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
Rattus norvegicus (Rat)
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 similarityCurated

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: RGD
  • cellular response to caffeine Source: UniProtKB
  • membrane depolarization during action potential Source: GO_Central
  • ossification Source: RGD

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
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi70983. Cacna1s.

Subcellular locationi

  • Cell membranesarcolemma By similarity; Multi-pass membrane protein By similarity

  • Note: Detected on T-tubules (extensions of the sarcolemma).By similarity

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 – 1850CytoplasmicCuratedAdd BLAST469

GO - Cellular componenti

  • L-type voltage-gated calcium channel complex Source: UniProtKB
  • sarcolemma Source: RGD
  • T-tubule Source: UniProtKB
  • voltage-gated calcium channel complex Source: RGD

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL4108.
GuidetoPHARMACOLOGYi528.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539461 – 1850Voltage-dependent L-type calcium channel subunit alpha-1SAdd BLAST1850

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi226 ↔ 254By similarity
Disulfide bondi245 ↔ 261By similarity
Disulfide bondi957 ↔ 968By similarity
Glycosylationi1141N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1338 ↔ 1352By similarity
Modified residuei1392Phosphoserine; by PKASequence analysis1
Modified residuei1575PhosphoserineCombined sources1
Modified residuei1579PhosphothreonineCombined sources1
Modified residuei1617PhosphoserineCombined sources1

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

PaxDbiQ02485.
PRIDEiQ02485.

PTM databases

iPTMnetiQ02485.
PhosphoSitePlusiQ02485.

Expressioni

Tissue specificityi

Skeletal muscle specific.

Gene expression databases

GenevisibleiB3XZL8. RN.

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. 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 (By similarity). Interacts with RYR1 (By similarity). Interacts with CALM (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067264.

Chemistry databases

BindingDBiQ02485.

Structurei

3D structure databases

ProteinModelPortaliQ02485.
ModBaseiSearch...
MobiDBiSearch...

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 subunitBy similarityAdd BLAST18
Regioni988 – 1077Dihydropyridine bindingBy similarityAdd BLAST90
Regioni1337 – 1403Dihydropyridine bindingBy similarityAdd BLAST67
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

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.
HOVERGENiHBG050763.
InParanoidiQ02485.
KOiK04857.

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:SF238. PTHR10037:SF238. 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: 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
MEPSSPQDEG LRKKQPKKPV PEILPRPPRA LFCLTLQNPL RKACISVVEW
60 70 80 90 100
KPFETIILLT IFANCVALAV YLPMPEDDNN TLNLGLEKLE YFFLIVFSIE
110 120 130 140 150
AAMKIIAYGF LFHQDAYLRS GWNVLDFIIV FLGVFTAILE 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 LLALFTIEML MKMYGLGLRQ YFMSIFNRFD
510 520 530 540 550
CFVVCSGILE ILLVESGAMT PLGISVLRCI RLLRLFKITK YWTSLSNLVA
560 570 580 590 600
SLLNSIRSIA SLLLLLFLFM IIFALLGMQL FGGRYDFEDT EVRRSNFDNF
610 620 630 640 650
PQALISVFQV LTGEDWNSVM YNGIMAYGGP SYPGVLVCIY FIILFVCGNY
660 670 680 690 700
ILLNVFLAIA VDNLAEAESL TSAQKAKAEE RKRRKMSRGL PDKSEEERST
710 720 730 740 750
MTKKLEQKPK GEGIPTTAKL KIDEFESNVN EVKDPYPSAD FPGDDEEDEP
760 770 780 790 800
EIPASPRPRP 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 FTLEMILKLI AFKPRGYFGD PWNVFDFLIV IGSIIDVILS
1210 1220 1230 1240 1250
EIDTLLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLIKLLSRA
1260 1270 1280 1290 1300
EGVRTLLWTF IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIAMVDGTQI
1310 1320 1330 1340 1350
NRNNNFQTFP QAVLLLFRCA TGEAWQEILL ACSYGKRCDP ESDYAPGEEY
1360 1370 1380 1390 1400
ACGTNFAYYY 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 HRAISGDLTA EEELERAMVE AAMEEGIFRR
1610 1620 1630 1640 1650
TGGLFGQVDN FLERTNSLPP VMANQRPLQF AEMEMEELES PVFLEDFPQN
1660 1670 1680 1690 1700
PGTHPLARAN TNNANANVAY GNSSHRNSPV FSSIRYEREL LEEAGRPVTR
1710 1720 1730 1740 1750
EGPFSQPCSV SGVNSRSHVD KLERQMSQRR MPKGQVPPSP CQLSQEKHPV
1760 1770 1780 1790 1800
HEEGKGPRSW STETSDSESF EERVPRNSAH KCTAPATTML IQEALVRGGL
1810 1820 1830 1840 1850
DSLAADANFV MATGQALADA CQMEPEEVEV AATELLKRES PKGGAMPREP
Length:1,850
Mass (Da):210,396
Last modified:June 7, 2017 - v2
Checksum:i309E38319F53FF23
GO
Isoform ROB1 (identifier: Q02485-2) [UniParc]FASTAAdd to basket

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

Show »
Length:1,831
Mass (Da):208,673
Checksum:i749460F6CF29D3AE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti714I → V in AAA40844 (PubMed:1335956).Curated1
Sequence conflicti1261I → T in AAA89158 (PubMed:7479909).Curated1
Sequence conflicti1323E → A in AAA89158 (PubMed:7479909).Curated1
Sequence conflicti1845 – 1850AMPREP → PCPGSLEPKVLPWAA in AAA40844 (PubMed:1335956).6

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0009391204 – 1222Missing in isoform ROB1. 1 PublicationAdd BLAST19

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB374360 mRNA. Translation: BAG54980.1.
L04684 mRNA. Translation: AAA40844.1.
M99220 mRNA. Translation: AAA40894.1.
U31816 mRNA. Translation: AAA89158.1.
PIRiA46422.
RefSeqiNP_446325.1. NM_053873.1.
UniGeneiRn.10738.
Rn.220579.

Genome annotation databases

GeneIDi682930.
KEGGirno:682930.

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiCAC1S_RAT
AccessioniPrimary (citable) accession number: Q02485
Secondary accession number(s): B3XZL8
, P70484, Q01553, Q62817
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 7, 2017
Last modified: July 5, 2017
This is version 129 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families