MYH6_HUMAN
ID MYH6_HUMAN Reviewed; 1939 AA.
AC P13533; A2RTX1; D9YZU2; Q13943; Q14906; Q14907;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 5.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Myosin-6;
DE AltName: Full=Myosin heavy chain 6;
DE AltName: Full=Myosin heavy chain, cardiac muscle alpha isoform;
DE Short=MyHC-alpha;
GN Name=MYH6; Synonyms=MYHCA;
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], AND VARIANTS ALA-1101 AND SER-1737.
RX PubMed=1776652; DOI=10.1002/ajmg.1320410435;
RA Matsuoka R., Beisel K.W., Furutani M., Arai S., Takao A.;
RT "Complete sequence of human cardiac alpha-myosin heavy chain gene and amino
RT acid comparison to other myosins based on structural and functional
RT differences.";
RL Am. J. Med. Genet. 41:537-547(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLN-88.
RX PubMed=8307559; DOI=10.1016/s0888-7543(11)80006-6;
RA Epp T.A., Dixon I.M., Wang H.Y., Sole M.J., Liew C.-C.;
RT "Structural organization of the human cardiac alpha-myosin heavy chain gene
RT (MYH6).";
RL Genomics 18:505-509(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (SEP-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-177 AND 1551-1939, AND VARIANT
RP GLN-88.
RX PubMed=2726733; DOI=10.1073/pnas.86.10.3504;
RA Yamauchi-Takihara K., Sole M.J., Liew J., Ing D., Liew C.-C.;
RT "Characterization of human cardiac myosin heavy chain genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3504-3508(1989).
RN [8]
RP ERRATUM OF PUBMED:2726733.
RA Yamauchi-Takihara K., Sole M.J., Liew J., Ing D., Liew C.-C.;
RL Proc. Natl. Acad. Sci. U.S.A. 86:7416-7417(1989).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
RX PubMed=3037493; DOI=10.1093/nar/15.13.5443;
RA Saez L.J., Gianola K.M., McNally E.M., Feghali R., Eddy R., Shows T.B.,
RA Leinwand L.A.;
RT "Human cardiac myosin heavy chain genes and their linkage in the genome.";
RL Nucleic Acids Res. 15:5443-5459(1987).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1407-1939.
RX PubMed=2969919; DOI=10.1172/jci113627;
RA Kurabayashi M., Tsuchimochi H., Komuro I., Takaku F., Yazaki Y.;
RT "Molecular cloning and characterization of human cardiac alpha- and beta-
RT form myosin heavy chain complementary DNA clones. Regulation of expression
RT during development and pressure overload in human atrium.";
RL J. Clin. Invest. 82:524-531(1988).
RN [11]
RP VARIANT CMH14 GLN-795.
RX PubMed=11815426; DOI=10.1161/hc0402.102990;
RA Niimura H., Patton K.K., McKenna W.J., Soults J., Maron B.J., Seidman J.G.,
RA Seidman C.E.;
RT "Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the
RT elderly.";
RL Circulation 105:446-451(2002).
RN [12]
RP VARIANTS CMD1EE LEU-830; SER-1004; LYS-1457 AND GLN-1502, VARIANT CMH14
RP HIS-1065, AND VARIANTS ARG-56; ASN-275; THR-1130 AND GLN-1295.
RX PubMed=15998695; DOI=10.1161/circulationaha.104.507699;
RA Carniel E., Taylor M.R., Sinagra G., Di Lenarda A., Ku L., Fain P.R.,
RA Boucek M.M., Cavanaugh J., Miocic S., Slavov D., Graw S.L., Feiger J.,
RA Zhu X.Z., Dao D., Ferguson D.A., Bristow M.R., Mestroni L.;
RT "Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and
RT hypertrophic phenotypes of cardiomyopathy.";
RL Circulation 112:54-59(2005).
RN [13]
RP VARIANT ASD3 ASN-820.
RX PubMed=15735645; DOI=10.1038/ng1526;
RA Ching Y.-H., Ghosh T.K., Cross S.J., Packham E.A., Honeyman L., Loughna S.,
RA Robinson T.E., Dearlove A.M., Ribas G., Bonser A.J., Thomas N.R.,
RA Scotter A.J., Caves L.S.D., Tyrrell G.P., Newbury-Ecob R.A., Munnich A.,
RA Bonnet D., Brook J.D.;
RT "Mutation in myosin heavy chain 6 causes atrial septal defect.";
RL Nat. Genet. 37:423-428(2005).
