Q13698 (CAC1S_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	CACNA1S
Synonyms:	CACH1, CACN1, CACNL1A3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1873 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Interacts with RYR1 By similarity.
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. 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.
Post-translational modification	Phosphorylation by PKA activates the calcium channel By similarity.
Involvement in disease	Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.10 Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily. [View classification]

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Calcium channel Ion channel Voltage-gated channel
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome endoplasmic reticulum organization Inferred from electronic annotation. Source: Compara extraocular skeletal muscle development Inferred from electronic annotation. Source: Compara muscle contraction Inferred from mutant phenotype Ref.12. Source: UniProtKB myoblast fusion Inferred from electronic annotation. Source: Compara neuromuscular junction development Inferred from electronic annotation. Source: Compara skeletal muscle adaptation Inferred from electronic annotation. Source: Compara skeletal system development Inferred from electronic annotation. Source: Compara striated muscle contraction Inferred from electronic annotation. Source: Compara
Cellular_component	I band Inferred from direct assay PubMed 11206130. Source: UniProtKB T-tubule Inferred from direct assay PubMed 17204937. Source: UniProtKB sarcoplasmic reticulum Inferred from electronic annotation. Source: Compara voltage-gated calcium channel complex Inferred from direct assay PubMed 9852570. Source: UniProtKB
Molecular_function	high voltage-gated calcium channel activity Inferred from direct assay PubMed 9852570. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1873

1873

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

PRO_0000053943

Regions

Topological domain

1 – 51

51

Cytoplasmic Potential

Transmembrane

52 – 70

19

Helical; Name=S1 of repeat I; Potential

Topological domain

71 – 88

18

Extracellular Potential

Transmembrane

89 – 108

20

Helical; Name=S2 of repeat I; Potential

Topological domain

109 – 120

12

Cytoplasmic Potential

Transmembrane

121 – 139

19

Helical; Name=S3 of repeat I; Potential

Topological domain

140 – 160

21

Extracellular Potential

Transmembrane

161 – 179

19

Helical; Name=S4 of repeat I; Potential

Topological domain

180 – 198

19

Cytoplasmic Potential

Transmembrane

199 – 218

20

Helical; Name=S5 of repeat I; Potential

Topological domain

219 – 309

91

Extracellular Potential

Transmembrane

310 – 334

25

Helical; Name=S6 of repeat I; Potential

Topological domain

335 – 432

98

Cytoplasmic Potential

Transmembrane

433 – 451

19

Helical; Name=S1 of repeat II; Potential

Topological domain

452 – 466

15

Extracellular Potential

Transmembrane

467 – 486

20

Helical; Name=S2 of repeat II; Potential

Topological domain

487 – 494

8

Cytoplasmic Potential

Transmembrane

495 – 513

19

Helical; Name=S3 of repeat II; Potential

Topological domain

514 – 523

10

Extracellular Potential

Transmembrane

524 – 542

19

Helical; Name=S4 of repeat II; Potential

Topological domain

543 – 561

19

Cytoplasmic Potential

Transmembrane

562 – 581

20

Helical; Name=S5 of repeat II; Potential

Topological domain

582 – 636

55

Extracellular Potential

Transmembrane

637 – 661

25

Helical; Name=S6 of repeat II; Potential

Topological domain

662 – 799

138

Cytoplasmic Potential

Transmembrane

800 – 818

19

Helical; Name=S1 of repeat III; Potential

Topological domain

819 – 834

16

Extracellular Potential

Transmembrane

835 – 854

20

Helical; Name=S2 of repeat III; Potential

Topological domain

855 – 866

12

Cytoplasmic Potential

Transmembrane

867 – 885

19

Helical; Name=S3 of repeat III; Potential

Topological domain

886 – 892

7

Extracellular Potential

Transmembrane

893 – 911

19

Helical; Name=S4 of repeat III; Potential

Topological domain

912 – 930

19

Cytoplasmic Potential

Transmembrane

931 – 950

20

Helical; Name=S5 of repeat III; Potential

Topological domain

951 – 1040

90

Extracellular Potential

Transmembrane

1041 – 1065

25

Helical; Name=S6 of repeat III; Potential

Topological domain

1066 – 1118

53

Cytoplasmic Potential

Transmembrane

1119 – 1137

19

Helical; Name=S1 of repeat IV; Potential

Topological domain

1138 – 1152

15

Extracellular Potential

Transmembrane

1153 – 1172

20

Helical; Name=S2 of repeat IV; Potential

Topological domain

1173 – 1180

8

Cytoplasmic Potential

Transmembrane

1181 – 1199

19

Helical; Name=S3 of repeat IV; Potential

Topological domain

1200 – 1231

32

Extracellular Potential

Transmembrane

1232 – 1250

19

Helical; Name=S4 of repeat IV; Potential

Topological domain

1251 – 1269

19

Cytoplasmic Potential

Transmembrane

1270 – 1289

20

Helical; Name=S5 of repeat IV; Potential

Topological domain

1290 – 1356

67

Extracellular Potential

Transmembrane

1357 – 1381

25

Helical; Name=S6 of repeat IV; Potential

Topological domain

1382 – 1873

492

Cytoplasmic Potential

Repeat

38 – 337

300

I

Repeat

418 – 664

247

II

Repeat

786 – 1068

283

III

Repeat

1105 – 1384

280

IV

Calcium binding

1410 – 1421

12

By similarity

Region

357 – 374

18

Binding to the beta subunit By similarity

Region

988 – 1077

90

Dihydropyridine binding By similarity

Region

1337 – 1403

67

Dihydropyridine binding By similarity

Region

1349 – 1392

44

Phenylalkylamine binding By similarity

Compositional bias

562 – 568

7

Poly-Leu

Sites

Site

292

1

Calcium ion selectivity and permeability By similarity

Site

614

1

Calcium ion selectivity and permeability By similarity

Site

1014

1

Calcium ion selectivity and permeability By similarity

Site

1323

1

Calcium ion selectivity and permeability By similarity

Amino acid modifications

Modified residue

687

1

Phosphoserine; by PKA By similarity

Modified residue

1392

1

Phosphoserine; by PKA Potential

Modified residue

1617

1

Phosphoserine By similarity

Glycosylation

79

1

N-linked (GlcNAc...) Potential

Glycosylation

257

1

N-linked (GlcNAc...) Potential

Glycosylation

1141

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

69

1

A → G.
Corresponds to variant rs12406479 [ dbSNP | Ensembl ].

VAR_046970

Natural variant

458

1

L → H. Ref.1 Ref.10
Corresponds to variant rs12742169 [ dbSNP | Ensembl ].

VAR_001498

Natural variant

528

1

R → G in HOKPP1. Ref.13

VAR_054953

Natural variant

528

1

R → H in HOKPP1. Ref.9 Ref.11 Ref.13

VAR_001499

Natural variant

900

1

R → S in HOKPP1. Ref.13

VAR_054954

Natural variant

1086

1

R → H in MHS5. Ref.10
Corresponds to variant rs1800559 [ dbSNP | Ensembl ].

VAR_001500

Natural variant

1239

1

R → G in HOKPP1. Ref.6 Ref.11 Ref.13
Corresponds to variant rs28930069 [ dbSNP | Ensembl ].

VAR_001501

Natural variant

1239

1

R → H in HOKPP1. Ref.6 Ref.11 Ref.12 Ref.13
Corresponds to variant rs28930068 [ dbSNP | Ensembl ].

VAR_001502

Natural variant

1539

1

R → C. Ref.10
Corresponds to variant rs3850625 [ dbSNP | Ensembl ].

VAR_001503

Natural variant

1658

1

R → H.
Corresponds to variant rs13374149 [ dbSNP | Ensembl ].

VAR_046971

Natural variant

1800

1

L → S. Ref.4
Corresponds to variant rs12139527 [ dbSNP | Ensembl ].

VAR_046972

Natural variant

1840

1

E → D. Ref.1 Ref.2
Corresponds to variant rs1042379 [ dbSNP | Ensembl ].

VAR_046973

Experimental info

Sequence conflict

26

1

R → S in AAB37235. Ref.2

Sequence conflict

265

1

W → C in AAA51902. Ref.1

Sequence conflict

265

1

W → C in AAB37235. Ref.2

Sequence conflict

574

1

A → R in AAA51902. Ref.1

Sequence conflict

574

1

A → R in AAB37235. Ref.2

Sequence conflict

627 – 628

2

YG → SS in AAA51902. Ref.1

Sequence conflict

628

1

G → R in AAB37235. Ref.2

Sequence conflict

916 – 919

4

Missing in AAB37235. Ref.2

Sequence conflict

918 – 919

2

VQ → AR in AAA51902. Ref.1

Sequence conflict

1180

1

D → N in AAA51902. Ref.1

Sequence conflict

1180

1

D → N in AAB37235. Ref.2

Sequence conflict

1294 – 1295

2

LV → FE in AAA20531. Ref.6

Sequence conflict

1318

1

R → RHA in AAB37235. Ref.2

Sequence conflict

1472

1

R → G in AAB37235. Ref.2

Sequence conflict

1510

1

I → M in AAB37235. Ref.2

Sequence conflict

1532

1

H → D in AAB37235. Ref.2

Sequence conflict

1671

1

G → A in AAA51902. Ref.1

Sequence conflict

1671

1

G → A in AAB37235. Ref.2

Sequence conflict

1710

1

V → S in AAA51902. Ref.1

Sequence conflict

1815

1

A → G in AAA51902. Ref.1

Sequence conflict

1815

1

A → G in AAB37235. Ref.2

Secondary structure

1

.

.

.

.

.

1873

Helix Strand Turn

Details...

Helix

1523 – 1536

14

Helix

1538 – 1541

4

Sequences

	Sequence		Length	Mass (Da)
	Q13698 [UniParc]. Last modified October 14, 2008. Version 4. Checksum: 7B7446727E578913	FASTA	1,873	212,350
	10 20 30 40 50 60 MEPSSPQDEG LRKKQPKKPV PEILPRPPRA LFCLTLENPL RKACISIVEW KPFETIILLT 70 80 90 100 110 120 IFANCVALAV YLPMPEDDNN SLNLGLEKLE YFFLIVFSIE AAMKIIAYGF LFHQDAYLRS 130 140 150 160 170 180 GWNVLDFTIV FLGVFTVILE QVNVIQSHTA PMSSKGAGLD VKALRAFRVL RPLRLVSGVP 190 200 210 220 230 240 SLQVVLNSIF KAMLPLFHIA LLVLFMVIIY AIIGLELFKG KMHKTCYFIG TDIVATVENE 250 260 270 280 290 300 EPSPCARTGS GRRCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIT MEGWTDVLYW 310 320 330 340 350 360 VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF QKLREKQQLD 370 380 390 400 410 420 EDLRGYMSWI TQGEVMDVED FREGKLSLDE GGSDTESLYE IAGLNKIIQF IRHWRQWNRI 430 440 450 460 470 480 FRWKCHDIVK SKVFYWLVIL IVALNTLSIA SEHHNQPLWL TRLQDIANRV LLSLFTTEML 490 500 510 520 530 540 MKMYGLGLRQ YFMSIFNRFD CFVVCSGILE ILLVESGAMT PLGISVLRCI RLLRIFKITK 550 560 570 580 590 600 YWTSLSNLVA SLLNSIRSIA SLLLLLFLFI VIFALLGMQL FGGRYDFEDT EVRRSNFDNF 610 620 630 640 650 660 PQALISVFQV LTGEDWTSMM YNGIMAYGGP SYPGMLVCIY FIILFVCGNY ILLNVFLAIA 670 680 690 700 710 720 VDNLAEAESL TSAQKAKAEE KKRRKMSKGL PDKSEEEKST MAKKLEQKPK GEGIPTTAKL 730 740 750 760 770 780 KIDEFESNVN EVKDPYPSAD FPGDDEEDEP EIPLSPRPRP LAELQLKEKA VPIPEASSFF 790 800 810 820 830 840 IFSPTNKIRV LCHRIVNATW FTNFILLFIL LSSAALAAED PIRADSMRNQ ILKHFDIGFT 850 860 870 880 890 900 SVFTVEIVLK MTTYGAFLHK GSFCRNYFNM LDLLVVAVSL ISMGLESSAI SVVKILRVLR 910 920 930 940 950 960 VLRPLRAINR AKGLKHVVQC MFVAISTIGN IVLVTTLLQF MFACIGVQLF KGKFFRCTDL 970 980 990 1000 1010 1020 SKMTEEECRG YYYVYKDGDP MQIELRHREW VHSDFHFDNV LSAMMSLFTV STFEGWPQLL 1030 1040 1050 1060 1070 1080 YKAIDSNAED VGPIYNNRVE MAIFFIIYII LIAFFMMNIF VGFVIVTFQE QGETEYKNCE 1090 1100 1110 1120 1130 1140 LDKNQRQCVQ YALKARPLRC YIPKNPYQYQ VWYIVTSSYF EYLMFALIML NTICLGMQHY 1150 1160 1170 1180 1190 1200 NQSEQMNHIS DILNVAFTII FTLEMILKLM 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 LVINLFVAVI 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 DIVQIQAGLR 1570 1580 1590 1600 1610 1620 TIEEEAAPEI CRTVSGDLAA EEELERAMVE AAMEEGIFRR TGGLFGQVDN FLERTNSLPP 1630 1640 1650 1660 1670 1680 VMANQRPLQF AEIEMEEMES PVFLEDFPQD PRTNPLARAN TNNANANVAY GNSNHSNSHV 1690 1700 1710 1720 1730 1740 FSSVHYEREF PEETETPATR GRALGQPCRV LGPHSKPCVE MLKGLLTQRA MPRGQAPPAP 1750 1760 1770 1780 1790 1800 CQCPRVESSM PEDRKSSTPG SLHEETPHSR STRENTSRCS APATALLIQK ALVRGGLGTL 1810 1820 1830 1840 1850 1860 AADANFIMAT GQALADACQM EPEEVEIMAT ELLKGREAPE GMASSLGCLN LGSSLGSLDQ 1870 HQGSQETLIP PRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3)." Hogan K., Powers P.A., Gregg R.G. Genomics 24:608-609(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-458 AND ASP-1840. Tissue: Skeletal muscle.
[2]	"The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3)." Hogan K., Gregg R.G., Powers P.A. Genomics 31:392-394(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASP-1840.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-1800.
[5]	"Assignment of the human gene for the alpha-1 subunit of the skeletal muscle DHP-sensitive calcium channel (CACNL1A3) to chromosome 1q31-q32." Gregg R.G., Couch F., Hogan K., Powers P.A. Genomics 15:107-112(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 788-830; 1019-1085 AND 1293-1318.
[6]	"Dihydropyridine receptor mutations cause hypokalemic periodic paralysis." Ptacek L.J., Tawil R., Griggs R.C., Engel A.G., Layzer R.B., Kwiecinski H., McManis P.G., Santiago L., Moore M., Fouad G., Bradley P., Leppert M.F. Cell 77:863-868(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1200-1300, VARIANTS HOKPP1 GLY-1239 AND HIS-1239.
[7]	"Human skeletal muscle L-type Ca2+ channel alpha 1S subunit gene shows splicing patterns similar to alpha 1C and alpha 1D genes in the region involved in hereditary disorders." Soldatov N.M. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1223-1413.
[8]	"Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis." Kung A.W., Lau K.S., Fong G.C., Chan V. J. Clin. Endocrinol. Metab. 89:1340-1345(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO TTPP1.
[9]	"A calcium channel mutation causing hypokalemic periodic paralysis." Jurkatt-Rott K., Lehmann-Horn F., Elbaz A., Heine R., Gregg R.G., Hogan K., Powers P.A., Lapie P., Vale-Santos J.E., Weissenbach J., Fontaine B. Hum. Mol. Genet. 3:1415-1419(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HOKPP1 HIS-528.
[10]	"Malignant-hyperthermia susceptibility is associated with a mutation of the alpha-1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle." Monnier N., Procaccio V., Stieglitz P., Lunardi J. Am. J. Hum. Genet. 60:1316-1325(1997) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION, VARIANT MHS5 HIS-1086, VARIANTS HIS-458 AND CYS-1539.
[11]	"The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis." Kim J.-B., Kim M.-H., Lee S.J., Kim D.-J., Lee B.C. J. Korean Med. Sci. 22:946-951(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HOKPP1 HIS-528; HIS-1239 AND GLY-1239.
[12]	"Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family." Houinato D., Laleye A., Adjien C., Adjagba M., Sternberg D., Hilbert P., Vallat J.M., Darboux R.B., Funalot B., Avode D.G. Neuromuscul. Disord. 17:419-422(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HOKPP1 HIS-1239.
[13]	"Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis." Matthews E., Labrum R., Sweeney M.G., Sud R., Haworth A., Chinnery P.F., Meola G., Schorge S., Kullmann D.M., Davis M.B., Hanna M.G. Neurology 72:1544-1547(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HOKPP1 GLY-528; HIS-528; SER-900; GLY-1239 AND HIS-1239.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L33798 mRNA. Translation: AAA51902.1.
U30707 , U30666, U30667, U30668, U30669, U30670, U30671, U30672, U30673, U30674, U30675, U30676, U30677, U30678, U30679, U30680, U30681, U30682, U30683, U30684, U30685, U30686, U30687, U30688, U30689, U30690, U30691, U30692, U30693, U30694, U30695, U30696, U30697, U30698, U30699, U30700, U30701, U30702, U30703, U30704, U30705, U30706 Genomic DNA. Translation: AAB37235.1.
AL358473, AL139159 Genomic DNA. Translation: CAI12386.1.
AL139159, AL358473 Genomic DNA. Translation: CAI23207.1.
BC133671 mRNA. Translation: AAI33672.1.
M87486 Genomic DNA. No translation available.
M87487 Genomic DNA. No translation available.
M87488 Genomic DNA. No translation available.
U09784 mRNA. Translation: AAA20531.1.
Z50091 Genomic DNA. No translation available.
Z50092 Genomic DNA. No translation available.
Z50093 Genomic DNA. No translation available.

IPI

IPI00299240.

PIR

A55645.
I38611.

RefSeq

NP_000060.2. NM_000069.2.

UniGene

Hs.1294.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2VAY	X-ray	1.94	B	1522-1542	[»]

ProteinModelPortal

Q13698.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13698. 1 interaction.

STRING

9606.ENSP00000355192.

PTM databases

PhosphoSite

Q13698.

Polymorphism databases

DMDM

209572767.

Proteomic databases

PaxDb

Q13698.

PRIDE

Q13698.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000362061; ENSP00000355192; ENSG00000081248.

GeneID

779.

KEGG

hsa:779.

UCSC

uc001gvv.3. human.

Organism-specific databases

CTD

779.

GeneCards

GC01M201008.

H-InvDB

HIX0028855.

HGNC

HGNC:1397. CACNA1S.

HPA

CAB009507.

MIM

114208. gene.
170400. phenotype.
188580. phenotype.
601887. phenotype.

neXtProt

NX_Q13698.

Orphanet

681. Hypokalemic periodic paralysis.
423. Malignant hyperthermia.
79102. Thyrotoxic periodic paralysis.

PharmGKB

PA85.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1226.

HOGENOM

HOG000231529.

HOVERGEN

HBG050763.

InParanoid

Q13698.

KO

K04857.

OMA

PPVMANQ.

OrthoDB

EOG45755Q.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

Q13698.

Bgee

Q13698.

CleanEx

HS_CACNA1S.

Genevestigator

Q13698.

GermOnline

ENSG00000081248. Homo sapiens.

Family and domain databases

InterPro

IPR005821. Ion_trans_dom.
IPR014873. VDCC_a1su_IQ.
IPR005450. VDCC_L_a1ssu.
IPR005446. VDCC_L_a1su.
IPR002077. VDCCAlpha1.
[Graphical view]

PANTHER

PTHR10037:SF105. PTHR10037:SF105. 1 hit.

Pfam

PF08763. Ca_chan_IQ. 1 hit.
PF00520. Ion_trans. 4 hits.
[Graphical view]

PRINTS

PR00167. CACHANNEL.
PR01630. LVDCCALPHA1.
PR01634. LVDCCALPHA1S.

SMART

SM01062. Ca_chan_IQ. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q13698.

ChEMBL

CHEMBL3805.

DrugBank

DB00653. Magnesium Sulfate.
DB00661. Verapamil.

EvolutionaryTrace

Q13698.

GenomeRNAi

779.

NextBio

3148.

SOURCE

Search...

Entry information

Entry name

CAC1S_HUMAN

Accession

Primary (citable) accession number: Q13698
Secondary accession number(s): A4IF51 , B1ALM2, Q12896, Q13934

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 139 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.