RYR3_HUMAN
ID RYR3_HUMAN Reviewed; 4870 AA.
AC Q15413; O15175; Q15412;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Ryanodine receptor 3;
DE Short=RYR-3;
DE Short=RyR3;
DE AltName: Full=Brain ryanodine receptor-calcium release channel;
DE AltName: Full=Brain-type ryanodine receptor;
DE AltName: Full=Type 3 ryanodine receptor;
GN Name=RYR3; Synonyms=HBRR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9395096; DOI=10.1016/s0014-5793(97)01275-1;
RA Nakashima Y., Nishimura S., Maeda A., Barsoumian E.L., Hakamata Y.,
RA Nakai J., Allen P.D., Imoto K., Kita T.;
RT "Molecular cloning and characterization of a human brain ryanodine
RT receptor.";
RL FEBS Lett. 417:157-162(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND VARIANTS
RP SER-261; ILE-494; CYS-693; VAL-731; GLY-1380 AND SER-2268 DEL.
RC TISSUE=Fetal brain;
RX PubMed=9515741; DOI=10.1016/s0014-5793(98)00124-0;
RA Leeb T., Brenig B.;
RT "cDNA cloning and sequencing of the human ryanodine receptor type 3 (RYR3)
RT reveals a novel alternative splice site in the RYR3 gene.";
RL FEBS Lett. 423:367-370(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 520-660, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=9607712; DOI=10.1016/s0306-4522(97)00612-x;
RA Martin C., Chapman K.E., Seckl J.R., Ashley R.H.;
RT "Partial cloning and differential expression of ryanodine receptor/calcium-
RT release channel genes in human tissues including the hippocampus and
RT cerebellum.";
RL Neuroscience 85:205-216(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3943-4870.
RC TISSUE=T-cell;
RX PubMed=7523185; DOI=10.1016/0014-5793(94)00955-4;
RA Hakamata Y., Nishimura S., Nakai J., Nakashima Y., Kita T., Imoto K.;
RT "Involvement of the brain type of ryanodine receptor in T-cell
RT proliferation.";
RL FEBS Lett. 352:206-210(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 4644-4842.
RC TISSUE=Cervix carcinoma, and Hepatoma;
RX PubMed=8276408; DOI=10.1006/geno.1993.1446;
RA Sorrentino V., Giannini G., Malzac P., Mattei M.-G.;
RT "Localization of a novel ryanodine receptor gene (RYR3) to human chromosome
RT 15q14-q15 by in situ hybridization.";
RL Genomics 18:163-165(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4652-4803.
RC TISSUE=Myometrium;
RX PubMed=7556644; DOI=10.1016/0014-5793(95)00924-x;
RA Lynn S., Morgan J.M., Lamb H.K., Meissner G., Gillespie J.I.;
RT "Isolation and partial cloning of ryanodine-sensitive Ca2+ release channel
RT protein isoforms from human myometrial smooth muscle.";
RL FEBS Lett. 372:6-12(1995).
RN [8]
RP FUNCTION.
RX PubMed=12354756; DOI=10.1074/jbc.m209061200;
RA Schwarzmann N., Kunerth S., Weber K., Mayr G.W., Guse A.H.;
RT "Knock-down of the type 3 ryanodine receptor impairs sustained Ca2+
RT signaling via the T cell receptor/CD3 complex.";
RL J. Biol. Chem. 277:50636-50642(2002).
RN [9]
RP INTERACTION WITH FKBP1A.
RX PubMed=22100703; DOI=10.1016/j.abb.2011.11.004;
RA Wen H., Kang S., Song Y., Song Y., Yang H.J., Kim M.H., Park S.;
RT "Characterization of the binding sites for the interactions between FKBP12
RT and intracellular calcium release channels.";
RL Arch. Biochem. Biophys. 517:37-42(2012).
RN [10] {ECO:0007744|PDB:4ERV}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 2597-2800.
