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P07293 (CAC1S_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Voltage-dependent L-type calcium channel subunit alpha-1S
Alternative name(s):
Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle
Voltage-gated calcium channel subunit alpha Cav1.1
Gene names
Name:CACNA1S
Synonyms:CACH1, CACNL1A3
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length1873 AA.
Sequence statusComplete.
Protein existenceEvidence 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-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.

Subunit structure

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 By similarity. Interacts with RYR1. Ref.3 Ref.9

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Skeletal muscle specific.

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. Ref.3

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. Ref.3

Post-translational modification

The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690.

Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation by PKA activates the calcium channel. Ref.7 Ref.8

Sequence similarities

Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily. [View classification]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 18731873Voltage-dependent L-type calcium channel subunit alpha-1S
PRO_0000053945

Regions

Topological domain1 – 5151Cytoplasmic Potential
Transmembrane52 – 7019Helical; Name=S1 of repeat I; Potential
Topological domain71 – 8818Extracellular Potential
Transmembrane89 – 10820Helical; Name=S2 of repeat I; Potential
Topological domain109 – 12012Cytoplasmic Potential
Transmembrane121 – 13919Helical; Name=S3 of repeat I; Potential
Topological domain140 – 16021Extracellular Potential
Transmembrane161 – 17919Helical; Name=S4 of repeat I; Potential
Topological domain180 – 19819Cytoplasmic Potential
Transmembrane199 – 21820Helical; Name=S5 of repeat I; Potential
Topological domain219 – 30991Extracellular Potential
Transmembrane310 – 33425Helical; Name=S6 of repeat I; Potential
Topological domain335 – 43298Cytoplasmic Potential
Transmembrane433 – 45119Helical; Name=S1 of repeat II; Potential
Topological domain452 – 46615Extracellular Potential
Transmembrane467 – 48620Helical; Name=S2 of repeat II; Potential
Topological domain487 – 4948Cytoplasmic Potential
Transmembrane495 – 51319Helical; Name=S3 of repeat II; Potential
Topological domain514 – 52310Extracellular Potential
Transmembrane524 – 54219Helical; Name=S4 of repeat II; Potential
Topological domain543 – 56119Cytoplasmic Potential
Transmembrane562 – 58120Helical; Name=S5 of repeat II; Potential
Topological domain582 – 63655Extracellular Potential
Transmembrane637 – 66125Helical; Name=S6 of repeat II; Potential
Topological domain662 – 799138Cytoplasmic Potential
Transmembrane800 – 81819Helical; Name=S1 of repeat III; Potential
Topological domain819 – 83416Extracellular Potential
Transmembrane835 – 85420Helical; Name=S2 of repeat III; Potential
Topological domain855 – 86612Cytoplasmic Potential
Transmembrane867 – 88519Helical; Name=S3 of repeat III; Potential
Topological domain886 – 8927Extracellular Potential
Transmembrane893 – 91119Helical; Name=S4 of repeat III; Potential
Topological domain912 – 93019Cytoplasmic Potential
Transmembrane931 – 95020Helical; Name=S5 of repeat III; Potential
Topological domain951 – 104090Extracellular Potential
Transmembrane1041 – 106525Helical; Name=S6 of repeat III; Potential
Topological domain1066 – 111853Cytoplasmic Potential
Transmembrane1119 – 113719Helical; Name=S1 of repeat IV; Potential
Topological domain1138 – 115215Extracellular Potential
Transmembrane1153 – 117220Helical; Name=S2 of repeat IV; Potential
Topological domain1173 – 11808Cytoplasmic Potential
Transmembrane1181 – 119919Helical; Name=S3 of repeat IV; Potential
Topological domain1200 – 123132Extracellular Potential
Transmembrane1232 – 125019Helical; Name=S4 of repeat IV; Potential
Topological domain1251 – 126919Cytoplasmic Potential
Transmembrane1270 – 128920Helical; Name=S5 of repeat IV; Potential
Topological domain1290 – 135667Extracellular Potential
Transmembrane1357 – 138125Helical; Name=S6 of repeat IV; Potential
Topological domain1382 – 1873492Cytoplasmic Potential
Repeat38 – 337300I
Repeat418 – 664247II
Repeat786 – 1068283III
Repeat1105 – 1384280IV
Calcium binding1410 – 142112 By similarity
Region357 – 37418Binding to the beta subunit
Region988 – 107790Dihydropyridine binding
Region1337 – 140367Dihydropyridine binding
Region1349 – 139143Phenylalkylamine binding
Compositional bias562 – 5687Poly-Leu

