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Protein

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

Gene

Cacna1s

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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-1S 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). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei301 – 3011Calcium ion selectivity and permeabilityBy similarity
Sitei610 – 6101Calcium ion selectivity and permeabilityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi697 – 70812By similarityAdd
BLAST

GO - Molecular functioni

  • high voltage-gated calcium channel activity Source: RGD
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • calcium ion transport Source: RGD
  • membrane depolarization during action potential Source: GO_Central
  • ossification Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel, Voltage-gated channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Voltage-dependent L-type calcium channel subunit alpha-1S
Alternative name(s):
Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle
ROB1
Voltage-gated calcium channel subunit alpha Cav1.1
Gene namesi
Name:Cacna1s
Synonyms:Cach1, Cacn1, Cacnl1a3, Cchl1a3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi70983. Cacna1s.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini‹1 – 86›86CytoplasmicSequence analysisAdd
BLAST
Transmembranei87 – 10519Helical; Name=S1 of repeat IIISequence analysisAdd
BLAST
Topological domaini106 – 12116ExtracellularSequence analysisAdd
BLAST
Transmembranei122 – 14120Helical; Name=S2 of repeat IIISequence analysisAdd
BLAST
Topological domaini142 – 15312CytoplasmicSequence analysisAdd
BLAST
Transmembranei154 – 17219Helical; Name=S3 of repeat IIISequence analysisAdd
BLAST
Topological domaini173 – 1797ExtracellularSequence analysis
Transmembranei180 – 19819Helical; Name=S4 of repeat IIISequence analysisAdd
BLAST
Topological domaini199 – 21719CytoplasmicSequence analysisAdd
BLAST
Transmembranei218 – 23720Helical; Name=S5 of repeat IIISequence analysisAdd
BLAST
Topological domaini238 – 32790ExtracellularSequence analysisAdd
BLAST
Transmembranei328 – 35225Helical; Name=S6 of repeat IIISequence analysisAdd
BLAST
Topological domaini353 – 40553CytoplasmicSequence analysisAdd
BLAST
Transmembranei406 – 42419Helical; Name=S1 of repeat IVSequence analysisAdd
BLAST
Topological domaini425 – 43915ExtracellularSequence analysisAdd
BLAST
Transmembranei440 – 45920Helical; Name=S2 of repeat IVSequence analysisAdd
BLAST
Topological domaini460 – 4678CytoplasmicSequence analysis
Transmembranei468 – 48619Helical; Name=S3 of repeat IVSequence analysisAdd
BLAST
Topological domaini487 – 51832ExtracellularSequence analysisAdd
BLAST
Transmembranei519 – 53719Helical; Name=S4 of repeat IVSequence analysisAdd
BLAST
Topological domaini538 – 55619CytoplasmicSequence analysisAdd
BLAST
Transmembranei557 – 57620Helical; Name=S5 of repeat IVSequence analysisAdd
BLAST
Topological domaini577 – 64367ExtracellularSequence analysisAdd
BLAST
Transmembranei644 – 66825Helical; Name=S6 of repeat IVSequence analysisAdd
BLAST
Topological domaini669 – 1146478CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • sarcolemma Source: RGD
  • voltage-gated calcium channel complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2095177.
GuidetoPHARMACOLOGYi528.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 1146›1146Voltage-dependent L-type calcium channel subunit alpha-1SPRO_0000053946Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi428 – 4281N-linked (GlcNAc...)Sequence analysis
Modified residuei679 – 6791Phosphoserine; by PKASequence analysis
Modified residuei862 – 8621PhosphoserineCombined sources
Modified residuei866 – 8661PhosphothreonineCombined sources
Modified residuei904 – 9041PhosphoserineCombined sources

Post-translational modificationi

Phosphorylation by PKA stimulates the calcium channel function.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ02485.
PRIDEiQ02485.

PTM databases

iPTMnetiQ02485.

Expressioni

Tissue specificityi

Skeletal muscle specific.