RX PubMed=22705209; DOI=10.1016/j.str.2012.04.015;
RA Yuchi Z., Lau K., Van Petegem F.;
RT "Disease mutations in the ryanodine receptor central region: crystal
RT structures of a phosphorylation hot spot domain.";
RL Structure 20:1201-1211(2012).
CC -!- FUNCTION: Calcium channel that mediates the release of Ca(2+) from the
CC sarcoplasmic reticulum into the cytoplasm in muscle and thereby plays a
CC role in triggering muscle contraction. May regulate Ca(2+) release by
CC other calcium channels. Calcium channel that mediates Ca(2+)-induced
CC Ca(2+) release from the endoplasmic reticulum in non-muscle cells.
CC Contributes to cellular calcium ion homeostasis (By similarity). Plays
CC a role in cellular calcium signaling. {ECO:0000250,
CC ECO:0000269|PubMed:12354756}.
CC -!- SUBUNIT: Homotetramer. Heterotetramer with RYR2. Interacts with CALM
CC (By similarity). Interacts with FKBP1A. Interacts with SELENON (By
CC similarity). {ECO:0000250|UniProtKB:Q9TS33,
CC ECO:0000269|PubMed:22100703}.
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}. Microsome membrane
CC {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Sarcoplasmic
CC reticulum {ECO:0000250|UniProtKB:Q9TS33}. 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15413-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15413-2; Sequence=VSP_005954;
CC Name=3;
CC IsoId=Q15413-3; Sequence=VSP_005955, VSP_005956;
CC -!- TISSUE SPECIFICITY: Brain, skeletal muscle, placenta and possibly liver
CC and kidney. In brain, highest levels are found in the cerebellum,
CC hippocampus, caudate nucleus and amygdala, with lower levels in the
CC corpus callosum, substantia nigra and thalamus.
CC {ECO:0000269|PubMed:9395096, ECO:0000269|PubMed:9607712}.
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 -!- MISCELLANEOUS: Channel activity is modulated by the alkaloid ryanodine
CC that binds to the open calcium-release channel with high affinity. At
CC 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 elevated cytoplasmic calcium levels in the micromolar
CC range, by caffeine and adenine nucleotides, such as AMP and ATP.
CC Inhibited by Mg(2+) and ruthenium red (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR3
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23795.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ryanodine receptor entry;
CC URL="https://en.wikipedia.org/wiki/Ryanodine_receptor";
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DR EMBL; AB001025; BAA23795.1; ALT_FRAME; mRNA.
DR EMBL; AJ001515; CAA04798.1; -; mRNA.
DR EMBL; AC010809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC055874; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC067793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087638; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AJ002512; CAA05503.1; -; mRNA.
DR EMBL; X74269; CAA52326.1; -; mRNA.
DR EMBL; X74270; CAA52327.1; -; Genomic_DNA.
DR CCDS; CCDS45210.1; -. [Q15413-1]
DR CCDS; CCDS58351.1; -. [Q15413-2]
DR PIR; S37537; S37537.
DR PIR; S66631; S66631.
DR RefSeq; NP_001027.3; NM_001036.4. [Q15413-1]
DR RefSeq; NP_001230925.1; NM_001243996.2. [Q15413-2]
DR PDB; 4ERV; X-ray; 1.75 A; A=2597-2800.
DR PDB; 6UHA; X-ray; 2.85 A; A/B=848-1055.
DR PDB; 6UHB; X-ray; 2.50 A; A/B=848-1055.
DR PDB; 6UHE; X-ray; 2.89 A; A/B/C/D=848-1055.
DR PDB; 6UHH; X-ray; 3.14 A; A/B/C/D=848-1055.
DR PDBsum; 4ERV; -.
DR PDBsum; 6UHA; -.
DR PDBsum; 6UHB; -.
DR PDBsum; 6UHE; -.
DR PDBsum; 6UHH; -.
DR SMR; Q15413; -.
DR BioGRID; 112175; 14.
DR ComplexPortal; CPX-3162; Ryanodine 3 complex.
DR IntAct; Q15413; 6.
DR STRING; 9606.ENSP00000373884; -.