RN [14]
RP INVOLVEMENT IN SUSCEPTIBILITY TO SSS3, AND VARIANT SSS3 TRP-721.
RX PubMed=21378987; DOI=10.1038/ng.781;
RA Holm H., Gudbjartsson D.F., Sulem P., Masson G., Helgadottir H.T.,
RA Zanon C., Magnusson O.T., Helgason A., Saemundsdottir J., Gylfason A.,
RA Stefansdottir H., Gretarsdottir S., Matthiasson S.E., Thorgeirsson G.M.,
RA Jonasdottir A., Sigurdsson A., Stefansson H., Werge T., Rafnar T.,
RA Kiemeney L.A., Parvez B., Muhammad R., Roden D.M., Darbar D.,
RA Thorleifsson G., Walters G.B., Kong A., Thorsteinsdottir U., Arnar D.O.,
RA Stefansson K.;
RT "A rare variant in MYH6 is associated with high risk of sick sinus
RT syndrome.";
RL Nat. Genet. 43:316-320(2011).
CC -!- FUNCTION: Muscle contraction.
CC -!- SUBUNIT: Muscle myosin is a hexameric protein that consists of 2 heavy
CC chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2
CC regulatory light chain subunits (MLC-2).
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril. Note=Thick filaments of the
CC myofibrils.
CC -!- DOMAIN: The rodlike tail sequence is highly repetitive, showing cycles
CC of a 28-residue repeat pattern composed of 4 heptapeptides,
CC characteristic for alpha-helical coiled coils.
CC -!- DOMAIN: Limited proteolysis of myosin heavy chain produces 1 light
CC meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further
CC cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment
CC (S2). {ECO:0000305}.
CC -!- DISEASE: Atrial septal defect 3 (ASD3) [MIM:614089]: A congenital heart
CC malformation characterized by incomplete closure of the wall between
CC the atria resulting in blood flow from the left to the right atria.
CC {ECO:0000269|PubMed:15735645}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cardiomyopathy, familial hypertrophic 14 (CMH14) [MIM:613251]:
CC A hereditary heart disorder characterized by ventricular hypertrophy,
CC which is usually asymmetric and often involves the interventricular
CC septum. The symptoms include dyspnea, syncope, collapse, palpitations,
CC and chest pain. They can be readily provoked by exercise. The disorder
CC has inter- and intrafamilial variability ranging from benign to
CC malignant forms with high risk of cardiac failure and sudden cardiac
CC death. {ECO:0000269|PubMed:11815426, ECO:0000269|PubMed:15998695}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Cardiomyopathy, dilated 1EE (CMD1EE) [MIM:613252]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:15998695}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Sick sinus syndrome 3 (SSS3) [MIM:614090]: The term 'sick
CC sinus syndrome' encompasses a variety of conditions caused by sinus
CC node dysfunction. The most common clinical manifestations are syncope,
CC presyncope, dizziness, and fatigue. Electrocardiogram typically shows
CC sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of
CC atrial tachycardias coexisting with sinus bradycardia ('tachycardia-
CC bradycardia syndrome') are also common in this disorder. SSS occurs
CC most often in the elderly associated with underlying heart disease or
CC previous cardiac surgery, but can also occur in the fetus, infant, or
CC child without heart disease or other contributing factors.
CC {ECO:0000269|PubMed:21378987}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC The lifetime risk of being diagnosed with sick sinus syndrome is higher
CC for carriers of variant p.Arg721Trp than for non-carriers.
CC {ECO:0000269|PubMed:21378987}.
CC -!- MISCELLANEOUS: The cardiac alpha isoform is a 'fast' ATPase myosin,
CC while the beta isoform is a 'slow' ATPase.
CC -!- SIMILARITY: Belongs to the TRAFAC class myosin-kinesin ATPase
CC superfamily. Myosin family. {ECO:0000305}.
CC -!- CAUTION: Represents a conventional myosin. This protein should not be
CC confused with the unconventional myosin-6 (MYO6). {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA29120.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; D00943; BAA00791.1; -; mRNA.
