E9Q401 (RYR2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ryanodine receptor 2
Short name=RYR-2
Short name=RyR2

Alternative name(s):
Cardiac muscle ryanodine receptor
Cardiac muscle ryanodine receptor-calcium release channel
Type 2 ryanodine receptor

Gene names

Name:

Ryr2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	4966 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 cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca2+ levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development. Ref.1 Ref.3 Ref.6 Ref.7
Subunit structure	Homotetramer. Can also form heterotetramers with RYR1 and RYR3. Interacts with CALM and S100A1; these interactions regulate channel activity. Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A By similarity. Interacts with FKBP1A and FKBP1B; these interactions may stabilize the channel in its closed state and prevent Ca2+ leaks. Ref.1 Ref.6 Ref.7
Subcellular location	Sarcoplasmic reticulum membrane; Multi-pass membrane protein Probable. 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 By similarity. Ref.1
Tissue specificity	Highly expressed in heart, lung, cerebellum and brain. Detected at lower levels in adrenal gland, stomach, thymus, esophagus and ovary. Ref.4 Ref.5
Domain	The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm Probable.
Post-translational modification	Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2807 and Ser-2813 increases the open probability of the calcium channel. Phosphorylation is increased in failing heart, leading to calcium leaks and increased cytoplasmic Ca2+ levels.
Disruption phenotype	Embryonically lethal. Embryos die at about 10 dpc, due to defects in heart tube development. Cardiac myotubes display enlarged rough endoplasmic reticulum and cytoplasmic vesicles that contain high levels of Ca2+. Ref.3
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.
Sequence similarities	Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2 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
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium Calmodulin-binding
Molecular function	Calcium channel Developmental protein Ion channel Ligand-gated ion channel
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from direct assay PubMed 17360443. Source: MGI Purkinje myocyte to ventricular cardiac muscle cell signaling Inferred from mutant phenotype PubMed 17872467. Source: BHF-UCL canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17360443. Source: MGI cardiac muscle contraction Inferred from electronic annotation. Source: Compara cardiac muscle hypertrophy Inferred from mutant phenotype PubMed 17431507. Source: MGI cellular response to caffeine Inferred from direct assay Ref.3. Source: UniProtKB detection of calcium ion Inferred from electronic annotation. Source: Compara embryonic heart tube morphogenesis Inferred from mutant phenotype Ref.3. Source: UniProtKB intrinsic apoptotic signaling pathway in response to osmotic stress Inferred from electronic annotation. Source: Compara left ventricular cardiac muscle tissue morphogenesis Inferred from mutant phenotype PubMed 17431507. Source: MGI positive regulation of heart rate Inferred from mutant phenotype PubMed 12089338PubMed 17431507. Source: MGI positive regulation of ryanodine-sensitive calcium-release channel activity by adrenergic receptor signaling pathway involved in positive regulation of cardiac muscle contraction Inferred from mutant phenotype PubMed 17872467. Source: BHF-UCL regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Inferred from genetic interaction PubMed 12837242. Source: BHF-UCL regulation of ventricular cardiac muscle cell action potential Inferred from mutant phenotype PubMed 17872467. Source: BHF-UCL release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Inferred from direct assay PubMed 20226167. Source: BHF-UCL response to hypoxia Inferred from direct assay PubMed 19120137. Source: BHF-UCL response to redox state Inferred from electronic annotation. Source: Compara
Cellular_component	Z disc Inferred from direct assay PubMed 16204356PubMed 19383796. Source: MGI calcium channel complex Inferred from electronic annotation. Source: Compara integral to membrane Inferred by curator PubMed 14593104. Source: MGI protein complex Inferred from sequence orthology PubMed 18468998. Source: MGI sarcoplasmic reticulum membrane Inferred from direct assay PubMed 14592808PubMed 16481613. Source: MGI
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calmodulin binding Inferred from direct assay PubMed 17431507. Source: MGI protein self-association Inferred from mutant phenotype Ref.1. Source: UniProtKB ryanodine-sensitive calcium-release channel activity Inferred from direct assay PubMed 14593104PubMed 17431507. Source: MGI suramin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Fkbp1b	Q9Z2I2	2	EBI-643628,EBI-6379859

