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Q01668

- CAC1D_HUMAN

UniProt

Q01668 - CAC1D_HUMAN

Protein

Voltage-dependent L-type calcium channel subunit alpha-1D

Gene

CACNA1D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (17 Oct 2006)
      Previous versions | rss
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    Functioni

    Voltage-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-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei364 – 3641Calcium ion selectivity and permeabilityBy similarity
    Sitei705 – 7051Calcium ion selectivity and permeabilityBy similarity
    Sitei1101 – 11011Calcium ion selectivity and permeabilityBy similarity
    Sitei1406 – 14061Calcium ion selectivity and permeabilityBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi1493 – 150412By similarityAdd
    BLAST

    GO - Molecular functioni

    1. alpha-actinin binding Source: BHF-UCL
    2. ankyrin binding Source: BHF-UCL
    3. high voltage-gated calcium channel activity Source: Ensembl
    4. metal ion binding Source: UniProtKB-KW
    5. voltage-gated calcium channel activity Source: UniProtKB
    6. voltage-gated calcium channel activity involved in cardiac muscle cell action potential Source: BHF-UCL
    7. voltage-gated calcium channel activity involved SA node cell action potential Source: BHF-UCL

    GO - Biological processi

    1. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: BHF-UCL
    2. axon guidance Source: Reactome
    3. calcium ion import Source: BHF-UCL
    4. calcium ion transmembrane transport Source: BHF-UCL
    5. calcium ion transport Source: UniProtKB
    6. energy reserve metabolic process Source: Reactome
    7. membrane depolarization during action potential Source: RefGenome
    8. membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
    9. membrane repolarization during SA node cell action potential Source: BHF-UCL
    10. positive regulation of calcium ion transport Source: BHF-UCL
    11. regulation of atrial cardiac muscle cell membrane repolarization Source: BHF-UCL
    12. regulation of heart rate by cardiac conduction Source: BHF-UCL
    13. regulation of insulin secretion Source: Reactome
    14. regulation of potassium ion transmembrane transport Source: BHF-UCL
    15. regulation of potassium ion transmembrane transporter activity Source: BHF-UCL
    16. sensory perception of sound Source: BHF-UCL
    17. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Calcium channel, Ion channel, Voltage-gated channel

    Keywords - Biological processi

    Calcium transport, Ion transport, Transport

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_18312. NCAM1 interactions.
    REACT_18325. Regulation of insulin secretion.
    REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Voltage-dependent L-type calcium channel subunit alpha-1D
    Alternative name(s):
    Calcium channel, L type, alpha-1 polypeptide, isoform 2
    Voltage-gated calcium channel subunit alpha Cav1.3
    Gene namesi
    Name:CACNA1D
    Synonyms:CACH3, CACN4, CACNL1A2, CCHL1A2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:1391. CACNA1D.

    Subcellular locationi

    Membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. plasma membrane Source: BHF-UCL
    2. voltage-gated calcium channel complex Source: UniProtKB
    3. Z disc Source: BHF-UCL

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Sinoatrial node dysfunction and deafness (SANDD) [MIM:614896]: A disease characterized by congenital severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent pronounced bradycardia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti403 – 4031G → GG in SANDD; the mutant channels are unable to conduct calcium ions currents and have abnormal voltage-dependent gating. 1 Publication
    VAR_069170
    Primary aldosteronism, seizures, and neurologic abnormalities (PASNA) [MIM:615474]: A disorder characterized by hypertension, hypokalemia, and high aldosterone levels with low plasma renin activity and an elevated aldosterone/renin ratio. Other features include generalized seizures, cerebral palsy, spasticity, intellectual disability, and developmental delay.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti403 – 4031G → D in PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density and impaired channel inactivation. 1 Publication
    VAR_070868
    Natural varianti750 – 7501I → M in PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density. 1 Publication
    VAR_070869

    Keywords - Diseasei

    Deafness, Disease mutation, Epilepsy

    Organism-specific databases

    MIMi614896. phenotype.
    615474. phenotype.
    Orphaneti85142. Aldosterone-producing adenoma.
    369929. Aldosterone-producing adenoma with seizures and neurological abnormalities.
    324321. Sinoatrial node dysfunction and deafness.
    PharmGKBiPA84.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 21612161Voltage-dependent L-type calcium channel subunit alpha-1DPRO_0000053933Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi155 – 1551N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi225 – 2251N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi329 – 3291N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1475 – 14751Phosphoserine; by PKASequence Analysis

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ01668.
    PRIDEiQ01668.

