RYR2_RABIT
ID RYR2_RABIT Reviewed; 4969 AA.
AC P30957;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 3.
DT 25-MAY-2022, entry version 155.
DE RecName: Full=Ryanodine receptor 2;
DE Short=RYR-2;
DE Short=RyR2;
DE AltName: Full=Cardiac muscle ryanodine receptor;
DE AltName: Full=Cardiac muscle ryanodine receptor-calcium release channel;
DE AltName: Full=Cardiac muscle-type ryanodine receptor;
DE AltName: Full=Type 2 ryanodine receptor;
GN Name=RYR2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart muscle;
RX PubMed=2380170; DOI=10.1016/s0021-9258(18)77371-7;
RA Otsu K., Willard H.F., Khanna V.K., Zorzato F., Green N.M., Maclennan D.H.;
RT "Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine
RT receptor) of rabbit cardiac muscle sarcoplasmic reticulum.";
RL J. Biol. Chem. 265:13472-13483(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8841406; DOI=10.1111/j.1432-1033.1996.0408h.x;
RA Nishida K., Otsu K., Hori M., Kuzuya T., Tada M.;
RT "Cloning and characterization of the 5'-upstream regulatory region of the
RT Ca(2+)-release channel gene of cardiac sarcoplasmic reticulum.";
RL Eur. J. Biochem. 240:408-415(1996).
RN [3]
RP PHOSPHORYLATION AT SER-2809 BY CAMK2D.
RX PubMed=1645727; DOI=10.1016/s0021-9258(18)99140-4;
RA Witcher D.R., Kovacs R.J., Schulman H., Cefali D.C., Jones L.R.;
RT "Unique phosphorylation site on the cardiac ryanodine receptor regulates
RT calcium channel activity.";
RL J. Biol. Chem. 266:11144-11152(1991).
RN [4]
RP INTERACTION WITH RYR1 AND RYR3, AND FUNCTION.
RX PubMed=12213830; DOI=10.1074/jbc.m208210200;
RA Xiao B., Masumiya H., Jiang D., Wang R., Sei Y., Zhang L., Murayama T.,
RA Ogawa Y., Lai F.A., Wagenknecht T., Chen S.R.;
RT "Isoform-dependent formation of heteromeric Ca2+ release channels
RT (ryanodine receptors).";
RL J. Biol. Chem. 277:41778-41785(2002).
RN [5]
RP INTERACTION WITH SELENON, AND SUBCELLULAR LOCATION.
RX PubMed=18713863; DOI=10.1073/pnas.0806015105;
RA Jurynec M.J., Xia R., Mackrill J.J., Gunther D., Crawford T.,
RA Flanigan K.M., Abramson J.J., Howard M.T., Grunwald D.J.;
RT "Selenoprotein N is required for ryanodine receptor calcium release channel
RT activity in human and zebrafish muscle.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12485-12490(2008).
CC -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from the
CC sarcoplasmic reticulum into the cytoplasm and thereby plays a key role
CC in triggering cardiac muscle contraction. Aberrant channel activation
CC can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is
CC triggered by increased Ca(2+) levels due to activation of the L-type
CC calcium channel CACNA1C. Required for cellular calcium ion homeostasis.
CC Required for embryonic heart development (By similarity). The calcium
CC channel activity is modulated by formation of heterotetramers with
CC RYR3. {ECO:0000250|UniProtKB:Q92736, ECO:0000269|PubMed:12213830}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity
CC and maintains the channel in an open conformation. Channel activity is
CC regulated by calmodulin (CALM). The calcium release channel is
CC activated by calcium ions and ATP. Channel activity is inhibited by
CC magnesium ions (By similarity). {ECO:0000250|UniProtKB:P11716}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR1 and
CC RYR3. Interacts with FKBP1A and FKBP1B; these interactions may
CC stabilize the channel in its closed state and prevent Ca(2+) leaks.