Sites

Site2921Calcium ion selectivity and permeability By similarity
Site6141Calcium ion selectivity and permeability By similarity
Site10141Calcium ion selectivity and permeability By similarity
Site13231Calcium ion selectivity and permeability By similarity
Site1690 – 16912Cleavage Probable

Amino acid modifications

Modified residue6871Phosphoserine; by PKA Ref.7
Modified residue13921Phosphoserine; by PKA Potential
Modified residue16171Phosphoserine; by PKA Ref.7
Glycosylation791N-linked (GlcNAc...) Potential
Glycosylation2571N-linked (GlcNAc...) Potential

Natural variations

Natural variant1651R → K.
Natural variant2581G → D.
Natural variant18701P → L.

Experimental info

Sequence conflict6941T → R in AAA31159. Ref.2
Sequence conflict18081T → M in AAA31159. Ref.2
Sequence conflict18151A → V in AAA31159. Ref.2
Sequence conflict18351A → E in AAA31159. Ref.2

Secondary structure

1 ...... 1873
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07293 [UniParc].

Last modified April 1, 1988. Version 1.
Checksum: 047B10D1946B0796

FASTA1,873212,029
        10         20         30         40         50         60 
MEPSSPQDEG LRKKQPKKPL PEVLPRPPRA LFCLTLQNPL RKACISIVEW KPFETIILLT 

        70         80         90        100        110        120 
IFANCVALAV YLPMPEDDNN SLNLGLEKLE YFFLTVFSIE AAMKIIAYGF LFHQDAYLRS 

       130        140        150        160        170        180 
GWNVLDFIIV FLGVFTAILE QVNVIQSNTA PMSSKGAGLD VKALRAFRVL RPLRLVSGVP 

       190        200        210        220        230        240 
SLQVVLNSIF KAMLPLFHIA LLVLFMVIIY AIIGLELFKG KMHKTCYYIG TDIVATVENE 

       250        260        270        280        290        300 
KPSPCARTGS GRPCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIT MEGWTDVLYW 

       310        320        330        340        350        360 
VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF QKLREKQQLE 

       370        380        390        400        410        420 
EDLRGYMSWI TQGEVMDVED LREGKLSLEE GGSDTESLYE IEGLNKIIQF IRHWRQWNRV 

       430        440        450        460        470        480 
FRWKCHDLVK SRVFYWLVIL IVALNTLSIA SEHHNQPLWL THLQDIANRV LLSLFTIEML 

       490        500        510        520        530        540 
LKMYGLGLRQ YFMSIFNRFD CFVVCSGILE LLLVESGAMT PLGISVLRCI RLLRLFKITK 

       550        560        570        580        590        600 
YWTSLSNLVA SLLNSIRSIA SLLLLLFLFI IIFALLGMQL FGGRYDFEDT EVRRSNFDNF 

       610        620        630        640        650        660 
PQALISVFQV LTGEDWNSVM YNGIMAYGGP SYPGVLVCIY FIILFVCGNY ILLNVFLAIA 

       670        680        690        700        710        720 
VDNLAEAESL TSAQKAKAEE RKRRKMSRGL PDKTEEEKSV MAKKLEQKPK GEGIPTTAKL 

       730        740        750        760        770        780 
KVDEFESNVN EVKDPYPSAD FPGDDEEDEP EIPVSPRPRP LAELQLKEKA VPIPEASSFF 

       790        800        810        820        830        840 
IFSPTNKVRV LCHRIVNATW FTNFILLFIL LSSAALAAED PIRAESVRNQ ILGYFDIAFT 