    PTM databases

    PhosphoSiteiQ01668.

    Expressioni

    Tissue specificityi

    Expressed in pancreatic islets and in brain, where it has been seen in cerebral cortex, hippocampus, basal ganglia, habenula and thalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in skeletal muscle.1 Publication

    Gene expression databases

    ArrayExpressiQ01668.
    BgeeiQ01668.
    CleanExiHS_CACNA1D.
    GenevestigatoriQ01668.

    Organism-specific databases

    HPAiHPA020215.

    Interactioni

    Subunit structurei

    Voltage-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. Channel activity is further modulated, depending on the presence of specific delta subunit isoforms. Interacts (via IQ domain) with CABP1 and CABP4 in a calcium independent manner By similarity. Interacts with RIMBP2 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi107230. 1 interaction.
    DIPiDIP-48998N.
    IntActiQ01668. 1 interaction.
    STRINGi9606.ENSP00000288139.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3LV3X-ray1.94C502-510[»]
    ProteinModelPortaliQ01668.
    SMRiQ01668. Positions 120-405, 420-448, 519-753, 882-1152, 1201-1465, 1548-1628.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 126126CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini146 – 16318ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini184 – 19512CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini215 – 23521ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini255 – 27319CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini294 – 38188ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini407 – 523117CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini544 – 55815ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini578 – 5858CytoplasmicSequence Analysis
    Topological domaini605 – 61410ExtracellularSequence Analysis
    Topological domaini634 – 65219CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini674 – 72754ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini753 – 886134CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini906 – 92116ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini942 – 95312CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini973 – 9786ExtracellularSequence Analysis
    Topological domaini999 – 101719CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1038 – 112790ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1149 – 120557CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1225 – 123915ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1260 – 12667CytoplasmicSequence Analysis
    Topological domaini1289 – 131325ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1334 – 135219CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini1373 – 143967ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1465 – 2161697CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei127 – 14519Helical; Name=S1 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei164 – 18320Helical; Name=S2 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei196 – 21419Helical; Name=S3 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei236 – 25419Helical; Name=S4 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei274 – 29320Helical; Name=S5 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei382 – 40625Helical; Name=S6 of repeat ISequence AnalysisAdd
    BLAST
    Transmembranei524 – 54320Helical; Name=S1 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei559 – 57719Helical; Name=S2 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei586 – 60419Helical; Name=S3 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei615 – 63319Helical; Name=S4 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei653 – 67321Helical; Name=S5 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei728 – 75225Helical; Name=S6 of repeat IISequence AnalysisAdd
    BLAST
    Transmembranei887 – 90519Helical; Name=S1 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei922 – 94120Helical; Name=S2 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei954 – 97219Helical; Name=S3 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei979 – 99820Helical; Name=S4 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1018 – 103720Helical; Name=S5 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1128 – 114821Helical; Name=S6 of repeat IIISequence AnalysisAdd
    BLAST
    Transmembranei1206 – 122419Helical; Name=S1 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1240 – 125920Helical; Name=S2 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1267 – 128822Helical; Name=S3 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1314 – 133320Helical; Name=S4 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1353 – 137220Helical; Name=S5 of repeat IVSequence AnalysisAdd
    BLAST
    Transmembranei1440 – 146425Helical; Name=S6 of repeat IVSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati113 – 409297IAdd
    BLAST
    Repeati509 – 755247IIAdd
    BLAST
    Repeati873 – 1155283IIIAdd
    BLAST
    Repeati1192 – 1467276IVAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni429 – 44618Binding to the beta subunitBy similarityAdd
    BLAST
    Regioni1075 – 116591Dihydropyridine bindingBy similarityAdd
    BLAST
    Regioni1420 – 148667Dihydropyridine bindingBy similarityAdd
    BLAST
    Regioni1432 – 147544Phenylalkylamine bindingBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1 – 77Poly-Met
    Compositional biasi653 – 6597Poly-Leu
    Compositional biasi827 – 83812Poly-GluAdd
    BLAST

    Domaini

    Each 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.

    Sequence similaritiesi

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG1226.
    HOGENOMiHOG000231529.
    HOVERGENiHBG050763.
    KOiK04851.
    OMAiFSDAWNT.
    OrthoDBiEOG7T1RBQ.
    PhylomeDBiQ01668.
    TreeFamiTF312805.

    Family and domain databases

    Gene3Di1.20.120.350. 5 hits.
    InterProiIPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR005452. LVDCC_a1dsu.
    IPR014873. VDCC_a1su_IQ.
    IPR005446. VDCC_L_a1su.
    IPR002077. VDCCAlpha1.
    [Graphical view]
    PfamiPF08763. Ca_chan_IQ. 1 hit.
    PF00520. Ion_trans. 4 hits.
    [Graphical view]
    PRINTSiPR00167. CACHANNEL.
    PR01630. LVDCCALPHA1.
    PR01636. LVDCCALPHA1D.
    SMARTiSM01062. Ca_chan_IQ. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform Neuronal-type (identifier: Q01668-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV     50
    LSWQAAIDAA RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS 100
    RPARALFCLS LNNPIRRACI SIVEWKPFDI FILLAIFANC VALAIYIPFP 150
    EDDSNSTNHN LEKVEYAFLI IFTVETFLKI IAYGLLLHPN AYVRNGWNLL 200
    DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR AFRVLRPLRL 250
    VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT 300
    CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF 350
    AFAMLTVFQC ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL 400
    VLGVLSGEFS KEREKAKARG DFQKLREKQQ LEEDLKGYLD WITQAEDIDP 450
    ENEEEGGEEG KRNTSMPTSE TESVNTENVS GEGENRGCCG SLCQAISKSK 500
    LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW 550
    LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT 600
    ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI 650
    ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ 700
    ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI 750
    AVDNLADAES LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD 800
    NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP AGPRPRRISE 850
    LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS 900
    AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF 950
    CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG 1000
    LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS 1050
    NPEECRGLFI LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF 1100
    EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA FFMMNIFVGF 1150
    VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY 1200
    VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV 1250
    EMVLKVIAFK PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP 1300
    TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL 1350
    PYVALLIAML FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF 1400
    RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA IVYFISFYML 1450
    CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI 1500
    KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL 1550
    FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE 1600
    VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI 1650
    GPEIRRAISC DLQDDEPEET KREEEDDVFK RNGALLGNHV NHVNSDRRDS 1700
    LQQTNTTHRP LHVQRPSIPP ASDTEKPLFP PAGNSVCHNH HNHNSIGKQV 1750
    PTSTNANLNN ANMSKAAHGK RPSIGNLEHV SENGHHSSHK HDREPQRRSS 1800
    VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL GEQEYFSSEE 1850
    CYEDDSSPTW SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY 1900
    DSRRSPRRRL LPPTPASHRR SSFNFECLRR QSSQEEVPSS PIFPHRTALP 1950
    LHLMQQQIMA VAGLDSSKAQ KYSPSHSTRS WATPPATPPY RDWTPCYTPL 2000
    IQVEQSEALD QVNGSLPSLH RSSWYTDEPD ISYRTFTPAS LTVPSSFRNK 2050
    NSDKQRSADS LVEAVLISEG LGRYARDPKF VSATKHEIAD ACDLTIDEME 2100
    SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE EPDPGRDEED 2150
    LADEMICITT L 2161
    Length:2,161
    Mass (Da):245,141
    Last modified:October 17, 2006 - v2
    Checksum:i31B0ADFCDB30B575
    GO
    Isoform Beta-cell-type (identifier: Q01668-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         373-392: MNDAMGFELPWVYFVSLVIF → VNDAIGWEWPWVYFVSLIIL
         493-493: C → WCWWRRRGAAKAGPSGCRRWG

    Show »
    Length:2,181
    Mass (Da):247,566
    Checksum:i93C3A848E89B5A76
    GO
    Isoform 4 (identifier: Q01668-4) [UniParc]FASTAAdd to Basket

    Also known as: Ca(V)1.3(42A)

    The sequence of this isoform differs from the canonical sequence as follows:
         1642-1647: AGLRTL → MLERML
         1648-2161: Missing.

    Note: Expressed at 5% to 15% of isoform Neuronal-type in brain tissues, increased current density.

    Show »
    Length:1,647
    Mass (Da):187,035
    Checksum:iD90F644342325721
    GO
    Isoform 3 (identifier: Q01668-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1291-1305: Missing.
         1803-1811: Missing.

    Show »
    Length:2,137
    Mass (Da):242,417
    Checksum:i0247ED997C1E6128
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti576 – 5761S → T in BAA07804. (PubMed:7557998)Curated
    Sequence conflicti637 – 6371S → C in AAA58402. (PubMed:1309651)Curated
    Sequence conflicti650 – 6501I → S in AAA58402. (PubMed:1309651)Curated
    Sequence conflicti918 – 9181I → T in BAA07804. (PubMed:7557998)Curated
    Sequence conflicti960 – 9601M → I in BAA07804. (PubMed:7557998)Curated
    Sequence conflicti1289 – 12902Missing in BAA07804. (PubMed:7557998)Curated
    Sequence conflicti1346 – 13461S → F in AAA58402. (PubMed:1309651)Curated
    Sequence conflicti1433 – 14331Y → H in AAA58402. (PubMed:1309651)Curated

    Polymorphismi

    A change from seven to eight ATG trinucleotide repeats, resulting in an additional N-terminal methionine, has been found in a patient with non-insulin-dependent diabetes mellitus (NIDDM).

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1 – 11M → MM in a NIDDM patient. 1 Publication
    VAR_001497
    Natural varianti403 – 4031G → D in PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density and impaired channel inactivation. 1 Publication
    VAR_070868
    Natural varianti403 – 4031G → GG in SANDD; the mutant channels are unable to conduct calcium ions currents and have abnormal voltage-dependent gating. 1 Publication
    VAR_069170
    Natural varianti750 – 7501I → M in PASNA; the mutant channel is activated at less depolarized potentials; results in increased current density. 1 Publication
    VAR_070869
    Natural varianti2097 – 20971D → N.
    Corresponds to variant rs41276455 [ dbSNP | Ensembl ].
    VAR_061103

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei373 – 39220MNDAM…SLVIF → VNDAIGWEWPWVYFVSLIIL in isoform Beta-cell-type. 1 PublicationVSP_000913Add
    BLAST
    Alternative sequencei493 – 4931C → WCWWRRRGAAKAGPSGCRRW G in isoform Beta-cell-type. 1 PublicationVSP_000914
    Alternative sequencei1291 – 130515Missing in isoform 3. 1 PublicationVSP_046743Add
    BLAST
    Alternative sequencei1642 – 16476AGLRTL → MLERML in isoform 4. CuratedVSP_047921
    Alternative sequencei1648 – 2161514Missing in isoform 4. CuratedVSP_047922Add
    BLAST
    Alternative sequencei1803 – 18119Missing in isoform 3. 1 PublicationVSP_046744

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M76558 mRNA. Translation: AAA58402.1.
    M83566 mRNA. Translation: AAA35629.1.
    D43747 Genomic DNA. Translation: BAA07804.1.
    EU363339 mRNA. Translation: ABY66526.1.
    AC005905 Genomic DNA. No translation available.
    AC012467 Genomic DNA. No translation available.
    AC024149 Genomic DNA. No translation available.
    AC132810 Genomic DNA. No translation available.
    AF055575 Genomic DNA. Translation: AAD08651.1.
    CCDSiCCDS2872.1. [Q01668-2]
    CCDS46848.1. [Q01668-1]
    CCDS46849.1. [Q01668-3]
    PIRiJH0564.
    RefSeqiNP_000711.1. NM_000720.3. [Q01668-2]
    NP_001122311.1. NM_001128839.2. [Q01668-3]
    NP_001122312.1. NM_001128840.2. [Q01668-1]
    UniGeneiHs.476358.

