DOK7_HUMAN
ID DOK7_HUMAN Reviewed; 504 AA.
AC Q18PE1; A2A499; A2RRD4; E9PB56; Q6P6A6; Q86XG5; Q8N2J3; Q8NBC1;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Protein Dok-7;
DE AltName: Full=Downstream of tyrosine kinase 7;
GN Name=DOK7; Synonyms=C4orf25;
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 1), AND TISSUE SPECIFICITY.
RX PubMed=16794080; DOI=10.1126/science.1127142;
RA Okada K., Inoue A., Okada M., Murata Y., Kakuta S., Jigami T., Kubo S.,
RA Shiraishi H., Eguchi K., Motomura M., Akiyama T., Iwakura Y., Higuchi O.,
RA Yamanashi Y.;
RT "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.";
RL Science 312:1802-1805(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), PARTIAL NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT ASP-461.
RC TISSUE=Brain, and Ovary;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-296
RP AND ASP-461.
RC TISSUE=Blood, and Mammary gland;
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 [5]
RP INTERACTION WITH MUSK, FUNCTION, CHARACTERIZATION OF VARIANTS CMS10 VAL-33
RP AND GLN-158, AND MUTAGENESIS OF SER-30; VAL-32 AND ARG-174.
RX PubMed=20603078; DOI=10.1016/j.molcel.2010.06.007;
RA Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.;
RT "The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine
RT kinase MuSK via dimerization.";
RL Mol. Cell 39:100-109(2010).
RN [6]
RP INVOLVEMENT IN FADS3.
RX PubMed=19261599; DOI=10.1136/jmg.2008.065425;
RA Vogt J., Morgan N.V., Marton T., Maxwell S., Harrison B.J., Beeson D.,
RA Maher E.R.;
RT "Germline mutation in DOK7 associated with fetal akinesia deformation
RT sequence.";
RL J. Med. Genet. 46:338-340(2009).
RN [7]
RP VARIANT CMS10 ALA-180.
RX PubMed=16917026; DOI=10.1126/science.1130837;
RA Beeson D., Higuchi O., Palace J., Cossins J., Spearman H., Maxwell S.,
RA Newsom-Davis J., Burke G., Fawcett P., Motomura M., Muller J.S.,
RA Lochmuller H., Slater C., Vincent A., Yamanashi Y.;
RT "Dok-7 mutations underlie a neuromuscular junction synaptopathy.";
RL Science 313:1975-1978(2006).
RN [8]
RP VARIANTS CMS10 VAL-33; GLN-132 AND HIS-469.
RX PubMed=17439981; DOI=10.1093/brain/awm068;
RA Muller J.S., Herczegfalvi A., Vilchez J.J., Colomer J., Bachinski L.L.,
RA Mihaylova V., Santos M., Schara U., Deschauer M., Shevell M., Poulin C.,
RA Dias A., Soudo A., Hietala M., Aarimaa T., Krahe R., Karcagi V.,
RA Huebner A., Beeson D., Abicht A., Lochmuller H.;
RT "Phenotypical spectrum of DOK7 mutations in congenital myasthenic
RT syndromes.";
RL Brain 130:1497-1506(2007).
RN [9]
RP VARIANTS CMS10 MET-116; LEU-146; ARG-157; ARG-171; ARG-172 AND VAL-180, AND
RP VARIANT LEU-45.
RX PubMed=20012313; DOI=10.1007/s00415-009-5405-y;
RA Ben Ammar A., Petit F., Alexandri N., Gaudon K., Bauche S., Rouche A.,
RA Gras D., Fournier E., Koenig J., Stojkovic T., Lacour A., Petiot P.,
RA Zagnoli F., Viollet L., Pellegrini N., Orlikowski D., Lazaro L., Ferrer X.,
RA Stoltenburg G., Paturneau-Jouas M., Hentati F., Fardeau M., Sternberg D.,
RA Hantai D., Richard P., Eymard B.;
RT "Phenotype genotype analysis in 15 patients presenting a congenital
RT myasthenic syndrome due to mutations in DOK7.";
RL J. Neurol. 257:754-766(2010).
RN [10]
RP VARIANTS CMS10 LYS-3; THR-31; MET-77; CYS-109; LEU-139; GLN-158; ARG-161;
RP ARG-166; ASP-171 AND ALA-180, VARIANTS LEU-45; VAL-99; ASN-197; HIS-261;
RP GLN-272; ARG-296; CYS-323; LYS-382; GLN-402; SER-415; THR-440; TRP-451;
RP ASP-461 AND THR-503, CHARACTERIZATION OF VARIANTS CMS10 LYS-3; THR-31;
RP MET-77; CYS-109; LEU-139; GLN-158; ARG-161; ARG-166; ASP-171 AND ALA-180,
RP AND CHARACTERIZATION OF VARIANT LEU-45.
