TISSUE SPECIFICITY: Expression in skeletal muscle and retina
CC (PubMed:10873387). Isoform 4 is expressed in retina (PubMed:27226626).
CC {ECO:0000269|PubMed:10873387, ECO:0000269|PubMed:27226626}.
CC -!- DOMAIN: Each of the four internal repeats contains five hydrophobic
CC transmembrane segments (S1, S2, S3, S5, S6) and one positively charged
CC transmembrane segment (S4). S4 segments probably represent the voltage-
CC sensor and are characterized by a series of positively charged amino
CC acids at every third position.
CC -!- DISEASE: Night blindness, congenital stationary, 2A (CSNB2A)
CC [MIM:300071]: A non-progressive retinal disorder characterized by
CC impaired night vision, often associated with nystagmus and myopia.
CC {ECO:0000269|PubMed:11281458, ECO:0000269|PubMed:12111638,
CC ECO:0000269|PubMed:12187427, ECO:0000269|PubMed:15897456,
CC ECO:0000269|PubMed:22194652, ECO:0000269|PubMed:9662399,
CC ECO:0000269|PubMed:9662400}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cone-rod dystrophy, X-linked 3 (CORDX3) [MIM:300476]: An
CC inherited retinal dystrophy characterized by retinal pigment deposits
CC visible on fundus examination, predominantly in the macular region, and
CC initial loss of cone photoreceptors followed by rod degeneration. This
CC leads to decreased visual acuity and sensitivity in the central visual
CC field, followed by loss of peripheral vision. Severe loss of vision
CC occurs earlier than in retinitis pigmentosa, due to cone photoreceptors
CC degenerating at a higher rate than rod photoreceptors.
CC {ECO:0000269|PubMed:16505158}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Aaland island eye disease (AIED) [MIM:300600]: A retinal
CC disease characterized by a combination of fundus hypopigmentation,
CC decreased visual acuity due to foveal hypoplasia, nystagmus,
CC astigmatism, protan color vision defect, myopia, and defective dark
CC adaptation. Except for progression of axial myopia, the disease can be
CC considered to be a stationary condition. Electroretinography reveals
CC abnormalities in both photopic and scotopic functions.
CC {ECO:0000269|PubMed:17525176, ECO:0000269|PubMed:22194652}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1F subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB92359.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the CCNA1F gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/cacnamut.htm";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ006216; CAA06916.1; -; Genomic_DNA.
DR EMBL; AF067227; AAD03587.1; -; mRNA.
DR EMBL; AJ224874; CAA12175.1; -; mRNA.
DR EMBL; AF201304; AAF15290.1; -; mRNA.
DR EMBL; JF701915; AED89557.1; -; mRNA.
DR EMBL; AF196779; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF235097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U93305; AAB92359.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS35253.1; -. [O60840-1]
DR CCDS; CCDS59166.1; -. [O60840-4]
DR CCDS; CCDS59167.1; -. [O60840-2]
DR RefSeq; NP_001243718.1; NM_001256789.2. [O60840-2]
DR RefSeq; NP_001243719.1; NM_001256790.2. [O60840-4]
DR RefSeq; NP_005174.2; NM_005183.3. [O60840-1]
DR AlphaFoldDB; O60840; -.
DR SMR; O60840; -.
DR BioGRID; 107232; 3.
DR IntAct; O60840; 3.
DR STRING; 9606.ENSP00000365441; -.
DR BindingDB; O60840; -.
DR ChEMBL; CHEMBL2363032; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB09229; Aranidipine.
DR DrugBank; DB09231; Benidipine.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB09232; Cilnidipine.
DR DrugBank; DB00568; Cinnarizine.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB06751; Drotaverine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB09236; Lacidipine.
DR DrugBank; DB00825; Levomenthol.
DR DrugBank; DB00653; Magnesium sulfate.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00393; Nimodipine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; O60840; -.
DR GuidetoPHARMACOLOGY; 531; -.
DR TCDB; 1.A.1.11.11; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; O60840; 1 site.
DR iPTMnet; O60840; -.
DR PhosphoSitePlus; O60840; -.
DR BioMuta; CACNA1F; -.
DR jPOST; O60840; -.
DR MassIVE; O60840; -.
DR PaxDb; O60840; -.
DR PeptideAtlas; O60840; -.
DR PRIDE; O60840; -.
DR ProteomicsDB; 49626; -. [O60840-1]
DR ProteomicsDB; 49627; -. [O60840-2]
DR ProteomicsDB; 50727; -.
DR Antibodypedia; 26145; 107 antibodies from 19 providers.
DR DNASU; 778; -.
