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UniProtKB/Swiss-Prot P27732 (CAC1D_RAT)
Last modified
January 19, 2010.
Version 86.
History...
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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
Names and origin
| Protein names | Recommended 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 Rat brain class D Short name=RBD | ||||
| Gene names |
| ||||
| Organism | Rattus norvegicus (Rat) | ||||
| Taxonomic identifier | 10116 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus |
Protein attributes
| Sequence length | 2203 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
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.8 |
| 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 with CABP1 and CABP4, resulting in a near elimination of calcium-dependent inactivation of the channel. Interacts with RIMBP2 By similarity. Ref.8 |
| Subcellular location | |
| Tissue specificity | Expressed in brain, pancreatic islets and B-lymphocytes. Ref.8 |
| 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. |
| Sequence similarities | Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. [View classification] |
Ontologies
| Keywords | |
|---|---|
| Biological process | Calcium transport Ion transport Transport |
| Cellular component | Membrane |
| Coding sequence diversity | Alternative splicing |
| Domain | Repeat Transmembrane |
| Ligand | Calcium |
| Molecular function | Calcium channel Ionic channel Voltage-gated channel |
| PTM | Disulfide bond Glycoprotein Phosphoprotein |
| Gene Ontology (GO) | |
| Biological process | calcium ion transport Inferred from electronic annotation. Source: UniProtKB-KW calcium-mediated signaling Ref.5Inferred from direct assay. Source: RGD memoryInferred from expression pattern. Source: RGD transmembrane transportInferred from electronic annotation. Source: InterPro |
| Cellular component | apical plasma membrane Inferred from direct assay. Source: RGD voltage-gated calcium channel complexTraceable author statement. Source: RGD |
| Molecular function | calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW voltage-gated calcium channel activityInferred from direct assay. Source: RGD |
| Complete GO annotation... | |
Alternative products
| This entry describes 13 isoforms produced by alternative splicing. [Align] [Select] Note: The region sequenced in isoforms ROB3 and RKC5 is identical to CACN4. | ||||||
| Isoform 1 (identifier: P27732-1) Also known as: CACN4A; 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: P27732-2) Also known as: CACN4B; The sequence of this isoform differs from the canonical sequence as follows: 1642-1668: DDEVTVGKFYATFLIQDYFRKFKKRKE → GNSRSGKSKAWWGNTLRRTPRSPYRRD 1669-2203: Missing. | ||||||
| Isoform 3 (identifier: P27732-3) Also known as: CACH3A; RB48; RBD-55; The sequence of this isoform differs from the canonical sequence as follows: 1349-1349: D → DPSDSENIPLPTATPG | ||||||
| Isoform 4 (identifier: P27732-4) Also known as: Delta-IV-S3; RKC6; The sequence of this isoform differs from the canonical sequence as follows: 1322-1349: Missing. | ||||||
| Isoform 5 (identifier: P27732-5) Also known as: Delta-IV-S4; The sequence of this isoform differs from the canonical sequence as follows: 1354-1368: Missing. | ||||||
| Isoform 6 (identifier: P27732-6) Also known as: RB9; The sequence of this isoform differs from the canonical sequence as follows: 1322-1348: GYFSDAWNTFDSLIVIGSIIDVALSEA → HYFTDAWNTFDALIVVGSVVDIAITEVN 1349-1349: D → DPSDSENIPLPTATPG | ||||||
| Isoform 7 (identifier: P27732-7) Also known as: RB11; The sequence of this isoform differs from the canonical sequence as follows: 493-512: Missing. | ||||||
| Isoform 8 (identifier: P27732-8) Also known as: RB34; The sequence of this isoform differs from the canonical sequence as follows: 481-492: Missing. | ||||||
| Isoform 9 (identifier: P27732-9) Also known as: RH1; The sequence of this isoform differs from the canonical sequence as follows: 1322-1392: Missing. | ||||||