CC Interacts with CALM and S100A1; these interactions regulate channel
CC activity. Identified in a complex composed of RYR2, FKBP1B, PKA
CC catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A
CC and PP1. Interacts directly with FKBP1B, PKA, PP1 and PP2A (By
CC similarity). Interacts with SELENON (PubMed:18713863). In cardiac
CC muscles, identified in a complex, composed of FSD2, CMYA5 and RYR2 (By
CC similarity). {ECO:0000250|UniProtKB:E9Q401,
CC ECO:0000250|UniProtKB:Q92736, ECO:0000269|PubMed:18713863}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}. Sarcoplasmic reticulum
CC {ECO:0000269|PubMed:18713863}. Note=The number of predicted
CC transmembrane domains varies between orthologs, but both N-terminus and
CC C-terminus seem to be cytoplasmic. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Heart and brain.
CC -!- DOMAIN: The calcium release channel activity resides in the C-terminal
CC region while the remaining part of the protein resides in the
CC cytoplasm. {ECO:0000305}.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2809 and Ser-2815 increases the open probability of the calcium
CC channel. Phosphorylation is increased in failing heart, leading to
CC calcium leaks and increased cytoplasmic Ca(2+) levels.
CC {ECO:0000269|PubMed:1645727}.
CC -!- PTM: Phosphorylation at Ser-2031 by PKA enhances the response to
CC lumenal calcium. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR2
CC subfamily. {ECO:0000305}.
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DR EMBL; M59743; AAA31179.1; -; mRNA.
DR PIR; A37113; A37113.
DR BMRB; P30957; -.
DR SMR; P30957; -.
DR IntAct; P30957; 1.
DR MINT; P30957; -.
DR STRING; 9986.ENSOCUP00000016860; -.
DR iPTMnet; P30957; -.
DR eggNOG; KOG2243; Eukaryota.
DR InParanoid; P30957; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:AgBase.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0015278; F:calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; IEA:InterPro.
DR GO; GO:0006816; P:calcium ion transport; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; ISS:UniProtKB.
DR CDD; cd12877; SPRY1_RyR; 1.
DR CDD; cd12878; SPRY2_RyR; 1.
DR CDD; cd12879; SPRY3_RyR; 1.
DR Gene3D; 2.60.120.920; -; 3.
DR InterPro; IPR001870; B30.2/SPRY.
DR InterPro; IPR043136; B30.2/SPRY_sf.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR014821; Ins145_P3_rcpt.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR036300; MIR_dom_sf.
DR InterPro; IPR016093; MIR_motif.
DR InterPro; IPR013662; RIH_assoc-dom.
DR InterPro; IPR000699; RIH_dom.
DR InterPro; IPR013333; Ryan_recept.
DR InterPro; IPR003032; Ryanodine_rcpt.
DR InterPro; IPR009460; Ryanrecept_TM4-6.
DR InterPro; IPR035910; RyR/IP3R_RIH_dom_sf.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR Pfam; PF08709; Ins145_P3_rec; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF02815; MIR; 1.
DR Pfam; PF08454; RIH_assoc; 1.
DR Pfam; PF06459; RR_TM4-6; 1.
DR Pfam; PF01365; RYDR_ITPR; 2.
DR Pfam; PF02026; RyR; 4.
DR Pfam; PF00622; SPRY; 3.
DR PRINTS; PR00795; RYANODINER.
DR SMART; SM00472; MIR; 4.
DR SMART; SM00449; SPRY; 3.
DR SUPFAM; SSF100909; SSF100909; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Calmodulin-binding;
KW Coiled coil; Developmental protein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..4969
FT /note="Ryanodine receptor 2"
FT /id="PRO_0000219362"
FT TOPO_DOM 1..4282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 4283..4303
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4505..4525
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4582..4602
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4732..4752
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4771..4791
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 4822..4831
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TRANSMEM 4852..4872
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4873..4969
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 110..165
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 172..217
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 225..280
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 286..345
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 351..408
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 599..809
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 853..966
FT /note="1"
FT REPEAT 967..1080
FT /note="2"
FT DOMAIN 1025..1222
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 1357..1562
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 2693..2811
FT /note="3"
FT REPEAT 2813..2926
FT /note="4"
FT REGION 853..2926
FT /note="4 X approximate repeats"
FT REGION 1855..1886
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2355..2380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3582..3611
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 4211..4231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4337..4362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4419..4470
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 4413..4446
FT /evidence="ECO:0000255"
FT COMPBIAS 1868..1886
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4213..4231
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4341..4362
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1341
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 1869
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B0LPN4"
FT MOD_RES 2031
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2698
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B0LPN4"
FT MOD_RES 2798
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2809
FT /note="Phosphoserine; by CaMK2D and PKA"
FT /evidence="ECO:0000269|PubMed:1645727"
FT MOD_RES 2812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
FT MOD_RES 2815
FT /note="Phosphoserine; by CaMK2D"
FT /evidence="ECO:0000250|UniProtKB:Q92736"
FT MOD_RES 2948