DR EMBL; Z20656; CAA79675.1; -; Genomic_DNA.
DR EMBL; GU324919; ADL14490.1; -; Genomic_DNA.
DR EMBL; AL049829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW66154.1; -; Genomic_DNA.
DR EMBL; BC132667; AAI32668.1; -; mRNA.
DR EMBL; M25140; AAA60386.1; -; Genomic_DNA.
DR EMBL; M25162; AAA60386.1; JOINED; Genomic_DNA.
DR EMBL; M25142; AAA60387.1; -; Genomic_DNA.
DR EMBL; M25141; AAA60387.1; JOINED; Genomic_DNA.
DR EMBL; X05632; CAA29120.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M21664; AAA36344.1; -; mRNA.
DR CCDS; CCDS9600.1; -.
DR PIR; A46762; A46762.
DR RefSeq; NP_002462.2; NM_002471.3.
DR AlphaFoldDB; P13533; -.
DR SMR; P13533; -.
DR BioGRID; 110709; 53.
DR IntAct; P13533; 33.
DR STRING; 9606.ENSP00000386041; -.
DR ChEMBL; CHEMBL3831286; -.
DR iPTMnet; P13533; -.
DR PhosphoSitePlus; P13533; -.
DR BioMuta; MYH6; -.
DR DMDM; 317373582; -.
DR UCD-2DPAGE; P13533; -.
DR EPD; P13533; -.
DR jPOST; P13533; -.
DR MassIVE; P13533; -.
DR MaxQB; P13533; -.
DR PaxDb; P13533; -.
DR PeptideAtlas; P13533; -.
DR PRIDE; P13533; -.
DR ProteomicsDB; 52924; -.
DR ABCD; P13533; 1 sequenced antibody.
DR Antibodypedia; 91; 166 antibodies from 27 providers.
DR DNASU; 4624; -.
DR Ensembl; ENST00000405093.9; ENSP00000386041.3; ENSG00000197616.13.
DR GeneID; 4624; -.
DR KEGG; hsa:4624; -.
DR MANE-Select; ENST00000405093.9; ENSP00000386041.3; NM_002471.4; NP_002462.2.
DR UCSC; uc001wjv.3; human.
DR CTD; 4624; -.
DR DisGeNET; 4624; -.
DR GeneCards; MYH6; -.
DR GeneReviews; MYH6; -.
DR HGNC; HGNC:7576; MYH6.
DR HPA; ENSG00000197616; Tissue enriched (heart).
DR MalaCards; MYH6; -.
DR MIM; 160710; gene.
DR MIM; 613251; phenotype.
DR MIM; 613252; phenotype.
DR MIM; 614089; phenotype.
DR MIM; 614090; phenotype.
DR neXtProt; NX_P13533; -.
DR OpenTargets; ENSG00000197616; -.
DR Orphanet; 99103; Atrial septal defect, ostium secundum type.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 166282; Familial sick sinus syndrome.
DR Orphanet; 155; NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy.
DR PharmGKB; PA31373; -.
DR VEuPathDB; HostDB:ENSG00000197616; -.
DR eggNOG; KOG0161; Eukaryota.
DR GeneTree; ENSGT00940000154805; -.
DR HOGENOM; CLU_000192_8_1_1; -.
DR InParanoid; P13533; -.
DR OMA; IRAWCTL; -.
DR OrthoDB; 47111at2759; -.
DR PhylomeDB; P13533; -.
DR TreeFam; TF314375; -.
DR PathwayCommons; P13533; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; P13533; -.
DR SIGNOR; P13533; -.
DR BioGRID-ORCS; 4624; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; MYH6; human.
DR GeneWiki; MYH6; -.
DR GenomeRNAi; 4624; -.
DR Pharos; P13533; Tbio.
DR PRO; PR:P13533; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P13533; protein.
DR Bgee; ENSG00000197616; Expressed in cardiac muscle of right atrium and 86 other tissues.
DR Genevisible; P13533; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005859; C:muscle myosin complex; TAS:UniProtKB.
DR GO; GO:0030016; C:myofibril; ISS:BHF-UCL.
DR GO; GO:0016459; C:myosin complex; TAS:HGNC-UCL.