DR ChEMBL; CHEMBL2062; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugCentral; Q15413; -.
DR GlyGen; Q15413; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q15413; -.
DR PhosphoSitePlus; Q15413; -.
DR BioMuta; RYR3; -.
DR DMDM; 325511382; -.
DR EPD; Q15413; -.
DR MassIVE; Q15413; -.
DR PaxDb; Q15413; -.
DR PeptideAtlas; Q15413; -.
DR PRIDE; Q15413; -.
DR ProteomicsDB; 60577; -. [Q15413-1]
DR ProteomicsDB; 60578; -. [Q15413-2]
DR ProteomicsDB; 60579; -. [Q15413-3]
DR Antibodypedia; 41923; 41 antibodies from 17 providers.
DR DNASU; 6263; -.
DR Ensembl; ENST00000415757.7; ENSP00000399610.3; ENSG00000198838.14. [Q15413-2]
DR Ensembl; ENST00000634891.2; ENSP00000489262.1; ENSG00000198838.14. [Q15413-1]
DR GeneID; 6263; -.
DR KEGG; hsa:6263; -.
DR MANE-Select; ENST00000634891.2; ENSP00000489262.1; NM_001036.6; NP_001027.3.
DR UCSC; uc001zhi.3; human. [Q15413-1]
DR CTD; 6263; -.
DR DisGeNET; 6263; -.
DR GeneCards; RYR3; -.
DR HGNC; HGNC:10485; RYR3.
DR HPA; ENSG00000198838; Group enriched (brain, choroid plexus, skeletal muscle, tongue).
DR MIM; 180903; gene.
DR neXtProt; NX_Q15413; -.
DR OpenTargets; ENSG00000198838; -.
DR PharmGKB; PA34897; -.
DR VEuPathDB; HostDB:ENSG00000198838; -.
DR eggNOG; KOG2243; Eukaryota.
DR GeneTree; ENSGT00940000155507; -.
DR HOGENOM; CLU_000040_2_0_1; -.
DR InParanoid; Q15413; -.
DR OMA; LMQSCRS; -.
DR OrthoDB; 5161at2759; -.
DR PhylomeDB; Q15413; -.
DR TreeFam; TF315244; -.
DR PathwayCommons; Q15413; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR SignaLink; Q15413; -.
DR BioGRID-ORCS; 6263; 15 hits in 1068 CRISPR screens.
DR ChiTaRS; RYR3; human.
DR GeneWiki; RYR3; -.
DR GenomeRNAi; 6263; -.
DR Pharos; Q15413; Tclin.
DR PRO; PR:Q15413; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q15413; protein.
DR Bgee; ENSG00000198838; Expressed in diaphragm and 146 other tissues.
DR ExpressionAtlas; Q15413; baseline and differential.
DR Genevisible; Q15413; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; 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:0030018; C:Z disc; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048763; F:calcium-induced calcium release activity; IBA:GO_Central.
DR GO; GO:0015278; F:calcium-release channel activity; IMP:UniProtKB.
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:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:InterPro.
DR GO; GO:0071318; P:cellular response to ATP; ISS:UniProtKB.
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:0071286; P:cellular response to magnesium ion; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; 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; IPR016024; ARM-type_fold.
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; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49899; SSF49899; 3.
DR SUPFAM; SSF82109; SSF82109; 2.
DR PROSITE; PS50188; B302_SPRY; 3.
