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Reviewed, UniProtKB/Swiss-Prot Q99246 (CAC1D_MOUSE)

Last modified January 19, 2010. Version 84. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismMus musculus (Mouse)
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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Protein attributes

Sequence length2179 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). Ref.7

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. Interacts with RIMBP2 By similarity. Ref.8

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in the inner hair cells (IHC) of the cochlea. Ref.7

Developmental stage

Isoform 2 and isoform 3 are expressed in heart at 12.5 dpc (at protein level). Expressed in the heart at 9.5, 12.5 and 15.5 dpc. Isoform 2 and isoform 3 are expressed in heart at 9.5 and 12.5 dpc. Ref.1

Induction

Up-regulated in CACNA1C knockout mice. Ref.1

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.

Disruption phenotype

deafness, bradycardia and diabetic traits. Ref.4 Ref.5 Ref.6

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 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99246-2)

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 2 (identifier: Q99246-3)

Also known as: Cav1.3(1a);

The sequence of this isoform differs from the canonical sequence as follows:
     493-513: WCWWKRRGAAKTGPSGCRRWG → C
     1311-1325: Missing.
Isoform 3 (identifier: Q99246-4)

Also known as: Cav1.3(1b);

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MMMMMMMKKMQHQRQHQEDHAN → MNLPTFSSDLILIKSVLSQETDARYKGRVVSAVESTEDFSQAFA
     493-513: WCWWKRRGAAKTGPSGCRRWG → C
     1311-1325: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 21792179Voltage-dependent L-type calcium channel subunit alpha-1D
PRO_0000053935

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 – 543137Cytoplasmic Potential
Transmembrane544 – 56320S1 of repeat II Potential
Topological domain564 – 57815Extracellular Potential
Transmembrane579 – 59719S2 of repeat II Potential
Topological domain598 – 6058Cytoplasmic Potential
Transmembrane606 – 62419S3 of repeat II Potential
Topological domain625 – 63410Extracellular Potential
Transmembrane635 – 65319S4 of repeat II Potential
Topological domain654 – 67219Cytoplasmic Potential
Transmembrane673 – 69321S5 of repeat II Potential
Topological domain694 – 74754Extracellular Potential
Transmembrane748 – 77225S6 of repeat II Potential
Topological domain773 – 906134Cytoplasmic Potential
Transmembrane907 – 92519S1 of repeat III Potential
Topological domain926 – 94116Extracellular Potential
Transmembrane942 – 96120S2 of repeat III Potential
Topological domain962 – 97312Cytoplasmic Potential
Transmembrane974 – 99219S3 of repeat III Potential
Topological domain993 – 9986Extracellular Potential
Transmembrane999 – 101820S4 of repeat III Potential
Topological domain1019 – 103719Cytoplasmic Potential
Transmembrane1038 – 105720S5 of repeat III Potential
Topological domain1058 – 114790Extracellular Potential
Transmembrane1148 – 116821S6 of repeat III Potential
Topological domain1169 – 122557Cytoplasmic Potential
Transmembrane1226 – 124419S1 of repeat IV Potential
Topological domain1245 – 125915Extracellular Potential
Transmembrane1260 – 127920S2 of repeat IV Potential
Topological domain1280 – 12867Cytoplasmic Potential
Transmembrane1287 – 130822S3 of repeat IV Potential
Topological domain1309 – 133325Extracellular Potential
Transmembrane1334 – 135320S4 of repeat IV Potential
Topological domain1354 – 137219Cytoplasmic Potential
Transmembrane1373 – 139220S5 of repeat IV Potential
Topological domain1393 – 145967Extracellular Potential
Transmembrane1460 – 148425S6 of repeat IV Potential
Topological domain1485 – 2179695Cytoplasmic Potential
Repeat113 – 409297I
Repeat529 – 775247II
Repeat893 – 1175283III
Repeat1212 – 1487276IV
Calcium binding1513 – 152412 By similarity
Region429 – 44618Binding to the beta subunit By similarity
Region1095 – 118591Dihydropyridine binding By similarity
Region1440 – 150667Dihydropyridine binding By similarity
Region1452 – 149544Phenylalkylamine binding By similarity
Coiled coil771 – 81040 Potential
Compositional bias1 – 77Poly-Met
Compositional bias673 – 6797Poly-Leu
Compositional bias847 – 85812Poly-Glu