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 4966

4966

Ryanodine receptor 2

PRO_0000415582

Regions

Topological domain

1 – 4231

4231

Cytoplasmic Potential

Transmembrane

4232 – 4252

21

Helical; Potential

Transmembrane

4278 – 4298

21

Helical; Potential

Transmembrane

4502 – 4522

21

Helical; Potential

Transmembrane

4579 – 4599

21

Helical; Potential

Transmembrane

4729 – 4749

21

Helical; Potential

Transmembrane

4768 – 4788

21

Helical; Potential

Intramembrane

4819 – 4828

10

Pore-forming; Probable

Transmembrane

4849 – 4869

21

Helical; Potential

Topological domain

4870 – 4966

97

Cytoplasmic Potential

Domain

110 – 165

56

MIR 1

Domain

172 – 217

46

MIR 2

Domain

225 – 280

56

MIR 3

Domain

286 – 343

58

MIR 4

Domain

351 – 408

58

MIR 5

Domain

599 – 809

211

B30.2/SPRY 1

Repeat

853 – 966

114

1

Repeat

967 – 1080

114

2

Domain

1025 – 1222

198

B30.2/SPRY 2

Domain

1357 – 1563

207

B30.2/SPRY 3

Repeat

2691 – 2809

119

3

Repeat

2811 – 2924

114

4

Region

853 – 2924

2072

4 X approximate repeats

Region

3580 – 3609

30

Interaction with CALM By similarity

Amino acid modifications

Modified residue

2807

1

Phosphoserine; by CaMK2D and PKA Ref.6 Ref.7

Modified residue

2813

1

Phosphoserine; by CaMK2D Ref.6

Experimental info

Mutagenesis

77

1

A → V: No change to global protein fold or protein stability. Alters local protein folding. Ref.9

Mutagenesis

186

1

V → M: No change to global protein fold or protein stability. Alters local protein folding. Ref.9

Mutagenesis

2813

1

S → A: Protects against tachycardia and subsequent death due to heart failure. Ref.6

Mutagenesis

2813

1

S → D: Abolishes phosphorylation by CaMK2D. Tendency to tachycardia and subsequent death due to heart failure. Ref.6

Mutagenesis

4819

1

G → A: Strongly reduced calcium channel activity. Abolishes ryanodine binding. Ref.1

Mutagenesis

4821

1

R → A: No effect on calcium channel activity. Abolishes ryanodine binding. Ref.1

Mutagenesis

4823

1

G → A: Reduced calcium channel activity. Reduces single channel conductance by 97%. No effect on ryaodine binding. Ref.1

Mutagenesis

4824

1

G → A: No effect on calcium channel activity. Abolishes ryanodine binding. Ref.1

Mutagenesis

4825

1

G → A: Strongly reduced calcium channel activity. Abolishes ryanodine binding. Ref.1

Mutagenesis

4827

1

G → A: No effect on calcium channel activity. Abolishes ryanodine binding. Ref.1

Mutagenesis

4828

1

D → A: No effect on calcium channel activity. Abolishes ryanodine binding. Ref.1

Sequence conflict

1332

1

N → S in AAG34081. Ref.1

Sequence conflict

1412

1

D → G in AAG34081. Ref.1

Sequence conflict

1962

1

R → K in AAG34081. Ref.1

Sequence conflict

2265

1

V → VA in AAG34081. Ref.1

Sequence conflict

2532

1

P → R in AAG34081. Ref.1

Sequence conflict

3192

1

A → T in AAG34081. Ref.1

Sequence conflict

3533

1

L → F in AAG34081. Ref.1

Sequence conflict

4324

1

I → T in CAA58785. Ref.4

Sequence conflict

4853

1

V → E in CAA58785. Ref.4

Secondary structure

1

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4966

Helix Strand Turn

Details...