DR PROSITE; PS50919; MIR; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Calmodulin-binding; Endoplasmic reticulum; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Microsome; Receptor;
KW Reference proteome; Repeat; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..4870
FT /note="Ryanodine receptor 3"
FT /id="PRO_0000219363"
FT TOPO_DOM 1..4186
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 4187..4207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4410..4430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4485..4505
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4610..4630
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4633..4653
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 4672..4692
FT /note="Helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 4723..4732
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TRANSMEM 4753..4773
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 4774..4870
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT DOMAIN 100..155
FT /note="MIR 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 162..207
FT /note="MIR 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 215..269
FT /note="MIR 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 275..333
FT /note="MIR 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 343..400
FT /note="MIR 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00131"
FT DOMAIN 585..796
FT /note="B30.2/SPRY 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 840..953
FT /note="1"
FT REPEAT 954..1068
FT /note="2"
FT DOMAIN 1012..1208
FT /note="B30.2/SPRY 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT DOMAIN 1254..1466
FT /note="B30.2/SPRY 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT REPEAT 2589..2707
FT /note="3"
FT REPEAT 2708..2820
FT /note="4"
FT REGION 840..2820
FT /note="4 X approximate repeats"
FT REGION 2322..2335
FT /note="Interaction with FKBP1A"
FT /evidence="ECO:0000269|PubMed:22100703"
FT REGION 3469..3498
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
FT REGION 4102..4121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4304..4360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 4315..4360
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 3883
FT /note="Important for activation by Ca(2+)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 3337..3341
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9395096"
FT /id="VSP_005954"
FT VAR_SEQ 3857..3859
FT /note="DSS -> GMW (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005955"
FT VAR_SEQ 3860..4870
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_005956"
FT VARIANT 261
FT /note="R -> S"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_024077"
FT VARIANT 358
FT /note="I -> T (in dbSNP:rs2304380)"
FT /id="VAR_057166"
FT VARIANT 494
FT /note="V -> I (in dbSNP:rs2077268)"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_024078"
FT VARIANT 693
FT /note="Y -> C"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_011404"
FT VARIANT 731
FT /note="I -> V (in dbSNP:rs2229116)"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_011405"
FT VARIANT 1380
FT /note="E -> G"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_011406"
FT VARIANT 2268
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:9515741"
FT /id="VAR_011407"
FT CONFLICT 932
FT /note="A -> T (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 1081
FT /note="A -> P (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 1336
FT /note="A -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 1480
FT /note="K -> E (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 1641
FT /note="R -> C (in Ref. 1; BAA23795 and 2; CAA04798)"
FT /evidence="ECO:0000305"
FT CONFLICT 2270
FT /note="G -> E (in Ref. 1; BAA23795 and 2; CAA04798)"
FT /evidence="ECO:0000305"
FT CONFLICT 2355
FT /note="A -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 2433
FT /note="A -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 2546
FT /note="F -> I (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 2580
FT /note="T -> S (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 2817
FT /note="A -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 3684
FT /note="S -> P (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 3698
FT /note="F -> S (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 4026
FT /note="E -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 4083
FT /note="E -> G (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 4537
FT /note="R -> P (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 4604
FT /note="I -> L (in Ref. 1; BAA23795)"
FT /evidence="ECO:0000305"
FT CONFLICT 4709
FT /note="C -> R (in Ref. 6; CAA52326)"
FT /evidence="ECO:0000305"
FT HELIX 863..865
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 866..886
FT /evidence="ECO:0007829|PDB:6UHB"
FT TURN 897..900
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 908..910
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 913..932
FT /evidence="ECO:0007829|PDB:6UHB"
FT STRAND 936..938
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 944..947
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 955..957
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 977..1000
FT /evidence="ECO:0007829|PDB:6UHB"
FT TURN 1011..1014
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 1022..1024
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 1027..1046
FT /evidence="ECO:0007829|PDB:6UHB"
FT STRAND 1050..1052
FT /evidence="ECO:0007829|PDB:6UHB"
FT HELIX 2612..2635
FT /evidence="ECO:0007829|PDB:4ERV"
FT TURN 2646..2649
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2657..2659
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2662..2681
FT /evidence="ECO:0007829|PDB:4ERV"
FT STRAND 2685..2688
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2695..2704
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2723..2725
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2730..2757
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2769..2771
FT /evidence="ECO:0007829|PDB:4ERV"
FT HELIX 2774..2792
FT /evidence="ECO:0007829|PDB:4ERV"
FT TURN 2793..2795
FT /evidence="ECO:0007829|PDB:4ERV"
FT STRAND 2796..2799
FT /evidence="ECO:0007829|PDB:4ERV"
SQ SEQUENCE 4870 AA; 552042 MW; B953487A89FD480F CRC64;
MAEGGEGGED EIQFLRTEDE VVLQCIATIH KEQRKFCLAA EGLGNRLCFL EPTSEAKYIP
PDLCVCNFVL EQSLSVRALQ EMLANTGENG GEGAAQGGGH RTLLYGHAVL LRHSFSGMYL
TCLTTSRSQT DKLAFDVGLR EHATGEACWW TIHPASKQRS EGEKVRIGDD LILVSVSSER
YLHLSVSNGN IQVDASFMQT LWNVHPTCSG SSIEEGYLLG GHVVRLFHGH DECLTIPSTD
QNDSQHRRIF YEAGGAGTRA RSLWRVEPLR ISWSGSNIRW GQAFRLRHLT TGHYLALTED
QGLILQDRAK SDTKSTAFSF RASKELKEKL DSSHKRDIEG MGVPEIKYGD SVCFVQHIAS
GLWVTYKAQD AKTSRLGPLK RKVILHQEGH MDDGLTLQRC QREESQAARI IRNTTALFSQ
FVSGNNRTAA PITLPIEEVL QTLQDLIAYF QPPEEEMRHE DKQNKLRSLK NRQNLFKEEG
MLALVLNCID RLNVYNSVAH FAGIAREESG MAWKEILNLL YKLLAALIRG NRNNCAQFSN
NLDWLISKLD RLESSSGILE VLHCILTESP EALNLIAEGH IKSIISLLDK HGRNHKVLDI
LCSLCLCNGV AVRANQNLIC DNLLPRRNLL LQTRLINDVT SIRPNIFLGV AEGSAQYKKW
YFELIIDQVD PFLTAEPTHL RVGWASSSGY APYPGGGEGW GGNGVGDDLY SYGFDGLHLW
SGRIPRAVAS INQHLLRSDD VVSCCLDLGV PSISFRINGQ PVQGMFENFN TDGLFFPVMS
FSAGVKVRFL MGGRHGEFKF LPPSGYAPCY EALLPKEKMR LEPVKEYKRD ADGIRDLLGT
TQFLSQASFI PCPVDTSQVI LPPHLEKIRD RLAENIHELW GMNKIELGWT FGKIRDDNKR
QHPCLVEFSK LPETEKNYNL QMSTETLKTL LALGCHIAHV NPAAEEDLKK VKLPKNYMMS
NGYKPAPLDL SDVKLLPPQE ILVDKLAENA HNVWAKDRIK QGWTYGIQQD LKNKRNPRLV
PYALLDERTK KSNRDSLREA VRTFVGYGYN IEPSDQELAD SAVEKVSIDK IRFFRVERSY
AVRSGKWYFE FEVVTGGDMR VGWARPGCRP DVELGADDQA FVFEGNRGQR WHQGSGYFGR
TWQPGDVVGC MINLDDASMI FTLNGELLIT NKGSELAFAD YEIENGFVPI CCLGLSQIGR
MNLGTDASTF KFYTMCGLQE GFEPFAVNMN RDVAMWFSKR LPTFVNVPKD HPHIEVMRID
GTMDSPPCLK VTHKTFGTQN SNADMIYCRL SMPVECHSSF SHSPCLDSEA FQKRKQMQEI
LSHTTTQCYY AIRIFAGQDP SCVWVGWVTP DYHLYSEKFD LNKNCTVTVT LGDERGRVHE
SVKRSNCYMV WGGDIVASSQ RSNRSNVDLE IGCLVDLAMG MLSFSANGKE LGTCYQVEPN
TKVFPAVFLQ PTSTSLFQFE LGKLKNAMPL SAAIFRSEEK NPVPQCPPRL DVQTIQPVLW
SRMPNSFLKV ETERVSERHG WVVQCLEPLQ MMALHIPEEN RCVDILELCE QEDLMRFHYH
TLRLYSAVCA LGNSRVAYAL CSHVDLSQLF YAIDNKYLPG LLRSGFYDLL ISIHLASAKE
RKLMMKNEYI IPITSTTRNI RLFPDESKRH GLPGVGLRTC LKPGFRFSTP CFVVTGEDHQ
KQSPEIPLES LRTKALSMLT EAVQCSGAHI RDPVGGSVEF QFVPVLKLIG TLLVMGVFDD
DDVRQILLLI DPSVFGEHSA GTEEGAEKEE VTQVEEKAVE AGEKAGKEAP VKGLLQTRLP
ESVKLQMCEL LSYLCDCELQ HRVEAIVAFG DIYVSKLQAN QKFRYNELMQ ALNMSAALTA
RKTKEFRSPP QEQINMLLNF QLGENCPCPE EIREELYDFH EDLLLHCGVP LEEEEEEEED
TSWTGKLCAL VYKIKGPPKP EKEQPTEEEE RCPTTLKELI SQTMICWAQE DQIQDSELVR
MMFNLLRRQY DSIGELLQAL RKTYTISHTS VSDTINLLAA LGQIRSLLSV RMGKEEELLM
INGLGDIMNN KVFYQHPNLM RVLGMHETVM EVMVNVLGTE KSQIAFPKMV ASCCRFLCYF
CRISRQNQKA MFEHLSYLLE NSSVGLASPS MRGSTPLDVA ASSVMDNNEL ALSLEEPDLE
KVVTYLAGCG LQSCPMLLAK GYPDVGWNPI EGERYLSFLR FAVFVNSESV EENASVVVKL
LIRRPECFGP ALRGEGGNGL LAAMQGAIKI SENPALDLPS QGYKREVSTG DDEEEEEIVH
MGNAIMSFYS ALIDLLGRCA PEMHLIQTGK GEAIRIRSIL RSLVPTEDLV GIISIPLKLP
SLNKDGSVSE PDMAANFCPD HKAPMVLFLD RVYGIKDQTF LLHLLEVGFL PDLRASASLD
TVSLSTTEAA LALNRYICSA VLPLLTRCAP LFAGTEHCTS LIDSTLQTIY RLSKGRSLTK
AQRDTIEECL LAICNHLRPS MLQQLLRRLV FDVPQLNEYC KMPLKLLTNH YEQCWKYYCL
PSGWGSYGLA VEEELHLTEK LFWGIFDSLS HKKYDPDLFR MALPCLSAIA GALPPDYLDT
RITATLEKQI SVDADGNFDP KPINTMNFSL PEKLEYIVTK YAEHSHDKWA CDKSQSGWKY
GISLDENVKT HPLIRPFKTL TEKEKEIYRW PARESLKTML AVGWTVERTK EGEALVQQRE
NEKLRSVSQA NQGNSYSPAP LDLSNVVLSR ELQGMVEVVA ENYHNIWAKK KKLELESKGG
GSHPLLVPYD TLTAKEKFKD REKAQDLFKF LQVNGIIVSR GMKDMELDAS SMEKRFAYKF
LKKILKYVDS AQEFIAHLEA IVSSGKTEKS PRDQEIKFFA KVLLPLVDQY FTSHCLYFLS
SPLKPLSSSG YASHKEKEMV AGLFCKLAAL VRHRISLFGS DSTTMVSCLH ILAQTLDTRT
VMKSGSELVK AGLRAFFENA AEDLEKTSEN LKLGKFTHSR TQIKGVSQNI NYTTVALLPI
LTSIFEHVTQ HQFGMDLLLG DVQISCYHIL CSLYSLGTGK NIYVERQRPA LGECLASLAA
AIPVAFLEPT LNRYNPLSVF NTKTPRERSI LGMPDTVEDM CPDIPQLEGL MKEINDLAES
GARYTEMPHV IEVILPMLCN YLSYWWERGP ENLPPSTGPC CTKVTSEHLS LILGNILKII
NNNLGIDEAS WMKRIAVYAQ PIISKARPDL LRSHFIPTLE KLKKKAVKTV QEEEQLKADG
KGDTQEAELL ILDEFAVLCR DLYAFYPMLI RYVDNNRSNW LKSPDADSDQ LFRMVAEVFI
LWCKSHNFKR EEQNFVIQNE INNLAFLTGD SKSKMSKAMQ VKSGGQDQER KKTKRRGDLY
SIQTSLIVAA LKKMLPIGLN MCTPGDQELI SLAKSRYSHR DTDEEVREHL RNNLHLQEKS
DDPAVKWQLN LYKDVLKSEE PFNPEKTVER VQRISAAVFH LEQVEQPLRS KKAVWHKLLS
KQRKRAVVAC FRMAPLYNLP RHRSINLFLH GYQRFWIETE EYSFEEKLVQ DLAKSPKVEE
EEEEETEKQP DPLHQIILYF SRNALTERSK LEDDPLYTSY SSMMAKSCQS GEDEEEDEDK
EKTFEEKEME KQKTLYQQAR LHERGAAEMV LQMISASKGE MSPMVVETLK LGIAILNGGN
AGVQQKMLDY LKEKKDAGFF QSLSGLMQSC SVLDLNAFER QNKAEGLGMV TEEGTLIVRE
RGEKVLQNDE FTRDLFRFLQ LLCEGHNSDF QNFLRTQMGN TTTVNVIIST VDYLLRLQES
ISDFYWYYSG KDIIDESGQH NFSKALAVTK QIFNSLTEYI QGPCIGNQQS LAHSRLWDAV
VGFLHVFANM QMKLSQDSSQ IELLKELLDL LQDMVVMLLS LLEGNVVNGT IGKQMVDTLV
ESSTNVEMIL KFFDMFLKLK DLTSSDTFKE YDPDGKGIIS KKEFQKAMEG QKQYTQSEID
FLLSCAEADE NDMFNYVDFV DRFHEPAKDI GFNVAVLLTN LSEHMPNDSR LKCLLDPAES
VLNYFEPYLG RIEIMGGAKK IERVYFEISE SSRTQWEKPQ VKESKRQFIF DVVNEGGEQE
KMELFVNFCE DTIFEMQLAS QISESDSADR PEEEEEDEDS SYVLEIAGEE EEDGSLEPAS
AFAMACASVK RNVTDFLKRA TLKNLRKQYR NVKKMTAKEL VKVLFSFFWM LFVGLFQLLF
TILGGIFQIL WSTVFGGGLV EGAKNIRVTK ILGDMPDPTQ FGIHDDTMEA ERAEVMEPGI
TTELVHFIKG EKGDTDIMSD LFGLHPKKEG SLKHGPEVGL GDLSEIIGKD EPPTLESTVQ
KKRKAQAAEM KAANEAEGKV ESEKADMEDG EKEDKDKEEE QAEYLWTEVT KKKKRRCGQK
VEKPEAFTAN FFKGLEIYQT KLLHYLARNF YNLRFLALFV AFAINFILLF YKVTEEPLEE
ETEDVANLWN SFNDEEEEEA MVFFVLQEST GYMAPTLRAL AIIHTIISLV CVVGYYCLKV
PLVVFKREKE IARKLEFDGL YITEQPSEDD IKGQWDRLVI NTPSFPNNYW DKFVKRKVIN
KYGDLYGAER IAELLGLDKN ALDFSPVEET KAEAASLVSW LSSIDMKYHI WKLGVVFTDN
SFLYLAWYTT MSVLGHYNNF FFAAHLLDIA MGFKTLRTIL SSVTHNGKQL VLTVGLLAVV
VYLYTVVAFN FFRKFYNKSE DDDEPDMKCD DMMTCYLFHM YVGVRAGGGI GDEIEDPAGD
PYEMYRIVFD ITFFFFVIVI LLAIIQGLII DAFGELRDQQ EQVREDMETK CFICGIGNDY
FDTTPHGFET HTLQEHNLAN YLFFLMYLIN KDETEHTGQE SYVWKMYQER CWDFFPAGDC
FRKQYEDQLG