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q401"
SQ SEQUENCE 4969 AA; 565073 MW; FF6E0684B974BB4D CRC64;
MADGGEGEDE IQFLRTDDEV VLQCTATIHK EQQKLCLAAE GFGNRLCFLE STSNSKNVPP
DLSICTFVLE QSLLVRALQE MLANTVEKSE GQVDVEKWKF MMKTAQGGGH RTLLYGHAIL
LRHSYSGMYL CCLSTSRSST DKLAFDVGLQ EDTTGEACWW TIHPASKQRS EGEKVRVGDD
LILVSVSSER YLHLSYGNGS LHVDAAFQQT LWSVAPISSG SEAAQGYLIG GDVLRLLHGH
MDECLTVPSG EHGEEQRRTV HYEGGAVSVH ARSLWRLETL RVAWSGSHIR WGQPFRLRHV
TTGKYLSLME DKNLLLMDKE KADVKSTAFT FRSSKEKLDG GVRKEVDGMG TSEIKYGDSI
CYIQHVDTGL WLTYQSVDVK SVRMGSIQRK AIMHHEGHMD DGLNLSRSQH EESRTARVIR
STVFLFNRFI RGLDALSKKA KASSVDLPIE SVSLSLQDLI GYFHPPDEHL EHEDKQNRLR
ALKNRQNLFQ EEGMINLVLE CIDRLHVYSS AAHFADVAGR EAGESWKSIL NSLYELLAAL
IRGNRKNCAQ FSGSLDWLIS RLERLEASSG ILEVLHCVLV ESPEALNIIK EGHIKSIISL
LDKHGRNHKV LDVLCSLCVC HGVAVRSNQH LICDNLLPGR DLLLQTRLVN HVSSMRPNIF
LGVSEGSAQY KKWYYELMVD HTEPFVTAEA THLRVGWAST EGYSPYPGGG EEWGGNGVGD
DLFSYGFDGL HLWSGCIART VSSPNQHLLR TDDVISCCLD LSAPSISFRI NGQPVQGMFE
NFNIDGLFFP VVSFSAGIKV RFLLGGRHGE FKFLPPPGYA PCYEAVLPKE KLKVEHSREY
KQERTYTRDL LGPTVSLTQA AFTPIPVDTS QIVLPPHLER IREKLAENIH ELWVMNKIEL
GWQYGPVRDD NKRQHPCLVE FSKLPEQERN YNLQMSLETL KTLLALGCHV GISDEHAEEK
VKKMKLPKNY QLTSGYKPAP MDLSFIKLTP SQEAMVDKLA ENAHNVWARD RIRQGWTYGI
QQDVKNRRNP RLVPYTLLDD RTKKSNKDSL REAVRTLLGY GYNLEAPDQD HAARAEVCSG
TGERFRIFRA EKTYAVKAGR WYFEFEAVTS GDMRVGWSRP GCQPDQELGS DERAFAFDGF
KAQRWHQGNE HYGRSWQAGD VVGCMVDMNE HTMMFTLNGE ILLDDSGSEL AFKDFDVGDG
FIPVCSLGVA QVGRMNFGKD VSTLKYFTIC GLQEGYEPFA VNTNRDITMW LSKRLPQFLQ
VPSNHEHIEV TRIDGTIDSS PCLKVTQKSF GSQNSNTDIM FYRLSMPIEC AEVFSKTVPG
GLPGAGLFGP KNDLEDYDAD SDFEVLMKTA HGHLVPDRVD KDKETTKAEF NNHKDYAQEK
PSRLKQRFLL RRTKPDYSTS HSARLTEDVL ADDRDDYDFL MQTSTYYYSV RIFPGQEPAN
VWVGWITSDF HQYDTGFDLD RVRTVTVTLG DEKGKVHESI KRSNCYMVCA GESMSPGQGR
NNNGLEIGCV VDAASGLLTF IANGKELSTY YQVEPSTKLF PAVFAQATSP NVFQFELGRI
KNVMPLSAGL FKSEHKNPVP QCPPRLHVQF LSHVLWSRMP NQFLKVDVSR ISERQGWLVQ
CLDPLQFMSL HIPEENRSVD ILELTEQEEL LKFHYHTLRL YSAVCALGNH RVAHALCSHV
DEPQLLYAIE NKYMPGLLRT GYYDLLIDIH LSSYATARLM MNNEFIVPMT EETKSITLFP
DENKKHGLPG IGLSTSLRPR MQFSSPSFVS INNECYQYSP EFPLDILKAK TIQMLTEAVK
EGSLHGRDPV GGTTEFLFVP LIKLFYTLLI MGIFHNEDLR HILQLIEPSV FKDAATPEEE
GDTLEEEPSV EDTKLEGAGE EEAKVGKRPK EGLLQMKLPE PVKLQMCLLL QYLCDCQVRH
RIEAIVAFSD DFVAKLQDNQ RFRYNEVMQA LNMSAALTAR KTKEFRSPPQ EQINMLLNFK
DDKSECPCPE EIRDQLLDFH EDLMTHCGIE LDEDGSLDGN SDLTIRGRLL SLVEKVTYLK
KKQTEKPVES DSRKSSTLQQ LISETMVRWA QESVIEDPEL VRAMFVLLHR QYDGIGGLVR
ALPKTYTING VSVEDTINLL ASLGQIRSLL SVRMGKEEEK LMIRGLGDIM NNKVFYQHPN
LMRALGMHET VMEVMVNVLG GGESKEITFP KMVANCCRFL CYFCRISRQN QKAMFDHLSY
LLENSSVGLA SPAMRGSTPL DVAAASVMDN NELALALREP DLEKVVVRYL AGCGLQSCQM
LVSKGYPDIG WNPVEGERYL DFLRFAVFCN GESVEENANV VVRLLIRRPE CFGPALRGEG
GNGLLAAMEE AIKIAEDPSR DGPSPTSGSS KTLDTEEEED DTIHMGNAIM TFYAALIDLL
GRCAPEMHLI HAGKGEAIRI RSILRSLIPL GDLVGVISIA FQMPTIAKDG NVVEPDMSAG