Beta strand

19 – 28

10

Beta strand

31 – 38

8

Beta strand

41 – 43

3

Beta strand

48 – 51

4

Helix

62 – 64

3

Beta strand

67 – 73

7

Helix

75 – 84

10

Beta strand

97 – 102

6

Beta strand

118 – 123

6

Turn

124 – 126

3

Beta strand

129 – 132

4

Beta strand

145 – 151

7

Beta strand

154 – 156

3

Beta strand

159 – 167

9

Beta strand

180 – 185

6

Turn

186 – 188

3

Beta strand

191 – 196

6

Beta strand

198 – 208

11

Beta strand

212 – 216

5

Helix

2714 – 2716

3

Helix

2717 – 2737

21

Turn

2748 – 2751

4

Helix

2759 – 2761

3

Helix

2764 – 2783

20

Beta strand

2787 – 2790

4

Helix

2796 – 2799

4

Helix

2817 – 2819

3

Helix

2827 – 2829

3

Helix

2834 – 2861

28

Helix

2873 – 2875

3

Helix

2878 – 2897

20

Beta strand

2900 – 2903

4

Sequences

	Sequence		Length	Mass (Da)
	E9Q401 [UniParc]. Last modified April 5, 2011. Version 1. Checksum: F43425091AF7114F	FASTA	4,966	564,819
	10 20 30 40 50 60 MADAGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP 70 80 90 100 110 120 DLSICTFVLE QSLSVRALQE MLANTVEKSE GQVDVEKWKF MMKTAQGGGH RTLLYGHAIL 130 140 150 160 170 180 LRHSYSGMYL CCLSTSRSST DKLAFDVGLQ EDTTGEACWW TIHPASKQRS EGEKVRVGDD 190 200 210 220 230 240 LILVSVSSER YLHLSYGNSS WHVDAAFQQT LWSVAPISSG SEAAQGYLIG GDVLRLLHGH 250 260 270 280 290 300 MDECLTVPSG EHGEEQRRTV HYEGGAVSVH ARSLWRLETL RVAWSGSHIR WGQPFRLRHV 310 320 330 340 350 360 TTGKYLSLME DKNLLLMDKE KADVKSTAFA FRSSKEKLDV GVRKEVDGMG TSEIKYGDSI 370 380 390 400 410 420 CYIQHVDTGL WLTYQAVDVK SARMGSIQRK AIMHHEGHMD DGLNLSRSQH EESRTARVIR 430 440 450 460 470 480 STVFLFNRFI RGLDALSKKV KLPTIDLPIE SVSLSLQDLI GYFHPPDEHL EHEDKQNRLR 490 500 510 520 530 540 ALKNRQNLFQ EEGMINLVLE CIDRLHVYSS AAHFADVAGR EAGESWKSIL NSLYELLAAL 550 560 570 580 590 600 IRGNRKNCAQ FSGSLDWLIS RLERLEASSG ILEVLHCVLV ESPEALNIIK EGHIKSIISL 610 620 630 640 650 660 LDKHGRNHKV LDVLCSLCVC HGVAVRSNQH LICDNLLPGR DLLLQTRLVN HVSSMRPNIF 670 680 690 700 710 720 LGVSEGSAQY KKWYYELMVD HTEPFVTAEA THLRVGWAST EGYSPYPGGG EEWGGNGVGD 730 740 750 760 770 780 DLFSYGFDGL HLWSGCIART VSSPNQHLLR TDDVISCCLD LSAPSISFRI NGQPVQGMFE 790 800 810 820 830 840 NFNIDGLFFP VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA ACYEAVLPKE KLKVEHSREY 850 860 870 880 890 900 KQERTYTRDL LGPTVSLTQA AFTPVPVDTS QIVLPPHLER IRERLAENIH ELWVMNKIEL 910 920 930 940 950 960 GWQYGPVRDD NKRQHPCLVE FCKLPEQERN YNLQMSLETL KTLLALGCHV GIADEHAEEK 970 980 990 1000 1010 1020 VKKMKLPKNY QLTSGYKPAP MDLSFIKLTP SQEAMVDKLA ENAHNVWARD RIRQGWTYGI 1030 1040 1050 1060 1070 1080 QQDVKNRRNP RLVPYTLLDD RTKKSNKDSL REAVRTLLGY GYHLEAPDQD HASRAEVCSG 1090 1100 1110 1120 1130 1140 TGERFRIFRA EKTYAVKAGR WYFEFEAVTA GDMRVGWSRP GCQPDLELGS DDRAFAFDGF 1150 1160 1170 1180 1190 1200 KAQRWHQGNE HYGRSWQAGD VVGCMVDMNE HTMMFTLNGE ILLDDSGSEL AFKDFDVGDG 1210 1220 1230 1240 1250 1260 FIPVCSLGVA QVGRMNFGKD VSTLKYFTIC GLQEGYEPFA VNTNRDITMW LSKRLPQFLQ 1270 1280 1290 1300 1310 1320 VPSNHEHIEV TRIDGTIDSS PCLKVTQKSF