DR Ensembl; ENST00000323022.10; ENSP00000321618.6; ENSG00000102001.13. [O60840-2]
DR Ensembl; ENST00000376251.5; ENSP00000365427.1; ENSG00000102001.13. [O60840-4]
DR Ensembl; ENST00000376265.2; ENSP00000365441.2; ENSG00000102001.13. [O60840-1]
DR GeneID; 778; -.
DR KEGG; hsa:778; -.
DR MANE-Select; ENST00000323022.10; ENSP00000321618.6; NM_001256789.3; NP_001243718.1. [O60840-2]
DR UCSC; uc004dnb.3; human. [O60840-1]
DR CTD; 778; -.
DR DisGeNET; 778; -.
DR GeneCards; CACNA1F; -.
DR GeneReviews; CACNA1F; -.
DR HGNC; HGNC:1393; CACNA1F.
DR HPA; ENSG00000102001; Tissue enriched (retina).
DR MalaCards; CACNA1F; -.
DR MIM; 300071; phenotype.
DR MIM; 300110; gene.
DR MIM; 300476; phenotype.
DR MIM; 300600; phenotype.
DR neXtProt; NX_O60840; -.
DR OpenTargets; ENSG00000102001; -.
DR Orphanet; 178333; Aaland Islands eye disease.
DR Orphanet; 1872; Cone rod dystrophy.
DR Orphanet; 215; Congenital stationary night blindness.
DR PharmGKB; PA26010; -.
DR VEuPathDB; HostDB:ENSG00000102001; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000159855; -.
DR HOGENOM; CLU_000540_0_1_1; -.
DR InParanoid; O60840; -.
DR OMA; RVCTLNQ; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; O60840; -.
DR TreeFam; TF312805; -.
DR PathwayCommons; O60840; -.
DR SignaLink; O60840; -.
DR BioGRID-ORCS; 778; 5 hits in 694 CRISPR screens.
DR ChiTaRS; CACNA1F; human.
DR GeneWiki; Cav1.4; -.
DR GenomeRNAi; 778; -.
DR Pharos; O60840; Tchem.
DR PRO; PR:O60840; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O60840; protein.
DR Bgee; ENSG00000102001; Expressed in granulocyte and 88 other tissues.
DR ExpressionAtlas; O60840; baseline and differential.
DR Genevisible; O60840; HS.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:Ensembl.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IMP:UniProtKB.
DR GO; GO:1901386; P:negative regulation of voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR031688; CAC1F_C.
DR InterPro; IPR031649; GPHH_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR014873; VDCC_a1su_IQ.
DR InterPro; IPR005446; VDCC_L_a1su.
DR InterPro; IPR002077; VDCCAlpha1.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08763; Ca_chan_IQ; 1.
DR Pfam; PF16885; CAC1F_C; 1.
DR Pfam; PF16905; GPHH; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR PRINTS; PR00167; CACHANNEL.
DR PRINTS; PR01630; LVDCCALPHA1.
DR SMART; SM01062; Ca_chan_IQ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Cone-rod dystrophy; Congenital stationary night blindness; Disease variant;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW Sensory transduction; Transmembrane; Transmembrane helix; Transport;
KW Vision; Voltage-gated channel.
FT CHAIN 1..1977
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1F"
FT /id="PRO_0000053950"
FT TOPO_DOM 1..92
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 93..111
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 112..129
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..149
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..180
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..220
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 221..239
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 240..259
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..347
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 348..372
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000255"
FT TOPO_DOM 373..529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 530..549
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..564
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 565..583
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 584..591
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 592..610
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 611..620
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 621..639
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 640..658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 659..679
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 680..733
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 734..758
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000255"
FT TOPO_DOM 759..871
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 872..890
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 891..906
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 907..926