    Genome annotation databases

    EnsembliENST00000288139; ENSP00000288139; ENSG00000157388. [Q01668-2]
    ENST00000350061; ENSP00000288133; ENSG00000157388. [Q01668-1]
    ENST00000422281; ENSP00000409174; ENSG00000157388. [Q01668-3]
    GeneIDi776.
    KEGGihsa:776.
    UCSCiuc003dgu.5. human. [Q01668-2]
    uc003dgv.5. human. [Q01668-1]

    Polymorphism databases

    DMDMi116241275.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism, Triplet repeat expansion

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M76558 mRNA. Translation: AAA58402.1 .
    M83566 mRNA. Translation: AAA35629.1 .
    D43747 Genomic DNA. Translation: BAA07804.1 .
    EU363339 mRNA. Translation: ABY66526.1 .
    AC005905 Genomic DNA. No translation available.
    AC012467 Genomic DNA. No translation available.
    AC024149 Genomic DNA. No translation available.
    AC132810 Genomic DNA. No translation available.
    AF055575 Genomic DNA. Translation: AAD08651.1 .
    CCDSi CCDS2872.1. [Q01668-2 ]
    CCDS46848.1. [Q01668-1 ]
    CCDS46849.1. [Q01668-3 ]
    PIRi JH0564.
    RefSeqi NP_000711.1. NM_000720.3. [Q01668-2 ]
    NP_001122311.1. NM_001128839.2. [Q01668-3 ]
    NP_001122312.1. NM_001128840.2. [Q01668-1 ]
    UniGenei Hs.476358.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3LV3 X-ray 1.94 C 502-510 [» ]
    ProteinModelPortali Q01668.
    SMRi Q01668. Positions 120-405, 420-448, 519-753, 882-1152, 1201-1465, 1548-1628.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107230. 1 interaction.
    DIPi DIP-48998N.
    IntActi Q01668. 1 interaction.
    STRINGi 9606.ENSP00000288139.

    Chemistry

    BindingDBi Q01668.
    ChEMBLi CHEMBL2095229.
    DrugBanki DB00661. Verapamil.
    GuidetoPHARMACOLOGYi 530.

    PTM databases

    PhosphoSitei Q01668.

    Polymorphism databases

    DMDMi 116241275.

    Proteomic databases

    PaxDbi Q01668.
    PRIDEi Q01668.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000288139 ; ENSP00000288139 ; ENSG00000157388 . [Q01668-2 ]
    ENST00000350061 ; ENSP00000288133 ; ENSG00000157388 . [Q01668-1 ]
    ENST00000422281 ; ENSP00000409174 ; ENSG00000157388 . [Q01668-3 ]
    GeneIDi 776.
    KEGGi hsa:776.
    UCSCi uc003dgu.5. human. [Q01668-2 ]
    uc003dgv.5. human. [Q01668-1 ]

    Organism-specific databases

    CTDi 776.
    GeneCardsi GC03P053504.
    HGNCi HGNC:1391. CACNA1D.
    HPAi HPA020215.
    MIMi 114206. gene.
    614896. phenotype.
    615474. phenotype.
    neXtProti NX_Q01668.
    Orphaneti 85142. Aldosterone-producing adenoma.
    369929. Aldosterone-producing adenoma with seizures and neurological abnormalities.
    324321. Sinoatrial node dysfunction and deafness.
    PharmGKBi PA84.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1226.
    HOGENOMi HOG000231529.
    HOVERGENi HBG050763.
    KOi K04851.
    OMAi FSDAWNT.
    OrthoDBi EOG7T1RBQ.
    PhylomeDBi Q01668.
    TreeFami TF312805.

    Enzyme and pathway databases

    Reactomei REACT_18312. NCAM1 interactions.
    REACT_18325. Regulation of insulin secretion.
    REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.