| Isoform 10 (identifier: P27732-10) Also known as: RH2; The sequence of this isoform differs from the canonical sequence as follows: 1322-1349: Missing. 1354-1368: Missing. | ||||||
| Isoform 11 (identifier: P27732-13) Also known as: RKC5; The sequence of this isoform is not available. | ||||||
| Isoform 12 (identifier: P27732-14) Also known as: ROB3; The sequence of this isoform is not available. | ||||||
| Isoform 13 (identifier: P27732-12) Also known as: Truncated; The sequence of this isoform differs from the canonical sequence as follows: 1686-1691: AGLRTL → MLERML 1692-2203: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2203 | 2203 | Voltage-dependent L-type calcium channel subunit alpha-1D | PRO_0000053936 | |||||
Regions | |||||||||
| Topological domain | 1 – 126 | 126 | Cytoplasmic Potential | ||||||
| Transmembrane | 127 – 145 | 19 | S1 of repeat I Potential | ||||||
| Topological domain | 146 – 163 | 18 | Extracellular Potential | ||||||
| Transmembrane | 164 – 183 | 20 | S2 of repeat I Potential | ||||||
| Topological domain | 184 – 195 | 12 | Cytoplasmic Potential | ||||||
| Transmembrane | 196 – 214 | 19 | S3 of repeat I Potential | ||||||
| Topological domain | 215 – 235 | 21 | Extracellular Potential | ||||||
| Transmembrane | 236 – 254 | 19 | S4 of repeat I Potential | ||||||
| Topological domain | 255 – 273 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 274 – 293 | 20 | S5 of repeat I Potential | ||||||
| Topological domain | 294 – 381 | 88 | Extracellular Potential | ||||||
| Transmembrane | 382 – 406 | 25 | S6 of repeat I Potential | ||||||
| Topological domain | 407 – 582 | 176 | Cytoplasmic Potential | ||||||
| Transmembrane | 583 – 602 | 20 | S1 of repeat II Potential | ||||||
| Topological domain | 603 – 617 | 15 | Extracellular Potential | ||||||
| Transmembrane | 618 – 636 | 19 | S2 of repeat II Potential | ||||||
| Topological domain | 637 – 644 | 8 | Cytoplasmic Potential | ||||||
| Transmembrane | 645 – 663 | 19 | S3 of repeat II Potential | ||||||
| Topological domain | 664 – 673 | 10 | Extracellular Potential | ||||||
| Transmembrane | 674 – 692 | 19 | S4 of repeat II Potential | ||||||
| Topological domain | 693 – 711 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 712 – 732 | 21 | S5 of repeat II Potential | ||||||
| Topological domain | 733 – 786 | 54 | Extracellular Potential | ||||||
| Transmembrane | 787 – 811 | 25 | S6 of repeat II Potential | ||||||
| Topological domain | 812 – 945 | 134 | Cytoplasmic Potential | ||||||
| Transmembrane | 946 – 964 | 19 | S1 of repeat III Potential | ||||||
| Topological domain | 965 – 980 | 16 | Extracellular Potential | ||||||
| Transmembrane | 981 – 1000 | 20 | S2 of repeat III Potential | ||||||
| Topological domain | 1001 – 1012 | 12 | Cytoplasmic Potential | ||||||
| Transmembrane | 1013 – 1031 | 19 | S3 of repeat III Potential | ||||||
| Topological domain | 1032 – 1037 | 6 | Extracellular Potential | ||||||
| Transmembrane | 1038 – 1057 | 20 | S4 of repeat III Potential | ||||||
| Topological domain | 1058 – 1076 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 1077 – 1096 | 20 | S5 of repeat III Potential | ||||||
| Topological domain | 1097 – 1186 | 90 | Extracellular Potential | ||||||
| Transmembrane | 1187 – 1207 | 21 | S6 of repeat III Potential | ||||||
| Topological domain | 1208 – 1264 | 57 | Cytoplasmic Potential | ||||||
| Transmembrane | 1265 – 1283 | 19 | S1 of repeat IV Potential | ||||||
| Topological domain | 1284 – 1298 | 15 | Extracellular Potential | ||||||
| Transmembrane | 1299 – 1318 | 20 | S2 of repeat IV Potential | ||||||
| Topological domain | 1319 – 1325 | 7 | Cytoplasmic Potential | ||||||
| Transmembrane | 1326 – 1347 | 22 | S3 of repeat IV Potential | ||||||
| Topological domain | 1348 – 1357 | 10 | Extracellular Potential | ||||||
| Transmembrane | 1358 – 1377 | 20 | S4 of repeat IV Potential | ||||||
| Topological domain | 1378 – 1396 | 19 | Cytoplasmic Potential | ||||||
| Transmembrane | 1397 – 1416 | 20 | S5 of repeat IV Potential | ||||||
