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Reviewed, UniProtKB/Swiss-Prot Q01668 (CAC1D_HUMAN)

Last modified January 19, 2010. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Voltage-dependent L-type calcium channel subunit alpha-1D
Alternative name(s):
    Voltage-gated calcium channel subunit alpha Cav1.3
    Calcium channel, L type, alpha-1 polypeptide, isoform 2
Gene names
Name: CACNA1D
Synonyms: CACH3, CACN4, CACNL1A2, CCHL1A2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length2161 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

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).

Subunit structure

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. Interacts (via IQ domain) with CABP1 and CABP4 in a calcium independent manner By similarity. Interacts with RIMBP2 By similarity.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

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. Ref.4

Domain

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.

Polymorphism

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).

Sequence similarities

Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. [View classification]

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform Neuronal-type (identifier: Q01668-1)

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.
Isoform Beta-cell-type (identifier: Q01668-2)

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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 21612161Voltage-dependent L-type calcium channel subunit alpha-1D
PRO_0000053933

Regions

Topological domain1 – 126126Cytoplasmic Potential
Transmembrane127 – 14519S1 of repeat I Potential
Topological domain146 – 16318Extracellular Potential
Transmembrane164 – 18320S2 of repeat I Potential
Topological domain184 – 19512Cytoplasmic Potential
Transmembrane196 – 21419S3 of repeat I Potential
Topological domain215 – 23521Extracellular Potential
Transmembrane236 – 25419S4 of repeat I Potential
Topological domain255 – 27319Cytoplasmic Potential
Transmembrane274 – 29320S5 of repeat I Potential
Topological domain294 – 38188Extracellular Potential
Transmembrane382 – 40625S6 of repeat I Potential
Topological domain407 – 523117Cytoplasmic Potential
Transmembrane524 – 54320S1 of repeat II Potential
Topological domain544 – 55815Extracellular Potential
Transmembrane559 – 57719S2 of repeat II Potential
Topological domain578 – 5858Cytoplasmic Potential
Transmembrane586 – 60419S3 of repeat II Potential
Topological domain605 – 61410Extracellular Potential
Transmembrane615 – 63319S4 of repeat II Potential
Topological domain634 – 65219Cytoplasmic Potential
Transmembrane653 – 67321S5 of repeat II Potential
Topological domain674 – 72754Extracellular Potential
Transmembrane728 – 75225S6 of repeat II Potential
Topological domain753 – 886134Cytoplasmic Potential
Transmembrane887 – 90519S1 of repeat III Potential
Topological domain906 – 92116Extracellular Potential
Transmembrane922 – 94120S2 of repeat III Potential
Topological domain942 – 95312Cytoplasmic Potential
Transmembrane954 – 97219S3 of repeat III Potential
Topological domain973 – 9786Extracellular Potential
Transmembrane979 – 99820S4 of repeat III Potential
Topological domain999 – 101719Cytoplasmic Potential
Transmembrane1018 – 103720S5 of repeat III Potential
Topological domain1038 – 112790Extracellular Potential
Transmembrane1128 – 114821S6 of repeat III Potential
Topological domain1149 – 120557Cytoplasmic Potential
Transmembrane1206 – 122419S1 of repeat IV Potential
Topological domain1225 – 123915Extracellular Potential
Transmembrane1240 – 125920S2 of repeat IV Potential
Topological domain1260 – 12667Cytoplasmic Potential
Transmembrane1267 – 128822S3 of repeat IV Potential
Topological domain1289 – 131325Extracellular Potential
Transmembrane1314 – 133320S4 of repeat IV Potential
Topological domain1334 – 135219Cytoplasmic Potential
Transmembrane1353 – 137220S5 of repeat IV Potential
Topological domain1373 – 143967Extracellular Potential
Transmembrane1440 – 146425S6 of repeat IV Potential
Topological domain1465 – 2161697Cytoplasmic Potential
Repeat113 – 409297I
Repeat509 – 755247II
Repeat873 – 1155283III
Repeat1192 – 1467276IV
Calcium binding1493 – 150412 By similarity
Region429 – 44618Binding to the beta subunit By similarity
Region1075 – 116591Dihydropyridine binding By similarity
Region1420 – 148667Dihydropyridine binding By similarity
Region1432 – 147544Phenylalkylamine binding By similarity
Compositional bias1 – 77Poly-Met
Compositional bias653 – 6597Poly-Leu
Compositional bias827 – 83812Poly-Glu

Sites

Site3641Calcium ion selectivity and permeability By similarity
Site7051Calcium ion selectivity and permeability By similarity
Site11011Calcium ion selectivity and permeability By similarity
Site14061Calcium ion selectivity and permeability By similarity

