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Protein

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

Gene

CACNA1S

Organism
Oryctolagus cuniculus (Rabbit)
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 (PubMed:9465115, PubMed:15201141). 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 (PubMed:9465115 PubMed:15201141). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.Curated2 Publications

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).4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi292CalciumCombined sources1 Publication1
Metal bindingi614CalciumCombined sources1 Publication1
Metal bindingi1014CalciumCombined sources1 Publication1

Regions

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

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB-KW
  • ion channel binding Source: CAFA
  • metal ion binding Source: UniProtKB-KW
  • voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  • calcium ion transmembrane transport Source: UniProtKB
  • cellular response to caffeine Source: UniProtKB
  • regulation of ryanodine-sensitive calcium-release channel activity Source: CAFA

Keywordsi

Molecular functionCalcium channel, Calmodulin-binding, Ion channel, Voltage-gated channel
Biological processCalcium transport, Ion transport, Transport
LigandCalcium, Metal-binding

Protein family/group databases

TCDBi1.A.1.11.2. the voltage-gated ion channel (vic) superfamily.

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 receptor alpha-1S subunit3 Publications
Short name:
DHPR2 Publications
Voltage-gated calcium channel subunit alpha Cav1.1
Gene namesi
Name:CACNA1S
Synonyms:CACH1, CACNL1A3
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

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 – 51Cytoplasmic1 PublicationAdd BLAST51
Transmembranei52 – 70Helical; Name=S1 of repeat I1 PublicationAdd BLAST19
Topological domaini71 – 85Extracellular1 PublicationAdd BLAST15
Transmembranei86 – 106Helical; Name=S2 of repeat I1 PublicationAdd BLAST21
Topological domaini107 – 115Cytoplasmic1 Publication9
Transmembranei116 – 136Helical; Name=S3 of repeat I1 PublicationAdd BLAST21
Topological domaini137 – 160Extracellular1 PublicationAdd BLAST24
Transmembranei161 – 179Helical; Name=S4 of repeat I1 PublicationAdd BLAST19
Topological domaini180 – 196Cytoplasmic1 PublicationAdd BLAST17
Transmembranei197 – 218Helical; Name=S5 of repeat I1 PublicationAdd BLAST22
Topological domaini219 – 279Extracellular1 PublicationAdd BLAST61
Intramembranei280 – 301Pore-forming2 PublicationsAdd BLAST22
Topological domaini302 – 309Extracellular1 Publication8
Transmembranei310 – 330Helical; Name=S6 of repeat I1 PublicationAdd BLAST21
Topological domaini331 – 432Cytoplasmic1 PublicationAdd BLAST102
Transmembranei433 – 451Helical; Name=S1 of repeat II1 PublicationAdd BLAST19
Topological domaini452 – 462Extracellular1 PublicationAdd BLAST11
Transmembranei463 – 483Helical; Name=S2 of repeat II1 PublicationAdd BLAST21
Topological domaini484 – 494Cytoplasmic1 PublicationAdd BLAST11
Transmembranei495 – 514Helical; Name=S3 of repeat II1 PublicationAdd BLAST20
Topological domaini515 – 523Extracellular1 Publication9
Transmembranei524 – 542Helical; Name=S4 of repeat II1 PublicationAdd BLAST19
Topological domaini543 – 561Cytoplasmic1 PublicationAdd BLAST19
Transmembranei562 – 581Helical; Name=S5 of repeat II1 PublicationAdd BLAST20
Topological domaini582 – 601Extracellular1 PublicationAdd BLAST20
Intramembranei602 – 623Pore-forming2 PublicationsAdd BLAST22
Topological domaini624 – 633Extracellular1 Publication10
Transmembranei634 – 653Helical; Name=S6 of repeat II1 PublicationAdd BLAST20
Topological domaini654 – 799Cytoplasmic1 PublicationAdd BLAST146
Transmembranei800 – 818Helical; Name=S1 of repeat III1 PublicationAdd BLAST19
Topological domaini819 – 830Extracellular1 PublicationAdd BLAST12
Transmembranei831 – 850Helical; Name=S2 of repeat III1 PublicationAdd BLAST20
Topological domaini851 – 866Cytoplasmic1 PublicationAdd BLAST16
Transmembranei867 – 885Helical; Name=S3 of repeat III1 PublicationAdd BLAST19
Topological domaini886 – 892Extracellular1 Publication7
Transmembranei893 – 911Helical; Name=S4 of repeat III1 PublicationAdd BLAST19
Topological domaini912 – 930Cytoplasmic1 PublicationAdd BLAST19
Transmembranei931 – 950Helical; Name=S5 of repeat III1 PublicationAdd BLAST20
Topological domaini951 – 1000Extracellular1 PublicationAdd BLAST50
Intramembranei1001 – 1021Pore-forming2 PublicationsAdd BLAST21
Topological domaini1022 – 1038Extracellular1 PublicationAdd BLAST17
Transmembranei1039 – 1060Helical; Name=S6 of repeat III1 PublicationAdd BLAST22
Topological domaini1061 – 1118Cytoplasmic1 PublicationAdd BLAST58
Transmembranei1119 – 1140Helical; Name=S1 of repeat IV1 PublicationAdd BLAST22
Topological domaini1141 – 1148Extracellular1 Publication8
Transmembranei1149 – 1170Helical; Name=S2 of repeat IV1 PublicationAdd BLAST22
Topological domaini1171 – 1180Cytoplasmic1 Publication10
Transmembranei1181 – 1200Helical; Name=S3 of repeat IV1 PublicationAdd BLAST20
Topological domaini1201 – 1231Extracellular1 PublicationAdd BLAST31
Transmembranei1232 – 1250Helical; Name=S4 of repeat IV1 PublicationAdd BLAST19
Topological domaini1251 – 1268Cytoplasmic1 PublicationAdd BLAST18
Transmembranei1269 – 1289Helical; Name=S5 of repeat IV1 PublicationAdd BLAST21
Topological domaini1290 – 1311Extracellular1 PublicationAdd BLAST22
Intramembranei1312 – 1330Pore-forming2 PublicationsAdd BLAST19
Topological domaini1331 – 1356Extracellular1 PublicationAdd BLAST26
Transmembranei1357 – 1381Helical; Name=S6 of repeat IV1 PublicationAdd BLAST25
Topological domaini1382 – 1873Cytoplasmic1 PublicationAdd BLAST492