Sites

Site3641Calcium ion selectivity and permeability By similarity
Site7251Calcium ion selectivity and permeability By similarity
Site11211Calcium ion selectivity and permeability By similarity
Site14261Calcium ion selectivity and permeability By similarity

Amino acid modifications

Modified residue14951Phosphoserine; by PKA By similarity
Modified residue19231Phosphoserine By similarity

Natural variations

Alternative sequence1 – 2222MMMMM…EDHAN → MNLPTFSSDLILIKSVLSQE TDARYKGRVVSAVESTEDFS QAFA in isoform 3.
VSP_027090
Alternative sequence493 – 51321WCWWK…CRRWG → C in isoform 2 and isoform 3.
VSP_027091
Alternative sequence1311 – 132515Missing in isoform 2 and isoform 3.
VSP_027092

Experimental info

Sequence conflict4451V → A in BAC77259. Ref.2
Sequence conflict8681T → I in BAC77259. Ref.2
Sequence conflict18711G → E in BAC77259. Ref.2
Sequence conflict20431Y → S in BAC77259. Ref.2

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 24, 2007. Version 2.
Checksum: 573A8D15211611EA

FASTA2,179247,005
        10         20         30         40         50         60 
MMMMMMMKKM QHQRQHQEDH ANEANYARGT RLPISGEGPT 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 YWVNDAIGWE WPWVYFVSLI ILGSFFVLNL VLGVLSGEFS KEREKAKARG 

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

       490        500        510        520        530        540 
GEGETQGCCG TLWCWWKRRG AAKTGPSGCR RWGQAISKSK LSRRWRRWNR FNRRRCRAAV 

       550        560        570        580        590        600 
KSVTFYWLVI VLVFLNTLTI SSEHYNQPDW LTQIQDIANK VLLALFTCEM LVKMYSLGLQ 

       610        620        630        640        650        660 
AYFVSLFNRF DCFVVCGGIT ETILVELELM SPLGVSVFRC VRLLRIFKVT RHWTSLSNLV 

       670        680        690        700        710        720 
ASLLNSMKSI ASLLLLLFLF IIIFSLLGMQ LFGGKFNFDE TQTKRSTFDN FPQALLTVFQ 

       730        740        750        760        770        780 
ILTGEDWNAV MYDGIMAYGG PSSSGMIVCI YFIILFICGN YILLNVFLAI AVDNLADAES 

       790        800        810        820        830        840 
LNTAQKEEAE EKERKKIARK ESLENKKNNK PEVNQIANSD NKVTIDDYQE DAEDKDPYPP 

       850        860        870        880        890        900 
CDVPVGEEEE EEEEDEPEVP AGPRPRRTSE LNMKEKIAPI PEGSAFFILS KTNPIRVGCH 

       910        920        930        940        950        960 
KLINHHIFTN LILVFIMLSS AALAAEDPIR SHSFRNTILG YFDYAFTAIF TVEILLKMTT 

       970        980        990       1000       1010       1020 
FGAFLHKGAF CRNYFNLLDM LVVGVSLVSF GIQSSAISVV KILRVLRVLR PLRAINRAKG 

      1030       1040       1050       1060       1070       1080 
LKHVVQCVFV AIRTIGNIMI VTTLLQFMFA CIGVQLFKGK FYRCTDEAKS NPEECRGLFI 

      1090       1100       1110       1120       1130       1140 
LYKDGDVDSP VVRERIWQNS DFNFDNVLSA MMALFTVSTF EGWPALLYKA IDSNGENVGP 

