RYR1_PIG
ID RYR1_PIG Reviewed; 5035 AA.
AC P16960;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Ryanodine receptor 1;
DE Short=RYR-1;
DE Short=RyR1;
DE AltName: Full=Skeletal muscle calcium release channel;
DE AltName: Full=Skeletal muscle ryanodine receptor;
DE AltName: Full=Skeletal muscle-type ryanodine receptor;
DE AltName: Full=Type 1 ryanodine receptor;
GN Name=RYR1; Synonyms=CRC;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Norwegian Landrace; TISSUE=Skeletal muscle;
RX PubMed=1329581; DOI=10.1111/j.1365-2052.1992.tb02157.x;
RA Harbitz I., Kristensen T., Bosnes M., Kran S., Davies W.;
RT "DNA sequence of the skeletal muscle calcium release channel cDNA and
RT verification of the Arg615-->Cys615 mutation, associated with porcine
RT malignant hyperthermia, in Norwegian landrace pigs.";
RL Anim. Genet. 23:395-402(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE OF 1129-2801.
RA Brenig B.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1129-2643.
RC STRAIN=German Landrace; TISSUE=Liver;
RX PubMed=8288238; DOI=10.1006/geno.1993.1475;
RA Leeb T., Schmolzl S., Brem G., Brenig B.;
RT "Genomic organization of the porcine skeletal muscle ryanodine receptor
RT (RYR1) gene coding region 4624 to 7929.";
RL Genomics 18:349-354(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4785-5035.
RX PubMed=2174405; DOI=10.1016/0888-7543(90)90278-3;
RA Harbitz I., Chowdhary B., Thomsen P.D., Davies W., Kaufman U., Kran S.,
RA Gustavsson I., Christensen K., Hauge J.G.;
RT "Assignment of the porcine calcium release channel gene, a candidate for
RT the malignant hyperthermia locus, to the 6p11-->q21 segment of chromosome
RT 6.";
RL Genomics 8:243-248(1990).
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 muscle contraction following depolarization of T-tubules
CC (By similarity). Repeated very high-level exercise increases the open
CC probability of the channel and leads to Ca(2+) leaking into the
CC cytoplasm (By similarity). Can also mediate the release of Ca(2+) from
CC intracellular stores in neurons, and may thereby promote prolonged
CC Ca(2+) signaling in the brain. Required for normal embryonic
CC development of muscle fibers and skeletal muscle. Required for normal
CC heart morphogenesis, skin development and ossification during
CC embryogenesis (By similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000250|UniProtKB:P11716}.
CC -!- ACTIVITY REGULATION: Channel activity is modulated by the alkaloid
CC ryanodine that binds to the open Ca-release channel with high affinity.
CC At low concentrations, ryanodine maintains the channel in an open
CC conformation. High ryanodine concentrations inhibit channel activity.
CC Channel activity is regulated by calmodulin (CALM). The calcium release
CC is activated by increased cytoplasmic calcium levels, by nitric oxyde
CC (NO), caffeine and ATP. Channel activity is inhibited by magnesium
CC ions, possibly by competition for calcium binding sites.
CC {ECO:0000250|UniProtKB:P11716}.
CC -!- SUBUNIT: Homotetramer. Can also form heterotetramers with RYR2 (By
CC similarity). Identified in a complex composed of RYR1, PDE4D, PKA,
CC FKBP1A and protein phosphatase 1 (PP1). Repeated very high-level
CC exercise decreases interaction with PDE4D and protein phosphatase 1
CC (PP1) (By similarity). Interacts with CALM; CALM with bound calcium
CC inhibits the RYR1 channel activity (By similarity). Interacts with
CC S100A1 (By similarity). Interacts with FKBP1A; this stabilizes the
CC closed conformation of the channel. Interacts with CACNA1S; interaction
CC with CACNA1S is important for activation of the RYR1 channel. Interacts
CC with CACNB1. Interacts with TRDN and ASPH; these interactions stimulate
CC RYR1 channel activity. Interacts with SELENON (By similarity).
CC Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42;
CC AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (By
CC similarity). {ECO:0000250|UniProtKB:E9PZQ0,
CC ECO:0000250|UniProtKB:P11716, ECO:0000250|UniProtKB:P21817}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P11716}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P11716}. Sarcoplasmic reticulum
CC {ECO:0000250|UniProtKB:P11716}. Membrane
CC {ECO:0000250|UniProtKB:P11716}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P11716}. Note=The number of predicted
CC transmembrane domains varies between orthologs, but the 3D-structures
CC show the presence of six transmembrane regions. Both N-terminus and C-
CC terminus are cytoplasmic. {ECO:0000250|UniProtKB:P11716}.