GSQNNNTDIM FYRLSMPIEC AEVFSKSVAG 1330 1340 1350 1360 1370 1380 GLPGAGFYGP KNDLEDFDVD SDFEVLMKTA HGHLVPDRID KDKETPKPEF NNHKDYAQEK 1390 1400 1410 1420 1430 1440 PSRLKQRFLL RRTKPDYSTG HSARLTEDVL ADDRDDYEYL MQTSTYYYSV RIFPGQEPAN 1450 1460 1470 1480 1490 1500 VWVGWITSDF HQYDTGFDLD RVRTVTVTLG DEKGKVHESI KRSNCYMVCA GESMSPGQGR 1510 1520 1530 1540 1550 1560 NNSNGLEIGC VVDAASGLLT FIANGKELST YYQVEPSTKL FPAVFAQATS PNVFQFELGR 1570 1580 1590 1600 1610 1620 IKNVMPLSAG LFKSEHKNPV PQCPPRLHVQ FLSHVLWSRM PNQFLKVDVS RISERQGWLV 1630 1640 1650 1660 1670 1680 QCLDPLQFMS LHIPEENRSV DILELTEQEE LLQFHYHTLR LYSAVCALGN HRVAHALCSH 1690 1700 1710 1720 1730 1740 VDEPQLLYAI ENKYMPGLLR AGYYDLLIDI HLSSYATARL MMNNEFIVPM TEETKSITLF 1750 1760 1770 1780 1790 1800 PDENKKHGLP GIGLSTSLRP RMRFSSPSFV SISNDCYQYS PEFPLDILKA KTIQMLTEAV 1810 1820 1830 1840 1850 1860 KEGSLHARDP VGGTTEFLFV PLIKLFYTLL IMGIFHNEDL KHILQLIEPS VFKEAAVPEE 1870 1880 1890 1900 1910 1920 EGGTPEKEIS IEDAKLEGEE EAKGGKRPKE GLLQMKLPEP VKLQMCLLLQ YLCDCQVRHR 1930 1940 1950 1960 1970 1980 IEAIVAFSDD FVAKLQDNQR FRYNEVMQAL NMSAALTARK TREFRSPPQE QINMLLNFKD 1990 2000 2010 2020 2030 2040 DKSECPCPEE IRDQLLDFHE DLMTHCGIEL DEDGSLDGSN DLTIRGRLLS LVEKVTYLKK 2050 2060 2070 2080 2090 2100 KQAEKPVASD SRKCSSLQQL ISETMVRWAQ ESVIEDPELV RAMFVLLHRQ YDGIGGLVRA 2110 2120 2130 2140 2150 2160 LPKTYTINGV SVEDTINLLA SLGQIRSLLS VRMGKEEEKL MIRGLGDIMN NKVFYQHPNL 2170 2180 2190 2200 2210 2220 MRALGMHETV MEVMVNVLGG GESKEITFPK MVANCCRFLC YFCRISRQNQ KAMFDHLSYL 2230 2240 2250 2260 2270 2280 LENSSVGLAS PAMRGSTPLD VAAASVMDNN ELALALREPD LEKVVRYLAG CGLQSCQMLV 2290 2300 2310 2320 2330 2340 SKGYPDIGWN PVEGERYLDF LRFAVFCNGE SVEENANVVV RLLIRRPECF GPALRGEGGN 2350 2360 2370 2380 2390 2400 GLLAAMEEAI KIAEDPSRDG PSPTSGSSKT LDIEEEEDDT IHMGNAIMTF YAALIDLLGR 2410 2420 2430 2440 2450 2460 CAPEMHLIHA GKGEAIRIRS ILRSLIPLGD LVGVISIAFQ MPTIAKDGKV VEPDMSAGFC 2470 2480 2490 2500 2510 2520 PDHKAAMVLF LDRVYGIEVQ DFLLHLLEVG FLPDLRAAAS LDTAALSATD MALALNRYLC 2530 2540 2550 2560 2570 2580 TAVLPLLTRC APLFAGTEHH ASLIDSLLHT VYRLSKGCSL TKAQRDSIEV CLLSICGQLR 2590 2600 2610 2620 2630 2640 PSMMQHLLRR LVFDVPLLNE HAKMPLKLLT NHYERCWKYY CLPGGWGNFG AASEEELHLS 2650 2660 2670 2680 2690 2700 RKLFWGIFDA LSQKKYEQEL FKLALPCLSA VAGALPPDYM ESNYVSMMEK QSSMDSEGNF 2710 2720 2730 2740 2750 2760 NPQPVDTSNI TIPEKLEYFI NKYAEHSHDK WSMDKLANGW IYGEIYSDSS KIQPLMKPYK 2770 2780 2790 2800 2810 2820 LLSEKEKEIY RWPIKESLKT MLAWGWRIER TREGDSMALY NRTRRISQTS QVSIDAAHGY 2830 2840 2850 2860 2870 2880 SPRAIDMSNV TLSRDLHAMA EMMAENYHNI WAKKKKLELE SKGGGNHPLL VPYDTLTAKE 2890 2900 2910 2920 2930 2940 KAKDREKAQD IFKFLQISGY VVSRGFKDLD LDTPSIEKRF AYSFLQQLIR YVDEAHQYIL 2950 2960 2970 2980 2990 3000 EFDGGSRSKG EHFPYEQEIK FFAKVVLPLI DQYFKNHRLY FLSAASRPLC TGGHASNKEK 3010 3020 3030 3040 3050 3060 EMVTSLFCKL GVLVRHRISL FGNDATSIVN CLHILGQTLD ARTVMKTGLD SVKSALRAFL 3070 3080 3090 3100 3110 3120 DNAAEDLEKT MENLKQGQFT HTRSQPKGVT QIINYTTVAL LPMLSSLFEH IGQHQFGEDL 3130 3140 3150 3160 3170 3180 ILEDVQVSCY RILTSLYALG TSKSIYVERQ RSALGECLAA FAGAFPIAFL ETHLDKHNVY 3190 3200 3210 3220 3230 3240 SIYNTRSSRE RAALSLPANV EDVCPNIPSL EKLMTEIIEL AESGIRYTQM PYMMEVVLPM 3250 3260 3270 3280 3290 3300 LCSYMSRWWE HGPENHPERA EMCCTALNSE HMNTLLGNIL KIIYNNLGID EGAWMKRLAV 3310 3320 3330 3340 3350 3360 FSQPIINKVK PQLLKTHFLP LMEKLKKKAA MVVSEEDHLK AEARGDMSEA ELLILDEFTT 3370 3380 3390 3400 3410 3420 LARDLYAFYP LLIRFVDYNR AKWLKEPNPE AEELFRMVAE VFIYWSKSHN FKREEQNFVV 3430 3440 3450 3460 3470 3480 QNEINNMSFL ITDTKSKMSK AAISDQERKK MKRKGDRYSM QTSLIVAALK RLLPIGLNIC 3490 3500 3510 3520 3530 3540 APGDQELIAL AKNRFSLKDT EEEVRDIIRS NIHLQGKLED PAIRWQMALY KDLPNRTEDP 3550 3560 3570 3580 3590 3600 SDPERTVERV LGIANVLFHL EQKSKYTGRG YFSLVEHPQR SKKAVWHKLL SKQRKRAVVA 3610 3620 3630 3640 3650 3660 CFRMAPLYNL PRHRAVNLFL QGYEKSWIET EEHYFEDKLI EDLAKPGAEL PEEDEAMKRV 3670 3680 3690 3700 3710 3720 DPLHQLILLF SRTALTEKCK LEEDFLYMAY ADIMAKSCHD EEDDDGEEEV KSFEEKEMEK 3730 3740 3750 3760 3770 3780 QKLLYQQARL HDRGAAEMVL QTISASKGET GPMVAATLKL GIAILNGGNS TVQQKMLDYL 3790 3800 3810 3820 3830 3840 KEKKDVGFFQ SLAGLMQSCS VLDLNAFERQ NKAEGLGMVT EEGSGEKVLQ DDEFTCDLFR 3850 3860 3870 3880 3890 3900 FLQLLCEGHN SDFQNYLRTQ TGNNTTVNII ISTVDYLLRV QESISDFYWY YSGKDIIDEQ 3910 3920 3930 3940 3950 3960 GQRNFSKAIQ VAKQVFNTLT EYIQGPCTGN QQSLAHSRLW DAVVGFLHVF AHMQMKLSQD 3970 3980 3990 4000 4010 4020 SSQIELLKEL MDLQKDMVVM LLSMLEGNVV NGTIGKQMVD MLVESSNNVE MILKFFDMFL 4030 4040 4050 4060 4070 4080 KLKDLTSSDT FKEYDPDGKG VISKRDFHKA MESHKHYTQS ETEFLLSCAE TDENETLDYE 4090 4100 4110 4120 4130 4140 EFVKRFHEPA KDIGFNVAVL LTNLSEHMPN DTRLQTFLEL AESVLNYFQP FLGRIEIMGS 4150 4160 4170 4180 4190 4200 AKRIERVYFE ISESSRTQWE KPQVKESKRQ FIFDVVNEGG EKEKMELFVN FCEDTIFEMQ 4210 4220 4230 4240 4250 4260 LAAQISESDL NERLANKEES EKERPEEQAP RMGFFSLLTI QSALFALRYN VLTLVRMLSL 4270 4280 4290 4300 4310 4320 KSLKKQMKRM KKMTVKDMVL AFFSSYWSVF VTLLHFVASV CRGFFRIVSS LLLGGSLVEG 4330 4340 4350 4360 4370 4380 AKKIKVAELL ANMPDPTQDE VRGDEEEGER KPLESALPSE DLTDLKELTE ESDLLSDIFG 4390 4400 4410 4420 4430 4440 LDLKREGGQY KLIPHNPNAG LSDLMTNPVP VPEVQEKFQE QKAKEEKEEK EETKSEPEKA 4450 4460 4470 4480 4490 4500 EGEDGEKEEK AKDEKSKQKL RQLHTHRYGE PEVPESAFWK KIIAYQQKLL NYFARNFYNM 4510 4520 4530 4540 4550 4560 RMLALFVAFA INFILLFYKV STSSVVEGKE LPTRTSSDTA KVTNSLDSSP HRIIAVHYVL 4570 4580 4590 4600 4610 4620 EESSGYMEPT LRILAILHTI ISFFCIIGYY CLKVPLVIFK REKEVARKLE FDGLYITEQP 4630 4640 4650 4660 4670 4680 SEDDIKGQWD RLVINTQSFP NNYWDKFVKR KVMDKYGEFY GRDRISELLG MDKAALDFSD 4690 4700 4710 4720 4730 4740 AREKKKPKKD SSLSAVLNSI DVKYQMWKLG VVFTDNSFLY LAWYMTMSVL GHYNNFFFAA 4750 4760 4770 4780 4790 4800 HLLDIAMGFK TLRTILSSVT HNGKQLVLTV GLLAVVVYLY TVVAFNFFRK FYNKSEDGDT 4810 4820 4830 4840 4850 4860 PDMKCDDMLT CYMFHMYVGV RAGGGIGDEI EDPAGDEYEI YRIIFDITFF FFVIVILLAI 4870 4880 4890 4900 4910 4920 IQGLIIDAFG ELRDQQEQVK EDMETKCFIC GIGNDYFDTV PHGFETHTLQ EHNLANYLFF 4930 4940 4950 4960 LMYLINKDET EHTGQESYVW KMYQERCWEF FPAGDCFRKQ YEDQLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular identification of the ryanodine receptor pore-forming segment." Zhao M., Li P., Li X., Zhang L., Winkfein R.J., Chen S.R. J. Biol. Chem. 274:25971-25974(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF GLY-4819; ARG-4821; GLY-4823; GLY-4824; GLY-4825; GLY-4827 AND ASP-4828.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2." Takeshima H., Komazaki S., Hirose K., Nishi M., Noda T., Iino M. EMBO J. 17:3309-3316(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16, FUNCTION, DISRUPTION PHENOTYPE.
[4]	"The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues." Giannini G., Conti A., Mammarella S., Scrobogna M., Sorrentino V. J. Cell Biol. 128:893-904(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4145-4966, TISSUE SPECIFICITY. Strain: BALB/c. Tissue: Brain.
[5]	"Ca(2+)-induced Ca2+ release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor." Takeshima H., Yamazawa T., Ikemoto T., Takekura H., Nishi M., Noda T., Iino M. EMBO J. 14:2999-3006(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4863-4966, TISSUE SPECIFICITY. Strain: C57BL/6J. Tissue: Heart.
[6]	"Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure." van Oort R.J., McCauley M.D., Dixit S.S., Pereira L., Yang Y., Respress J.L., Wang Q., De Almeida A.C., Skapura D.G., Anderson M.E., Bers D.M., Wehrens X.H. Circulation 122:2669-2679(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-2807 AND SER-2813, INTERACTION WITH FKBP1B, MUTAGENESIS OF SER-2813.
[7]	"Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks." Guo T., Cornea R.L., Huke S., Camors E., Yang Y., Picht E., Fruen B.R., Bers D.M. Circ. Res. 106:1743-1752(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH FKBP1A AND FKBP1B, PHOSPHORYLATION AT SER-2807.
[8]	"Ryanodine receptor studies using genetically engineered mice." Kushnir A., Betzenhauser M.J., Marks A.R. FEBS Lett. 584:1956-1965(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"Crystal structures of the N-terminal domains of cardiac and skeletal muscle ryanodine receptors: insights into disease mutations." Lobo P.A., Van Petegem F. Structure 17:1505-1514(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-217, MUTAGENESIS OF ALA-77 AND VAL-186.
[10]	"The deletion of exon 3 in the cardiac ryanodine receptor is rescued by beta strand switching." Lobo P.A., Kimlicka L., Tung C.C., Van Petegem F. Structure 19:790-798(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-217.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF295105 mRNA. Translation: AAG34081.1.
AC131329 Genomic DNA. No translation available.
AC159208 Genomic DNA. No translation available.
CT010468 Genomic DNA. No translation available.
CT572985 Genomic DNA. No translation available.
AB012003 Genomic DNA. Translation: BAA25137.1.
X83933 mRNA. Translation: CAA58785.1.
D38217 mRNA. Translation: BAA07392.1.