      1150       1160       1170       1180       1190       1200 
VYNYRVEISI FFIIYIIIVA FFMMNIFVGF VIVTFQEQGE KEYKNCELDK NQRQCVEYAL 

      1210       1220       1230       1240       1250       1260 
KARPLRRYIP KNPYQYKFWY VVNSSPFEYM MFVLIMLNTL CLAMQHYEQS KMFNDAMDIL 

      1270       1280       1290       1300       1310       1320 
NMVFTGVFTV EMVLKVIAFK PKGYFSDAWN TFDSLIVIGS IIDVALSEAD PSESETIPLP 

      1330       1340       1350       1360       1370       1380 
TATPGNSEES NRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIAML 

      1390       1400       1410       1420       1430       1440 
FFIYAVIGMQ MFGKVAMRDN NQINRNNNFQ TFPQAVLLLF RCATGEAWQE IMLACLPGKL 

      1450       1460       1470       1480       1490       1500 
CDPDSDYNPG EEYTCGSNFA IVYFISFYML CAFLIINLFV AVIMDNFDYL TRDWSILGPH 

      1510       1520       1530       1540       1550       1560 
HLDEFKRIWS EYDPEAKGRI KHLDVVTLLR RIQPPLGFGK LCPHRVACKR LVAMNMPLNS 

      1570       1580       1590       1600       1610       1620 
DGTVMFNATL FALVRTALKI KTEGNLEQAN EELRAVIKKI WKKTSMKLLD QVVPPAGDDE 

      1630       1640       1650       1660       1670       1680 
VTVGKFYATF LIQDYFRKFK KRKEQGLVGK YPAKNTTIAL QAGLRTLHDI GPEIRRAISC 

      1690       1700       1710       1720       1730       1740 
DLQDDEPEDS KPEEEDVFKR NGALLGNHVN HVNSDRRDSL QQTNTTHRPL HVQRPSMPPA 

      1750       1760       1770       1780       1790       1800 
SDTEKPLFPP AGNSGCHNHH NHNSIGKQAP TSTNANLNNA NMSKAAHGKP PSIGNLEHVS 

      1810       1820       1830       1840       1850       1860 
ENGHYSCKHD RELQRRSSIK RTRYYETYIR SESGDEQFPT ICREDPEIHG YFRDPRCLGE 

      1870       1880       1890       1900       1910       1920 
QEYFSSEECC GDDSSPTWSR QNYNYYNRYP GSSMDFERPR GYHHPQGFLE DDDSPTGYDS 

      1930       1940       1950       1960       1970       1980 
RRSPRRRLLP PTPPSHRRSS FNFECLRRQS SQDDVLPSPA LPHRAALPLH LMQQQIMAVA 

      1990       2000       2010       2020       2030       2040 
GLDSSKAQKY SPSHSTRSWA TPPATPPYRD WSPCYTPLIQ VDRSESMDQV NGSLPSLHRS 

      2050       2060       2070       2080       2090       2100 
SWYTDEPDIS YRTFTPASLT VPSSFRNKNS DKQRSADSLV EAVLISEGLG RYARDPKFVS 

      2110       2120       2130       2140       2150       2160 
ATKHEIADAC DLTIDEMESA ASTLLNGSVC PRANGDMGPI SHRQDYELQD FGPGYSDEEP 

      2170 
DPGREEEDLA DEMICITTL

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Isoform 2 (Cav1.3(1a)).

Checksum: B8A9A050FFD50B75
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FASTA2,144243,142
Isoform 3 (Cav1.3(1b)).