    Miscellaneous databases

    GeneWikii Cav1.3.
    GenomeRNAii 776.
    NextBioi 3136.
    PROi Q01668.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q01668.
    Bgeei Q01668.
    CleanExi HS_CACNA1D.
    Genevestigatori Q01668.

    Family and domain databases

    Gene3Di 1.20.120.350. 5 hits.
    InterProi IPR027359. Channel_four-helix_dom.
    IPR005821. Ion_trans_dom.
    IPR005452. LVDCC_a1dsu.
    IPR014873. VDCC_a1su_IQ.
    IPR005446. VDCC_L_a1su.
    IPR002077. VDCCAlpha1.
    [Graphical view ]
    Pfami PF08763. Ca_chan_IQ. 1 hit.
    PF00520. Ion_trans. 4 hits.
    [Graphical view ]
    PRINTSi PR00167. CACHANNEL.
    PR01630. LVDCCALPHA1.
    PR01636. LVDCCALPHA1D.
    SMARTi SM01062. Ca_chan_IQ. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype."
      Williams M.E., Feldman D.H., McCue A.F., Brenner R., Velicelebi G., Ellis S.B., Harpold M.M.
      Neuron 8:71-84(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NEURONAL-TYPE).
      Tissue: Neuroblastoma.
    2. "Cloning of the alpha 1 subunit of a voltage-dependent calcium channel expressed in pancreatic beta cells."
      Seino S., Chen L., Seino M., Blondel O., Takeda J., Johnson J.H., Bell G.I.
      Proc. Natl. Acad. Sci. U.S.A. 89:584-588(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA-CELL-TYPE).
      Tissue: Pancreatic islet.
    3. "The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes."
      Yamada Y., Masuda K., Li Q., Ihara Y., Kubota A., Miura T., Nakamura K., Fujii Y., Seino S., Seino Y.
      Genomics 27:312-319(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM BETA-CELL-TYPE), VARIANT MET-1 INS.
    4. "Modulation of voltage- and Ca2+-dependent gating of CaV1.3 L-type calcium channels by alternative splicing of a C-terminal regulatory domain."
      Singh A., Gebhart M., Fritsch R., Sinnegger-Brauns M.J., Poggiani C., Hoda J.C., Engel J., Romanin C., Striessnig J., Koschak A.
      J. Biol. Chem. 283:20733-20744(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING (ISOFORM 4).
      Tissue: Pancreas.
    5. "The DNA sequence, annotation and analysis of human chromosome 3."
      Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
      , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
      Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Genomic structure of the regulatory region of the voltage-gated calcium channel alpha 1D."
      Kim H.-L., Chang Y.J., Lee S.M., Hong Y.-S.
      Exp. Mol. Med. 30:246-251(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-125.
    7. "Molecular diversity of neuronal-type calcium channels identified in small cell lung carcinoma."
      Oguro-Okano M., Griesmann G.E., Wieben E.D., Slaymaker S.J., Snutch T.P., Lennon V.A.
      Mayo Clin. Proc. 67:1150-1159(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 747-1039, TISSUE SPECIFICITY.
      Tissue: Lung carcinoma.
    8. "Loss of recognition by cross-reactive T cells and its relation to a C-terminus-induced conformational reorientation of an HLA-B*2705-bound peptide."
      Loll B., Ruckert C., Hee C.S., Saenger W., Uchanska-Ziegler B., Ziegler A.
      Protein Sci. 20:278-290(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 502-510 IN COMPLEX WITH HLA.
    9. Cited for: VARIANT SANDD GLY-403 INS, CHARACTERIZATION OF VARIANT SANDD GLY-403 INS.
    10. Cited for: VARIANTS PASNA ASP-403 AND MET-750, CHARACTERIZATION OF VARIANTS PASNA ASP-403 AND MET-750.

    Entry informationi

    Entry nameiCAC1D_HUMAN
    AccessioniPrimary (citable) accession number: Q01668
    Secondary accession number(s): B0FYA3
    , Q13916, Q13931, Q71UT1, Q9UDC3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: October 17, 2006
    Last modified: October 1, 2014
    This is version 150 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3