DR GO; GO:0032982; C:myosin filament; IBA:GO_Central.
DR GO; GO:0016460; C:myosin II complex; IBA:GO_Central.
DR GO; GO:0030017; C:sarcomere; TAS:HGNC-UCL.
DR GO; GO:0001725; C:stress fiber; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0000146; F:microfilament motor activity; IDA:BHF-UCL.
DR GO; GO:0017018; F:myosin phosphatase activity; TAS:Reactome.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0007512; P:adult heart development; IMP:HGNC-UCL.
DR GO; GO:0046034; P:ATP metabolic process; IDA:BHF-UCL.
DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IMP:HGNC-UCL.
DR GO; GO:0055013; P:cardiac muscle cell development; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; ISS:BHF-UCL.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; ISS:BHF-UCL.
DR GO; GO:0006936; P:muscle contraction; IDA:HGNC-UCL.
DR GO; GO:0030049; P:muscle filament sliding; IMP:HGNC-UCL.
DR GO; GO:0030239; P:myofibril assembly; ISS:BHF-UCL.
DR GO; GO:0043462; P:regulation of ATP-dependent activity; ISS:BHF-UCL.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:BHF-UCL.
DR GO; GO:0008016; P:regulation of heart contraction; ISS:BHF-UCL.
DR GO; GO:0060420; P:regulation of heart growth; IEA:Ensembl.
DR GO; GO:0002027; P:regulation of heart rate; IDA:HGNC-UCL.
DR GO; GO:0002026; P:regulation of the force of heart contraction; IDA:BHF-UCL.
DR GO; GO:0045214; P:sarcomere organization; ISS:BHF-UCL.
DR GO; GO:0006941; P:striated muscle contraction; IMP:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:HGNC-UCL.
DR GO; GO:0007522; P:visceral muscle development; ISS:BHF-UCL.
DR Gene3D; 1.20.5.370; -; 5.
DR Gene3D; 2.30.30.360; -; 1.
DR Gene3D; 3.40.850.10; -; 1.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR036961; Kinesin_motor_dom_sf.
DR InterPro; IPR001609; Myosin_head_motor_dom.
DR InterPro; IPR004009; Myosin_N.
DR InterPro; IPR008989; Myosin_S1_N.
DR InterPro; IPR002928; Myosin_tail.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR014751; XRCC4-like_C.
DR Pfam; PF00063; Myosin_head; 1.
DR Pfam; PF02736; Myosin_N; 1.
DR Pfam; PF01576; Myosin_tail_1; 1.
DR PRINTS; PR00193; MYOSINHEAVY.
DR SMART; SM00242; MYSc; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS51456; MYOSIN_MOTOR; 1.
DR PROSITE; PS51844; SH3_LIKE; 1.
PE 1: Evidence at protein level;
KW Actin-binding; ATP-binding; Atrial septal defect; Calmodulin-binding;
KW Cardiomyopathy; Coiled coil; Cytoplasm; Disease variant; Methylation;
KW Motor protein; Muscle protein; Myosin; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Thick filament.
FT CHAIN 1..1939
FT /note="Myosin-6"
FT /id="PRO_0000123401"
FT DOMAIN 32..81
FT /note="Myosin N-terminal SH3-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01190"
FT DOMAIN 85..780
FT /note="Myosin motor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00782"
FT DOMAIN 783..812
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT REGION 657..679
FT /note="Actin-binding"
FT REGION 759..773
FT /note="Actin-binding"
FT REGION 1826..1849
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1909..1939
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 842..1939
FT /evidence="ECO:0000255"
FT BINDING 178..185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 129
FT /note="N6,N6,N6-trimethyllysine"
FT /evidence="ECO:0000255"
FT MOD_RES 379
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 417
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1261
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1271
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02566"
FT MOD_RES 1277
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1284
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1310
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1311
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT MOD_RES 1512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02566"
FT MOD_RES 1515
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02563"
FT VARIANT 56
FT /note="G -> R (in dbSNP:rs28711516)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063550"
FT VARIANT 88
FT /note="E -> Q (in dbSNP:rs442275)"
FT /evidence="ECO:0000269|PubMed:2726733,
FT ECO:0000269|PubMed:8307559"
FT /id="VAR_030203"
FT VARIANT 275
FT /note="I -> N (in dbSNP:rs201327273)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063551"
FT VARIANT 721
FT /note="R -> W (in SSS3; rare variant predisposing to sick
FT sinus syndrome; dbSNP:rs387906656)"
FT /evidence="ECO:0000269|PubMed:21378987"
FT /id="VAR_065561"
FT VARIANT 783
FT /note="L -> M (in dbSNP:rs11847151)"
FT /id="VAR_030204"
FT VARIANT 795
FT /note="R -> Q (in CMH14; late onset; dbSNP:rs267606907)"
FT /evidence="ECO:0000269|PubMed:11815426"
FT /id="VAR_031882"
FT VARIANT 820
FT /note="I -> N (in ASD3; dbSNP:rs267606903)"
FT /evidence="ECO:0000269|PubMed:15735645"
FT /id="VAR_031883"
FT VARIANT 830
FT /note="P -> L (in CMD1EE; dbSNP:rs267606906)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063552"
FT VARIANT 1004
FT /note="A -> S (in CMD1EE; dbSNP:rs143978652)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063553"
FT VARIANT 1065
FT /note="Q -> H (in CMH14; dbSNP:rs267606904)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063554"
FT VARIANT 1101
FT /note="V -> A (in dbSNP:rs365990)"
FT /evidence="ECO:0000269|PubMed:1776652"
FT /id="VAR_030205"
FT VARIANT 1130
FT /note="A -> T (in dbSNP:rs28730771)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063555"
FT VARIANT 1295
FT /note="E -> Q (in dbSNP:rs34935550)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063556"
FT VARIANT 1457
FT /note="E -> K (in CMD1EE; dbSNP:rs267606905)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063557"
FT VARIANT 1502
FT /note="R -> Q (in CMD1EE; unknown pathological
FT significance; dbSNP:rs199936506)"
FT /evidence="ECO:0000269|PubMed:15998695"
FT /id="VAR_063558"
FT VARIANT 1593
FT /note="Q -> L (in dbSNP:rs45574136)"
FT /id="VAR_061364"
FT VARIANT 1737
FT /note="T -> S (in dbSNP:rs1059854)"
FT /evidence="ECO:0000269|PubMed:1776652"
FT /id="VAR_030206"
FT CONFLICT 4
FT /note="A -> S (in Ref. 9; CAA29120)"
FT /evidence="ECO:0000305"
FT CONFLICT 11..12
FT /note="AA -> T (in Ref. 9; CAA29120)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="Q -> P (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 608