Amino acid modifications

Modified residue14751Phosphoserine; by PKA Potential
Modified residue19051Phosphoserine Ref.5
Glycosylation1551N-linked (GlcNAc...) Potential
Glycosylation2251N-linked (GlcNAc...) Potential
Glycosylation3291N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence373 – 39220MNDAM…SLVIF → VNDAIGWEWPWVYFVSLIIL in isoform Beta-cell-type.
VSP_000913
Alternative sequence4931C → WCWWRRRGAAKAGPSGCRRW G in isoform Beta-cell-type.
VSP_000914
Natural variant11M → MM in a NIDDM patient. Ref.3
VAR_001497
Natural variant20971D → N: dbSNP rs41276455.
VAR_061103

Experimental info

Sequence conflict5761S → T in BAA07804. Ref.3
Sequence conflict6371S → C in AAA58402. Ref.1
Sequence conflict6501I → S in AAA58402. Ref.1
Sequence conflict9181I → T in BAA07804. Ref.3
Sequence conflict9601M → I in BAA07804. Ref.3
Sequence conflict1289 – 12902Missing in BAA07804. Ref.3
Sequence conflict13461S → F in AAA58402. Ref.1
Sequence conflict14331Y → H in AAA58402. Ref.1

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Sequences

Sequence LengthMass (Da)Tools
Isoform Neuronal-type [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 31B0ADFCDB30B575

FASTA2,161245,141
        10         20         30         40         50         60 
MMMMMMMKKM QHQRQQQADH ANEANYARGT RLPLSGEGPT SQPNSSKQTV LSWQAAIDAA 

        70         80         90        100        110        120 
RQAKAAQTMS TSAPPPVGSL SQRKRQQYAK SKKQGNSSNS RPARALFCLS LNNPIRRACI 

       130        140        150        160        170        180 
SIVEWKPFDI FILLAIFANC VALAIYIPFP EDDSNSTNHN LEKVEYAFLI IFTVETFLKI 

       190        200        210        220        230        240 
IAYGLLLHPN AYVRNGWNLL DFVIVIVGLF SVILEQLTKE TEGGNHSSGK SGGFDVKALR 

       250        260        270        280        290        300 
AFRVLRPLRL VSGVPSLQVV LNSIIKAMVP LLHIALLVLF VIIIYAIIGL ELFIGKMHKT 

       310        320        330        340        350        360 
CFFADSDIVA EEDPAPCAFS GNGRQCTANG TECRSGWVGP NGGITNFDNF AFAMLTVFQC 

       370        380        390        400        410        420 
ITMEGWTDVL YWMNDAMGFE LPWVYFVSLV IFGSFFVLNL VLGVLSGEFS KEREKAKARG 

       430        440        450        460        470        480 
DFQKLREKQQ LEEDLKGYLD WITQAEDIDP ENEEEGGEEG KRNTSMPTSE TESVNTENVS 

       490        500        510        520        530        540 
GEGENRGCCG SLCQAISKSK LSRRWRRWNR FNRRRCRAAV KSVTFYWLVI VLVFLNTLTI 

       550        560        570        580        590        600 
SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ AYFVSLFNRF DCFVVCGGIT 

       610        620        630        640        650        660 
ETILVELEIM SPLGISVFRC VRLLRIFKVT RHWTSLSNLV ASLLNSMKSI ASLLLLLFLF 

       670        680        690        700        710        720 
IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ ILTGEDWNAV MYDGIMAYGG 

       730        740        750        760        770        780 
PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES LNTAQKEEAE EKERKKIARK 

       790        800        810        820        830        840 
ESLENKKNNK PEVNQIANSD NKVTIDDYRE EDEDKDPYPP CDVPVGEEEE EEEEDEPEVP 

       850        860        870        880        890        900 
AGPRPRRISE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH KLINHHIFTN LILVFIMLSS 

       910        920        930        940        950        960 
AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT FGAFLHKGAF CRNYFNLLDM 

       970        980        990       1000       1010       1020 
LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG LKHVVQCVFV AIRTIGNIMI 

      1030       1040       1050       1060       1070       1080 
VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI LYKDGDVDSP VVRERIWQNS 

      1090       1100       1110       1120       1130       1140 
DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENIGP IYNHRVEISI FFIIYIIIVA 

      1150       1160       1170       1180       1190       1200 
FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL KARPLRRYIP KNPYQYKFWY 

      1210       1220       1230       1240       1250       1260 
VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL NMVFTGVFTV EMVLKVIAFK 

      1270       1280       1290       1300       1310       1320 
PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PTESENVPVP TATPGNSEES NRISITFFRL 

      1330       1340       1350       1360       1370       1380 
FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML FFIYAVIGMQ MFGKVAMRDN 

      1390       1400       1410       1420       1430       1440 
NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL CDPESDYNPG EEYTCGSNFA 

