Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

Cacna1s

Organism
Mus musculus (Mouse)
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)DescriptionActionsGraphical viewLength
Sitei292Calcium ion selectivity and permeabilityBy similarity1
Sitei614Calcium ion selectivity and permeabilityBy similarity1
Sitei1014Calcium ion selectivity and permeabilityBy similarity1
Sitei1323Calcium ion selectivity and permeabilityBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi1410 – 1421By similarityAdd BLAST12

GO - Molecular functioni

GO - Biological processi

  • calcium ion transport Source: MGI
  • endoplasmic reticulum organization Source: MGI
  • extraocular skeletal muscle development Source: MGI
  • membrane depolarization during action potential Source: GO_Central
  • muscle cell development Source: MGI
  • muscle contraction Source: MGI
  • myoblast fusion Source: MGI
  • neuromuscular junction development Source: MGI
  • skeletal muscle adaptation Source: MGI
  • skeletal muscle fiber development Source: MGI
  • skeletal muscle tissue development Source: MGI
  • skeletal system development Source: MGI
  • striated muscle contraction Source: MGI
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
Voltage-gated calcium channel subunit alpha Cav1.1
Gene namesi
Name:Cacna1s
Synonyms:Cach1, Cach1b, Cacn1, Cacnl1a3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88294. Cacna1s.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 51CytoplasmicSequence analysisAdd BLAST51
Transmembranei52 – 70Helical; Name=S1 of repeat ISequence analysisAdd BLAST19
Topological domaini71 – 88ExtracellularSequence analysisAdd BLAST18
Transmembranei89 – 108Helical; Name=S2 of repeat ISequence analysisAdd BLAST20
Topological domaini109 – 120CytoplasmicSequence analysisAdd BLAST12
Transmembranei121 – 139Helical; Name=S3 of repeat ISequence analysisAdd BLAST19
Topological domaini140 – 160ExtracellularSequence analysisAdd BLAST21
Transmembranei161 – 179Helical; Name=S4 of repeat ISequence analysisAdd BLAST19
Topological domaini180 – 198CytoplasmicSequence analysisAdd BLAST19
Transmembranei199 – 218Helical; Name=S5 of repeat ISequence analysisAdd BLAST20
Topological domaini219 – 309ExtracellularSequence analysisAdd BLAST91
Transmembranei310 – 334Helical; Name=S6 of repeat ISequence analysisAdd BLAST25
Topological domaini335 – 432CytoplasmicSequence analysisAdd BLAST98
Transmembranei433 – 451Helical; Name=S1 of repeat IISequence analysisAdd BLAST19
Topological domaini452 – 466ExtracellularSequence analysisAdd BLAST15
Transmembranei467 – 486Helical; Name=S2 of repeat IISequence analysisAdd BLAST20
Topological domaini487 – 494CytoplasmicSequence analysis8
Transmembranei495 – 513Helical; Name=S3 of repeat IISequence analysisAdd BLAST19
Topological domaini514 – 523ExtracellularSequence analysis10
Transmembranei524 – 542Helical; Name=S4 of repeat IISequence analysisAdd BLAST19
Topological domaini543 – 561CytoplasmicSequence analysisAdd BLAST19
Transmembranei562 – 581Helical; Name=S5 of repeat IISequence analysisAdd BLAST20
Topological domaini582 – 636ExtracellularSequence analysisAdd BLAST55
Transmembranei637 – 661Helical; Name=S6 of repeat IISequence analysisAdd BLAST25
Topological domaini662 – 799CytoplasmicSequence analysisAdd BLAST138
Transmembranei800 – 818Helical; Name=S1 of repeat IIISequence analysisAdd BLAST19
Topological domaini819 – 834ExtracellularSequence analysisAdd BLAST16
Transmembranei835 – 854Helical; Name=S2 of repeat IIISequence analysisAdd BLAST20
Topological domaini855 – 866CytoplasmicSequence analysisAdd BLAST12
Transmembranei867 – 885Helical; Name=S3 of repeat IIISequence analysisAdd BLAST19
Topological domaini886 – 892ExtracellularSequence analysis7
Transmembranei893 – 911Helical; Name=S4 of repeat IIISequence analysisAdd BLAST19
Topological domaini912 – 930CytoplasmicSequence analysisAdd BLAST19
Transmembranei931 – 950Helical; Name=S5 of repeat IIISequence analysisAdd BLAST20
Topological domaini951 – 1040ExtracellularSequence analysisAdd BLAST90
Transmembranei1041 – 1065Helical; Name=S6 of repeat IIISequence analysisAdd BLAST25
Topological domaini1066 – 1118CytoplasmicSequence analysisAdd BLAST53
Transmembranei1119 – 1137Helical; Name=S1 of repeat IVSequence analysisAdd BLAST19
Topological domaini1138 – 1152ExtracellularSequence analysisAdd BLAST15
Transmembranei1153 – 1172Helical; Name=S2 of repeat IVSequence analysisAdd BLAST20
Topological domaini1173 – 1180CytoplasmicSequence analysis8
Transmembranei1181 – 1199Helical; Name=S3 of repeat IVSequence analysisAdd BLAST19
Topological domaini1200 – 1231ExtracellularSequence analysisAdd BLAST32
Transmembranei1232 – 1250Helical; Name=S4 of repeat IVSequence analysisAdd BLAST19
Topological domaini1251 – 1269CytoplasmicSequence analysisAdd BLAST19
Transmembranei1270 – 1289Helical; Name=S5 of repeat IVSequence analysisAdd BLAST20
Topological domaini1290 – 1356ExtracellularSequence analysisAdd BLAST67
Transmembranei1357 – 1381Helical; Name=S6 of repeat IVSequence analysisAdd BLAST25
Topological domaini1382 – 1880CytoplasmicSequence analysisAdd BLAST499

GO - Cellular componenti

  • cytoplasm Source: MGI
  • I band Source: MGI
  • plasma membrane Source: MGI
  • sarcoplasmic reticulum Source: MGI
  • T-tubule Source: MGI
  • voltage-gated calcium channel complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Defects in Cacna1s are the cause of muscular dysgenesis (MDG), a lethal autosomal recessive disorder in which there is total lack of excitation-contraction coupling in homozygotes, and which results in complete skeletal muscle paralysis. A single nucleotide deletion yields a protein with an altered and truncated C-terminus.

Chemistry databases

GuidetoPHARMACOLOGYi528.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539441 – 1880Voltage-dependent L-type calcium channel subunit alpha-1SAdd BLAST1880

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi79N-linked (GlcNAc...)Sequence analysis1
Glycosylationi257N-linked (GlcNAc...)Sequence analysis1
Modified residuei393PhosphoserineCombined sources1
Modified residuei397PhosphoserineCombined sources1
Modified residuei687Phosphoserine; by PKABy similarity1
Glycosylationi1141N-linked (GlcNAc...)Sequence analysis1
Modified residuei1392Phosphoserine; by PKASequence analysis1
Modified residuei1575PhosphoserineBy similarity1
Modified residuei1579PhosphothreonineBy similarity1
Modified residuei1617PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by PKA activates the calcium channel.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ02789.
PaxDbiQ02789.
PRIDEiQ02789.

PTM databases

iPTMnetiQ02789.
PhosphoSitePlusiQ02789.

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 RYR1 (By similarity). Interacts with DYSF and JSRP1.By similarity3 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000107695.

Structurei

Secondary structure

11880
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi358 – 372Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZW2X-ray1.86B357-374[»]
ProteinModelPortaliQ02789.
SMRiQ02789.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati38 – 337IAdd BLAST300
Repeati418 – 664IIAdd BLAST247
Repeati768 – 1068IIIAdd BLAST301
Repeati1105 – 1384IVAdd BLAST280

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni357 – 374Binding to the beta subunitBy similarityAdd BLAST18
Regioni988 – 1077Dihydropyridine bindingBy similarityAdd BLAST90
Regioni1337 – 1403Dihydropyridine bindingBy similarityAdd BLAST67
Regioni1349 – 1392Phenylalkylamine bindingBy similarityAdd BLAST44

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi562 – 568Poly-Leu7

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.
HOGENOMiHOG000231529.
HOVERGENiHBG050763.
InParanoidiQ02789.
PhylomeDBiQ02789.

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
PANTHERiPTHR10037:SF190. PTHR10037:SF190. 2 hits.
PfamiPF08763. Ca_chan_IQ. 1 hit.
PF16905. GPHH. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]
PRINTSiPR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01634. LVDCCALPHA1S.
SMARTiSM01062. Ca_chan_IQ. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q02789-1) [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
MEPPSPQDEG LRKKQPKKPV PEILPRPPRA LFCLTLQNPL RKACISIVEW
60 70 80 90 100
KPFETIILLT IFANCVALAV YLPMPEDDNN TLNLGLEKLE YFFLIVFSIE
110 120 130 140 150
AAMKIIAYGF LFHQDAYLRS GWNVLDFIIV FLGVFTVILE QVNIIQTNTA
160 170 180 190 200
PMSSKGAGLD VKALRAFRVL RPLRLVSGVP SLQVVLNSIF KAMLPLFHIA
210 220 230 240 250
LLVLFMVIIY AIIGLELFKG KMHKTCYFIG TDIVATVENE KPSPCARTGS
260 270 280 290 300
GRPCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIS MEGWTDVLYW
310 320 330 340 350
VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF
360 370 380 390 400
QKLREKQQLE EDLRGYMSWI TQGEVMDVDD LREGKLSLDE GGSDTESLYE
410 420 430 440 450
IEGLNKIIQF IRHWRQWNRV FRWKCHDLVK SKVFYWLVIL IVALNTLSIA
460 470 480 490 500
SEHHNQPLWL THLQDVANRV LLTLFTIEML MKMYGLGLRQ YFMSIFNRFD
510 520 530 540 550
CFVVCSGILE ILLVESGAMS PLGISVLRCI RLLRLFKITK YWTSLSNLVA
560 570 580 590 600
SLLNSIRSIA SLLLLLFLFI IIFALLGMQL FGGRYDFEDT EVRRSNFDNF
610 620 630 640 650
PQALISVFQV LTGEDWNSVM YNGIMAYGGP TYPGVLVCIY FIILFVCGNY
660 670 680 690 700
ILLNVFLAIA VDNLAEAESL TSAQKAKAEE RKRRKMSKGL PDKSEEERAT
710 720 730 740 750
VTKKLEQKSK GEGIPTTAKL KIDEFESNVN EVKDPYPSAD FPGDDEEDEP
760 770 780 790 800
EIPVSPRPRP LAELQLKEKA VPIPEASSFF IFSPTNKIRV LCHRIVNATW
810 820 830 840 850
FTNFILLFIL LSSAALAAED PIRADSMRNQ ILEYFDYVFT AVFTVEIVLK
860 870 880 890 900
MTTYGAFLHK GSFCRNYFNI LDLLVVAVSL ISMGLESSAI SVVKILRVLR
910 920 930 940 950
VLRPLRAINR AKGLKHVVQC VFVAIRTIGN IVLVTTLLQF MFACIGVQLF
960 970 980 990 1000
KGKFYSCNDL SKMTEEECRG YYYIYKDGDP TQIELRPRQW IHNDFHFDNV
1010 1020 1030 1040 1050
LSAMMSLFTV STFEGWPQLL YKAIDSNEED TGPVYNNRVE MAIFFIIYII
1060 1070 1080 1090 1100
LIAFFMMNIF VGFVIVTFQE QGETEYKNCE LDKNQRQCVQ YALKARPLRC
1110 1120 1130 1140 1150
YIPKNPYQYQ VWYVVTSSYF EYLMFALIML NTICLGMQHY NQSEQMNHIS
1160 1170 1180 1190 1200
DILNVAFTII FTLEMVLKLI AFKPRAYFGD PWNVFDFLIV IGSIIDVILS
1210 1220 1230 1240 1250
EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLVKLLNRA
1260 1270 1280 1290 1300
EGVRTLLWTF IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIAMVDGTQI
1310 1320 1330 1340 1350
NRNNNFQTFP QAVLLLFRCA TGEAWQEILL ACSYGKLCDP ESDYAPGEEH
1360 1370 1380 1390 1400
TCGTNFAYYY FISFYMLCAF LIINLFVAVI MDNFDYLTRD WSILGPHHLD
1410 1420 1430 1440 1450
EFKAIWAEYD PEAKGRIKHL DVVTLLRRIQ PPLGFGKFCP HRVACKRLVG
1460 1470 1480 1490 1500
MNMPLNSDGT VTFNATLFAL VRTALKIKTE GNFEQANEEL RAIIKKIWKR
1510 1520 1530 1540 1550
TSMKLLDQVI PPIGDDEVTV GKFYATFLIQ EHFRKFMKRQ EEYYGYRPKK
1560 1570 1580 1590 1600
DTVQIQAGLR TIEEEAAPEI HRAISGDPTA EEELERAMVE AAMEEGIFRR
1610 1620 1630 1640 1650
TGGLFGQVDN FLERTNSLPP VMANQRPLQF AEIEMEELES PVFLEDFPQN
1660 1670 1680 1690 1700
PGTHPLARAN TNNANANVAY GNSSHRNNPV FSSICYEREF LGEADMPVTR
1710 1720 1730 1740 1750
EGPLSQPCSG SGPHSRSHVD KLKRPMTQRG MPEGQVPPSP CQLSQAEHPV
1760 1770 1780 1790 1800
QKEGKGPTSR FLETPNSRNF EEHVPRNSAH RCTAPATAML IQEALVRGGL
1810 1820 1830 1840 1850
DSLAADANFV MATGQALADA CQMEPEEVEV AATELLKQES PEAGPCLGAL
1860 1870 1880
SLRSSPGPPE SDDWGSQTTL ITPRCEAYTE
Length:1,880
Mass (Da):213,260
Last modified:October 25, 2004 - v2
Checksum:i9D1AD7675218D20E
GO
Isoform 2 (identifier: Q02789-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1204-1222: Missing.

Show »
Length:1,861
Mass (Da):211,502
Checksum:iDBB557BD604810CA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1176A → G in AAA03684 (PubMed:2173707).Curated1
Sequence conflicti1176A → G in AAA63290 (PubMed:2173707).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0504201204 – 1222Missing in isoform 2. 2 PublicationsAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06234 mRNA. Translation: AAB59700.1. Different termination.
M57968 mRNA. Translation: AAA03684.1.
M57976 mRNA. Translation: AAA63290.1.
PIRiA45099.
UniGeneiMm.4418.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06234 mRNA. Translation: AAB59700.1. Different termination.
M57968 mRNA. Translation: AAA03684.1.
M57976 mRNA. Translation: AAA63290.1.
PIRiA45099.
UniGeneiMm.4418.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ZW2X-ray1.86B357-374[»]
ProteinModelPortaliQ02789.
SMRiQ02789.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000107695.

Chemistry databases

GuidetoPHARMACOLOGYi528.

PTM databases

iPTMnetiQ02789.
PhosphoSitePlusiQ02789.

Proteomic databases

MaxQBiQ02789.
PaxDbiQ02789.
PRIDEiQ02789.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:88294. Cacna1s.

Phylogenomic databases

eggNOGiKOG2301. Eukaryota.
ENOG410XNP6. LUCA.
HOGENOMiHOG000231529.
HOVERGENiHBG050763.
InParanoidiQ02789.
PhylomeDBiQ02789.

Miscellaneous databases

PROiQ02789.
SOURCEiSearch...

Family and domain databases

Gene3Di1.20.120.350. 4 hits.
InterProiIPR027359. Channel_four-helix_dom.
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]
PANTHERiPTHR10037:SF190. PTHR10037:SF190. 2 hits.
PfamiPF08763. Ca_chan_IQ. 1 hit.
PF16905. GPHH. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]
PRINTSiPR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01634. LVDCCALPHA1S.
SMARTiSM01062. Ca_chan_IQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCAC1S_MOUSE
AccessioniPrimary (citable) accession number: Q02789
Secondary accession number(s): Q99240
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: October 25, 2004
Last modified: November 2, 2016
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.