CC -!- DOMAIN: The calcium release channel activity resides in the C-terminal
CC region while the remaining part of the protein constitutes the 'foot'
CC structure spanning the junctional gap between the sarcoplasmic
CC reticulum (SR) and the T-tubule. Pore opening is mediated via the
CC cytoplasmic calcium-binding domains that mediate a small rotation of
CC the channel-forming transmembrane regions that then leads to channel
CC opening. {ECO:0000250|UniProtKB:P11716}.
CC -!- PTM: Channel activity is modulated by phosphorylation. Phosphorylation
CC at Ser-2844 may increase channel activity. Repeated very high-level
CC exercise increases phosphorylation at Ser-2844.
CC {ECO:0000250|UniProtKB:P21817}.
CC -!- PTM: Activated by reversible S-nitrosylation (By similarity). Repeated
CC very high-level exercise increases S-nitrosylation (By similarity).
CC {ECO:0000250|UniProtKB:P11716, ECO:0000250|UniProtKB:P21817}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1
CC subfamily. {ECO:0000305}.
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DR EMBL; X62880; CAA44674.1; ALT_SEQ; mRNA.
DR EMBL; X68247; CAA48318.1; -; Genomic_DNA.
DR EMBL; X69465; CAA49225.1; -; Genomic_DNA.
DR EMBL; M32501; AAA31022.1; -; mRNA.
DR SMR; P16960; -.
DR STRING; 9823.ENSSSCP00000003203; -.
DR PaxDb; P16960; -.
DR PeptideAtlas; P16960; -.
DR PRIDE; P16960; -.
DR eggNOG; KOG2243; Eukaryota.
DR InParanoid; P16960; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0031301; C:integral component of organelle membrane; ISS:UniProtKB.
DR GO; GO:1990425; C:ryanodine receptor complex; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IBA:GO_Central.
DR GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0033017; C:sarcoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0014802; C:terminal cisterna; ISS:UniProtKB.
DR GO; GO:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048763; F:calcium-induced calcium release activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005219; F:ryanodine-sensitive calcium-release channel activity; ISS:UniProtKB.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:InterPro.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; ISS:UniProtKB.
DR GO; GO:0043931; P:ossification involved in bone maturation; ISS:UniProtKB.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; 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; 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; IPR033215; RyR1.
DR InterPro; IPR035761; SPRY1_RyR.
DR InterPro; IPR035764; SPRY2_RyR.
DR InterPro; IPR035762; SPRY3_RyR.
DR InterPro; IPR003877; SPRY_dom.
DR PANTHER; PTHR13715:SF15; PTHR13715:SF15; 1.
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; 3.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
PE 2: Evidence at transcript level;
KW ATP-binding; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Developmental protein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; S-nitrosylation;
KW Sarcoplasmic reticulum; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..5035
FT /note="Ryanodine receptor 1"
FT /id="PRO_0000219359"
FT TOPO_DOM 1..4556
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4557..4577
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4578..4638