Interactioni

Subunit structurei

Multisubunit complex 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. An additional gamma subunit is present only in skeletal muscle L-type channel. Interacts with DYSF and JSRP1. Interacts with RYR1 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067264.

Chemistry

BindingDBiQ02485.

Structurei

3D structure databases

ProteinModelPortaliQ02485.
SMRiQ02485. Positions 804-830.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati73 – 355283IIIAdd
BLAST
Repeati392 – 671280IVAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni275 – 36490Dihydropyridine bindingBy similarityAdd
BLAST
Regioni624 – 69067Dihydropyridine bindingBy similarityAdd
BLAST
Regioni636 – 67944Phenylalkylamine bindingBy similarityAdd
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.
The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction.

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
HOVERGENiHBG050763.
InParanoidiQ02485.

Family and domain databases

Gene3Di1.20.120.350. 2 hits.
InterProiIPR031688. CAC1F_C.
IPR027359. Channel_four-helix_dom.
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
[Graphical view]
PANTHERiPTHR10037:SF190. PTHR10037:SF190. 2 hits.
PfamiPF08763. Ca_chan_IQ. 1 hit.
PF16885. CAC1F_C. 1 hit.
PF16905. GPHH. 1 hit.
PF00520. Ion_trans. 2 hits.
[Graphical view]
SMARTiSM01062. Ca_chan_IQ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Fragment.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q02485-1) [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

        10         20         30         40         50
VPTTAKLKID EFESNVNEVK DPYPSADFPG DDEEDEPEIP ASPRPRPLAE
60 70 80 90 100
LQLKEKAVPI PEASSFFIFS PTNKIRVLCH RIVNATWFTN FILLFILLSS
110 120 130 140 150
AALAAEDPIR ADSMRNQILE YFDYVFTAVF TVEIVLKMTT YGAFLHKGSF
160 170 180 190 200
CRNYFNILDL LVVAVSLISM GLESSAISVV KILRVLRVLR PLRAINRAKG
210 220 230 240 250
LKHVVQCVFV AIRTIGNIVL VTTLLQFMFA CIGVQLFKGK FYSCNDLSKM
260 270 280 290 300
TEEECRGYYY IYKDGDPTQI ELRPRQWIHN DFHFDNVLSA MMSLFTVSTF
310 320 330 340 350
EGWPQLLYKA IDSNEEDTGP VYNNRVEMAI FFIIYIILIA FFMMNIFVGF
360 370 380 390 400
VIVTFQEQGE TEYKNCELDK NQRQCVQYAL KARPLRCYIP KNPYQYQVWY
410 420 430 440 450
VVTSSYFEYL MFALIMLNTI CLGMQHYNQS EQMNHISDIL NVAFTIIFTL
460 470 480 490 500
EMILKLIAFK PRGYFGDPWN VFDFLIVIGS IIDVILSEID TLLASSGGLY
510 520 530 540 550
CLGGGCGNVD PDESARISSA FFRLFRVMRL IKLLSRAEGV RTLLWTFIKS
560 570 580 590 600
FQALPYVALL IVMLFFIYAV IGMQMFGKIA MVDGTQINRN NNFQTFPQAV
610 620 630 640 650
LLLFRCATGE AWQEILLACS YGKRCDPESD YAPGEEYACG TNFAYYYFIS
660 670 680 690 700
FYMLCAFLII NLFVAVIMDN FDYLTRDWSI LGPHHLDEFK AIWAEYDPEA
710 720 730 740 750
KGRIKHLDVV TLLRRIQPPL GFGKFCPHRV ACKRLVGMNM PLNSDGTVTF
760 770 780 790 800
NATLFALVRT ALKIKTEGNF EQANEELRAI IKKIWKRTSM KLLDQVIPPI
810 820 830 840 850
GDDEVTVGKF YATFLIQEHF RKFMKRQEEY YGYRPKKDTV QIQAGLRTIE
860 870 880 890 900
EEAAPEIHRA ISGDLTAEEE LERAMVEAAM EEGIFRRTGG LFGQVDNFLE
910 920 930 940 950
RTNSLPPVMA NQRPLQFAEM EMEELESPVF LEDFPQNPGT HPLARANTNN
960 970 980 990 1000
ANANVAYGNS SHRNSPVFSS IRYERELLEE AGRPVTREGP FSQPCSVSGV
1010 1020 1030 1040 1050
NSRSHVDKLE RQMSQRRMPK GQVPPSPCQL SQEKHPVHEE GKGPRSWSTE
1060 1070 1080 1090 1100
TSDSESFEER VPRNSAHKCT APATTMLIQE ALVRGGLDSL AADANFVMAT
1110 1120 1130 1140
GQALADACQM EPEEVEVAAT ELLKRESPKG GPCPGSLEPK VLPWAA
Length:1,146
Mass (Da):130,144
Last modified:November 1, 1996 - v1
Checksum:i4BBE944261BE1A95
GO
Isoform ROB1 (identifier: Q02485-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-509: Missing.