       850        860        870        880        890        900 
SVFTVEIVLK MTTYGAFLHK GSFCRNYFNI LDLLVVAVSL ISMGLESSTI SVVKILRVLR 

       910        920        930        940        950        960 
VLRPLRAINR AKGLKHVVQC VFVAIRTIGN IVLVTTLLQF MFACIGVQLF KGKFFSCNDL 

       970        980        990       1000       1010       1020 
SKMTEEECRG YYYVYKDGDP TQMELRPRQW IHNDFHFDNV LSAMMSLFTV STFEGWPQLL 

      1030       1040       1050       1060       1070       1080 
YRAIDSNEED MGPVYNNRVE MAIFFIIYII LIAFFMMNIF VGFVIVTFQE QGETEYKNCE 

      1090       1100       1110       1120       1130       1140 
LDKNQRQCVQ YALKARPLRC YIPKNPYQYQ VWYVVTSSYF EYLMFALIML NTICLGMQHY 

      1150       1160       1170       1180       1190       1200 
HQSEEMNHIS DILNVAFTII FTLEMILKLL AFKARGYFGD PWNVFDFLIV IGSIIDVILS 

      1210       1220       1230       1240       1250       1260 
EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLIKLLSRA EGVRTLLWTF 

      1270       1280       1290       1300       1310       1320 
IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIALVDGTQI NRNNNFQTFP QAVLLLFRCA 

      1330       1340       1350       1360       1370       1380 
TGEAWQEILL ACSYGKLCDP ESDYAPGEEY TCGTNFAYYY FISFYMLCAF LIINLFVAVI 

      1390       1400       1410       1420       1430       1440 
MDNFDYLTRD WSILGPHHLD EFKAIWAEYD PEAKGRIKHL DVVTLLRRIQ PPLGFGKFCP 

      1450       1460       1470       1480       1490       1500 
HRVACKRLVG MNMPLNSDGT VTFNATLFAL VRTALKIKTE GNFEQANEEL RAIIKKIWKR 

      1510       1520       1530       1540       1550       1560 
TSMKLLDQVI PPIGDDEVTV GKFYATFLIQ EHFRKFMKRQ EEYYGYRPKK DTVQIQAGLR 

      1570       1580       1590       1600       1610       1620 
TIEEEAAPEI RRTISGDLTA EEELERAMVE AAMEERIFRR TGGLFGQVDT FLERTNSLPP 

      1630       1640       1650       1660       1670       1680 
VMANQRPLQF AEIEMEELES PVFLEDFPQD ARTNPLARAN TNNANANVAY GNSNHSNNQM 

      1690       1700       1710       1720       1730       1740 
FSSVHCEREF PGEAETPAAG RGALSHSHRA LGPHSKPCAG KLNGQLVQPG MPINQAPPAP 

      1750       1760       1770       1780       1790       1800 
CQQPSTDPPE RGQRRTSLTG SLQDEAPQRR SSEGSTPRRP APATALLIQE ALVRGGLDTL 

      1810       1820       1830       1840       1850       1860 
AADAGFVTAT SQALADACQM EPEEVEVAAT ELLKARESVQ GMASVPGSLS RRSSLGSLDQ 