| Topological domain | 1417 – 1483 | 67 | Extracellular Potential | ||||||
| Transmembrane | 1484 – 1508 | 25 | S6 of repeat IV Potential | ||||||
| Topological domain | 1509 – 2203 | 695 | Cytoplasmic Potential | ||||||
| Repeat | 112 – 408 | 297 | I | ||||||
| Repeat | 528 – 774 | 247 | II | ||||||
| Repeat | 892 – 1174 | 283 | III | ||||||
| Repeat | 1211 – 1486 | 276 | IV | ||||||
| Calcium binding | 1537 – 1548 | 12 | Potential | ||||||
| Region | 429 – 446 | 18 | Binding to the beta subunit By similarity | ||||||
| Region | 1134 – 1224 | 91 | Dihydropyridine binding By similarity | ||||||
| Region | 1464 – 1530 | 67 | Dihydropyridine binding By similarity | ||||||
| Region | 1476 – 1519 | 44 | Phenylalkylamine binding By similarity | ||||||
| Compositional bias | 1 – 7 | 7 | Poly-Met | ||||||
| Compositional bias | 712 – 718 | 7 | Poly-Leu | ||||||
| Compositional bias | 886 – 897 | 12 | Poly-Glu | ||||||
Sites | |||||||||
| Site | 364 | 1 | Calcium ion selectivity and permeability By similarity | ||||||
| Site | 763 | 1 | Calcium ion selectivity and permeability By similarity | ||||||
| Site | 1160 | 1 | Calcium ion selectivity and permeability By similarity | ||||||
| Site | 1450 | 1 | Calcium ion selectivity and permeability By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 1519 | 1 | Phosphoserine; by PKA Potential | ||||||
| Modified residue | 1947 | 1 | Phosphoserine By similarity | ||||||
| Glycosylation | 155 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 225 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 329 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Alternative sequence | 481 – 492 | 12 | Missing in isoform 8. | VSP_000916 | |||||
| Alternative sequence | 493 – 512 | 20 | Missing in isoform 7. | VSP_000917 | |||||
| Alternative sequence | 1322 – 1392 | 71 | Missing in isoform 9. | VSP_000918 | |||||
| Alternative sequence | 1322 – 1349 | 28 | Missing in isoform 4 and isoform 10. | VSP_000919 | |||||
| Alternative sequence | 1322 – 1348 | 27 | GYFSD…ALSEA → HYFTDAWNTFDALIVVGSVV DIAITEVN in isoform 6. | VSP_000920 | |||||
| Alternative sequence | 1349 | 1 | D → DPSDSENIPLPTATPG in isoform 6 and isoform 3. | VSP_000921 | |||||
| Alternative sequence | 1354 – 1368 | 15 | Missing in isoform 10 and isoform 5. | VSP_000922 | |||||
| Alternative sequence | 1642 – 1668 | 27 | DDEVT…KKRKE → GNSRSGKSKAWWGNTLRRTP RSPYRRD in isoform 2. | VSP_000923 | |||||
| Alternative sequence | 1669 – 2203 | 535 | Missing in isoform 2. | VSP_000924 | |||||
| Alternative sequence | 1686 – 1691 | 6 | AGLRTL → MLERML in isoform 13. | VSP_000925 | |||||
| Alternative sequence | 1692 – 2203 | 512 | Missing in isoform 13. | VSP_000926 | |||||
Experimental info | |||||||||
| Mutagenesis | 1656 – 1657 | 2 | IQ → AA: Loss of calcium-dependent inactivation related to the C-terminal lobe of calmodulin. Ref.8 | ||||||
| Sequence conflict | 124 | 1 | D → N in AAA42015. Ref.2 | ||||||
| Sequence conflict | 183 | 1 | S → Y in AAA42015. Ref.2 | ||||||
| Sequence conflict | 192 | 1 | S → Y in AAA42015. Ref.2 | ||||||
| Sequence conflict | 513 | 1 | G → C Ref.2 | ||||||
| Sequence conflict | 522 – 560 | 39 | Missing Ref.2 | ||||||
| Sequence conflict | 1452 | 1 | W → R in AAA89156. Ref.5 | ||||||
Sequences
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References
| [1] | "Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells." Ihara Y., Yamada Y., Fujii Y., Gonoi T., Yano H., Yasuda K., Inagaki N., Seino Y., Seino S. Mol. Endocrinol. 9:121-130(1995) [PubMed: 7760845] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Insulinoma. |
| [2] | "Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha-1 subunit of the voltage-dependent calcium channel." Hui A., Ellinor P.T., Krizanova O., Wang J.-J., Diebold R.J., Schwartz A. Neuron 7:35-44(1991) [PubMed: 1648940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 6; 7; 8 AND 13). Tissue: Brain. |
| [3] | "Transcriptional regulation of the neuronal L-type calcium channel alpha 1D subunit gene." Kamp T.J., Mitas M., Fields K.L., Asoh S., Chin H., Marban E., Nirenberg M. Cell. Mol. Neurobiol. 15:307-326(1995) [PubMed: 7553731] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-125. |