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4639..4659
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4660..4777
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4778..4800
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4801
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4802..4818
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4819..4833
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4834..4854
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4855..4877
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT INTRAMEM 4878..4897
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4898..4917
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TRANSMEM 4918..4938
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT TOPO_DOM 4939..5035
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT DOMAIN 98..153
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 160..205
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 211..265
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 271..334
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 336..393
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 582..798
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 842..955
FT /note="1"
FT REPEAT 956..1069
FT /note="2"
FT DOMAIN 1014..1209
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1345..1360
FT /note="3; truncated"
FT DOMAIN 1358..1571
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 1373..1388
FT /note="4; truncated"
FT REPEAT 2727..2846
FT /note="5"
FT REPEAT 2847..2960
FT /note="6"
FT DOMAIN 4070..4098
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 670..681
FT /note="Interaction with FKBP1A"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT REGION 842..2960
FT /note="6 X approximate repeats"
FT REGION 1308..1386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1399..1419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1869..1923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2391..2414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2829..2860
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3476..3495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3610..3639
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 4247..4281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4378..4534
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4586..4618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 4892..4898
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT COMPBIAS 1322..1351
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1371..1386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1871..1920
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2829..2844
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3481..3495
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4249..4263
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4481..4495
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4496..4513
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4514..4529
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3888
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 3962
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4206..4210
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4714