Checksum: 105BEB972F305637
Show »

FASTA2,166245,161

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References

[1]"Enhanced expression of L-type Cav1.3 calcium channels in murine embryonic hearts from Cav1.2-deficient mice."
Xu M., Welling A., Paparisto S., Hofmann F., Klugbauer N.
J. Biol. Chem. 278:40837-40841(2003) [PubMed: 12900400] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), INDUCTION, DEVELOPMENTAL STAGE.
Strain: C57BL/6.
Tissue: Heart.
[2]"Cloning of the L-type Ca2+ channel alpha1D-subunit from mouse brain and characterization of its expression in the liver."
Okamoto T., Kobayashi T., Hino O.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Strain: BALB/c.
Tissue: Brain.
[3]"Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes."
Perez-Reyes E., Wei X., Castellano A., Birnbaumer L.
J. Biol. Chem. 265:20430-20436(1990) [PubMed: 2173707] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1168-1463 (ISOFORMS 2/3).
Strain: ICR.
Tissue: Ovary.
[4]"Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels."
Platzer J., Engel J., Schrott-Fischer A., Stephan K., Bova S., Chen H., Zheng H., Striessnig J.
Cell 102:89-97(2000) [PubMed: 10929716] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Requirement for the L-type Ca(2+) channel alpha(1D) subunit in postnatal pancreatic beta cell generation."
Namkung Y., Skrypnyk N., Jeong M.J., Lee T., Lee M.S., Kim H.L., Chin H., Suh P.G., Kim S.S., Shin H.S.
J. Clin. Invest. 108:1015-1022(2001) [PubMed: 11581302] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[6]"Functional role of L-type Cav1.3 Ca2+ channels in cardiac pacemaker activity."
Mangoni M.E., Couette B., Bourinet E., Platzer J., Reimer D., Striessnig J., Nargeot J.
Proc. Natl. Acad. Sci. U.S.A. 100:5543-5548(2003) [PubMed: 12700358] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[7]"Few CaV1.3 channels regulate the exocytosis of a synaptic vesicle at the hair cell ribbon synapse."
Brandt A., Khimich D., Moser T.
J. Neurosci. 25:11577-11585(2005) [PubMed: 16354915] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells."
Cui G., Meyer A.C., Calin-Jageman I., Neef J., Haeseleer F., Moser T., Lee A.
J. Physiol. (Lond.) 585:791-803(2007) [PubMed: 17947313] [Abstract]
Cited for: INTERACTION WITH CABP1 AND CABP4.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AJ437291 mRNA. Translation: CAD26883.1.
AJ437292 mRNA. Translation: CAD26884.1.
AB086123 mRNA. Translation: BAC77259.1.
M57975 mRNA. Translation: AAA63292.1.
IPIIPI00230232.
IPI00380726.
IPI00855172.
RefSeqNP_001077085.1.
NP_083257.2.
UniGeneMm.9772

3D structure databases

SMRQ99246. Positions 123-204, 1219-1488, 1620-1648.
ModBaseSearch...

Protein-protein interaction databases

STRINGQ99246.

PTM databases

PhosphoSiteQ99246.

Proteomic databases

PRIDEQ99246.

Genome annotation databases

EnsemblENSMUST00000057695; ENSMUSP00000057745; ENSMUSG00000015968; Mus musculus. [Genome view]
ENSMUST00000112249; ENSMUSP00000107868; ENSMUSG00000015968; Mus musculus. [Genome view]
ENSMUST00000112250; ENSMUSP00000107869; ENSMUSG00000015968; Mus musculus. [Genome view]
GeneID12289.
KEGGmmu:12289.

Organism-specific databases

CTD12289.
MGIMGI:88293. Cacna1d.

Phylogenomic databases

eggNOGroNOG09300.
HOVERGENQ99246.

Gene expression databases

ArrayExpressQ99246.
BgeeQ99246.
GenevestigatorQ99246.
GermOnlineENSMUSG00000015968. Mus musculus.

Family and domain databases

InterProIPR005821. Ion_trans.
IPR005452. LVDCC_a1dsu.
IPR014873. VDCC_a1su_IQ.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
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

NextBio280770.
SOURCESearch...

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Entry information

Entry nameCAC1D_MOUSE
AccessionPrimary (citable) accession number: Q99246
Secondary accession number(s): Q7TSD2, Q8R2I9, Q8R2J0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 24, 2007
Last modified: January 19, 2010
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

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