IPI

IPI00338309.

PIR

I48742.

RefSeq

NP_076357.2. NM_023868.2.

UniGene

Mm.239871.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IM5	X-ray	2.55	A/B	1-217	[»]
3IM6	X-ray	1.70	A	1-217	[»]
3IM7	X-ray	2.21	A	1-217	[»]
3QR5	X-ray	2.30	A/B	1-217	[»]
4ETV	X-ray	1.65	A/B	2699-2904	[»]

ProteinModelPortal

E9Q401.

SMR

E9Q401. Positions 12-217, 2700-2904, 3580-3606.

ModBase

Search...

Protein-protein interaction databases

IntAct

E9Q401. 5 interactions.

PTM databases

PhosphoSite

E9Q401.

Proteomic databases

PRIDE

E9Q401.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000021750; ENSMUSP00000021750; ENSMUSG00000021313.

GeneID

20191.

KEGG

mmu:20191.

Organism-specific databases

CTD

6262.

MGI

MGI:99685. Ryr2.

Phylogenomic databases

eggNOG

NOG247670.

GeneTree

ENSGT00690000101961.

HOGENOM

HOG000231428.

HOVERGEN

HBG006699.

KO

K04962.

OMA

SIVNCLH.

Gene expression databases

ArrayExpress

E9Q401.

Bgee

E9Q401.

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.
IPR002048. EF_hand_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

SM00054. EFh. 2 hits.
SM00472. MIR. 4 hits.
SM00449. SPRY. 3 hits.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.
SSF82109. MIR. 1 hit.

PROSITE

PS50188. B302_SPRY. 3 hits.
PS50919. MIR. 5 hits.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL4745.

EvolutionaryTrace

Q9ERN6.

NextBio

297739.

SOURCE

Search...

Entry information

Entry name

RYR2_MOUSE

Accession

Primary (citable) accession number: E9Q401
Secondary accession number(s): O70181 , Q62174, Q62197, Q9ERN6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2012
Last sequence update:	April 5, 2011
Last modified:	May 1, 2013
This is version 22 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program