FT /note="A -> G (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 744
FT /note="T -> A (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 790
FT /note="M -> I (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1014
FT /note="V -> A (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1021
FT /note="S -> T (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1290
FT /note="A -> S (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1373
FT /note="W -> C (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1533
FT /note="K -> N (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1540
FT /note="L -> M (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1577..1578
FT /note="KL -> NV (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1705..1706
FT /note="EQ -> DR (in Ref. 1; BAA00791 and 7; AAA60387)"
FT /evidence="ECO:0000305"
FT CONFLICT 1733
FT /note="E -> D (in Ref. 1; BAA00791 and 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1734
FT /note="S -> A (in Ref. 1; BAA00791, 7; AAA60387 and 10;
FT AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1763
FT /note="D -> H (in Ref. 1; BAA00791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1788
FT /note="M -> I (in Ref. 7; AAA60387)"
FT /evidence="ECO:0000305"
FT CONFLICT 1871
FT /note="D -> N (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1882
FT /note="R -> G (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1890
FT /note="Q -> R (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
FT CONFLICT 1933
FT /note="Missing (in Ref. 10; AAA36344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1939 AA; 223735 MW; 424211CC048C8004 CRC64;
MTDAQMADFG AAAQYLRKSE KERLEAQTRP FDIRTECFVP DDKEEFVKAK ILSREGGKVI
AETENGKTVT VKEDQVLQQN PPKFDKIEDM AMLTFLHEPA VLFNLKERYA AWMIYTYSGL
FCVTVNPYKW LPVYNAEVVA AYRGKKRSEA PPHIFSISDN AYQYMLTDRE NQSILITGES
GAGKTVNTKR VIQYFASIAA IGDRGKKDNA NANKGTLEDQ IIQANPALEA FGNAKTVRND
NSSRFGKFIR IHFGATGKLA SADIETYLLE KSRVIFQLKA ERNYHIFYQI LSNKKPELLD
MLLVTNNPYD YAFVSQGEVS VASIDDSEEL MATDSAFDVL GFTSEEKAGV YKLTGAIMHY
GNMKFKQKQR EEQAEPDGTE DADKSAYLMG LNSADLLKGL CHPRVKVGNE YVTKGQSVQQ
VYYSIGALAK AVYEKMFNWM VTRINATLET KQPRQYFIGV LDIAGFEIFD FNSFEQLCIN
FTNEKLQQFF NHHMFVLEQE EYKKEGIEWT FIDFGMDLQA CIDLIEKPMG IMSILEEECM
FPKATDMTFK AKLYDNHLGK SNNFQKPRNI KGKQEAHFSL IHYAGTVDYN ILGWLEKNKD
PLNETVVALY QKSSLKLMAT LFSSYATADT GDSGKSKGGK KKGSSFQTVS ALHRENLNKL
MTNLRTTHPH FVRCIIPNER KAPGVMDNPL VMHQLRCNGV LEGIRICRKG FPNRILYGDF
RQRYRILNPV AIPEGQFIDS RKGTEKLLSS LDIDHNQYKF GHTKVFFKAG LLGLLEEMRD
ERLSRIITRM QAQARGQLMR IEFKKIVERR DALLVIQWNI RAFMGVKNWP WMKLYFKIKP
LLKSAETEKE MATMKEEFGR IKETLEKSEA RRKELEEKMV SLLQEKNDLQ LQVQAEQDNL
NDAEERCDQL IKNKIQLEAK VKEMNERLED EEEMNAELTA KKRKLEDECS ELKKDIDDLE
LTLAKVEKEK HATENKVKNL TEEMAGLDEI IAKLTKEKKA LQEAHQQALD DLQVEEDKVN
SLSKSKVKLE QQVDDLEGSL EQEKKVRMDL ERAKRKLEGD LKLTQESIMD LENDKLQLEE
KLKKKEFDIN QQNSKIEDEQ VLALQLQKKL KENQARIEEL EEELEAERTA RAKVEKLRSD
LSRELEEISE RLEEAGGATS VQIEMNKKRE AEFQKMRRDL EEATLQHEAT AAALRKKHAD
SVAELGEQID NLQRVKQKLE KEKSEFKLEL DDVTSNMEQI IKAKANLEKV SRTLEDQANE
YRVKLEEAQR SLNDFTTQRA KLQTENGELA RQLEEKEALI SQLTRGKLSY TQQMEDLKRQ
LEEEGKAKNA LAHALQSARH DCDLLREQYE EETEAKAELQ RVLSKANSEV AQWRTKYETD
AIQRTEELEE AKKKLAQRLQ DAEEAVEAVN AKCSSLEKTK HRLQNEIEDL MVDVERSNAA
AAALDKKQRN FDKILAEWKQ KYEESQSELE SSQKEARSLS TELFKLKNAY EESLEHLETF
KRENKNLQEE ISDLTEQLGE GGKNVHELEK VRKQLEVEKL ELQSALEEAE ASLEHEEGKI
LRAQLEFNQI KAEIERKLAE KDEEMEQAKR NHQRVVDSLQ TSLDAETRSR NEVLRVKKKM
EGDLNEMEIQ LSHANRMAAE AQKQVKSLQS LLKDTQIQLD DAVRANDDLK ENIAIVERRN
NLLQAELEEL RAVVEQTERS RKLAEQELIE TSERVQLLHS QNTSLINQKK KMESDLTQLQ
SEVEEAVQEC RNAEEKAKKA ITDAAMMAEE LKKEQDTSAH LERMKKNMEQ TIKDLQHRLD
EAEQIALKGG KKQLQKLEAR VRELEGELEA EQKRNAESVK GMRKSERRIK ELTYQTEEDK
KNLLRLQDLV DKLQLKVKAY KRQAEEAEEQ ANTNLSKFRK VQHELDEAEE RADIAESQVN
KLRAKSRDIG AKQKMHDEE