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1086R → H: Shifts the threshold potential to more negative values and lowers the concentration threshold for channel activation by caffeine. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4169.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539451 – 1873Voltage-dependent L-type calcium channel subunit alpha-1SAdd BLAST1873

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi79N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi226 ↔ 254Combined sources1 Publication
Disulfide bondi245 ↔ 261Combined sources1 Publication
Glycosylationi257N-linked (GlcNAc...) asparagineCombined sources1
Modified residuei393PhosphoserineBy similarity1
Modified residuei397PhosphoserineBy similarity1
Modified residuei687Phosphoserine; by PKA1 Publication1
Disulfide bondi957 ↔ 968Combined sources1 Publication
Disulfide bondi1338 ↔ 1352Combined sources1 Publication
Modified residuei1392Phosphoserine; by PKASequence analysis1
Modified residuei1575PhosphoserineBy similarity1
Modified residuei1579PhosphothreonineBy similarity1
Modified residuei1617Phosphoserine; by PKA1 Publication1

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-1690.1 Publication
Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation by PKA activates the calcium channel.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1690 – 1691CleavageCurated2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP07293.

PTM databases

iPTMnetiP07293.
SwissPalmiP07293.

Expressioni

Tissue specificityi

Detected in skeletal muscle T-tubules (at protein level).4 Publications

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 (PubMed:3037387, PubMed:15134636, PubMed:25667046, PubMed:26680202, PubMed:27580036). 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 (PubMed:15134636, PubMed:25667046, PubMed:26680202, PubMed:27580036). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (By similarity). Interacts with RYR1 (PubMed:10388749). Interacts with CALM (By similarity).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PASKQ96RG22EBI-8613624,EBI-1042651From Homo sapiens.