FT /ligand="caffeine"
FT /ligand_id="ChEBI:CHEBI:27732"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4952..4957
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4977..4983
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT BINDING 4999
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT MOD_RES 1338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2346
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 2844
FT /note="Phosphoserine; by PKA and PKG"
FT /evidence="ECO:0000250|UniProtKB:E9PZQ0"
FT MOD_RES 3631
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P11716"
FT MOD_RES 4463
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LMY4"
FT MOD_RES 4861
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P21817"
FT MOD_RES 4864
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21817"
FT CONFLICT 2092
FT /note="A -> P (in Ref. 3; CAA49225)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 5035 AA; 565332 MW; E00613F2027B94A4 CRC64;
MGDGGEGEDE VQFLRTDDEV VLQCNATVLK EQLKLCLAAE GFGNRLCFLE PTSNAQNVPP
DLAICCFVLE QSLSVRALQE MLANTVEAGV ESSQGGGHRT LLYGHAILLR HAHSGMYLSC
LTTSRSMTDK LAFDVGLQED ATGEACWWTT HPASKQRSEG EKVRVGDDLI LVSVSSERYL
HLSTASGELQ VDASFMQTLW NMNPICSGCE EGYVTGGHVL RLFHGHMDEC LTISPADSDD
QRRLVYYEGG SVCTHARSLW RLEPLRISWS GSHLRWGQPL RIRHVTTGRY LALIEDQGLV
VVDASKAHTK ATSFCFRISK EKLDTAPKRD VEGMGPPEIK YGESLCFVQH VASGLWLTYA
APDPKALRLG VLKKKAILHQ EGHMDDALSL TRCQQEESQA ARMIYSTAGL YNHFIKGLDS
FSGKPRGSGA PAGTALPLEG VILSLQDLIG YFEPPSEELQ HEEKQSKLRS LRNRQSLFQE
EGMLSLVLNC IDRLNVYTTA AHFAEFAGEE AAESWKEIVN LLYEILASLI RGNRANCALF
SNNLDWLVSK LDRLEASSGI LEVLYCVLIE SPEVLNIIQE NHIKSIISLL DKHGRNHKVL
DVLCSLCVCN GVAVRSNQDL ITENLLPGRE LLLQTNLINY VTSIRPNIFV GRAEGTTQYS
KWYFEVMVDE VVPFLTAQAT HLRVGWALTE GYSPYPGGGE GWGGNGVGDD LYSYGFDGLH
LWTGHVPRLV TSPGQHLLAP EDVVSCCLDL SVPSISFRIN GCPVQGVFEA FNLNGLFFPV
VSFSAGVKVR FLLGGRHGEF KFLPPPGYAP CHEAVLPRER LRLEPIKEYR REGPRGPHLV
GPSRCLSHTD FVPCPVDTVQ IVLPPHLERI REKLAENIHE LWALTRIEQG WTYGPVRDDN
KRLHPCLVDF HSLPEPERNY NLQMSGETLK TLLALGCHVG MADEKAEDNL RKTKLPKTYM
MSNGYKPAPL DLSHVRLTPA QTTLVDRLAE NGHNVWARDR VAQGWSYSAV QDIPARRNPR
LVPYRLLDEA TKRSNRDSLC QAVRTLLGYG YNIEPPDQEP SQVESQSRWD RVRIFRAEKS
YAVQSGRWYF EFEAVTTGEM RVGWARPELR PDVELGADEL AYVFNGHRGQ RWHLGSELFG
RPWQSGDVVG CMIDLTENTI IFTLNGEVLM SDSGSETAFR DIEVGDGFLP VCSLGPGQVG
HLNLGQDVSS LRFFAICGLQ EGFEPFAINM QRPVTTWFSK SLPQFEAVPL EHPHYEVSRV
DGTVDTPPCL RLTHRTWGSQ NSLVEMLFLR LSLPVQFHQH FRCTAGATPL APPGLQPPAE
DEARAAEPDP DYENLRRSAG RWGEAEGGKE GTAKEGAPGG TAQAGVEAQP PRAENEKDAT
TEKNKKRGFL FKAKKAAMMT QPPATPTLPR LPHEVVPADD RDDPDIILNT TTYYYSVRVF
AGQEPSCVWV GWVTPDYHQH DMNFDLTKVR AVTVTMGDEQ GNIHSSLKCS NCYMVWGGDF
VSPGQQGRIS HTDLVIGCLV DLATGLMTFT ANGKESNTFF QVEPNTKLFP AVFVLPTHQN
VIQFELGKQK NIMPLSAAMF LSERKNPAPQ CPPRLEMQML MPVSWSRMPN HFLRVETRRA
GERLGWAVQC QEPLTMMALH IPEENRCMDI LELSERLDLQ QFHSHTLRLY RAVCALGNNR
VAHALCSHVD QAQLLHALED AHLPGPLRAG YYDLLISIHL ESACRSRRSM LSEYIVPLTP
ETRAITLFPP GKRTENGPRR HGLPGVGVTT SLRPPHHFSA PCFVAALPAV GAAEAPARLS
PSIPLEALRD KALRMLGEAV RDGGQHARDP VGGSVEFQFV PVLKLVSTLL VMGIFGDEDV
KQILKMIEPE VFTEEEEEEE EEEEEEEEDE EEKEEDEEEE AREKEDEEKE EEETAEGEKE
EYLEEGLLQM KLPESVKLQM CNLLEYFCDQ ELQHRVESLA AFAERYVDKL QANQRDRYGI
LMKAFTMTAA ETARRTREFR SPPQEQINML LHFKDGEDEE DCPLPDEIRQ DLLEFHQDLL
THCGIQLEGE EEEPEEEATL GSRLMSLLEK VRLVKKKEEK SEEEPPAEES KAQSLQELVS