Show »
Length:1,127
Mass (Da):128,420
Checksum:iCC15C2D5A53754D4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Sequence conflicti548 – 5481I → T in AAA89158 (PubMed:7479909).Curated
Sequence conflicti610 – 6101E → A in AAA89158 (PubMed:7479909).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei491 – 50919Missing in isoform ROB1. 1 PublicationVSP_000939Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L04684 mRNA. Translation: AAA40844.1.
M99220 mRNA. Translation: AAA40894.1.
U31816 mRNA. Translation: AAA89158.1.
PIRiA46422.
UniGeneiRn.10738.
Rn.220579.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L04684 mRNA. Translation: AAA40844.1.
M99220 mRNA. Translation: AAA40894.1.
U31816 mRNA. Translation: AAA89158.1.
PIRiA46422.
UniGeneiRn.10738.
Rn.220579.

3D structure databases

ProteinModelPortaliQ02485.
SMRiQ02485. Positions 804-830.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067264.

Chemistry

BindingDBiQ02485.
ChEMBLiCHEMBL2095177.
GuidetoPHARMACOLOGYi528.

PTM databases

iPTMnetiQ02485.

Proteomic databases

PaxDbiQ02485.
PRIDEiQ02485.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi70983. Cacna1s.

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
HOVERGENiHBG050763.
InParanoidiQ02485.

Family and domain databases

Gene3Di1.20.120.350. 2 hits.
InterProiIPR031688. CAC1F_C.
IPR027359. Channel_four-helix_dom.
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
[Graphical view]
PANTHERiPTHR10037:SF190. PTHR10037:SF190. 2 hits.
PfamiPF08763. Ca_chan_IQ. 1 hit.
PF16885. CAC1F_C. 1 hit.
PF16905. GPHH. 1 hit.
PF00520. Ion_trans. 2 hits.
[Graphical view]
SMARTiSM01062. Ca_chan_IQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The gene for the alpha-1 subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (Cchl1a3) maps to mouse chromosome 1."
    Chin H., Krall M., Kim H.-L., Kozak C.A., Mock B.A.
    Genomics 14:1089-1091(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 597-691.
    Tissue: Kidney.
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 359-658 (ISOFORM ROB1).
    Tissue: Osteosarcoma.
  4. "Cyclic AMP-dependent phosphorylation of two size forms of alpha 1 subunits of L-type calcium channels in rat skeletal muscle cells."
    Lai Y., Seagar M.J., Takahashi M., Catterall W.A.
    J. Biol. Chem. 265:20839-20848(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY PKA.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-862; THR-866 AND SER-904, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiCAC1S_RAT
AccessioniPrimary (citable) accession number: Q02485
Secondary accession number(s): P70484, Q01553, Q62817
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: July 6, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.