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 927..938
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 939..957
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 958..963
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 964..983
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 984..1002
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1003..1022
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1023..1112
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1113..1133
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1134..1190
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1191..1209
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1210..1224
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1225..1244
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1245..1251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1252..1273
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1274..1290
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1291..1310
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1311..1329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1330..1349
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1350..1416
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1417..1441
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1442..1977
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 79..375
FT /note="I"
FT REPEAT 515..761
FT /note="II"
FT REPEAT 858..1140
FT /note="III"
FT REPEAT 1177..1444
FT /note="IV"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..412
FT /note="Binding to the beta subunit"
FT /evidence="ECO:0000250"
FT REGION 418..441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..488
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 767..830
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1060..1150
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250"
FT REGION 1397..1463
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250"
FT REGION 1409..1452
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250"
FT REGION 1637..1754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1816..1841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 456..479
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 769..783
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 803..829
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1637..1655
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1697..1722
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 330
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 711
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1086
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 9..86
FT /note="DTTPEPSPANGAGPGPEWGLCPGPPAVEGESSGASGLGTPKRRNQHSKHKTV
FT AVASAQRSPRALFCLTLANPLRRSCI -> GERILPSLQTLGA (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9662400"
FT /id="VSP_045172"
FT VAR_SEQ 427..437
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:19029287,
FT ECO:0000303|PubMed:9662399"
FT /id="VSP_036785"
FT VAR_SEQ 1756..1775
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:27226626"
FT /id="VSP_058923"
FT VAR_SEQ 1836..1901
FT /note="Missing (in isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:27226626"
FT /id="VSP_058924"
FT VARIANT 14
FT /note="P -> L (in dbSNP:rs6520408)"
FT /id="VAR_030807"
FT VARIANT 74
FT /note="C -> R (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030808"
FT VARIANT 150
FT /note="G -> R (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12187427"
FT /id="VAR_030809"
FT VARIANT 229
FT /note="S -> P (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030810"
FT VARIANT 261
FT /note="G -> R (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030811"
FT VARIANT 369
FT /note="G -> D (in CSNB2A; dbSNP:rs122456133)"
FT /evidence="ECO:0000269|PubMed:11281458,
FT ECO:0000269|PubMed:12111638, ECO:0000269|PubMed:9662399"
FT /id="VAR_001504"
FT VARIANT 519
FT /note="R -> Q (in CSNB2A; dbSNP:rs34162630)"
FT /evidence="ECO:0000269|PubMed:9662399"
FT /id="VAR_001505"
FT VARIANT 603
FT /note="G -> R (in AIED and CSNB2A; dbSNP:rs201654095)"
FT /evidence="ECO:0000269|PubMed:22194652"
FT /id="VAR_071433"
FT VARIANT 635
FT /note="V -> I (in CSNB2A; unknown pathological
FT significance; dbSNP:rs141010716)"
FT /evidence="ECO:0000269|PubMed:12187427"