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB-KW
  • ion channel binding Source: CAFA

Protein-protein interaction databases

DIPiDIP-61879N.
IntActiP07293. 4 interactors.
MINTiMINT-8146707.

Structurei

Secondary structure

11873
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi359 – 372Combined sources14
Helixi672 – 677Combined sources6
Turni678 – 681Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DU1NMR-A671-690[»]
1JZPNMR-A671-690[»]
1T3LX-ray2.20B357-374[»]
3JBRelectron microscopy4.20A1-1395[»]
A1521-1873[»]
5GJVelectron microscopy3.60A1-1873[»]
5GJWelectron microscopy3.90A1-1873[»]
DisProtiDP00228.
ProteinModelPortaliP07293.
SMRiP07293.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07293.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati38 – 337ICuratedAdd BLAST300
Repeati418 – 664IICuratedAdd BLAST247
Repeati786 – 1068IIICuratedAdd BLAST283
Repeati1105 – 1384IVCuratedAdd BLAST280

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni357 – 374Binding to the beta subunit1 PublicationAdd BLAST18
Regioni988 – 1077Dihydropyridine binding2 PublicationsAdd BLAST90
Regioni1337 – 1403Dihydropyridine binding1 PublicationAdd BLAST67
Regioni1349 – 1391Phenylalkylamine binding1 PublicationAdd BLAST43
Regioni1522 – 1542Interaction with calmodulinBy similarityAdd BLAST21

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi290 – 293Selectivity filter of repeat I2 Publications4
Motifi612 – 615Selectivity filter of repeat II2 Publications4
Motifi1012 – 1015Selectivity filter of repeat III2 Publications4
Motifi1321 – 1324Selectivity filter of repeat IV2 Publications4

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.2 Publications
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.3 Publications

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000231529.
HOVERGENiHBG050763.
InParanoidiP07293.
KOiK04857.

Family and domain databases

InterProiView protein in InterPro
IPR031688. CAC1F_C.
IPR031649. GPHH_dom.
IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
PANTHERiPTHR10037:SF238. PTHR10037:SF238. 1 hit.
PfamiView protein in Pfam
PF08763. Ca_chan_IQ. 1 hit.
PF16885. CAC1F_C. 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.

Sequencei

Sequence statusi: Complete.

P07293-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPSSPQDEG LRKKQPKKPL PEVLPRPPRA LFCLTLQNPL RKACISIVEW
60 70 80 90 100
KPFETIILLT IFANCVALAV YLPMPEDDNN SLNLGLEKLE YFFLTVFSIE
110 120 130 140 150
AAMKIIAYGF LFHQDAYLRS GWNVLDFIIV FLGVFTAILE QVNVIQSNTA
160 170 180 190 200
PMSSKGAGLD VKALRAFRVL RPLRLVSGVP SLQVVLNSIF KAMLPLFHIA
210 220 230 240 250
LLVLFMVIIY AIIGLELFKG KMHKTCYYIG TDIVATVENE KPSPCARTGS
260 270 280 290 300
GRPCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIT MEGWTDVLYW
310 320 330 340 350
VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF
360 370 380 390 400
QKLREKQQLE EDLRGYMSWI TQGEVMDVED LREGKLSLEE GGSDTESLYE
410 420 430 440 450
IEGLNKIIQF IRHWRQWNRV FRWKCHDLVK SRVFYWLVIL IVALNTLSIA
460 470 480 490 500
SEHHNQPLWL THLQDIANRV LLSLFTIEML LKMYGLGLRQ YFMSIFNRFD
510 520 530 540 550
CFVVCSGILE LLLVESGAMT PLGISVLRCI RLLRLFKITK YWTSLSNLVA
560 570 580 590 600
SLLNSIRSIA SLLLLLFLFI IIFALLGMQL FGGRYDFEDT EVRRSNFDNF
610 620 630 640 650
PQALISVFQV LTGEDWNSVM YNGIMAYGGP SYPGVLVCIY FIILFVCGNY
660 670 680 690 700
ILLNVFLAIA VDNLAEAESL TSAQKAKAEE RKRRKMSRGL PDKTEEEKSV
710 720 730 740 750
MAKKLEQKPK GEGIPTTAKL KVDEFESNVN EVKDPYPSAD FPGDDEEDEP
760 770 780 790 800
EIPVSPRPRP LAELQLKEKA VPIPEASSFF IFSPTNKVRV LCHRIVNATW
810 820 830 840 850
FTNFILLFIL LSSAALAAED PIRAESVRNQ ILGYFDIAFT SVFTVEIVLK
860 870 880 890 900
MTTYGAFLHK GSFCRNYFNI LDLLVVAVSL ISMGLESSTI SVVKILRVLR
910 920 930 940 950
VLRPLRAINR AKGLKHVVQC VFVAIRTIGN IVLVTTLLQF MFACIGVQLF
960 970 980 990 1000
KGKFFSCNDL SKMTEEECRG YYYVYKDGDP TQMELRPRQW IHNDFHFDNV
1010 1020 1030 1040 1050
LSAMMSLFTV STFEGWPQLL YRAIDSNEED MGPVYNNRVE MAIFFIIYII
1060 1070 1080 1090 1100
LIAFFMMNIF VGFVIVTFQE QGETEYKNCE LDKNQRQCVQ YALKARPLRC
1110 1120 1130 1140 1150
YIPKNPYQYQ VWYVVTSSYF EYLMFALIML NTICLGMQHY HQSEEMNHIS
1160 1170 1180 1190 1200
DILNVAFTII FTLEMILKLL AFKARGYFGD PWNVFDFLIV IGSIIDVILS
1210 1220 1230 1240 1250
EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLIKLLSRA
1260 1270 1280 1290 1300
EGVRTLLWTF IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIALVDGTQI
1310 1320 1330 1340 1350
NRNNNFQTFP QAVLLLFRCA TGEAWQEILL ACSYGKLCDP ESDYAPGEEY
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 RRTISGDLTA EEELERAMVE AAMEERIFRR
1610 1620 1630 1640 1650
TGGLFGQVDT FLERTNSLPP VMANQRPLQF AEIEMEELES PVFLEDFPQD
1660 1670 1680 1690 1700
ARTNPLARAN TNNANANVAY GNSNHSNNQM FSSVHCEREF PGEAETPAAG
1710 1720 1730 1740 1750
RGALSHSHRA LGPHSKPCAG KLNGQLVQPG MPINQAPPAP CQQPSTDPPE
1760 1770 1780 1790 1800
RGQRRTSLTG SLQDEAPQRR SSEGSTPRRP APATALLIQE ALVRGGLDTL
1810 1820 1830 1840 1850
AADAGFVTAT SQALADACQM EPEEVEVAAT ELLKARESVQ GMASVPGSLS
1860 1870
RRSSLGSLDQ VQGSQETLIP PRP
Length:1,873
Mass (Da):212,029
Last modified:April 1, 1988 - v1
Checksum:i047B10D1946B0796
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti694T → R in AAA31159 (PubMed:2458626).Curated1
Sequence conflicti1808T → M in AAA31159 (PubMed:2458626).Curated1
Sequence conflicti1815A → V in AAA31159 (PubMed:2458626).Curated1
Sequence conflicti1835A → E in AAA31159 (PubMed:2458626).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti165R → K. 1
Natural varianti258G → D. 1
Natural varianti1870P → L. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05921 mRNA. Translation: CAA29355.1.
M23919 mRNA. Translation: AAA31159.1.
PIRiA30063.
RefSeqiNP_001095190.1. NM_001101720.1.
UniGeneiOcu.1826.

Genome annotation databases

GeneIDi100009585.
KEGGiocu:100009585.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCAC1S_RABIT
AccessioniPrimary (citable) accession number: P07293
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: September 27, 2017
This is version 148 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families