      1450       1460       1470       1480       1490       1500 
IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH HLDEFKRIWS EYDPEAKGRI 

      1510       1520       1530       1540       1550       1560 
KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS DGTVMFNATL FALVRTALKI 

      1570       1580       1590       1600       1610       1620 
KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE VTVGKFYATF LIQDYFRKFK 

      1630       1640       1650       1660       1670       1680 
KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC DLQDDEPEET KREEEDDVFK 

      1690       1700       1710       1720       1730       1740 
RNGALLGNHV NHVNSDRRDS LQQTNTTHRP LHVQRPSIPP ASDTEKPLFP PAGNSVCHNH 

      1750       1760       1770       1780       1790       1800 
HNHNSIGKQV PTSTNANLNN ANMSKAAHGK RPSIGNLEHV SENGHHSSHK HDREPQRRSS 

      1810       1820       1830       1840       1850       1860 
VKRTRYYETY IRSDSGDEQL PTICREDPEI HGYFRDPHCL GEQEYFSSEE CYEDDSSPTW 

      1870       1880       1890       1900       1910       1920 
SRQNYGYYSR YPGRNIDSER PRGYHHPQGF LEDDDSPVCY DSRRSPRRRL LPPTPASHRR 

      1930       1940       1950       1960       1970       1980 
SSFNFECLRR QSSQEEVPSS PIFPHRTALP LHLMQQQIMA VAGLDSSKAQ KYSPSHSTRS 

      1990       2000       2010       2020       2030       2040 
WATPPATPPY RDWTPCYTPL IQVEQSEALD QVNGSLPSLH RSSWYTDEPD ISYRTFTPAS 

      2050       2060       2070       2080       2090       2100 
LTVPSSFRNK NSDKQRSADS LVEAVLISEG LGRYARDPKF VSATKHEIAD ACDLTIDEME 

      2110       2120       2130       2140       2150       2160 
SAASTLLNGN VRPRANGDVG PLSHRQDYEL QDFGPGYSDE EPDPGRDEED LADEMICITT 


L

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Isoform Beta-cell-type.

Checksum: 93C3A848E89B5A76
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FASTA2,181247,566

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References

« Hide 'large scale' references
[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: 1309651] [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: 1309948] [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: 7557998] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM BETA-CELL-TYPE), VARIANT MET-1 INS.
[4]"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: 1335101] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 747-1039, TISSUE SPECIFICITY.
Tissue: Lung carcinoma.
[5]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1905, MASS SPECTROMETRY.
Tissue: Epithelium.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M76558 mRNA. Translation: AAA58402.1.
M83566 mRNA. Translation: AAA35629.1.
D43747 Genomic DNA. Translation: BAA07804.1.
IPIIPI00009008.
IPI00216354.
PIRJH0564.
RefSeqNP_000711.1.
NP_001122311.1.
NP_001122312.1.
UniGeneHs.476358

3D structure databases

SMRQ01668. Positions 124-201, 1199-1468, 1600-1628.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ01668.

PTM databases

PhosphoSiteQ01668.

Proteomic databases

PRIDEQ01668.

Genome annotation databases

EnsemblENST00000350061; ENSP00000288133; ENSG00000157388; Homo sapiens. [Genome view]
GeneID776.
KEGGhsa:776.
UCSCuc003dgu.2. human.
uc003dgv.2. human.

Organism-specific databases

CTD776.
GeneCardsGC03P053504.
H-InvDBHIX0030870.
HGNCHGNC:1391. CACNA1D.
HPACAB009777.
HPA020215.
MIM114206. gene.
PharmGKBPA84.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08933.
HOVERGENQ01668.
OMAQIQDIAN.
PhylomeDBQ01668.

Enzyme and pathway databases

ReactomeREACT_1505. Integration of energy metabolism.
REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpressQ01668.
BgeeQ01668.
CleanExHS_CACNA1D.
GenevestigatorQ01668.
GermOnlineENSG00000157388. Homo sapiens.

Family and domain databases

InterProIPR011992. EF-hand-like_dom.
IPR005821. Ion_trans.
IPR005452. LVDCC_a1dsu.
IPR014873. VDCC_a1su_IQ.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
Gene3DG3DSA:1.10.238.10. EF-Hand_type. 1 hit.
PANTHERPTHR10037:SF48. LVDCCAlpha1D. 1 hit.
PfamPF08763. Ca_chan_IQ. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]
PRINTSPR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01636. LVDCCALPHA1D.
ProtoNetSearch...

Other Resources

DrugBankDB00661. Verapamil.
NextBio3136.
SOURCESearch...

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Entry information

Entry nameCAC1D_HUMAN
AccessionPrimary (citable) accession number: Q01668
Secondary accession number(s): Q13916, Q13931, Q9UDC3
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: October 17, 2006
Last modified: January 19, 2010
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents