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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

Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca2+ release from the sarcplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.By similarity

Enzyme regulationi

Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). It is however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi292CalciumBy similarity1
Metal bindingi614CalciumBy similarity1
Metal bindingi1014CalciumBy similarity1

Regions

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

GO - Molecular functioni

GO - Biological processi

  • calcium ion transport Source: MGI
  • cellular response to caffeine Source: UniProtKB
  • 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

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, 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
Dihydropyridine receptor2 Publications
Short name:
DHPRCurated
Voltage-gated calcium channel subunit alpha Cav1.1
Gene namesi
Name:Cacna1s
Synonyms:Cach1, Cach1b, Cacn1, Cacnl1a3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88294. Cacna1s.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 51CytoplasmicCuratedAdd BLAST51
Transmembranei52 – 70Helical; Name=S1 of repeat IBy similarityAdd BLAST19
Topological domaini71 – 85ExtracellularCuratedAdd BLAST15
Transmembranei86 – 106Helical; Name=S2 of repeat IBy similarityAdd BLAST21
Topological domaini107 – 115CytoplasmicCurated9
Transmembranei116 – 136Helical; Name=S3 of repeat IBy similarityAdd BLAST21
Topological domaini137 – 160ExtracellularCuratedAdd BLAST24
Transmembranei161 – 179Helical; Name=S4 of repeat IBy similarityAdd BLAST19
Topological domaini180 – 196CytoplasmicCuratedAdd BLAST17
Transmembranei197 – 218Helical; Name=S5 of repeat IBy similarityAdd BLAST22
Topological domaini219 – 279ExtracellularCuratedAdd BLAST61
Intramembranei280 – 301Pore-formingBy similarityAdd BLAST22
Topological domaini302 – 309ExtracellularCurated8
Transmembranei310 – 330Helical; Name=S6 of repeat IBy similarityAdd BLAST21
Topological domaini331 – 432CytoplasmicCuratedAdd BLAST102
Transmembranei433 – 451Helical; Name=S1 of repeat IIBy similarityAdd BLAST19
Topological domaini452 – 462ExtracellularCuratedAdd BLAST11
Transmembranei463 – 483Helical; Name=S2 of repeat IIBy similarityAdd BLAST21
Topological domaini484 – 494CytoplasmicCuratedAdd BLAST11
Transmembranei495 – 514Helical; Name=S3 of repeat IIBy similarityAdd BLAST20
Topological domaini515 – 523ExtracellularCurated9
Transmembranei524 – 542Helical; Name=S4 of repeat IIBy similarityAdd BLAST19
Topological domaini543 – 561CytoplasmicCuratedAdd BLAST19
Transmembranei562 – 581Helical; Name=S5 of repeat IIBy similarityAdd BLAST20
Topological domaini582 – 601ExtracellularCuratedAdd BLAST20
Intramembranei602 – 623Pore-formingBy similarityAdd BLAST22
Topological domaini624 – 633ExtracellularCurated10
Transmembranei634 – 653Helical; Name=S6 of repeat IIBy similarityAdd BLAST20
Topological domaini654 – 799CytoplasmicCuratedAdd BLAST146
Transmembranei800 – 818Helical; Name=S1 of repeat IIIBy similarityAdd BLAST19
Topological domaini819 – 830ExtracellularCuratedAdd BLAST12
Transmembranei831 – 850Helical; Name=S2 of repeat IIIBy similarityAdd BLAST20
Topological domaini851 – 866CytoplasmicCuratedAdd BLAST16
Transmembranei867 – 885Helical; Name=S3 of repeat IIIBy similarityAdd BLAST19
Topological domaini886 – 892ExtracellularCurated7
Transmembranei893 – 911Helical; Name=S4 of repeat IIIBy similarityAdd BLAST19
Topological domaini912 – 930CytoplasmicCuratedAdd BLAST19
Transmembranei931 – 950Helical; Name=S5 of repeat IIIBy similarityAdd BLAST20
Topological domaini951 – 1000ExtracellularCuratedAdd BLAST50
Intramembranei1001 – 1021Pore-formingBy similarityAdd BLAST21
Topological domaini1022 – 1038ExtracellularCuratedAdd BLAST17
Transmembranei1039 – 1060Helical; Name=S6 of repeat IIIBy similarityAdd BLAST22
Topological domaini1061 – 1118CytoplasmicCuratedAdd BLAST58
Transmembranei1119 – 1140Helical; Name=S1 of repeat IVBy similarityAdd BLAST22
Topological domaini1141 – 1148ExtracellularCurated8
Transmembranei1149 – 1170Helical; Name=S2 of repeat IVBy similarityAdd BLAST22
Topological domaini1171 – 1180CytoplasmicCurated10
Transmembranei1181 – 1200Helical; Name=S3 of repeat IVBy similarityAdd BLAST20
Topological domaini1201 – 1231ExtracellularCuratedAdd BLAST31
Transmembranei1232 – 1250Helical; Name=S4 of repeat IVBy similarityAdd BLAST19
Topological domaini1251 – 1268CytoplasmicCuratedAdd BLAST18
Transmembranei1269 – 1289Helical; Name=S5 of repeat IVBy similarityAdd BLAST21
Topological domaini1290 – 1311ExtracellularCuratedAdd BLAST22
Intramembranei1312 – 1330Pore-formingBy similarityAdd BLAST19
Topological domaini1331 – 1356ExtracellularCuratedAdd BLAST26
Transmembranei1357 – 1381Helical; Name=S6 of repeat IVBy similarityAdd BLAST25
Topological domaini1382 – 1880CytoplasmicCuratedAdd BLAST499

Keywords - Cellular componenti

Cell membrane, 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.1 Publication

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...) asparagineSequence analysis1
Disulfide bondi226 ↔ 254By similarity
Disulfide bondi245 ↔ 261By similarity
Glycosylationi257N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei393PhosphoserineCombined sources1
Modified residuei397PhosphoserineCombined sources1
Modified residuei687Phosphoserine; by PKABy similarity1
Disulfide bondi957 ↔ 968By similarity
Glycosylationi1141N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1338 ↔ 1352By similarity
Modified residuei1392Phosphoserine; by PKASequence analysis1
Modified residuei1575PhosphoserineBy similarity1
Modified residuei1579PhosphothreonineBy similarity1
Modified residuei1617PhosphoserineBy similarity1

Post-translational modificationi

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.By similarity
Both the minor and major forms are phosphorylated in vitro by PKA. 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

Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (Ref. 7). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (PubMed:12871958, PubMed:16550931, PubMed:16638807). Interacts with RYR1 (By similarity). Interacts with CALM (By similarity).By similarity4 Publications

GO - Molecular functioni

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 – 337ICuratedAdd BLAST300
Repeati418 – 664IICuratedAdd BLAST247
Repeati768 – 1068IIICuratedAdd BLAST301
Repeati1105 – 1384IVCuratedAdd BLAST280

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni357 – 374Binding to the beta subunit1 PublicationAdd BLAST18
Regioni988 – 1077Dihydropyridine bindingBy similarityAdd BLAST90
Regioni1337 – 1403Dihydropyridine bindingBy similarityAdd BLAST67
Regioni1349 – 1392Phenylalkylamine bindingBy similarityAdd BLAST44
Regioni1349 – 1391Phenylalkylamine bindingBy similarityAdd BLAST43
Regioni1522 – 1542Interaction with calmodulinBy similarityAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi290 – 293Selectivity filter of repeat IBy similarity4
Motifi612 – 615Selectivity filter of repeat IIBy similarity4
Motifi1012 – 1015Selectivity filter of repeat IIIBy similarity4
Motifi1321 – 1324Selectivity filter of repeat IVBy similarity4

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.By similarity
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.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
PANTHERiPTHR10037:SF190. PTHR10037:SF190. 1 hit.
PfamiView protein in Pfam
PF08763. Ca_chan_IQ. 1 hit.
PF16905. GPHH. 1 hit.
PF00520. Ion_trans. 4 hits.
PRINTSiPR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01634. LVDCCALPHA1S.
SMARTiView protein in SMART
SM01062. Ca_chan_IQ. 1 hit.

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

Similar proteinsi

Entry informationi

Entry nameiCAC1S_MOUSE
AccessioniPrimary (citable) accession number: Q02789
Secondary accession number(s): Q99240
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: October 25, 2004
Last modified: October 25, 2017
This is version 139 of the entry and version 2 of the sequence. See 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