HTVVRWAQED FVQSPELVRA MFSLLHRQYD GLGELLRALP RAYTISPSSV EDTMSLLECL
GQIRSLLIVQ MGPQEENLMI QSIGNIMNNK VFYQHPNLMR ALGMHETVME VMVNVLGGGE
SKEIRFPKMV TSCCRFLCYF CRISRQNQRS MFDHLSYLLE NSGIGLGMQG STPLDVAAAS
VIDNNELALA LQEQDLEKVV SYLAGCGLQS CPMLLAKGYP DIGWNPCGGE RYLDFLRFAV
FVNGESVEEN ANVVVRLLIR KPECFGPALR GEGGSGLLAT IEEAIRISED PARDGPGVRR
DRRREHFGEE PPEENRVHLG HAIMSFYAAL IDLLGRCAPE MHLIQAGKGE ALRIRAILRS
LVPLDDLVGI ISLPLQIPTL GKDGALVQPK MSASFVPDHK ASMVLFLDRV YGIENQDFLL
HVLDVGFLPD MRAAASLDTA TFSTTEMALA LNRYLCLAVL PLITKCAPLF AGTEHRAIMV
DSMLHTVYRL SRGRSLTKAQ RDVIEECLMA LCRYIRPSML QHLLRRLVFD VPILNEFAKM
PLKLLTNHYE RCWKYYCLPT GWANFGVTSE EELHLTRKLF WGIFDSLAHK KYDPELYRMA
MPCLCAIAGA LPPDYVDASY SSKAEKKATV DAEGNFDPRP VETLNVIIPE KLDSFINKFA
EYTHEKWAFD KIQNNWSYGE NIDEELKTHP MLRPYKTFSE KDKEIYRWPI KESLKAMIAW
EWTIEKAREG EEEKTEKKKT RKISQSAQTY DAREGYNPQP PDLSGVTLSR ELQAMAEQLA
ENYHNTWGRK KKQELEAKGG GTHPLLVPYD TLTAKEKARD REKAQELLKF LQMNGYAVTR
GLKDMELDTS SIEKRFAFGF LQQLLRWMDI SQEFIAHLEA VVSSGRVEKS PHEQEIKFFA
KILLPLINQY FTNHCLYFLS TPAKVLGSGG HASNKEKEMI TSLFCKLAAL VRHRVSLFGT
DAPAVVNCLH ILARSLDART VMKSGPEIVK AGLRSFFESA SEDIEKMVEN LRLGKVSQAR
TQVKGVGQNL TYTTVALLPV LTTLFQHIAQ HQFGDDVILD DVQVSCYRTL CSIYSLGTTR
NPYVEKLRPA LGECLARLAA AMPVAFLEPQ LNEYNACSVY TTKSPRERAI LGLPNSVEEM
CPDIPVLERL MADIGGLAES GARYTEMPHV IEITLPMLCS YLPRWWERGP EAPPPALPAG
APPPCTAVTS DHLNSLLGNI LRIIVNNLGI DEASWMKRLA VFAQPIVSRA RPELLHSHFI
PTIGRLRKRA GKVVAEEEQL RLEAKAEAEE GELLVRDEFS VLCRDLYALY PLLIRYVDNN
RAHWLTEPNP SAEELFRMVG EIFIYWSKSH NFKREEQNFV VQNEINNMSF LTADNKSKMA
KSGGSDQERT KKKRLGDRYS VQTSLIVATL KKMLPIGLNM CAPTDQELIT LAKTRYALKD
TDEEVREFLQ NNLHLQGKVE GSPSLRWQMA LYRGLPGREE DADDPEKIVR RVQEVSAVLY
HLEQMEHPYK SKKAVWHKLL SKQRRRAVVA CFRMTPLYNL PTHRACNMFL ESYKAAWILT
EDHSFEDRMI DDLSKAGEQE EEEEEVEEKK PDPLHQLVLH FSRTALTEKS KLDEDYLYMA
YADIMAKSCH LEEGGENGEA QEEVEVSFEE KEMEKQRLLY QQARLHNRGA AEMVLQMISA
CKGETGAMVS STLKLGISIL NGGNADVQQK MLDYLKDKKE VGFFQSIQAL MQTCSVLDLN
AFERQNKAEG LGMVNEDGTV INRQNGEKVM ADDEFTQDLF RFLQLLCEGH NNDFQNYLRT
QTGNTTTINI IICTVDYLLR LQESISDFYW YYSGKDVIEE QGKRNFSKAM SVAKQVFNSL
TEYIQGPCTG NQQSLAHSRL WDAVVGFLHV FAHMMMKLAQ DSSQIELLKE LLDLQKDMVV
MLLSLLEGNV VNGMIARQMV DMLVESSSNV EMILKFFDMF LKLKDIVGSE AFQDYVTDPR
GLISKKDFQK AMDSQKQFTG PEIQFLLSCS EADENEMIDC EEFANRFQEP ARDIGFNVAV
LLTNLSEHVP HDPRLRNFLE LAESILEYFR PYLGRIEIMG ASRRIERIYF EISETNRAQW
EMPQVKESKR QFIFDVVNEG GESEKMELFV SFCEDTIFEM QIAAQISEPE GEPEEDEDEG
AGLAEAGAEG AEEGAVGPEG AAGTAAAGLT ARLAAATSRA LRGLSYRSLR RRVRRLRRLT
AREAATALAA LLWAALAHAG AAGAGAAAGA LRLLWGSLFG GGLVEGAKKV TVTELLAGMP
DPTGDEVHGE QPAGPGGEAD GEGAGEGAGE AWEGAGDEEV AVQEAGPGGA DGAVAVAEGG
PFRPEGAGGL GDMGDTTPAE PPTPEGSPII KRKLGVDGEE EELPPEPEPE PEPEPEKADA
ENGEKEEVPK PPPEPPKKTA PPPPPPKKEE GGSGGLEFWG ELEVQRVKFL NYLSRNFYTL
RFLALFLAFA INFILLFYKV SDSPPGEDDM EGSAAGDLSG AGSGGGSGWG SGAGEEVEGD
EDENMVYYFL EESTGYMEPA LRCLSLLHTL VAFLCIIGYN CLKVPLVIFK REKELARKLE
FDGLYITEQP EDDDVKGQWD RLVLNTPSFP SNYWDKFVKR KVLDKHGDIY GRERIAELLG
MDLATLEITA HNERKPEPPP GLLTWLMSID VKYQIWKFGV IFTDNSFLYL GWYMVMSLLG
HYNNFFFAAH LLDIAMGVKT LRTILSSVTH NGKQLVMTVG LLAVVVYLYT VVAFNFFRKF
YNKSEDEDEP DMKCDDMMTC YLFHMYVGVR AGGGIGDEIE DPAGDEYELY RVVFDITFFF
FVIVILLAII QGLIIDAFGE LRDQQEQVRE DMETKCFICG IGSDYFDTTP HRFETHTLEE
HNLANYMFFL MYLINKDETE HTGQESYVWK MYQERCWDFF PAGDCFRKQY EDQLS