      1870 
VQGSQETLIP PRP

« Hide

References

[1]"Primary structure of the receptor for calcium channel blockers from skeletal muscle."
Tanabe T., Takeshima H., Mikami A., Flockerzi V., Takahashi H., Kangawa K., Kojima M., Matsuo H., Hirose T., Numa S.
Nature 328:313-318(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Skeletal muscle.
[2]"Sequence and expression of mRNAs encoding the alpha 1 and alpha 2 subunits of a DHP-sensitive calcium channel."
Ellis S.B., Williams M.E., Ways N.R., Brenner R., Sharp A.H., Leung A.T., Campbell K.P., McKenna E., Koch W.J., Hui A., Schwartz A., Harpold M.M.
Science 241:1661-1664(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[3]"Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit."
Pragnell M., de Waard M., Mori Y., Tanabe T., Snutch T.P., Campbell K.P.
Nature 368:67-70(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: BETA-SUBUNIT BINDING DOMAIN.
[4]"Identification of a phenylalkylamine binding region within the alpha 1 subunit of skeletal muscle Ca2+ channels."
Striessnig J., Glossmann H., Catterall W.A.
Proc. Natl. Acad. Sci. U.S.A. 87:9108-9112(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PHENYLALKYLAMINE-BINDING SITE.
[5]"Identification of 1,4-dihydropyridine binding regions within the alpha 1 subunit of skeletal muscle Ca2+ channels by photoaffinity labeling with diazipine."
Nakayama H., Taki M., Striessnig J., Glossmann H., Catterall W.A., Kanaoka Y.
Proc. Natl. Acad. Sci. U.S.A. 88:9203-9207(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DIHYDROPYRIDINE-BINDING SITE.
[6]"Dihydropyridine receptor of L-type Ca2+ channels: identification of binding domains for [3H](+)-PN200-110 and [3H]azidopine within the alpha 1 subunit."
Striessnig J., Murphy B.J., Catterall W.A.
Proc. Natl. Acad. Sci. U.S.A. 88:10769-10773(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DIHYDROPYRIDINE-BINDING SITE.
[7]"CAMP-dependent protein kinase rapidly phosphorylates serine-687 of the skeletal muscle receptor for calcium channel blockers."
Roehrkasten A., Meyer H.E., Nastainczyk W., Sieber M., Hofmann F.
J. Biol. Chem. 263:15325-15329(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-687 AND SER-1617.
[8]"Activation of purified calcium channels by stoichiometric protein phosphorylation."
Nunoki K., Florio V., Catterall W.A.
Proc. Natl. Acad. Sci. U.S.A. 86:6816-6820(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKA.
[9]"Activation and inhibition of skeletal RyR channels by a part of the skeletal DHPR II-III loop: effects of DHPR Ser687 and FKBP12."
Dulhunty A.F., Laver D.R., Gallant E.M., Casarotto M.G., Pace S.M., Curtis S.
Biophys. J. 77:189-203(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RYR1.
[10]"A structural requirement for activation of skeletal ryanodine receptors by peptides of the dihydropyridine receptor II-III loop."
Casarotto M.G., Gibson F., Pace S.M., Curtis S.M., Mulcair M., Dulhunty A.F.
J. Biol. Chem. 275:11631-11637(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 671-690.
[11]"Structural analysis of the voltage-dependent calcium channel beta subunit functional core and its complex with the alpha1 interaction domain."
Opatowsky Y., Chen C.-C., Campbell K.P., Hirsch J.A.
Neuron 42:387-399(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 34-415 IN COMPLEX WITH CACNB2.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X05921 mRNA. Translation: CAA29355.1.
M23919 mRNA. Translation: AAA31159.1.
PIRA30063.
RefSeqNP_001095190.1. NM_001101720.1.
UniGeneOcu.1826.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DU1NMR-A671-690[»]
1T3LX-ray2.20B357-374[»]
DisProtDP00228.
DP00440.
ProteinModelPortalP07293.
SMRP07293. Positions 1517-1543.
ModBaseSearch...

Protein-protein interaction databases

MINTMINT-8146707.
STRING9986.ENSOCUP00000003147.

Protein family/group databases

TCDB1.A.1.11.2. voltage-gated ion channel (VIC) superfamily.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009585.

Organism-specific databases

CTD779.

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000231529.
HOVERGENHBG050763.
OrthoDBEOG45755Q.

Family and domain databases

Gene3D1.20.120.350. 4 hits.
InterProIPR005821. Ion_trans_dom.
IPR027359. K_channel_four-helix_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
PANTHERPTHR10037:SF105. PTHR10037:SF105. 1 hit.
PfamPF08763. Ca_chan_IQ. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]
PRINTSPR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01634. LVDCCALPHA1S.
SMARTSM01062. Ca_chan_IQ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChEMBLCHEMBL4169.
EvolutionaryTraceP07293.

Entry information

Entry nameCAC1S_RABIT
AccessionPrimary (citable) accession number: P07293
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: May 29, 2013
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Recent format changes

Overview of recent format changes

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents