P21817 (RYR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ryanodine receptor 1
Short name=RYR-1
Short name=RyR1

Alternative name(s):
Skeletal muscle calcium release channel
Skeletal muscle ryanodine receptor
Skeletal muscle-type ryanodine receptor
Type 1 ryanodine receptor

Gene names

Name:	RYR1
Synonyms:	RYDR

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	5038 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium channel that mediates the release of Ca2+ from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca2+ leaking into the cytoplasm. Can also mediate the release of Ca2+ from intracellular stores in neurons, and may thereby promote prolonged Ca2+ signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis By similarity. Ref.13
Subunit structure	Homotetramer. Can also form heterotetramers with RYR2. Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity. Interacts with S100A1. Interacts with FKBP1A; this stabilizes the closed conformation of the channel. Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel. Interacts with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity By similarity. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1). Ref.12 Ref.13
Subcellular location	Sarcoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein Probable. Note: The number of predicted transmembrane domains varies between orthologs, but both N-terminus and C-terminus seem to be cytoplasmic.
Tissue specificity	Skeletal muscle and brain (cerebellum and hippocampus). Ref.10
Domain	The calcium release channel activity resides in the C-terminal region while the remaining part of the protein constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic reticulum (SR) and the T-tubule By similarity.
Post-translational modification	Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2843 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2843. Activated by reversible S-nitrosylation. Repeated very high-level exercise increases S-nitrosylation.
Involvement in disease	Malignant hyperthermia 1 (MHS1) [MIM:145600]: Autosomal dominant pharmacogenetic disorder of skeletal muscle and is one of the main causes of death due to anesthesia. In susceptible people, an MH episode can be triggered by all commonly used inhalational anesthetics such as halothane and by depolarizing muscle relaxants such as succinylcholine. The clinical features of the myopathy are hyperthermia, accelerated muscle metabolism, contractures, metabolic acidosis, tachycardia and death, if not treated with the postsynaptic muscle relaxant, dantrolene. Susceptibility to MH can be determined with the 'in vitro' contracture test (IVCT): observing the magnitude of contractures induced in strips of muscle tissue by caffeine alone and halothane alone. Patients with normal response are MH normal (MHN), those with abnormal response to caffeine alone or halothane alone are MH equivocal (MHE(C) and MHE(H) respectively). Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.7 Ref.8 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.38 Ref.39 Ref.40 Ref.41 Ref.43 Ref.44 Ref.45 Ref.46 Ref.48 Ref.51 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.65 Ref.66 Central core disease of muscle (CCD) [MIM:117000]: Autosomal dominant congenital myopathy, but a severe autosomal recessive form also exists. Both clinical and histological variability is observed. Affected individuals typically display hypotonia and proximal muscle weakness in infancy, leading to the delay of motor milestones. The clinical course of the disorder is usually slow or nonprogressive in adulthood, and the severity of the symptoms may vary from normal to significant muscle weakness. Microscopic examination of CCD-affected skeletal muscle reveals a predominance of type I fibers containing amorphous-looking areas (cores) that do not stain with oxidative and phosphorylase histochemical techniques. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.17 Ref.18 Ref.25 Ref.28 Ref.29 Ref.33 Ref.36 Ref.37 Ref.42 Ref.47 Ref.49 Ref.50 Ref.52 Ref.54 Ref.57 Ref.61 Ref.62 Ref.63 Ref.64 Ref.66 Ref.68 Multiminicore disease with external ophthalmoplegia (MMDO) [MIM:255320]: Clinically heterogeneous neuromuscular disorder. General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed minicores) in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.53 Ref.54 Ref.60 Congenital myopathy with fiber-type disproportion (CFTD) [MIM:255310]: Genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.54 Ref.67 Defects in RYR1 may be a cause of Samaritan myopathy, a congenital myopathy with benign course. Patients display severe hypotonia and respiratory distress at birth. Unlike other congenital myopathies, the health status constantly improves and patients are minimally affected at adulthood. Ref.54
Miscellaneous	Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by increased cytoplasmic calcium levels, by nitric oxyde (NO), caffeine and ATP. Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites By similarity. Coexpression of normal and mutant Thr-4898 RYR1 in a 1:1 ratio, produces RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca2+ release are reduced by 67%. Binding of [3H]ryanodine indicates that the heterozygous channel is activated by Ca2+ concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells shows a significantly increased resting cytoplasmic Ca2+ level and a significantly reduced luminal Ca2+ level. These data indicated a leaky channel, possibly caused by a reduction in the Ca2+ concentration required for channel activation. Comparison with 2 other coexpressed mutant/normal channels suggests that the Thr-4898 mutation produces one of the most abnormal RYR1 channels that has been investigated, and this level of abnormality is reflected in the severe and penetrant phenotype of affected CCD individuals.
Sequence similarities	Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 subfamily. [View classification] Contains 3 B30.2/SPRY domains. Contains 5 MIR domains.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium Calmodulin-binding
Molecular function	Calcium channel Developmental protein Ion channel Ligand-gated ion channel Receptor
PTM	Phosphoprotein S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to caffeine Inferred from sequence or structural similarity. Source: UniProtKB muscle contraction Inferred from sequence or structural similarity. Source: UniProtKB ossification involved in bone maturation Inferred from sequence or structural similarity. Source: UniProtKB outflow tract morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Inferred from sequence or structural similarity. Source: UniProtKB response to hypoxia Inferred from direct assay PubMed 19120137. Source: BHF-UCL skeletal muscle fiber development Inferred from sequence or structural similarity. Source: UniProtKB skin development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	I band Inferred from direct assay PubMed 11206130. Source: UniProtKB T-tubule Inferred from electronic annotation. Source: Compara cell cortex Inferred from direct assay PubMed 11206130. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc junctional membrane complex Inferred from electronic annotation. Source: Compara junctional sarcoplasmic reticulum membrane Traceable author statement PubMed 19095005. Source: BHF-UCL smooth endoplasmic reticulum Traceable author statement Ref.1. Source: ProtInc terminal cisterna Inferred from sequence or structural similarity PubMed 1374404. Source: BHF-UCL
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calmodulin binding Inferred from sequence or structural similarity. Source: BHF-UCL ryanodine-sensitive calcium-release channel activity Inferred from sequence or structural similarity. Source: UniProtKB voltage-gated calcium channel activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MYOM2	P54296	2	EBI-1221290,EBI-5357134

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: P21817-1)

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.

Isoform 2 (identifier: P21817-2)

The sequence of this isoform differs from the canonical sequence as follows:
     3481-3485: Missing.

Isoform 3 (identifier: P21817-3)

The sequence of this isoform differs from the canonical sequence as follows:
     3865-3869: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 5038	5038	Ryanodine receptor 1		PRO_0000219358
Regions
	Topological domain	1 – 4326	4326	Cytoplasmic Potential
	Transmembrane	4327 – 4347	21	Helical; Potential
	Transmembrane	4348 – 4368	21	Helical; Potential
	Transmembrane	4560 – 4580	21	Helical; Potential
	Transmembrane	4652 – 4672	21	Helical; Potential
	Transmembrane	4781 – 4801	21	Helical; Potential
	Transmembrane	4808 – 4828	21	Helical; Potential
	Transmembrane	4840 – 4860	21	Helical; Potential
	Intramembrane	4891 – 4900	10	Pore-forming; By similarity
	Transmembrane	4921 – 4941	21	Helical; Potential
	Topological domain	4942 – 5038	97	Cytoplasmic Potential
	Domain	97 – 152	56	MIR 1
	Domain	159 – 204	46	MIR 2
	Domain	210 – 264	55	MIR 3
	Domain	270 – 327	58	MIR 4
	Domain	335 – 392	58	MIR 5
	Domain	581 – 797	217	B30.2/SPRY 1
	Repeat	841 – 954	114	1
	Repeat	955 – 1068	114	2
	Domain	1013 – 1208	196	B30.2/SPRY 2
	Repeat	1344 – 1359	16	3; truncated
	Domain	1356 – 1570	215	B30.2/SPRY 3
	Repeat	1372 – 1387	16	4; truncated
	Repeat	2726 – 2845	120	5
	Repeat	2846 – 2959	114	6
	Region	841 – 2959	2119	6 X approximate repeats
	Region	3614 – 3643	30	Interaction with CALM
	Compositional bias	1873 – 1924	52	Glu-rich (acidic)
	Compositional bias	4462 – 4532	71	Pro-rich
Amino acid modifications
	Modified residue	2843	1	Phosphoserine; by PKA and PKG By similarity
	Modified residue	3635	1	S-nitrosocysteine Ref.11
	Modified residue	4864	1	Phosphotyrosine Ref.14
	Modified residue	4867	1	Phosphoserine Ref.14
Natural variations
	Alternative sequence	3481 – 3485	5	Missing in isoform 2.		VSP_005951
	Alternative sequence	3865 – 3869	5	Missing in isoform 3.		VSP_005952
	Natural variant	13	1	L → R in MHS1. Ref.65		VAR_058560
	Natural variant	13	1	L → V in CCD; autosomal recessive form. Ref.64		VAR_045694
	Natural variant	35	1	C → R in MHS1. Ref.22 Ref.59		VAR_005589
	Natural variant	44	1	R → C in CCD and MHS1. Ref.51		VAR_045695
	Natural variant	109	1	R → W in MMDO. Ref.60		VAR_032910
	Natural variant	160	1	E → G in CCD. Ref.57 Ref.68		VAR_045696
	Natural variant	163	1	R → C in CCD and MHS1; 2-3% of the cases. Ref.17 Ref.35 Ref.40 Ref.41 Ref.44 Ref.55 Ref.59		VAR_005590
	Natural variant	163	1	R → L in MHS1; induces an increase sensitivity to caffeine. Ref.59		VAR_045697
	Natural variant	165	1	G → R in MHS1. Ref.59		VAR_045698
	Natural variant	166	1	D → N in MHS1. Ref.40 Ref.59		VAR_045699
	Natural variant	177	1	R → C in MHS1. Ref.59		VAR_045700
	Natural variant	178	1	Y → C in MHS1. Ref.59		VAR_045701
	Natural variant	215	1	G → E in CCD; autosomal recessive form. Ref.50		VAR_045702
	Natural variant	226	1	M → K in MHS1. Ref.65		VAR_058561
	Natural variant	227	1	D → V in MHS1. Ref.59		VAR_045703
	Natural variant	248	1	G → R in MHS1; unknown pathological significance. Ref.2 Ref.35 Ref.55 Ref.59 Corresponds to variant rs1801086 [ dbSNP | Ensembl ].		VAR_005591
	Natural variant	291	1	A → T. Corresponds to variant rs2229140 [ dbSNP | Ensembl ].		VAR_051890
	Natural variant	328	1	R → W in MHS1; has increased sensitivity to both caffeine and halothane. Ref.48 Ref.59		VAR_045704
	Natural variant	341	1	G → R in MHS1; 10% of the cases. Ref.19 Ref.40 Ref.41 Ref.59 Corresponds to variant rs28933997 [ dbSNP | Ensembl ].		VAR_005592
	Natural variant	367	1	R → L in MHS1. Ref.65		VAR_058562
	Natural variant	382	1	H → N in MHS1. Ref.66		VAR_068510
	Natural variant	401	1	R → C in MHS1. Ref.43 Ref.44		VAR_045705
	Natural variant	401	1	R → H in MHS1. Ref.40 Ref.59		VAR_045706
	Natural variant	401	1	R → S in MHS1. Ref.59		VAR_045707
	Natural variant	402	1	M → T in CFTD. Ref.67		VAR_063846
	Natural variant	403	1	I → M in CCD and MHS1. Ref.17 Ref.59		VAR_005593
	Natural variant	471	1	R → C. Ref.2		VAR_005594
	Natural variant	485	1	M → V. Ref.60		VAR_032911
	Natural variant	522	1	Y → S in CCD and MHS1. Ref.18 Ref.59		VAR_005595
	Natural variant	530	1	R → H in MHS1. Ref.65		VAR_058563
	Natural variant	533	1	R → C in MHS1. Ref.51		VAR_045708
	Natural variant	533	1	R → H in MHS1.		VAR_008971
	Natural variant	544	1	D → Y in MHS1. Ref.65		VAR_058564
	Natural variant	552	1	R → W in MHS1. Ref.24 Ref.59		VAR_005596
	Natural variant	614	1	R → C in CCD and MHS1; 3-5% of the cases. Ref.7 Ref.8 Ref.35 Ref.40 Ref.41 Ref.50 Ref.55 Ref.57 Ref.59 Corresponds to variant rs28933996 [ dbSNP | Ensembl ].		VAR_005597
	Natural variant	614	1	R → L in MHS1. Ref.23 Ref.59		VAR_005598
	Natural variant	1043	1	R → C in MHS1. Ref.65		VAR_058565
	Natural variant	1058	1	E → K in MHS1. Ref.66		VAR_068511
	Natural variant	1088	1	Y → C Probable disease-associated mutation found in a family with Samaritan myopathy. Ref.16		VAR_068512
	Natural variant	1109	1	R → K. Corresponds to variant rs35719391 [ dbSNP | Ensembl ].		VAR_032912
	Natural variant	1342	1	S → G. Ref.65 Corresponds to variant rs34694816 [ dbSNP | Ensembl ].		VAR_032913
	Natural variant	1352	1	A → G in MHS1. Ref.65		VAR_058566
	Natural variant	1393	1	K → R May be associated with susceptibility to malignant hyperthermia. Ref.66 Corresponds to variant rs137933390 [ dbSNP | Ensembl ].		VAR_068513
	Natural variant	1489	1	S → N. Corresponds to variant rs34404839 [ dbSNP | Ensembl ].		VAR_032914
	Natural variant	1679	1	R → H May be associated with susceptibility to malignant hyperthermia. Ref.66 Corresponds to variant rs146504767 [ dbSNP | Ensembl ].		VAR_068514
	Natural variant	1704	1	G → S in CCD; autosomal recessive form. Ref.64		VAR_045709
	Natural variant	1787	1	P → L. Ref.2 Ref.65 Ref.68 Corresponds to variant rs34934920 [ dbSNP | Ensembl ].		VAR_005599
	Natural variant	1832	1	G → A. Ref.4 Ref.46 Ref.65		VAR_045710
	Natural variant	2035	1	H → L in CFTD. Ref.67		VAR_063847
	Natural variant	2060	1	G → C. Ref.2 Ref.60 Ref.65 Ref.68 Corresponds to variant rs35364374 [ dbSNP | Ensembl ].		VAR_005600
	Natural variant	2101	1	M → K. Ref.51		VAR_045711
	Natural variant	2117	1	V → L in MHS1. Ref.51		VAR_045712
	Natural variant	2129	1	D → E in MHS1. Ref.38 Ref.40		VAR_045713
	Natural variant	2163	1	R → C in MHS1. Ref.25 Ref.55 Ref.59 Corresponds to variant rs28933998 [ dbSNP | Ensembl ].		VAR_005601
	Natural variant	2163	1	R → H in CCD and MHS1. Ref.25 Ref.44 Ref.59 Corresponds to variant rs28933999 [ dbSNP | Ensembl ].		VAR_005602
	Natural variant	2163	1	R → P in MHS1. Ref.51		VAR_008972
	Natural variant	2168	1	V → M in CCD and MHS1; no difference in the thapsigargin-sensitive calcium stores of cells carrying this mutation and the wild-type. Ref.25 Ref.35 Ref.36 Ref.37 Ref.40 Ref.51 Ref.55 Ref.59		VAR_005603
	Natural variant	2204	1	H → Q in CCD. Ref.68		VAR_068515
	Natural variant	2206	1	T → M in MHS1; induces an increase sensitivity to caffeine. Ref.25 Ref.35 Ref.40 Ref.44 Ref.55 Ref.59 Corresponds to variant rs28934000 [ dbSNP | Ensembl ].		VAR_005604
	Natural variant	2206	1	T → R in MHS1. Ref.59		VAR_008973
	Natural variant	2214	1	V → I in MHS1. Ref.35 Ref.55		VAR_045714
	Natural variant	2280	1	V → I in MHS1. Ref.44		VAR_045715
	Natural variant	2321	1	I → V. Ref.65 Corresponds to variant rs34390345 [ dbSNP | Ensembl ].		VAR_058567
	Natural variant	2336	1	R → H in MHS1. Ref.65		VAR_058568
	Natural variant	2342	1	N → S in MHS1. Ref.58		VAR_045716
	Natural variant	2344	1	E → D in MHS1; uncertain pathogenicity. Ref.59		VAR_045717
	Natural variant	2346	1	V → M in MHS1. Ref.57 Ref.59		VAR_045718
	Natural variant	2347	1	Missing in MHS1. Ref.34		VAR_045719
	Natural variant	2348	1	E → G in MHS1. Ref.57		VAR_045720
	Natural variant	2350	1	A → T in MHS1; reveals an altered calcium dependence and increased caffeine sensitivity. Ref.39 Ref.55 Ref.59		VAR_045721
	Natural variant	2355	1	R → C in MHS1. Ref.45		VAR_045722
	Natural variant	2367	1	A → T in MHS1. Ref.35 Ref.55		VAR_045723
	Natural variant	2404	1	E → K in MHS1. Ref.65		VAR_058569
	Natural variant	2421	1	A → P in CCD; autosomal recessive form. Ref.64		VAR_045724
	Natural variant	2423	1	M → K in MMDO and CCD; autosomal recessive form. Ref.60 Ref.64		VAR_032915
	Natural variant	2428	1	A → T in MHS1; induces an increase sensitivity to caffeine. Ref.40 Ref.59		VAR_045725
	Natural variant	2431	1	D → N in MHS1. Ref.35 Ref.55		VAR_045726
	Natural variant	2434	1	G → R in MHS1. Ref.20 Ref.21 Ref.35 Ref.40 Ref.44 Ref.55 Ref.59		VAR_005605
	Natural variant	2435	1	R → H in CCD and MHS1. Ref.3 Ref.40 Ref.59 Corresponds to variant rs28933396 [ dbSNP | Ensembl ].		VAR_005606
	Natural variant	2435	1	R → L in MHS1. Ref.28 Ref.44 Ref.51		VAR_008974
	Natural variant	2437	1	A → V in MHS1. Ref.55		VAR_045727
	Natural variant	2452	1	R → W in MHS1. Ref.30 Ref.40 Ref.57		VAR_045728
	Natural variant	2454	1	R → C in MHS1; induces an increase sensitivity to caffeine. Ref.32 Ref.41 Ref.59		VAR_008975
	Natural variant	2454	1	R → H in CCD and MHS1; severe form; induces an increase sensitivity to caffeine. Ref.28 Ref.30 Ref.35 Ref.40 Ref.51 Ref.55 Ref.59		VAR_008976
	Natural variant	2458	1	R → C in MHS1. Ref.26 Ref.44 Ref.59 Corresponds to variant rs28933397 [ dbSNP | Ensembl ].		VAR_008977
	Natural variant	2458	1	R → H in MHS1. Ref.26 Ref.57		VAR_008978
	Natural variant	2508	1	R → G in CCD. Ref.66		VAR_068516
	Natural variant	2509	1	V → I. Corresponds to variant rs2071088 [ dbSNP | Ensembl ].		VAR_051891
	Natural variant	2550	1	L → V. Ref.2 Ref.4 Ref.65		VAR_058570
	Natural variant	2676	1	R → W in MHS1; located on the same allele as S-2787. Ref.56 Ref.59 Ref.65 Corresponds to variant rs28934001 [ dbSNP | Ensembl ].		VAR_045729
	Natural variant	2730	1	D → G in MHS1. Ref.65		VAR_058571
	Natural variant	2779	1	E → K. Corresponds to variant rs2915952 [ dbSNP | Ensembl ].		VAR_051892
	Natural variant	2787	1	T → S in MHS1; located on the same allele as W-2676. Ref.56 Ref.59 Ref.65 Corresponds to variant rs35180584 [ dbSNP | Ensembl ].		VAR_045730
	Natural variant	2880	1	E → K in MHS1. Ref.65		VAR_058572
	Natural variant	3118	1	A → V. Corresponds to variant rs2915960 [ dbSNP | Ensembl ].		VAR_045731
	Natural variant	3217	1	S → P in MHS1. Ref.65		VAR_058573
	Natural variant	3290	1	E → K in MHS1. Ref.65		VAR_058574
	Natural variant	3326	1	N → K in CFTD. Ref.67		VAR_063848
	Natural variant	3366	1	R → H in CCD. Ref.68		VAR_068517
	Natural variant	3402	1	C → G in CFTD. Ref.67		VAR_063849
	Natural variant	3527	1	P → S in CCD; autosomal recessive form. Ref.42		VAR_045732
	Natural variant	3539	1	R → H in CCD; autosomal recessive form. Ref.64		VAR_045733
	Natural variant	3583	1	E → Q. Ref.65 Corresponds to variant rs55876273 [ dbSNP | Ensembl ].		VAR_058575
	Natural variant	3756	1	Q → E. Ref.46 Ref.65 Corresponds to variant rs4802584 [ dbSNP | Ensembl ].		VAR_032916
	Natural variant	3772	1	R → Q in CCD; autosomal recessive form. Ref.64		VAR_045734
	Natural variant	3772	1	R → W in MHS1. Ref.65		VAR_058576
	Natural variant	3806	1	G → R in MHS1. Ref.65		VAR_058577
	Natural variant	3916	1	I → M in MHS1. Ref.41 Ref.59		VAR_045735
	Natural variant	3933	1	Y → C in CCD. Ref.68		VAR_068518
	Natural variant	4136	1	R → S in MHS1. Ref.44		VAR_045736
	Natural variant	4214 – 4216	3	Missing in CCD.		VAR_045737
	Natural variant	4234	1	V → L in MHS1. Ref.44		VAR_045738
	Natural variant	4493	1	P → A. Ref.68		VAR_068519
	Natural variant	4501	1	P → L in MHS1. Ref.65		VAR_058578
	Natural variant	4558	1	R → Q in CCD; autosomal recessive form. Ref.62 Ref.64		VAR_045739
	Natural variant	4637	1	T → A in CCD. Ref.33		VAR_045740
	Natural variant	4637	1	T → I in core/rod disease. Ref.54		VAR_045741
	Natural variant	4638	1	G → D in CCD. Ref.54 Ref.57		VAR_045742
	Natural variant	4647 – 4648	2	Missing in CCD.		VAR_045743
	Natural variant	4650	1	L → P in CCD; autosomal recessive form. Ref.50		VAR_045744
	Natural variant	4651	1	H → P in CCD. Ref.54		VAR_045745
	Natural variant	4668	1	P → S. Ref.46		VAR_045746
	Natural variant	4684	1	F → S in MHS1. Ref.59		VAR_045747
	Natural variant	4724	1	K → Q in CCD; autosomal recessive form. Ref.50		VAR_045748
	Natural variant	4737	1	R → Q in MHS1. Ref.59		VAR_045749
	Natural variant	4737	1	R → W in MHS1. Ref.44 Ref.59		VAR_045750
	Natural variant	4743	1	G → D in CCD. Ref.68		VAR_068520
	Natural variant	4793	1	L → P in CCD. Ref.36		VAR_045751
	Natural variant	4796	1	Y → C in CCD. Ref.36		VAR_045752
	Natural variant	4814	1	L → F in CCD. Ref.57		VAR_045753
	Natural variant	4824	1	L → P in MHS1. Ref.55 Ref.57		VAR_045754
	Natural variant	4825	1	R → C in CCD. Ref.36		VAR_045755
	Natural variant	4826	1	T → I in MHS1. Ref.31 Ref.59		VAR_045756
	Natural variant	4838	1	L → V in MHS1. Ref.46 Ref.59 Ref.65		VAR_045757
	Natural variant	4842	1	V → M in CCD; autosomal recessive form. Ref.64		VAR_045758
	Natural variant	4846	1	A → V in CCD; autosomal recessive form. Ref.61 Ref.62		VAR_045759
	Natural variant	4849	1	V → I in MHS1 and CCD; autosomal recessive form. Ref.47 Ref.59 Ref.62 Ref.64		VAR_045760
	Natural variant	4860	1	Missing in CCD. Ref.36		VAR_045761
	Natural variant	4861	1	R → C in CCD. Ref.54 Ref.62		VAR_045762
	Natural variant	4861	1	R → H in CCD; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR; smaller thapsigargin-sensitive intracellular calcium stores; normal sensitivity of the calcium release to the RYR inhibitor dantrolene. Ref.36 Ref.37 Ref.49 Ref.54 Ref.57 Ref.62		VAR_045763
	Natural variant	4863 – 4869	7	FYNKSED → Y in CCD.		VAR_045764
	Natural variant	4864	1	Y → C in CCD. Ref.49		VAR_045765
	Natural variant	4876	1	K → R in MHS1. Ref.59 Ref.65		VAR_045766
	Natural variant	4882	1	T → M in CCD. Ref.63		VAR_068521
	Natural variant	4891	1	G → R in CCD. Ref.37		VAR_045767
	Natural variant	4893	1	R → Q in CCD. Ref.54		VAR_045768
	Natural variant	4893	1	R → W in CCD; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR; smaller thapsigargin-sensitive intracellular calcium stores; normal sensitivity of the calcium release to the RYR inhibitor dantrolene. Ref.36 Ref.37 Ref.49		VAR_045769
	Natural variant	4897	1	G → V in CCD. Ref.62		VAR_045770
	Natural variant	4898	1	I → T in CCD; severe phenotype; also present in some patients with MHS1; no response to the agonists halothane and caffeine. Ref.29 Ref.36 Ref.37 Ref.54		VAR_045771
	Natural variant	4899	1	G → E in CCD. Ref.36 Ref.50		VAR_045772
	Natural variant	4899	1	G → R in CCD; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR; smaller thapsigargin-sensitive intracellular calcium stores; normal sensitivity of the calcium release to the RYR inhibitor dantrolene. Ref.37		VAR_045773
	Natural variant	4906	1	A → V in CCD. Ref.37		VAR_045774
	Natural variant	4914	1	R → G in CCD. Ref.36 Ref.54		VAR_045775
	Natural variant	4914	1	R → T in CCD. Ref.54 Ref.62		VAR_045776
	Natural variant	4927 – 4928	2	Missing in CCD.		VAR_045777
	Natural variant	4938	1	I → M in CCD. Ref.57		VAR_045778
	Natural variant	4938	1	I → T in MHS1. Ref.65		VAR_058579
	Natural variant	4939	1	D → E in MHS1. Ref.57 Ref.59		VAR_045779
	Natural variant	4940	1	A → T in CCD. Ref.49 Ref.54		VAR_045780
	Natural variant	4942	1	G → V in MHS1. Ref.44		VAR_045781
	Natural variant	4973	1	P → L in MHS1. Ref.41 Ref.44 Ref.59		VAR_045782
Experimental info
	Sequence conflict	1365 – 1368	4	GEAQ → RGA AA sequence Ref.1
	Sequence conflict	2324	1	N → K AA sequence Ref.1
	Sequence conflict	2840	1	R → A AA sequence Ref.1
	Sequence conflict	3380	1	R → A AA sequence Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 13, 2006. Version 3. Checksum: EC32277F4885CC7F	FASTA	5,038	565,176
	10 20 30 40 50 60 MGDAEGEDEV QFLRTDDEVV LQCSATVLKE QLKLCLAAEG FGNRLCFLEP TSNAQNVPPD 70 80 90 100 110 120 LAICCFVLEQ SLSVRALQEM LANTVEAGVE SSQGGGHRTL LYGHAILLRH AHSRMYLSCL 130 140 150 160 170 180 TTSRSMTDKL AFDVGLQEDA TGEACWWTMH PASKQRSEGE KVRVGDDIIL VSVSSERYLH 190 200 210 220 230 240 LSTASGELQV DASFMQTLWN MNPICSRCEE GFVTGGHVLR LFHGHMDECL TISPADSDDQ 250 260 270 280 290 300 RRLVYYEGGA VCTHARSLWR LEPLRISWSG SHLRWGQPLR VRHVTTGQYL ALTEDQGLVV 310 320 330 340 350 360 VDASKAHTKA TSFCFRISKE KLDVAPKRDV EGMGPPEIKY GESLCFVQHV ASGLWLTYAA 370 380 390 400 410 420 PDPKALRLGV LKKKAMLHQE GHMDDALSLT RCQQEESQAA RMIHSTNGLY NQFIKSLDSF 430 440 450 460 470 480 SGKPRGSGPP AGTALPIEGV ILSLQDLIIY FEPPSEDLQH EEKQSKLRSL RNRQSLFQEE 490 500 510 520 530 540 GMLSMVLNCI DRLNVYTTAA HFAEFAGEEA AESWKEIVNL LYELLASLIR GNRSNCALFS 550 560 570 580 590 600 TNLDWLVSKL DRLEASSGIL EVLYCVLIES PEVLNIIQEN HIKSIISLLD KHGRNHKVLD 610 620 630 640 650 660 VLCSLCVCNG VAVRSNQDLI TENLLPGREL LLQTNLINYV TSIRPNIFVG RAEGTTQYSK 670 680 690 700 710 720 WYFEVMVDEV TPFLTAQATH LRVGWALTEG YTPYPGAGEG WGGNGVGDDL YSYGFDGLHL 730 740 750 760 770 780 WTGHVARPVT SPGQHLLAPE DVISCCLDLS VPSISFRING CPVQGVFESF NLDGLFFPVV 790 800 810 820 830 840 SFSAGVKVRF LLGGRHGEFK FLPPPGYAPC HEAVLPRERL HLEPIKEYRR EGPRGPHLVG 850 860 870 880 890 900 PSRCLSHTDF VPCPVDTVQI VLPPHLERIR EKLAENIHEL WALTRIEQGW TYGPVRDDNK 910 920 930 940 950 960 RLHPCLVDFH SLPEPERNYN LQMSGETLKT LLALGCHVGM ADEKAEDNLK KTKLPKTYMM 970 980 990 1000 1010 1020 SNGYKPAPLD LSHVRLTPAQ TTLVDRLAEN GHNVWARDRV GQGWSYSAVQ DIPARRNPRL 1030 1040 1050 1060 1070 1080 VPYRLLDEAT KRSNRDSLCQ AVRTLLGYGY NIEPPDQEPS QVENQSRCDR VRIFRAEKSY 1090 1100 1110 1120 1130 1140 TVQSGRWYFE FEAVTTGEMR VGWARPELRP DVELGADELA YVFNGHRGQR WHLGSEPFGR 1150 1160 1170 1180 1190 1200 PWQPGDVVGC MIDLTENTII FTLNGEVLMS DSGSETAFRE IEIGDGFLPV CSLGPGQVGH 1210 1220 1230 1240 1250 1260 LNLGQDVSSL RFFAICGLQE GFEPFAINMQ RPVTTWFSKG LPQFEPVPLE HPHYEVSRVD 1270 1280 1290 1300 1310 1320 GTVDTPPCLR LTHRTWGSQN SLVEMLFLRL SLPVQFHQHF RCTAGATPLA PPGLQPPAED 1330 1340 1350 1360 1370 1380 EARAAEPDPD YENLRRSAGG WSEAENGKEG TAKEGAPGGT PQAGGEAQPA RAENEKDATT 1390 1400 1410 1420 1430 1440 EKNKKRGFLF KAKKVAMMTQ PPATPTLPRL PHDVVPADNR DDPEIILNTT TYYYSVRVFA 1450 1460 1470 1480 1490 1500 GQEPSCVWAG WVTPDYHQHD MSFDLSKVRV VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV 1510 1520 1530 1540 1550 1560 SPGQQGRISH TDLVIGCLVD LATGLMTFTA NGKESNTFFQ VEPNTKLFPA VFVLPTHQNV 1570 1580 1590 1600 1610 1620 IQFELGKQKN IMPLSAAMFQ SERKNPAPQC PPRLEMQMLM PVSWSRMPNH FLQVETRRAG 1630 1640 1650 1660 1670 1680 ERLGWAVQCQ EPLTMMALHI PEENRCMDIL ELSERLDLQR FHSHTLRLYR AVCALGNNRV 1690 1700 1710 1720 1730 1740 AHALCSHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTPE 1750 1760 1770 1780 1790 1800 TRAITLFPPG RSTENGHPRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG AAEAPARLSP 1810 1820 1830 1840 1850 1860 AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK 1870 1880 1890 1900 1910 1920 QILKMIEPEV FTEEEEEEDE EEEGEEEDEE EKEEDEEETA QEKEDEEKEE EEAAEGEKEE 1930 1940 1950 1960 1970 1980 GLEEGLLQMK LPESVKLQMC HLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYGLL 1990 2000 2010 2020 2030 2040 IKAFSMTAAE TARRTREFRS PPQEQINMLL QFKDGTDEED CPLPEEIRQD LLDFHQDLLA 2050 2060 2070 2080 2090 2100 HCGIQLDGEE EEPEEETTLG SRLMSLLEKV RLVKKKEEKP EEERSAEESK PRSLQELVSH 2110 2120 2130 2140 2150 2160 MVVRWAQEDF VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG 2170 2180 2190 2200 2210 2220 QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGES 2230 2240 2250 2260 2270 2280 KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV 2290 2300 2310 2320 2330 2340 IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLVAKGYPD IGWNPCGGER YLDFLRFAVF 2350 2360 2370 2380 2390 2400 VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGIRRD 2410 2420 2430 2440 2450 2460 RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL 2470 2480 2490 2500 2510 2520 VPLEDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH 2530 2540 2550 2560 2570 2580 VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD 2590 2600 2610 2620 2630 2640 SMLHTVYRLS RGRSLTKAQR DVIEDCLMSL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP 2650 2660 2670 2680 2690 2700 LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDPELYRMAM 2710 2720 2730 2740 2750 2760 PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE 2770 2780 2790 2800 2810 2820 YTHEKWAFDK IQNNWSYGEN IDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE 2830 2840 2850 2860 2870 2880 WTIEKAREGE EEKTEKKKTR KISQSAQTYD PREGYNPQPP DLSAVTLSRE LQAMAEQLAE 2890 2900 2910 2920 2930 2940 NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG 2950 2960 2970 2980 2990 3000 LKDMELDSSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK 3010 3020 3030 3040 3050 3060 ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD 3070 3080 3090 3100 3110 3120 APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART 3130 3140 3150 3160 3170 3180 QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN 3190 3200 3210 3220 3230 3240 TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC 3250 3260 3270 3280 3290 3300 PDIPVLERLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPSALPAGA 3310 3320 3330 3340 3350 3360 PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EASWMKRLAV FAQPIVSRAR PELLQSHFIP 3370 3380 3390 3400 3410 3420 TIGRLRKRAG KVVSEEEQLR LEAKAEAQEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR 3430 3440 3450 3460 3470 3480 AQWLTEPNPS AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADNKSKMAK 3490 3500 3510 3520 3530 3540 AGDIQSGGSD QERTKKKRRG DRYSVQTSLI VATLKKMLPI GLNMCAPTDQ DLITLAKTRY 3550 3560 3570 3580 3590 3600 ALKDTDEEVR EFLHNNLHLQ GKVEGSPSLR WQMALYRGVP GREEDADDPE KIVRRVQEVS 3610 3620 3630 3640 3650 3660 AVLYYLDQTE HPYKSKKAVW HKLLSKQRRR AVVACFRMTP LYNLPTHRAC NMFLESYKAA 3670 3680 3690 3700 3710 3720 WILTEDHSFE DRMIDDLSKA GEQEEEEEEV EEKKPDPLHQ LVLHFSRTAL TEKSKLDEDY 3730 3740 3750 3760 3770 3780 LYMAYADIMA KSCHLEEGGE NGEAEEEVEV SFEEKQMEKQ RLLYQQARLH TRGAAEMVLQ 3790 3800 3810 3820 3830 3840 MISACKGETG AMVSSTLKLG ISILNGGNAE VQQKMLDYLK DKKEVGFFQS IQALMQTCSV 3850 3860 3870 3880 3890 3900 LDLNAFERQN KAEGLGMVNE DGTVINRQNG EKVMADDEFT QDLFRFLQLL CEGHNNDFQN 3910 3920 3930 3940 3950 3960 YLRTQTGNTT TINIIICTVD YLLRLQESIS DFYWYYSGKD VIEEQGKRNF SKAMSVAKQV 3970 3980 3990 4000 4010 4020 FNSLTEYIQG PCTGNQQSLA HSRLWDAVVG FLHVFAHMMM KLAQDSSQIE LLKELLDLQK 4030 4040 4050 4060 4070 4080 DMVVMLLSLL EGNVVNGMIA RQMVDMLVES SSNVEMILKF FDMFLKLKDI VGSEAFQDYV 4090 4100 4110 4120 4130 4140 TDPRGLISKK DFQKAMDSQK QFSGPEIQFL LSCSEADENE MINCEEFANR FQEPARDIGF 4150 4160 4170 4180 4190 4200 NVAVLLTNLS EHVPHDPRLH NFLELAESIL EYFRPYLGRI EIMGASRRIE RIYFEISETN 4210 4220 4230 4240 4250 4260 RAQWEMPQVK ESKRQFIFDV VNEGGEAEKM ELFVSFCEDT IFEMQIAAQI SEPEGEPETD 4270 4280 4290 4300 4310 4320 EDEGAGAAEA GAEGAEEGAA GLEGTAATAA AGATARVVAA AGRALRGLSY RSLRRRVRRL 4330 4340 4350 4360 4370 4380 RRLTAREAAT AVAALLWAAV TRAGAAGAGA AAGALGLLWG SLFGGGLVEG AKKVTVTELL 4390 4400 4410 4420 4430 4440 AGMPDPTSDE VHGEQPAGPG GDADGEGASE GAGDAAEGAG DEEEAVHEAG PGGADGAVAV 4450 4460 4470 4480 4490 4500 TDGGPFRPEG AGGLGDMGDT TPAEPPTPEG SPILKRKLGV DGVEEELPPE PEPEPEPELE 4510 4520 4530 4540 4550 4560 PEKADAENGE KEEVPEPTPE PPKKQAPPSP PPKKEEAGGE FWGELEVQRV KFLNYLSRNF 4570 4580 4590 4600 4610 4620 YTLRFLALFL AFAINFILLF YKVSDSPPGE DDMEGSAAGD VSGAGSGGSS GWGLGAGEEA 4630 4640 4650 4660 4670 4680 EGDEDENMVY YFLEESTGYM EPALRCLSLL HTLVAFLCII GYNCLKVPLV IFKREKELAR 4690 4700 4710 4720 4730 4740 KLEFDGLYIT EQPEDDDVKG QWDRLVLNTP SFPSNYWDKF VKRKVLDKHG DIYGRERIAE 4750 4760 4770 4780 4790 4800 LLGMDLATLE ITAHNERKPN PPPGLLTWLM SIDVKYQIWK FGVIFTDNSF LYLGWYMVMS 4810 4820 4830 4840 4850 4860 LLGHYNNFFF AAHLLDIAMG VKTLRTILSS VTHNGKQLVM TVGLLAVVVY LYTVVAFNFF 4870 4880 4890 4900 4910 4920 RKFYNKSEDE DEPDMKCDDM MTCYLFHMYV GVRAGGGIGD EIEDPAGDEY ELYRVVFDIT 4930 4940 4950 4960 4970 4980 FFFFVIVILL AIIQGLIIDA FGELRDQQEQ VKEDMETKCF ICGIGSDYFD TTPHGFETHT 4990 5000 5010 5020 5030 LEEHNLANYM FFLMYLINKD ETEHTGQESY VWKMYQERCW DFFPAGDCFR KQYEDQLS
	Isoform 2 [UniParc]. Checksum: 59C8B257F3ED6BF2	FASTA	5,033	564,691
	10 20 30 40 50 60 MGDAEGEDEV QFLRTDDEVV LQCSATVLKE QLKLCLAAEG FGNRLCFLEP TSNAQNVPPD 70 80 90 100 110 120 LAICCFVLEQ SLSVRALQEM LANTVEAGVE SSQGGGHRTL LYGHAILLRH AHSRMYLSCL 130 140 150 160 170 180 TTSRSMTDKL AFDVGLQEDA TGEACWWTMH PASKQRSEGE KVRVGDDIIL VSVSSERYLH 190 200 210 220 230 240 LSTASGELQV DASFMQTLWN MNPICSRCEE GFVTGGHVLR LFHGHMDECL TISPADSDDQ 250 260 270 280 290 300 RRLVYYEGGA VCTHARSLWR LEPLRISWSG SHLRWGQPLR VRHVTTGQYL ALTEDQGLVV 310 320 330 340 350 360 VDASKAHTKA TSFCFRISKE KLDVAPKRDV EGMGPPEIKY GESLCFVQHV ASGLWLTYAA 370 380 390 400 410 420 PDPKALRLGV LKKKAMLHQE GHMDDALSLT RCQQEESQAA RMIHSTNGLY NQFIKSLDSF 430 440 450 460 470 480 SGKPRGSGPP AGTALPIEGV ILSLQDLIIY FEPPSEDLQH EEKQSKLRSL RNRQSLFQEE 490 500 510 520 530 540 GMLSMVLNCI DRLNVYTTAA HFAEFAGEEA AESWKEIVNL LYELLASLIR GNRSNCALFS 550 560 570 580 590 600 TNLDWLVSKL DRLEASSGIL EVLYCVLIES PEVLNIIQEN HIKSIISLLD KHGRNHKVLD 610 620 630 640 650 660 VLCSLCVCNG VAVRSNQDLI TENLLPGREL LLQTNLINYV TSIRPNIFVG RAEGTTQYSK 670 680 690 700 710 720 WYFEVMVDEV TPFLTAQATH LRVGWALTEG YTPYPGAGEG WGGNGVGDDL YSYGFDGLHL 730 740 750 760 770 780 WTGHVARPVT SPGQHLLAPE DVISCCLDLS VPSISFRING CPVQGVFESF NLDGLFFPVV 790 800 810 820 830 840 SFSAGVKVRF LLGGRHGEFK FLPPPGYAPC HEAVLPRERL HLEPIKEYRR EGPRGPHLVG 850 860 870 880 890 900 PSRCLSHTDF VPCPVDTVQI VLPPHLERIR EKLAENIHEL WALTRIEQGW TYGPVRDDNK 910 920 930 940 950 960 RLHPCLVDFH SLPEPERNYN LQMSGETLKT LLALGCHVGM ADEKAEDNLK KTKLPKTYMM 970 980 990 1000 1010 1020 SNGYKPAPLD LSHVRLTPAQ TTLVDRLAEN GHNVWARDRV GQGWSYSAVQ DIPARRNPRL 1030 1040 1050 1060 1070 1080 VPYRLLDEAT KRSNRDSLCQ AVRTLLGYGY NIEPPDQEPS QVENQSRCDR VRIFRAEKSY 1090 1100 1110 1120 1130 1140 TVQSGRWYFE FEAVTTGEMR VGWARPELRP DVELGADELA YVFNGHRGQR WHLGSEPFGR 1150 1160 1170 1180 1190 1200 PWQPGDVVGC MIDLTENTII FTLNGEVLMS DSGSETAFRE IEIGDGFLPV CSLGPGQVGH 1210 1220 1230 1240 1250 1260 LNLGQDVSSL RFFAICGLQE GFEPFAINMQ RPVTTWFSKG LPQFEPVPLE HPHYEVSRVD 1270 1280 1290 1300 1310 1320 GTVDTPPCLR LTHRTWGSQN SLVEMLFLRL SLPVQFHQHF RCTAGATPLA PPGLQPPAED 1330 1340 1350 1360 1370 1380 EARAAEPDPD YENLRRSAGG WSEAENGKEG TAKEGAPGGT PQAGGEAQPA RAENEKDATT 1390 1400 1410 1420 1430 1440 EKNKKRGFLF KAKKVAMMTQ PPATPTLPRL PHDVVPADNR DDPEIILNTT TYYYSVRVFA 1450 1460 1470 1480 1490 1500 GQEPSCVWAG WVTPDYHQHD MSFDLSKVRV VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV 1510 1520 1530 1540 1550 1560 SPGQQGRISH TDLVIGCLVD LATGLMTFTA NGKESNTFFQ VEPNTKLFPA VFVLPTHQNV 1570 1580 1590 1600 1610 1620 IQFELGKQKN IMPLSAAMFQ SERKNPAPQC PPRLEMQMLM PVSWSRMPNH FLQVETRRAG 1630 1640 1650 1660 1670 1680 ERLGWAVQCQ EPLTMMALHI PEENRCMDIL ELSERLDLQR FHSHTLRLYR AVCALGNNRV 1690 1700 1710 1720 1730 1740 AHALCSHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTPE 1750 1760 1770 1780 1790 1800 TRAITLFPPG RSTENGHPRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG AAEAPARLSP 1810 1820 1830 1840 1850 1860 AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK 1870 1880 1890 1900 1910 1920 QILKMIEPEV FTEEEEEEDE EEEGEEEDEE EKEEDEEETA QEKEDEEKEE EEAAEGEKEE 1930 1940 1950 1960 1970 1980 GLEEGLLQMK LPESVKLQMC HLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYGLL 1990 2000 2010 2020 2030 2040 IKAFSMTAAE TARRTREFRS PPQEQINMLL QFKDGTDEED CPLPEEIRQD LLDFHQDLLA 2050 2060 2070 2080 2090 2100 HCGIQLDGEE EEPEEETTLG SRLMSLLEKV RLVKKKEEKP EEERSAEESK PRSLQELVSH 2110 2120 2130 2140 2150 2160 MVVRWAQEDF VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG 2170 2180 2190 2200 2210 2220 QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGES 2230 2240 2250 2260 2270 2280 KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV 2290 2300 2310 2320 2330 2340 IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLVAKGYPD IGWNPCGGER YLDFLRFAVF 2350 2360 2370 2380 2390 2400 VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGIRRD 2410 2420 2430 2440 2450 2460 RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL 2470 2480 2490 2500 2510 2520 VPLEDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH 2530 2540 2550 2560 2570 2580 VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD 2590 2600 2610 2620 2630 2640 SMLHTVYRLS RGRSLTKAQR DVIEDCLMSL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP 2650 2660 2670 2680 2690 2700 LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDPELYRMAM 2710 2720 2730 2740 2750 2760 PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE 2770 2780 2790 2800 2810 2820 YTHEKWAFDK IQNNWSYGEN IDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE 2830 2840 2850 2860 2870 2880 WTIEKAREGE EEKTEKKKTR KISQSAQTYD PREGYNPQPP DLSAVTLSRE LQAMAEQLAE 2890 2900 2910 2920 2930 2940 NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG 2950 2960 2970 2980 2990 3000 LKDMELDSSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK 3010 3020 3030 3040 3050 3060 ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD 3070 3080 3090 3100 3110 3120 APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART 3130 3140 3150 3160 3170 3180 QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN 3190 3200 3210 3220 3230 3240 TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC 3250 3260 3270 3280 3290 3300 PDIPVLERLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPSALPAGA 3310 3320 3330 3340 3350 3360 PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EASWMKRLAV FAQPIVSRAR PELLQSHFIP 3370 3380 3390 3400 3410 3420 TIGRLRKRAG KVVSEEEQLR LEAKAEAQEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR 3430 3440 3450 3460 3470 3480 AQWLTEPNPS AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADNKSKMAK 3490 3500 3510 3520 3530 3540 SGGSDQERTK KKRRGDRYSV QTSLIVATLK KMLPIGLNMC APTDQDLITL AKTRYALKDT 3550 3560 3570 3580 3590 3600 DEEVREFLHN NLHLQGKVEG SPSLRWQMAL YRGVPGREED ADDPEKIVRR VQEVSAVLYY 3610 3620 3630 3640 3650 3660 LDQTEHPYKS KKAVWHKLLS KQRRRAVVAC FRMTPLYNLP THRACNMFLE SYKAAWILTE 3670 3680 3690 3700 3710 3720 DHSFEDRMID DLSKAGEQEE EEEEVEEKKP DPLHQLVLHF SRTALTEKSK LDEDYLYMAY 3730 3740 3750 3760 3770 3780 ADIMAKSCHL EEGGENGEAE EEVEVSFEEK QMEKQRLLYQ QARLHTRGAA EMVLQMISAC 3790 3800 3810 3820 3830 3840 KGETGAMVSS TLKLGISILN GGNAEVQQKM LDYLKDKKEV GFFQSIQALM QTCSVLDLNA 3850 3860 3870 3880 3890 3900 FERQNKAEGL GMVNEDGTVI NRQNGEKVMA DDEFTQDLFR FLQLLCEGHN NDFQNYLRTQ 3910 3920 3930 3940 3950 3960 TGNTTTINII ICTVDYLLRL QESISDFYWY YSGKDVIEEQ GKRNFSKAMS VAKQVFNSLT 3970 3980 3990 4000 4010 4020 EYIQGPCTGN QQSLAHSRLW DAVVGFLHVF AHMMMKLAQD SSQIELLKEL LDLQKDMVVM 4030 4040 4050 4060 4070 4080 LLSLLEGNVV NGMIARQMVD MLVESSSNVE MILKFFDMFL KLKDIVGSEA FQDYVTDPRG 4090 4100 4110 4120 4130 4140 LISKKDFQKA MDSQKQFSGP EIQFLLSCSE ADENEMINCE EFANRFQEPA RDIGFNVAVL 4150 4160 4170 4180 4190 4200 LTNLSEHVPH DPRLHNFLEL AESILEYFRP YLGRIEIMGA SRRIERIYFE ISETNRAQWE 4210 4220 4230 4240 4250 4260 MPQVKESKRQ FIFDVVNEGG EAEKMELFVS FCEDTIFEMQ IAAQISEPEG EPETDEDEGA 4270 4280 4290 4300 4310 4320 GAAEAGAEGA EEGAAGLEGT AATAAAGATA RVVAAAGRAL RGLSYRSLRR RVRRLRRLTA 4330 4340 4350 4360 4370 4380 REAATAVAAL LWAAVTRAGA AGAGAAAGAL GLLWGSLFGG GLVEGAKKVT VTELLAGMPD 4390 4400 4410 4420 4430 4440 PTSDEVHGEQ PAGPGGDADG EGASEGAGDA AEGAGDEEEA VHEAGPGGAD GAVAVTDGGP 4450 4460 4470 4480 4490 4500 FRPEGAGGLG DMGDTTPAEP PTPEGSPILK RKLGVDGVEE ELPPEPEPEP EPELEPEKAD 4510 4520 4530 4540 4550 4560 AENGEKEEVP EPTPEPPKKQ APPSPPPKKE EAGGEFWGEL EVQRVKFLNY LSRNFYTLRF 4570 4580 4590 4600 4610 4620 LALFLAFAIN FILLFYKVSD SPPGEDDMEG SAAGDVSGAG SGGSSGWGLG AGEEAEGDED 4630 4640 4650 4660 4670 4680 ENMVYYFLEE STGYMEPALR CLSLLHTLVA FLCIIGYNCL KVPLVIFKRE KELARKLEFD 4690 4700 4710 4720 4730 4740 GLYITEQPED DDVKGQWDRL VLNTPSFPSN YWDKFVKRKV LDKHGDIYGR ERIAELLGMD 4750 4760 4770 4780 4790 4800 LATLEITAHN ERKPNPPPGL LTWLMSIDVK YQIWKFGVIF TDNSFLYLGW YMVMSLLGHY 4810 4820 4830 4840 4850 4860 NNFFFAAHLL DIAMGVKTLR TILSSVTHNG KQLVMTVGLL AVVVYLYTVV AFNFFRKFYN 4870 4880 4890 4900 4910 4920 KSEDEDEPDM KCDDMMTCYL FHMYVGVRAG GGIGDEIEDP AGDEYELYRV VFDITFFFFV 4930 4940 4950 4960 4970 4980 IVILLAIIQG LIIDAFGELR DQQEQVKEDM ETKCFICGIG SDYFDTTPHG FETHTLEEHN 4990 5000 5010 5020 5030 LANYMFFLMY LINKDETEHT GQESYVWKMY QERCWDFFPA GDCFRKQYED QLS
	Isoform 3 [UniParc]. Checksum: C2A4DBEA0FDEEE8B	FASTA	5,033	564,550
	10 20 30 40 50 60 MGDAEGEDEV QFLRTDDEVV LQCSATVLKE QLKLCLAAEG FGNRLCFLEP TSNAQNVPPD 70 80 90 100 110 120 LAICCFVLEQ SLSVRALQEM LANTVEAGVE SSQGGGHRTL LYGHAILLRH AHSRMYLSCL 130 140 150 160 170 180 TTSRSMTDKL AFDVGLQEDA TGEACWWTMH PASKQRSEGE KVRVGDDIIL VSVSSERYLH 190 200 210 220 230 240 LSTASGELQV DASFMQTLWN MNPICSRCEE GFVTGGHVLR LFHGHMDECL TISPADSDDQ 250 260 270 280 290 300 RRLVYYEGGA VCTHARSLWR LEPLRISWSG SHLRWGQPLR VRHVTTGQYL ALTEDQGLVV 310 320 330 340 350 360 VDASKAHTKA TSFCFRISKE KLDVAPKRDV EGMGPPEIKY GESLCFVQHV ASGLWLTYAA 370 380 390 400 410 420 PDPKALRLGV LKKKAMLHQE GHMDDALSLT RCQQEESQAA RMIHSTNGLY NQFIKSLDSF 430 440 450 460 470 480 SGKPRGSGPP AGTALPIEGV ILSLQDLIIY FEPPSEDLQH EEKQSKLRSL RNRQSLFQEE 490 500 510 520 530 540 GMLSMVLNCI DRLNVYTTAA HFAEFAGEEA AESWKEIVNL LYELLASLIR GNRSNCALFS 550 560 570 580 590 600 TNLDWLVSKL DRLEASSGIL EVLYCVLIES PEVLNIIQEN HIKSIISLLD KHGRNHKVLD 610 620 630 640 650 660 VLCSLCVCNG VAVRSNQDLI TENLLPGREL LLQTNLINYV TSIRPNIFVG RAEGTTQYSK 670 680 690 700 710 720 WYFEVMVDEV TPFLTAQATH LRVGWALTEG YTPYPGAGEG WGGNGVGDDL YSYGFDGLHL 730 740 750 760 770 780 WTGHVARPVT SPGQHLLAPE DVISCCLDLS VPSISFRING CPVQGVFESF NLDGLFFPVV 790 800 810 820 830 840 SFSAGVKVRF LLGGRHGEFK FLPPPGYAPC HEAVLPRERL HLEPIKEYRR EGPRGPHLVG 850 860 870 880 890 900 PSRCLSHTDF VPCPVDTVQI VLPPHLERIR EKLAENIHEL WALTRIEQGW TYGPVRDDNK 910 920 930 940 950 960 RLHPCLVDFH SLPEPERNYN LQMSGETLKT LLALGCHVGM ADEKAEDNLK KTKLPKTYMM 970 980 990 1000 1010 1020 SNGYKPAPLD LSHVRLTPAQ TTLVDRLAEN GHNVWARDRV GQGWSYSAVQ DIPARRNPRL 1030 1040 1050 1060 1070 1080 VPYRLLDEAT KRSNRDSLCQ AVRTLLGYGY NIEPPDQEPS QVENQSRCDR VRIFRAEKSY 1090 1100 1110 1120 1130 1140 TVQSGRWYFE FEAVTTGEMR VGWARPELRP DVELGADELA YVFNGHRGQR WHLGSEPFGR 1150 1160 1170 1180 1190 1200 PWQPGDVVGC MIDLTENTII FTLNGEVLMS DSGSETAFRE IEIGDGFLPV CSLGPGQVGH 1210 1220 1230 1240 1250 1260 LNLGQDVSSL RFFAICGLQE GFEPFAINMQ RPVTTWFSKG LPQFEPVPLE HPHYEVSRVD 1270 1280 1290 1300 1310 1320 GTVDTPPCLR LTHRTWGSQN SLVEMLFLRL SLPVQFHQHF RCTAGATPLA PPGLQPPAED 1330 1340 1350 1360 1370 1380 EARAAEPDPD YENLRRSAGG WSEAENGKEG TAKEGAPGGT PQAGGEAQPA RAENEKDATT 1390 1400 1410 1420 1430 1440 EKNKKRGFLF KAKKVAMMTQ PPATPTLPRL PHDVVPADNR DDPEIILNTT TYYYSVRVFA 1450 1460 1470 1480 1490 1500 GQEPSCVWAG WVTPDYHQHD MSFDLSKVRV VTVTMGDEQG NVHSSLKCSN CYMVWGGDFV 1510 1520 1530 1540 1550 1560 SPGQQGRISH TDLVIGCLVD LATGLMTFTA NGKESNTFFQ VEPNTKLFPA VFVLPTHQNV 1570 1580 1590 1600 1610 1620 IQFELGKQKN IMPLSAAMFQ SERKNPAPQC PPRLEMQMLM PVSWSRMPNH FLQVETRRAG 1630 1640 1650 1660 1670 1680 ERLGWAVQCQ EPLTMMALHI PEENRCMDIL ELSERLDLQR FHSHTLRLYR AVCALGNNRV 1690 1700 1710 1720 1730 1740 AHALCSHVDQ AQLLHALEDA HLPGPLRAGY YDLLISIHLE SACRSRRSML SEYIVPLTPE 1750 1760 1770 1780 1790 1800 TRAITLFPPG RSTENGHPRH GLPGVGVTTS LRPPHHFSPP CFVAALPAAG AAEAPARLSP 1810 1820 1830 1840 1850 1860 AIPLEALRDK ALRMLGEAVR DGGQHARDPV GGSVEFQFVP VLKLVSTLLV MGIFGDEDVK 1870 1880 1890 1900 1910 1920 QILKMIEPEV FTEEEEEEDE EEEGEEEDEE EKEEDEEETA QEKEDEEKEE EEAAEGEKEE 1930 1940 1950 1960 1970 1980 GLEEGLLQMK LPESVKLQMC HLLEYFCDQE LQHRVESLAA FAERYVDKLQ ANQRSRYGLL 1990 2000 2010 2020 2030 2040 IKAFSMTAAE TARRTREFRS PPQEQINMLL QFKDGTDEED CPLPEEIRQD LLDFHQDLLA 2050 2060 2070 2080 2090 2100 HCGIQLDGEE EEPEEETTLG SRLMSLLEKV RLVKKKEEKP EEERSAEESK PRSLQELVSH 2110 2120 2130 2140 2150 2160 MVVRWAQEDF VQSPELVRAM FSLLHRQYDG LGELLRALPR AYTISPSSVE DTMSLLECLG 2170 2180 2190 2200 2210 2220 QIRSLLIVQM GPQEENLMIQ SIGNIMNNKV FYQHPNLMRA LGMHETVMEV MVNVLGGGES 2230 2240 2250 2260 2270 2280 KEIRFPKMVT SCCRFLCYFC RISRQNQRSM FDHLSYLLEN SGIGLGMQGS TPLDVAAASV 2290 2300 2310 2320 2330 2340 IDNNELALAL QEQDLEKVVS YLAGCGLQSC PMLVAKGYPD IGWNPCGGER YLDFLRFAVF 2350 2360 2370 2380 2390 2400 VNGESVEENA NVVVRLLIRK PECFGPALRG EGGSGLLAAI EEAIRISEDP ARDGPGIRRD 2410 2420 2430 2440 2450 2460 RRREHFGEEP PEENRVHLGH AIMSFYAALI DLLGRCAPEM HLIQAGKGEA LRIRAILRSL 2470 2480 2490 2500 2510 2520 VPLEDLVGII SLPLQIPTLG KDGALVQPKM SASFVPDHKA SMVLFLDRVY GIENQDFLLH 2530 2540 2550 2560 2570 2580 VLDVGFLPDM RAAASLDTAT FSTTEMALAL NRYLCLAVLP LITKCAPLFA GTEHRAIMVD 2590 2600 2610 2620 2630 2640 SMLHTVYRLS RGRSLTKAQR DVIEDCLMSL CRYIRPSMLQ HLLRRLVFDV PILNEFAKMP 2650 2660 2670 2680 2690 2700 LKLLTNHYER CWKYYCLPTG WANFGVTSEE ELHLTRKLFW GIFDSLAHKK YDPELYRMAM 2710 2720 2730 2740 2750 2760 PCLCAIAGAL PPDYVDASYS SKAEKKATVD AEGNFDPRPV ETLNVIIPEK LDSFINKFAE 2770 2780 2790 2800 2810 2820 YTHEKWAFDK IQNNWSYGEN IDEELKTHPM LRPYKTFSEK DKEIYRWPIK ESLKAMIAWE 2830 2840 2850 2860 2870 2880 WTIEKAREGE EEKTEKKKTR KISQSAQTYD PREGYNPQPP DLSAVTLSRE LQAMAEQLAE 2890 2900 2910 2920 2930 2940 NYHNTWGRKK KQELEAKGGG THPLLVPYDT LTAKEKARDR EKAQELLKFL QMNGYAVTRG 2950 2960 2970 2980 2990 3000 LKDMELDSSS IEKRFAFGFL QQLLRWMDIS QEFIAHLEAV VSSGRVEKSP HEQEIKFFAK 3010 3020 3030 3040 3050 3060 ILLPLINQYF TNHCLYFLST PAKVLGSGGH ASNKEKEMIT SLFCKLAALV RHRVSLFGTD 3070 3080 3090 3100 3110 3120 APAVVNCLHI LARSLDARTV MKSGPEIVKA GLRSFFESAS EDIEKMVENL RLGKVSQART 3130 3140 3150 3160 3170 3180 QVKGVGQNLT YTTVALLPVL TTLFQHIAQH QFGDDVILDD VQVSCYRTLC SIYSLGTTKN 3190 3200 3210 3220 3230 3240 TYVEKLRPAL GECLARLAAA MPVAFLEPQL NEYNACSVYT TKSPRERAIL GLPNSVEEMC 3250 3260 3270 3280 3290 3300 PDIPVLERLM ADIGGLAESG ARYTEMPHVI EITLPMLCSY LPRWWERGPE APPSALPAGA 3310 3320 3330 3340 3350 3360 PPPCTAVTSD HLNSLLGNIL RIIVNNLGID EASWMKRLAV FAQPIVSRAR PELLQSHFIP 3370 3380 3390 3400 3410 3420 TIGRLRKRAG KVVSEEEQLR LEAKAEAQEG ELLVRDEFSV LCRDLYALYP LLIRYVDNNR 3430 3440 3450 3460 3470 3480 AQWLTEPNPS AEELFRMVGE IFIYWSKSHN FKREEQNFVV QNEINNMSFL TADNKSKMAK 3490 3500 3510 3520 3530 3540 AGDIQSGGSD QERTKKKRRG DRYSVQTSLI VATLKKMLPI GLNMCAPTDQ DLITLAKTRY 3550 3560 3570 3580 3590 3600 ALKDTDEEVR EFLHNNLHLQ GKVEGSPSLR WQMALYRGVP GREEDADDPE KIVRRVQEVS 3610 3620 3630 3640 3650 3660 AVLYYLDQTE HPYKSKKAVW HKLLSKQRRR AVVACFRMTP LYNLPTHRAC NMFLESYKAA 3670 3680 3690 3700 3710 3720 WILTEDHSFE DRMIDDLSKA GEQEEEEEEV EEKKPDPLHQ LVLHFSRTAL TEKSKLDEDY 3730 3740 3750 3760 3770 3780 LYMAYADIMA KSCHLEEGGE NGEAEEEVEV SFEEKQMEKQ RLLYQQARLH TRGAAEMVLQ 3790 3800 3810 3820 3830 3840 MISACKGETG AMVSSTLKLG ISILNGGNAE VQQKMLDYLK DKKEVGFFQS IQALMQTCSV 3850 3860 3870 3880 3890 3900 LDLNAFERQN KAEGLGMVNE DGTVGEKVMA DDEFTQDLFR FLQLLCEGHN NDFQNYLRTQ 3910 3920 3930 3940 3950 3960 TGNTTTINII ICTVDYLLRL QESISDFYWY YSGKDVIEEQ GKRNFSKAMS VAKQVFNSLT 3970 3980 3990 4000 4010 4020 EYIQGPCTGN QQSLAHSRLW DAVVGFLHVF AHMMMKLAQD SSQIELLKEL LDLQKDMVVM 4030 4040 4050 4060 4070 4080 LLSLLEGNVV NGMIARQMVD MLVESSSNVE MILKFFDMFL KLKDIVGSEA FQDYVTDPRG 4090 4100 4110 4120 4130 4140 LISKKDFQKA MDSQKQFSGP EIQFLLSCSE ADENEMINCE EFANRFQEPA RDIGFNVAVL 4150 4160 4170 4180 4190 4200 LTNLSEHVPH DPRLHNFLEL AESILEYFRP YLGRIEIMGA SRRIERIYFE ISETNRAQWE 4210 4220 4230 4240 4250 4260 MPQVKESKRQ FIFDVVNEGG EAEKMELFVS FCEDTIFEMQ IAAQISEPEG EPETDEDEGA 4270 4280 4290 4300 4310 4320 GAAEAGAEGA EEGAAGLEGT AATAAAGATA RVVAAAGRAL RGLSYRSLRR RVRRLRRLTA 4330 4340 4350 4360 4370 4380 REAATAVAAL LWAAVTRAGA AGAGAAAGAL GLLWGSLFGG GLVEGAKKVT VTELLAGMPD 4390 4400 4410 4420 4430 4440 PTSDEVHGEQ PAGPGGDADG EGASEGAGDA AEGAGDEEEA VHEAGPGGAD GAVAVTDGGP 4450 4460 4470 4480 4490 4500 FRPEGAGGLG DMGDTTPAEP PTPEGSPILK RKLGVDGVEE ELPPEPEPEP EPELEPEKAD 4510 4520 4530 4540 4550 4560 AENGEKEEVP EPTPEPPKKQ APPSPPPKKE EAGGEFWGEL EVQRVKFLNY LSRNFYTLRF 4570 4580 4590 4600 4610 4620 LALFLAFAIN FILLFYKVSD SPPGEDDMEG SAAGDVSGAG SGGSSGWGLG AGEEAEGDED 4630 4640 4650 4660 4670 4680 ENMVYYFLEE STGYMEPALR CLSLLHTLVA FLCIIGYNCL KVPLVIFKRE KELARKLEFD 4690 4700 4710 4720 4730 4740 GLYITEQPED DDVKGQWDRL VLNTPSFPSN YWDKFVKRKV LDKHGDIYGR ERIAELLGMD 4750 4760 4770 4780 4790 4800 LATLEITAHN ERKPNPPPGL LTWLMSIDVK YQIWKFGVIF TDNSFLYLGW YMVMSLLGHY 4810 4820 4830 4840 4850 4860 NNFFFAAHLL DIAMGVKTLR TILSSVTHNG KQLVMTVGLL AVVVYLYTVV AFNFFRKFYN 4870 4880 4890 4900 4910 4920 KSEDEDEPDM KCDDMMTCYL FHMYVGVRAG GGIGDEIEDP AGDEYELYRV VFDITFFFFV 4930 4940 4950 4960 4970 4980 IVILLAIIQG LIIDAFGELR DQQEQVKEDM ETKCFICGIG SDYFDTTPHG FETHTLEEHN 4990 5000 5010 5020 5030 LANYMFFLMY LINKDETEHT GQESYVWKMY QERCWDFFPA GDCFRKQYED QLS

References

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[1]	"Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum." Zorzato F., Fujii J., Otsu K., Phillips M.S., Green N.M., Lai F.A., Meissner G., Maclennan D.H. J. Biol. Chem. 265:2244-2256(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE. Tissue: Skeletal muscle.
[2]	"Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia." Gillard E.F., Otsu K., Fujii J., Duff C.L., de Leon S., Khanna V.K., Britt B.A., Worton R.G., McLennan D.H. Genomics 13:1247-1254(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 2324; 2840 AND 3380, VARIANT MHS1 ARG-248, VARIANTS CYS-471; LEU-1787; CYS-2060 AND VAL-2550. Tissue: Muscle.
[3]	"A mutation in the human ryanodine receptor gene associated with central core disease." Zhang Y., Chen H.S., Khanna V.K., de Leon S., Phillips M.S., Schappert K.T., Britt B.A., Brownell A.K.W., McLennan D.H. Nat. Genet. 5:46-50(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 1365-1368, VARIANT CCD/MHS1 HIS-2435, ALTERNATIVE SPLICING. Tissue: Muscle.
[4]	"The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene." Phillips M.S., Fujii J., Khanna V.K., de Leon S., Yokobata K., de Jong P.J., McLennan D.H. Genomics 34:24-41(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, VARIANTS ALA-1832 AND VAL-2550.
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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[7]	"A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia." Gillard E.F., Otsu K., Fujii J., Khanna V.K., de Leon S., Derdemezi J., Britt B.A., Duff C.L., Worton R.G., MacLennan D.H. Genomics 11:751-755(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-641, VARIANT MHS1 CYS-614.
[8]	"Ryanodine receptor gene point mutation and malignant hyperthermia susceptibility." Moroni I., Gonano E.F., Comi G.P., Tegazzin V., Prelle A., Bordoni A., Bresolin N., Scarlato G. J. Neurol. 242:127-133(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 603-627, VARIANT MHS1 CYS-614.
[9]	"Isolation and partial cloning of ryanodine-sensitive Ca2+ release channel protein isoforms from human myometrial smooth muscle." Lynn S., Morgan J.M., Lamb H.K., Meissner G., Gillespie J.I. FEBS Lett. 372:6-12(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4696-4974. Tissue: Myometrium.
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[12]	"S100A1 and calmodulin compete for the same binding site on ryanodine receptor." Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F., Weber D.J. J. Biol. Chem. 283:26676-26683(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CALM AND S100A1.
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[14]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-4864 AND SER-4867, MASS SPECTROMETRY. Tissue: Liver.
[15]	"Ryanodine receptors: structure, expression, molecular details, and function in calcium release." Lanner J.T., Georgiou D.K., Joshi A.D., Hamilton S.L. Cold Spring Harb. Perspect. Biol. 2:E3996-E3996(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[16]	"Samaritan myopathy, an ultimately benign congenital myopathy, is caused by a RYR1 mutation." Bohm J., Leshinsky-Silver E., Vassilopoulos S., Le Gras S., Lerman-Sagie T., Ginzberg M., Jost B., Lev D., Laporte J. Acta Neuropathol. 124:575-581(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SAMARITAN MYOPATHY, VARIANT CYS-1088.
[17]	"Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia." Quane K.A., Healy J.M.S., Keating K.E., Manning B.M., Couch F.J., Palmucci L.M., Doriguzzi C., Fagerlund T.H., Berg K., Ording H., Bendixen D., Mortier W., Linz U., Muller C.R., McCarthy T.V. Nat. Genet. 5:51-55(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD/MHS1 CYS-163 AND MET-403.
[18]	"Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores." Quane K.A., Keating K.E., Healy J.M.S., Manning B.M., Krivosic-Horber R., Krivosic I., Monnier N., Lunardi J., McCarthy T.V. Genomics 23:236-239(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD/MHS1 SER-522.
[19]	"Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies." Quane K.A., Keating K.E., Manning B.M., Healy J.M.S., Monsieurs K., Heffron J.J.A., Lehane M., Heytens L., Krivosic-Horber R., Adnet P., Ellis F.R., Monnier N., Lunardi J., McCarthy T.V. Hum. Mol. Genet. 3:471-476(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 ARG-341.
[20]	"Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees." Keating K.E., Quane K.A., Manning B.M., Lehane M., Hartung E., Censier K., Urwyler A., Klausnitzer M., Muller C.R., Heffron J.J.A., McCarthy T.V. Hum. Mol. Genet. 3:1855-1858(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 ARG-2434.
[21]	"The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia." Phillips M.S., Khanna V.K., de Leon S., Frodis W., Britt B.A., McLennan D.H. Hum. Mol. Genet. 3:2181-2186(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 ARG-2434.
[22]	"Identification of heterozygous and homozygous individuals with the novel RYR1 mutation Cys35Arg in a large kindred." Lynch P.J., Krivosic-Horber R., Reyford H., Monnier N., Quane K.A., Adnet P., Haudecoeur G., Krivosic I., McCarthy T.V., Lunardi J. Anesthesiology 86:620-626(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 ARG-35.
[23]	"Detection of a novel mutation at amino acid position 614 in the ryanodine receptor in malignant hyperthermia." Quane K.A., Ording H., Keating K.E., Manning B.M., Heine R., Bendixen D., Berg K., Krivosic-Horber R., Lehmann-Horn F., Fagerlund T.H., McCarthy T.V. Br. J. Anaesth. 79:332-337(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 LEU-614.
[24]	"Detection of a novel mutation in the ryanodine receptor gene in an Irish malignant hyperthermia pedigree: correlation of the IVCT response with the affected and unaffected haplotypes." Keating K.E., Giblin L., Lynch P.J., Quane K.A., Lehane M., Heffron J.J.A., McCarthy T.V. J. Med. Genet. 34:291-296(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 TRP-552.
[25]	"Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation." Manning B.M., Quane K.A., Ording H., Urwyler A., Tegazzin V., Lehane M., O'Halloran J., Hartung E., Giblin L.M., Lynch P.J., Vaughan P., Censier K., Bendixen D., Comi G.P., Heytens L., Monsieurs K., Fagerlund T.H., Wolz W. , Heffron J.J.A., Mueller C.R., McCarthy T.V. Am. J. Hum. Genet. 62:599-609(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-2163; MET-2168 AND MET-2206, VARIANT CCD/MHS1 HIS-2163.
[26]	"Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia." Manning B.M., Quane K.A., Lynch P.J., Urwyler A., Tegazzin V., Krivosic-Horber R., Censier K., Comi G.P., Adnet P., Wolz W., Lunardi J., Muller C.R., McCarthy T.V. Hum. Mutat. 11:45-50(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-2458 AND HIS-2458.
[27]	"Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test." Brandt A., Schleithoff L., Jurkat-Rott K., Klingler W., Baur C., Lehmann-Horn F. Hum. Mol. Genet. 8:2055-2062(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1.
[28]	"Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families." Barone V., Massa O., Intravaia E., Bracco A., Di Martino A., Tegazzin V., Cozzolino S., Sorrentino V. J. Med. Genet. 36:115-118(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 LEU-2435, VARIANT CCD/MHS1 HIS-2454.
[29]	"A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease." Lynch P.J., Tong J., Lehane M., Mallet A., Giblin L., Heffron J.J.A., Vaughan P., Zafra G., MacLennan D.H., McCarthy T.V. Proc. Natl. Acad. Sci. U.S.A. 96:4164-4169(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD THR-4898, CHARACTERIZATION OF VARIANT CCD THR-4898.
[30]	"Malignant hyperthermia in infancy and identification of novel RYR1 mutation." Chamley D., Pollock N.A., Stowell K.M., Brown R.L. Br. J. Anaesth. 84:500-504(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 TRP-2452 AND HIS-2454.
[31]	"A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree." Brown R.L., Pollock A.N., Couchman K.G., Hodges M., Hutchinson D.O., Waaka R., Lynch P., McCarthy T.V., Stowell K.M. Hum. Mol. Genet. 9:1515-1524(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 ILE-4826.
[32]	"Novel mutation in the RYR1 gene (R2454C) in a patient with malignant hyperthermia." Gencik M., Gencik A., Mortier W., Epplen J.T. Hum. Mutat. 15:122-122(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 CYS-2454.
[33]	"A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy." Scacheri P.C., Hoffman E.P., Fratkin J.D., Semino-Mora C., Senchak A., Davis M.R., Laing N.G., Vedanarayanan V., Subramony S.H. Neurology 55:1689-1696(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD ALA-4637.
[34]	"Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype." Sambuughin N., McWilliams S., de Bantel A., Sivakumar K., Nelson T.E. Am. J. Hum. Genet. 69:204-208(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 GLU-2347 DEL.
[35]	"North American malignant hyperthermia population: screening of the ryanodine receptor gene and identification of novel mutations." Sambuughin N., Sei Y., Gallagher K.L., Wyre H.W., Madsen D., Nelson T.E., Fletcher J.E., Rosenberg H., Muldoon S.M. Anesthesiology 95:594-599(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-163; ARG-248; CYS-614; MET-2168; MET-2206; ILE-2214; THR-2367; ASN-2431; ARG-2434 AND HIS-2454.
[36]	"Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor." Monnier N., Romero N.B., Lerale J., Landrieu P., Nivoche Y., Fardeau M., Lunardi J. Hum. Mol. Genet. 10:2581-2592(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD MET-2168; 4214-ARG--4216-PHE DEL; 4647-LEU-SER-4648 DEL; PRO-4793; CYS-4796; CYS-4825; PHE-4860 DEL; HIS-4861; TRP-4893; THR-4898; GLU-4899 AND GLY-4914.
[37]	"Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis." Tilgen N., Zorzato F., Halliger-Keller B., Muntoni F., Sewry C., Palmucci L.M., Schneider C., Hauser E., Lehmann-Horn F., Mueller C.R., Treves S. Hum. Mol. Genet. 10:2879-2887(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD HIS-4861; ARG-4891; THR-4898; ARG-4899 AND VAL-4906, CHARACTERIZATION OF VARIANTS CCD MET-2168; HIS-4861; TRP-4893; THR-4898 AND ARG-4899.
[38]	"Identification of a novel mutation in the ryanodine receptor gene (RYR1) in patients with malignant hyperthermia." Rueffert H., Kraus H., Olthoff D., Deutrich C., Froster U.G. Hum. Mutat. 17:238-238(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 GLU-2129.
[39]	"Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families." Sambuughin N., Nelson T.E., Jankovic J., Xin C., Meissner G., Mullakandov M., Ji J., Rosenberg H., Sivakumar K., Goldfarb L.G. Neuromuscul. Disord. 11:530-537(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 THR-2350, CHARACTERIZATION OF VARIANT MHS1 THR-2350.
[40]	"Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients susceptible to malignant hyperthermia who show definite IVCT results: identification of three novel mutations." Rueffert H., Olthoff D., Deutrich C., Meinecke C.D., Froster U.G. Acta Anaesthesiol. Scand. 46:692-698(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-163; ASN-166; ARG-341; HIS-401; CYS-614; GLU-2129; MET-2168; MET-2206; THR-2428; ARG-2434; HIS-2435; TRP-2452 AND HIS-2454.
[41]	"Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility." Monnier N., Krivosic-Horber R., Payen J.-F., Kozak-Ribbens G., Nivoche Y., Adnet P., Reyford H., Lunardi J. Anesthesiology 97:1067-1074(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-163; ARG-341; CYS-614; CYS-2454; MET-3916 AND LEU-4973.
[42]	"A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene." Ferreiro A., Monnier N., Romero N.B., Leroy J.-P., Boennemann C., Haenggeli C.-A., Straub V., Voss W.D., Nivoche Y., Jungbluth H., Lemainque A., Voit T., Lunardi J., Fardeau M., Guicheney P. Ann. Neurol. 51:750-759(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD SER-3527.
[43]	"Malignant hyperthermia associated with exercise-induced rhabdomyolysis or congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees." Davis M., Brown R., Dickson A., Horton H., James D., Laing N., Marston R., Norgate M., Perlman D., Pollock N., Stowell K. Br. J. Anaesth. 88:508-515(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 CYS-401.
[44]	"Mutations in the RYR1 gene in Italian patients at risk for malignant hyperthermia: evidence for a cluster of novel mutations in the C-terminal region." Galli L., Orrico A., Cozzolino S., Pietrini V., Tegazzin V., Sorrentino V. Cell Calcium 32:143-151(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-163; CYS-401; HIS-2163; MET-2206; ILE-2280; ARG-2434; LEU-2435; CYS-2458; SER-4136; LEU-4234; TRP-4737; VAL-4942 AND LEU-4973.
[45]	"Novel skeletal muscle ryanodine receptor mutation in a large Brazilian family with malignant hyperthermia." McWilliams S., Nelson T., Sudo R.T., Zapata-Sudo G., Batti M., Sambuughin N. Clin. Genet. 62:80-83(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 CYS-2355.
[46]	"Novel mutations in C-terminal channel region of the ryanodine receptor in malignant hyperthermia patients." Oyamada H., Oguchi K., Saitoh N., Yamazawa T., Hirose K., Kawana Y., Wakatsuki K., Oguchi K., Tagami M., Hanaoka K., Endo M., Iino M. Jpn. J. Pharmacol. 88:159-166(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 VAL-4838, VARIANTS ALA-1832; GLU-3756 AND SER-4668.
[47]	"Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores." Jungbluth H., Muller C.R., Halliger-Keller B., Brockington M., Brown S.C., Feng L., Chattopadhyay A., Mercuri E., Manzur A.Y., Ferreiro A., Laing N.G., Davis M.R., Roper H.P., Dubowitz V., Bydder G., Sewry C.A., Muntoni F. Neurology 59:284-287(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD ILE-4849.
[48]	"Detection of a novel ryanodine receptor subtype 1 mutation (R328W) in a malignant hyperthermia family by sequencing of a leukocyte transcript." Loke J.C.P., Kraev N., Sharma P., Du G., Patel L., Kraev A., MacLennan D.H. Anesthesiology 99:297-302(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 TRP-328, CHARACTERIZATION OF VARIANT MHS1 TRP-328.
[49]	"Central core disease: clinical, pathological, and genetic features." Quinlivan R.M., Muller C.R., Davis M., Laing N.G., Evans G.A., Dwyer J., Dove J., Roberts A.P., Sewry C.A. Arch. Dis. Child. 88:1051-1055(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD HIS-4861; CYS-4864; TRP-4893 AND THR-4940.
[50]	"Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia." Romero N.B., Monnier N., Viollet L., Cortey A., Chevallay M., Leroy J.P., Lunardi J., Fardeau M. Brain 126:2341-2349(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD GLU-215; CYS-614; PRO-4650; GLN-4724 AND GLU-4899.
[51]	"Scanning for mutations of the ryanodine receptor (RYR1) gene by denaturing HPLC: detection of three novel malignant hyperthermia alleles." Tammaro A., Bracco A., Cozzolino S., Esposito M., Di Martino A., Savoia G., Zeuli L., Piluso G., Aurino S., Nigro V. Clin. Chem. 49:761-768(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-44; CYS-533; LEU-2117; PRO-2163; MET-2168; LEU-2435 AND HIS-2454, VARIANT LYS-2101.
[52]	"Clinical and functional effects of a deletion in a COOH-terminal lumenal loop of the skeletal muscle ryanodine receptor." Zorzato F., Yamaguchi N., Xu L., Meissner G., Mueller C.R., Pouliquin P., Muntoni F., Sewry C., Girard T., Treves S. Hum. Mol. Genet. 12:379-388(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD 4863-ARG--ASP-4869 DELINS TYR.
[53]	"A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia." Monnier N., Ferreiro A., Marty I., Labarre-Vila A., Mezin P., Lunardi J. Hum. Mol. Genet. 12:1171-1178(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MMDO.
[54]	"Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene." Davis M.R., Haan E., Jungbluth H., Sewry C., North K., Muntoni F., Kuntzer T., Lamont P., Bankier A., Tomlinson P., Sanchez A., Walsh P., Nagarajan L., Oley C., Colley A., Gedeon A., Quinlivan R., Dixon J. , James D., Mueller C.R., Laing N.G. Neuromuscul. Disord. 13:151-157(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CORE/ROD DISEASE ILE-4637, VARIANTS CCD ASP-4638; PRO-4651; CYS-4861; HIS-4861; GLN-4893; THR-4898; GLY-4914; THR-4914; 4927-VAL-ILE-4928 DEL AND THR-4940.
[55]	"Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene." Sei Y., Sambuughin N.N., Davis E.J., Sachs D., Cuenca P.B., Brandom B.W., Tautz T., Rosenberg H., Nelson T.E., Muldoon S.M. Anesthesiology 101:824-830(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 CYS-163; ARG-248; CYS-614; CYS-2163; MET-2168; MET-2206; ILE-2214; THR-2350; THR-2367; ASN-2431; ARG-2434; VAL-2437; HIS-2454 AND PRO-4824.
[56]	"Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization." Guis S., Figarella-Branger D., Monnier N., Bendahan D., Kozak-Ribbens G., Mattei J.-P., Lunardi J., Cozzone P.J., Pellissier J.-F. Arch. Neurol. 61:106-113(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 TRP-2676 AND SER-2787.
[57]	"RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene." Shepherd S., Ellis F., Halsall J., Hopkins P., Robinson R. J. Med. Genet. 41:E33-E33(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD GLY-160; ASP-4638; PHE-4814; HIS-4861 AND MET-4938, VARIANTS MHS1 CYS-614; MET-2346; GLY-2348; TRP-2452; HIS-2458; PRO-4824 AND GLU-4939.
[58]	"Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia." Marchant C.L., Ellis F.R., Halsall P.J., Hopkins P.M., Robinson R.L. Muscle Nerve 30:114-117(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MHS1 SER-2342.
[59]	"Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility." Monnier N., Kozak-Ribbens G., Krivosic-Horber R., Nivoche Y., Qi D., Kraev N., Loke J., Sharma P., Tegazzin V., Figarella-Branger D., Romero N., Mezin P., Bendahan D., Payen J.-F., Depret T., Maclennan D.H., Lunardi J. Hum. Mutat. 26:413-425(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 ARG-35; CYS-163; LEU-163; ARG-165; ASN-166; CYS-177; CYS-178; VAL-227; ARG-248; TRP-328; ARG-341; SER-401; HIS-401; MET-403; SER-522; TRP-552; CYS-614; LEU-614; CYS-2163; HIS-2163; MET-2168; MET-2206; ARG-2206; ASP-2344; MET-2346; THR-2350; THR-2428; ARG-2434; HIS-2435; CYS-2454; HIS-2454; CYS-2458; TRP-2676; SER-2787; MET-3916; SER-4684; GLN-4737; TRP-4737; ILE-4826; VAL-4838; ILE-4849; ARG-4876; GLU-4939 AND LEU-4973, CHARACTERIZATION OF VARIANTS MHS1 LEU-163; MET-2206; THR-2428; CYS-2454 AND HIS-2454.
[60]	"Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene." Jungbluth H., Zhou H., Hartley L., Halliger-Keller B., Messina S., Longman C., Brockington M., Robb S.A., Straub V., Voit T., Swash M., Ferreiro A., Bydder G., Sewry C.A., Mueller C., Muntoni F. Neurology 65:1930-1935(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MMDO TRP-109 AND LYS-2423, VARIANTS VAL-485 AND CYS-2060.
[61]	"Inheritance of a novel RYR1 mutation in a family with myotonic dystrophy type 1." Gambelli S., Malandrini A., Berti G., Gaudiano C., Zicari E., Brunori P., Perticoni G., Orrico A., Galli L., Sorrentino V., Lunardi J., Federico A., Dotti M.T. Clin. Genet. 71:93-94(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD VAL-4846.
[62]	"Central core disease due to recessive mutations in RYR1 gene: is it more common than described?" Kossugue P.M., Paim J.F., Navarro M.M., Silva H.C., Pavanello R.C.M., Gurgel-Giannetti J., Zatz M., Vainzof M. Muscle Nerve 35:670-674(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD GLN-4558; VAL-4846; ILE-4849; HIS-4861; CYS-4861; VAL-4897 AND THR-4914.
[63]	"Novel RYR1 missense mutation causes core rod myopathy." von der Hagen M., Kress W., Hahn G., Brocke K.S., Mitzscherling P., Huebner A., Muller-Reible C., Stoltenburg-Didinger G., Kaindl A.M. Eur. J. Neurol. 15:E31-E32(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CCD MET-4882.
[64]	"Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores." Monnier N., Marty I., Faure J., Castiglioni C., Desnuelle C., Sacconi S., Estournet B., Ferreiro A., Romero N., Laquerriere A., Lazaro L., Martin J.-J., Morava E., Rossi A., Van der Kooi A., de Visser M., Verschuuren C., Lunardi J. Hum. Mutat. 29:670-678(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD VAL-13; SER-1704; PRO-2421; LYS-2423; HIS-3539; GLN-3772; GLN-4558; MET-4842 AND ILE-4849.
[65]	"Increasing the number of diagnostic mutations in malignant hyperthermia." Levano S., Vukcevic M., Singer M., Matter A., Treves S., Urwyler A., Girard T. Hum. Mutat. 30:590-598(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 ARG-13; LYS-226; LEU-367; HIS-530; TYR-544; CYS-1043; GLY-1352; HIS-2336; LYS-2404; TRP-2676; GLY-2730; SER-2787; LYS-2880; PRO-3217; LYS-3290; TRP-3772; ARG-3806; LEU-4501; VAL-4838; ARG-4876 AND THR-4938, VARIANTS GLY-1342; LEU-1787; ALA-1832; CYS-2060; VAL-2321; VAL-2550; GLN-3583 AND GLU-3756.
[66]	"Functional properties of RYR1 mutations identified in Swedish patients with malignant hyperthermia and central core disease." Vukcevic M., Broman M., Islander G., Bodelsson M., Ranklev-Twetman E., Muller C.R., Treves S. Anesth. Analg. 111:185-190(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS MHS1 ASN-382 AND LYS-1058, VARIANT CCD GLY-2508, VARIANTS ARG-1393 AND HIS-1679.
[67]	"Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion." Clarke N.F., Waddell L.B., Cooper S.T., Perry M., Smith R.L.L., Kornberg A.J., Muntoni F., Lillis S., Straub V., Bushby K., Guglieri M., King M.D., Farrell M.A., Marty I., Lunardi J., Monnier N., North K.N. Hum. Mutat. 31:E1544-E1550(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CFTD THR-402; LEU-2035; LYS-3326 AND GLY-3402.
[68]	"Dominant and recessive RYR1 mutations in adults with core lesions and mild muscle symptoms." Duarte S.T., Oliveira J., Santos R., Pereira P., Barroso C., Conceicao I., Evangelista T. Muscle Nerve 44:102-108(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CCD GLY-160; GLN-2204; HIS-3366; CYS-3933 AND ASP-4743, VARIANTS LEU-1787; CYS-2060 AND ALA-4493.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Ryanodine receptor entry

Wikipedia

RYR1 entry

Leiden Muscular Dystrophy pages Ryanodine receptor 1 (skeletal) (RYR1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases
EMBL GenBank DDBJ	J05200 mRNA. Translation: AAA60294.1. U48508 , U48449, U48450, U48451, U48452, U48453, U48454, U48455, U48456, U48457, U48458, U48459, U48460, U48461, U48462, U48463, U48464, U48465, U48466, U48467, U48468, U48469, U48470, U48471, U48472, U48473, U48474, U48475, U48476, U48477, U48478, U48479, U48480, U48481, U48482, U48483, U48484, U48485, U48486, U48487, U48488, U48489, U48490, U48491, U48492, U48493, U48494, U48495, U48496, U48497, U48498, U48499, U48500, U48501, U48502, U48503, U48504, U48505, U48506, U48507 Genomic DNA. Translation: AAC51191.1. AC067969 Genomic DNA. Translation: AAF66076.1. AC005933 Genomic DNA. Translation: AAC71651.1. AC011469 Genomic DNA. No translation available. M91455 Genomic DNA. Translation: AAA60295.1. S78717 Genomic DNA. Translation: AAB21245.2. S77392 Genomic DNA. Translation: AAB34356.1.
IPI	IPI00220558. IPI00334799. IPI00783826.
PIR	A35041.
RefSeq	NP_000531.2. NM_000540.2. NP_001036188.1. NM_001042723.1.
UniGene	Hs.466664.
3D structure databases
ProteinModelPortal	P21817.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29708N.
IntAct	P21817. 8 interactions.
MINT	MINT-1605046.
STRING	9606.ENSP00000352608.
Protein family/group databases
TCDB	1.A.3.1.2. ryanodine-inositol 1,4,5-triphosphate receptor Ca2+ channel (RIR-CaC) family.
PTM databases
PhosphoSite	P21817.
Polymorphism databases
DMDM	108935904.
Proteomic databases
PaxDb	P21817.
PRIDE	P21817.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355481; ENSP00000347667; ENSG00000196218. ENST00000359596; ENSP00000352608; ENSG00000196218. ENST00000360985; ENSP00000354254; ENSG00000196218.
GeneID	6261.
KEGG	hsa:6261.
UCSC	uc002oit.3. human. uc002oiu.3. human.
Organism-specific databases
CTD	6261.
GeneCards	GC19P038924.
H-InvDB	HIX0039957.
HGNC	HGNC:10483. RYR1.
HPA	CAB006835.
MIM	117000. phenotype. 145600. phenotype. 180901. gene. 255310. phenotype. 255320. phenotype.
neXtProt	NX_P21817.
Orphanet	169189. Autosomal dominant centronuclear myopathy. 597. Central core disease. 98905. Congenital multicore myopathy with external ophthalmoplegia. 99741. King-Denborough syndrome. 423. Malignant hyperthermia. 598. Multiminicore myopathy.
PharmGKB	PA34896.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG247670.
HOGENOM	HOG000231428.
HOVERGEN	HBG006699.
InParanoid	P21817.
KO	K04961.
OMA	TENTIIF.
Gene expression databases
ArrayExpress	P21817.
Bgee	P21817.
CleanEx	HS_RYR1.
Genevestigator	P21817.
GermOnline	ENSG00000196218. Homo sapiens.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR001870. B30.2/SPRY. IPR000699. Ca-rel_channel. IPR008985. ConA-like_lec_gl_sf. IPR011992. EF-hand-like_dom. IPR014821. Ins145_P3_rcpt. IPR005821. Ion_trans_dom. IPR016093. MIR_motif. IPR013662. RIH_assoc-dom. IPR013333. Ryan_recept. IPR003032. Ryanodine_rcpt. IPR015925. Ryanodine_recept-rel. IPR009460. Ryanrecept_TM4-6. IPR018355. SPla/RYanodine_receptor_subgr. IPR003877. SPRY_rcpt. [Graphical view]
PANTHER	PTHR13715. PTHR13715. 1 hit.
Pfam	PF08709. Ins145_P3_rec. 1 hit. PF00520. Ion_trans. 1 hit. PF02815. MIR. 1 hit. PF08454. RIH_assoc. 1 hit. PF06459. RR_TM4-6. 1 hit. PF01365. RYDR_ITPR. 2 hits. PF02026. RyR. 4 hits. PF00622. SPRY. 3 hits. [Graphical view]
PRINTS	PR00795. RYANODINER.
SMART	SM00472. MIR. 4 hits. SM00449. SPRY. 3 hits. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 3 hits. SSF82109. MIR. 1 hit.
PROSITE	PS50188. B302_SPRY. 3 hits. PS50919. MIR. 5 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P21817.
ChEMBL	CHEMBL1846.
DrugBank	DB01219. Dantrolene.
GenomeRNAi	6261.
NextBio	24319.
SOURCE	Search...

Entry information

Entry name

RYR1_HUMAN

Accession

Primary (citable) accession number: P21817
Secondary accession number(s): Q16314 , Q16368, Q9NPK1, Q9P1U4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	June 13, 2006
Last modified:	May 1, 2013
This is version 156 of the entry and version 3 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.