FCPDHKAAMV LFLDRVYGIE VQDFLLHLLE VGFLPDLRAA ASLDTAALSA TDMALALNRY
LCTAVLPLLT RCAPLFAGTE HHASLIDSLL HTVYRLSKGC SLTKAQRDSI EVCLLSICGQ
LRPSMMQHLL RRLVFDVPLL NEHAKMPLKL LTNHYERCWK YYCLPGGWGN FGAASEEELH
LSRKLFWGIF DALSQKKYEQ ELFKLALPCL SAVAGALPPD YMESNYVSMM EKQSSMDSEG
NFNPQPVDTS NIIIPEKLEY FINKYAEHSH DKWSMDKLAN GWIYGEIYSD SSKIQPLMKP
YKLLSEKEKE IYRWPIKESL KTMLAWGWRI ERTREGDSMA LYNRTRRISQ TSQVSVDAAH
GYSPRAIDMS NVTLSRDLHA MAEMMAENYH NIWAKKKKLE LESKGGGNHP LLVPYDTLTA
KEKAKDREKA QDILKFLQIN GYAVSRGFKD LELDTPSIEK RFAYSFLQQL IRYVDEAHQY
ILEFDGGSRS KGEHFPYEQE IKFFAKVVLP LIDQYFKNHR LYFLSAASRP LCSGGHASNK
EKEMVTSLFC KLGVLVRHRI SLFGNDATSI VNCLHILGQT LDARTVMKTG LESVKSALRA
FLDNAAEDLE KTMENLKQGQ FTHTRNQPRG VTQIINYTTV ALLPMLSSLF EHIGQHQFGE
DLILEDVQVS CYRILTSLYA LGTSKSIYVE RQRSALGECL AAFAGAFPVA FLETHLNKHN
IYSIYNTKSS RERAALSLPA NVEDVCPNIP SLEKLMEEIV ELAESGIRYT QMPHVMEVIL
PMLCSYMSRW WEHGPESNPG RAEMCCTALN SEHMNTLLGN ILKIIYNNLG IDEGAWMKRL
AVFSQPIINK VKPQLLKTHF LPLMEKLKKK AAMVVSEEDH LKAEARGDMS EAELLILDEF
TTLARDLYAF YPLLIRFVDY NRAKWLKEPT PEAEELFRMV AEVFIYWSKS HNFKREEQNF
VVQNEINNMS FLITDTKSKM SKAAVSDQER KKMKRKGDRY SMQTSLIVAA LKRLLPIGLN
ICAPGDQELI ALAKNRFSLK ATEDEVRDII RNNIHLQGKL EDPAIRWQMA LYKDLPNRTE
ETSDPEKTVE RVLDIANVLF HLEQKSKFIG RRYYNLVEHP QRSKKAVWHK LLSKQRKRAV
VACFRMAPLY NLPRHRAVNL FLQGYEKSWI ETEEHYFEDK LIEDLAKPGA EPPEEDEVTK
RVDPLHQLIL LFSRTALTEK CKLEEDFLYM AYADIMAKSC HDEEDDDGEE EVKSFEEKEM
EKQKLLYQQA RLHDRGAAEM VLQTISASKG ETGPMVAATL KLGIAILNGG NSTVQQKMLD
YLKEKKDVGF FQSLAGLMQS CSVLDLNAFE RQNKAEGLGM VTEEGSGEKV LQDDEFTCDL
FRFLQLLCEG HNSDFQNYLR TQTGNNTTVN IIISTVDYLL RVQESISDFY WYYSGKDVID
EQGQRNFSKA IQVAKQVFNT LTEYIQGPCT GNQQSLAHSR LWDAVVGFLH VFAHMQMKLS
QDSSQIELLK ELMDLQKDMV VMLLSMLEGN VVNGTIGKQM VDMLVESSNN VEMILKFFDM
FLKLKDLTSS DTFKEYDPDG KGIISKRDFH KAMESHKHYT QSETEFLLSC AETDENETLD
YEEFVKRFHE PAKDIGFNVA VLLTNLSEHM PNDTRLQTFL ELAESVLNYF QPFLGRIEIM
GSAKRIERVY FEISESSRTQ WEKPQVKESK RQFIFDVVNE GGEKEKMELF VNFCEDTIFE
MQLAAQISES DLNERSANKE ESEKERPEEQ GPKMGFFSVL TVRSALFALR YNILTLMRML
SLKSLKKQMK KMKKMTVKDM VTAFFSSYWS IFMTLLHFVA SVFRGFFRIV CSLLLGGSLV
EGAKKIKVAE LLANMPDPTQ DEVRGDGEEG ERKPMETTLP SEDLTDLKEL TEESDLLSDI
FGLDLKREGG QYKLIPHNPN AGLSDLMSNP VLIPEEQEKF QEQKTKEEEK EEKEETKSEP
EKAEGEDGEK EEKVKEDKGK QKLRQLHTHR YGEPEVPESA FWKKIIAYQQ KLLNYLARNF
YNMRMLALFV AFAINFILLF YKVSTSSVVE GKELPSRSTS ENAKVTTSLD SSSHRIIAVH
YVLEESSGYM EPTLRILAIL HTVISFFCII GYYCLKVPLV IFKREKEVAR KLEFDGLYIT
EQPSEDDIKG QWDRLVINTQ SFPNNYWDKF VKRKVMDKYG EFYGRDRISE LLGMDKAALD
FSDAREKKKP KKDSSLSAVL NSIDVKYQMW KLGVVFTDNS FLYLAWYMTM SILGHYNNFF
FAAHLLDIAM GFKTLRTILS SVTHNGKQLV LTVGLLAVVV YLYTVVAFNF FRKFYNKSED
GDTPDMKCDD MLTCYMFHMY VGVRAGGGIG DEIEDPAGDE YEIYRIIFDI TFFFFVIVIL
LAIIQGLIID AFGELRDQQE QVKEDMETKC FICGIGNDYF DTVPHGFETH TLQEHNLANY
LFFLMYLINK DETEHTGQES YVWKMYQERC WEFFPAGDCF RKQYEDQLN