| [4] | "Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney." Yu A.S.L., Hebert S.C., Brenner B.M., Lytton J. Proc. Natl. Acad. Sci. U.S.A. 89:10494-10498(1992) [PubMed: 1279681] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1100-1410 (ISOFORMS 4 AND 11). Tissue: Kidney. |
| [5] | "Multiple calcium channel transcripts in rat osteosarcoma cells: selective activation of alpha 1D isoform by parathyroid hormone." Barry E.L.R., Gesek F.A., Froehner S.C., Friedman P.A. Proc. Natl. Acad. Sci. U.S.A. 92:10914-10918(1995) [PubMed: 7479909] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1218-1498 (ISOFORM 12). Tissue: Osteosarcoma. |
| [6] | "Novel variants of voltage-operated calcium channel alpha-1 subunit transcripts in a rat liver-derived cell line: deletion in the IVS4 voltage sensing region." Brereton H.M., Harland M.L., Froscio M., Petronijevic T., Barritt G.J. Cell Calcium 22:39-52(1997) [PubMed: 9232351] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1200-1493 (ISOFORMS 3; 4; 5; 9 AND 10). Tissue: Hepatoma. |
| [7] | "Rat brain expresses a heterogeneous family of calcium channels." Snutch T.P., Leonard J.P., Gilbert M.M., Lester H.A., Davidson N. Proc. Natl. Acad. Sci. U.S.A. 87:3391-3395(1990) [PubMed: 1692134] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1307-1479 (ISOFORM 3). |
| [8] | "Switching of Ca2+-dependent inactivation of Ca(v)1.3 channels by calcium binding proteins of auditory hair cells." Yang P.S., Alseikhan B.A., Hiel H., Grant L., Mori M.X., Yang W., Fuchs P.A., Yue D.T. J. Neurosci. 26:10677-10689(2006) [PubMed: 17050707] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF 1656-ILE-GLN-1657, INTERACTION WITH CABP1 AND CABP4, TISSUE SPECIFICITY. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | D38101 mRNA. Translation: BAA07282.1. D38102 mRNA. Translation: BAA07283.1. M57682 mRNA. Translation: AAA42015.1. U14005 Genomic DNA. Translation: AAB60515.1. M99221 mRNA. Translation: AAA40895.1. U31772 mRNA. Translation: AAA89156.1. U49126 mRNA. Translation: AAB61634.1. U49127 mRNA. Translation: AAB61635.1. U49128 mRNA. Translation: AAB61636.1. |
| IPI | IPI00199764. IPI00231109. IPI00231110. IPI00231111. IPI00231112. IPI00231113. IPI00231114. IPI00231116. IPI00231117. IPI00231808. IPI00231809. |
| PIR | JH0422. T42742. |
| RefSeq | NP_058994.1. |
| UniGene | Rn.89671 |
3D structure databases | |
| SMR | P27732. Positions 123-205, 1259-1338, 1644-1672. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P27732. |
Protein family/group databases | |
| TCDB | 1.A.1.11.1. voltage-gated ion channel (VIC) superfamily. |
PTM databases | |
| PhosphoSite | P27732. |
Proteomic databases | |
| PRIDE | P27732. |
Genome annotation databases | |
| Ensembl | ENSRNOT00000048459; ENSRNOP00000043046; ENSRNOG00000013147; Rattus norvegicus. [Genome view] |
| GeneID | 29716. |
| KEGG | rno:29716. |
Organism-specific databases | |
| CTD | 29716. |
| RGD | 70973. Cacna1d. |
Phylogenomic databases | |
| eggNOG | maNOG12879. |
| HOVERGEN | P27732. |
Gene expression databases | |
| ArrayExpress | P27732. |
| Genevestigator | P27732. |
| GermOnline | ENSRNOG00000013147. Rattus norvegicus. |
Family and domain databases | |
| InterPro | IPR011992. EF-hand-like_dom. IPR005821. Ion_trans. IPR005452. LVDCC_a1dsu. IPR014873. VDCC_a1su_IQ. IPR005446. VDCC_L_a1su. IPR002077. VDCCAlpha1. [Graphical view] |
| Gene3D | G3DSA:1.10.238.10. EF-Hand_type. 1 hit. |
| PANTHER | PTHR10037:SF48. LVDCCAlpha1D. 1 hit. |
| Pfam | PF08763. Ca_chan_IQ. 1 hit. PF00520. Ion_trans. 4 hits. [Graphical view] |
| PRINTS | PR00167. CACHANNEL. PR01630. LVDCCALPHA1. PR01636. LVDCCALPHA1D. |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 610169. |
Entry information
| Entry name | CAC1D_RAT | ||||||||
| Accession | Primary (citable) accession number: P27732 Secondary accession number(s): O09022  Q63492 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