FT /id="VAR_030812"
FT VARIANT 674
FT /note="G -> D (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:11281458"
FT /id="VAR_030813"
FT VARIANT 746
FT /note="N -> T (in dbSNP:rs141159097)"
FT /evidence="ECO:0000269|PubMed:16960802"
FT /id="VAR_029376"
FT VARIANT 753
FT /note="F -> C (in CSNB2A; dbSNP:rs1602644716)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030814"
FT VARIANT 756
FT /note="I -> T (in CSNB2A; increases the number of mutant
FT channels open at physiologic membrane potential and allows
FT for persistent Ca(2+) entry due to reduced channel
FT inactivation resulting in a gain-of-function defect;
FT dbSNP:rs122456136)"
FT /evidence="ECO:0000269|PubMed:15897456"
FT /id="VAR_030815"
FT VARIANT 860
FT /note="L -> P (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030816"
FT VARIANT 928
FT /note="A -> D (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:11281458"
FT /id="VAR_030817"
FT VARIANT 1018
FT /note="G -> R (in CSNB2A; dbSNP:rs1249437161)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030818"
FT VARIANT 1060
FT /note="R -> W (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638,
FT ECO:0000269|PubMed:9662399"
FT /id="VAR_001506"
FT VARIANT 1079
FT /note="L -> P (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030819"
FT VARIANT 1259
FT /note="A -> T (in dbSNP:rs34308720)"
FT /id="VAR_055662"
FT VARIANT 1270
FT /note="A -> T (in dbSNP:rs34308720)"
FT /id="VAR_031822"
FT VARIANT 1375
FT /note="L -> H (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:9662399"
FT /id="VAR_001507"
FT VARIANT 1499
FT /note="C -> R (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030820"
FT VARIANT 1500
FT /note="P -> R (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030821"
FT VARIANT 1508
FT /note="L -> P (in CSNB2A)"
FT /evidence="ECO:0000269|PubMed:12111638"
FT /id="VAR_030822"
FT VARIANT 1930
FT /note="R -> H (in dbSNP:rs33910054)"
FT /id="VAR_054818"
FT CONFLICT 1236
FT /note="E -> V (in Ref. 6; AAB92359)"
FT /evidence="ECO:0000305"
FT CONFLICT 1860
FT /note="A -> G (in Ref. 6; AAB92359)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1977 AA; 220678 MW; 354336550C6D8E73 CRC64;
MSESEGGKDT TPEPSPANGA GPGPEWGLCP GPPAVEGESS GASGLGTPKR RNQHSKHKTV
AVASAQRSPR ALFCLTLANP LRRSCISIVE WKPFDILILL TIFANCVALG VYIPFPEDDS
NTANHNLEQV EYVFLVIFTV ETVLKIVAYG LVLHPSAYIR NGWNLLDFII VVVGLFSVLL
EQGPGRPGDA PHTGGKPGGF DVKALRAFRV LRPLRLVSGV PSLHIVLNSI MKALVPLLHI
ALLVLFVIII YAIIGLELFL GRMHKTCYFL GSDMEAEEDP SPCASSGSGR ACTLNQTECR
GRWPGPNGGI TNFDNFFFAM LTVFQCVTME GWTDVLYWMQ DAMGYELPWV YFVSLVIFGS
FFVLNLVLGV LSGEFSKERE KAKARGDFQK QREKQQMEED LRGYLDWITQ AEELDMEDPS
ADDNLGSMAE EGRAGHRPQL AELTNRRRGR LRWFSHSTRS THSTSSHASL PASDTGSMTE
TQGDEDEEEG ALASCTRCLN KIMKTRVCRR LRRANRVLRA RCRRAVKSNA CYWAVLLLVF
LNTLTIASEH HGQPVWLTQI QEYANKVLLC LFTVEMLLKL YGLGPSAYVS SFFNRFDCFV
VCGGILETTL VEVGAMQPLG ISVLRCVRLL RIFKVTRHWA SLSNLVASLL NSMKSIASLL
LLLFLFIIIF SLLGMQLFGG KFNFDQTHTK RSTFDTFPQA LLTVFQILTG EDWNVVMYDG
IMAYGGPFFP GMLVCIYFII LFICGNYILL NVFLAIAVDN LASGDAGTAK DKGGEKSNEK
DLPQENEGLV PGVEKEEEEG ARREGADMEE EEEEEEEEEE EEEEEGAGGV ELLQEVVPKE
KVVPIPEGSA FFCLSQTNPL RKGCHTLIHH HVFTNLILVF IILSSVSLAA EDPIRAHSFR
NHILGYFDYA FTSIFTVEIL LKMTVFGAFL HRGSFCRSWF NMLDLLVVSV SLISFGIHSS
AISVVKILRV LRVLRPLRAI NRAKGLKHVV QCVFVAIRTI GNIMIVTTLL QFMFACIGVQ
LFKGKFYTCT DEAKHTPQEC KGSFLVYPDG DVSRPLVRER LWVNSDFNFD NVLSAMMALF
TVSTFEGWPA LLYKAIDAYA EDHGPIYNYR VEISVFFIVY IIIIAFFMMN IFVGFVIITF
RAQGEQEYQN CELDKNQRQC VEYALKAQPL RRYIPKNPHQ YRVWATVNSA AFEYLMFLLI
LLNTVALAMQ HYEQTAPFNY AMDILNMVFT GLFTIEMVLK IIAFKPKHYF TDAWNTFDAL
IVVGSIVDIA VTEVNNGGHL GESSEDSSRI SITFFRLFRV MRLVKLLSKG EGIRTLLWTF
IKSFQALPYV ALLIAMIFFI YAVIGMQMFG KVALQDGTQI NRNNNFQTFP QAVLLLFRCA
TGEAWQEIML ASLPGNRCDP ESDFGPGEEF TCGSNFAIAY FISFFMLCAF LIINLFVAVI
MDNFDYLTRD WSILGPHHLD EFKRIWSEYD PGAKGRIKHL DVVALLRRIQ PPLGFGKLCP
HRVACKRLVA MNMPLNSDGT VTFNATLFAL VRTSLKIKTE GNLEQANQEL RIVIKKIWKR
MKQKLLDEVI PPPDEEEVTV GKFYATFLIQ DYFRKFRRRK EKGLLGNDAA PSTSSALQAG
LRSLQDLGPE MRQALTCDTE EEEEEGQEGV EEEDEKDLET NKATMVSQPS ARRGSGISVS
LPVGDRLPDS LSFGPSDDDR GTPTSSQPSV PQAGSNTHRR GSGALIFTIP EEGNSQPKGT
KGQNKQDEDE EVPDRLSYLD EQAGTPPCSV LLPPHRAQRY MDGHLVPRRR LLPPTPAGRK
PSFTIQCLQR QGSCEDLPIP GTYHRGRNSG PNRAQGSWAT PPQRGRLLYA PLLLVEEGAA
GEGYLGRSSG PLRTFTCLHV PGTHSDPSHG KRGSADSLVE AVLISEGLGL FARDPRFVAL
AKQEIADACR LTLDEMDNAA SDLLAQGTSS LYSDEESILS RFDEEDLGDE MACVHAL