RX PubMed=22661499; DOI=10.1093/hmg/dds198;
RA Cossins J., Liu W.W., Belaya K., Maxwell S., Oldridge M., Lester T.,
RA Robb S., Beeson D.;
RT "The spectrum of mutations that underlie the neuromuscular junction
RT synaptopathy in DOK7 congenital myasthenic syndrome.";
RL Hum. Mol. Genet. 21:3765-3775(2012).
CC -!- FUNCTION: Probable muscle-intrinsic activator of MUSK that plays an
CC essential role in neuromuscular synaptogenesis. Acts in aneural
CC activation of MUSK and subsequent acetylcholine receptor (AchR)
CC clustering in myotubes. Induces autophosphorylation of MUSK.
CC {ECO:0000269|PubMed:20603078}.
CC -!- SUBUNIT: Homodimer (By similarity). Forms a heterotetramer composed of
CC 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-
CC autophosphorylation on tyrosine residue and activation (By similarity).
CC Interacts (via IRS-type PTB domain) with MUSK (via cytoplasmic part);
CC requires MUSK phosphorylation. {ECO:0000250,
CC ECO:0000269|PubMed:20603078}.
CC -!- INTERACTION:
CC Q18PE1; O95967: EFEMP2; NbExp=3; IntAct=EBI-3046647, EBI-743414;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Synapse {ECO:0000250}. Note=Accumulates at
CC neuromuscular junctions. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q18PE1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q18PE1-2; Sequence=VSP_020633, VSP_020634;
CC Name=4;
CC IsoId=Q18PE1-4; Sequence=VSP_047252, VSP_047253;
CC Name=3;
CC IsoId=Q18PE1-3; Sequence=VSP_020635;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in skeletal muscle and
CC heart. Present in thigh muscle, diaphragm and heart but not in the
CC liver or spleen (at protein level). {ECO:0000269|PubMed:16794080}.
CC -!- DOMAIN: The PH domain mediated binding to phospholipids with
CC phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-
CC trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and
CC phosphatidylinositol 4,5-bisphosphate (By similarity). {ECO:0000250}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 10 (CMS10) [MIM:254300]: A
CC form of congenital myasthenic syndrome, a group of disorders
CC characterized by failure of neuromuscular transmission, including pre-
CC synaptic, synaptic, and post-synaptic disorders that are not of
CC autoimmune origin. Clinical features are easy fatigability and muscle
CC weakness affecting the axial and limb muscles (with hypotonia in early-
CC onset forms), the ocular muscles (leading to ptosis and
CC ophthalmoplegia), and the facial and bulbar musculature (affecting
CC sucking and swallowing, and leading to dysphonia). The symptoms
CC fluctuate and worsen with physical effort. CMS10 is an autosomal
CC recessive, post-synaptic form characterized by a typical 'limb girdle'
CC pattern of muscle weakness with small, simplified neuromuscular
CC junctions but normal acetylcholine receptor and acetylcholinesterase
CC function. {ECO:0000269|PubMed:16917026, ECO:0000269|PubMed:17439981,
CC ECO:0000269|PubMed:20012313, ECO:0000269|PubMed:20603078,
CC ECO:0000269|PubMed:22661499}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Fetal akinesia deformation sequence 3 (FADS3) [MIM:618389]: A
CC clinically and genetically heterogeneous group of disorders with
CC congenital malformations related to impaired fetal movement. Clinical
CC features include fetal akinesia, intrauterine growth retardation,
CC polyhydramnios, arthrogryposis, pulmonary hypoplasia, craniofacial
CC abnormalities, and cryptorchidism. FADS3 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:19261599}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11367.1; Type=Miscellaneous discrepancy; Note=Contains a poly-A tail in the 5'region.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=The Leiden Muscular Dystrophy pages, Docking protein
CC 7 (DOK7); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/DOK7";
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DR EMBL; AB220918; BAE96739.1; -; mRNA.
DR EMBL; AK075037; BAC11367.1; ALT_SEQ; mRNA.
DR EMBL; AK091037; BAC03572.1; -; mRNA.
DR EMBL; AL590235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043568; AAH43568.1; -; mRNA.
DR EMBL; BC062369; AAH62369.1; -; mRNA.
DR EMBL; BC131544; AAI31545.1; -; mRNA.
DR EMBL; BC141852; AAI41853.1; -; mRNA.
DR CCDS; CCDS3370.2; -. [Q18PE1-1]
DR CCDS; CCDS54717.1; -. [Q18PE1-4]
DR RefSeq; NP_001158145.1; NM_001164673.1. [Q18PE1-4]
DR RefSeq; NP_001243825.1; NM_001256896.1.
DR RefSeq; NP_001288000.1; NM_001301071.1. [Q18PE1-3]
DR RefSeq; NP_775931.3; NM_173660.4. [Q18PE1-1]
DR AlphaFoldDB; Q18PE1; -.
DR SMR; Q18PE1; -.
DR BioGRID; 130124; 8.
DR IntAct; Q18PE1; 5.
DR STRING; 9606.ENSP00000344432; -.
DR iPTMnet; Q18PE1; -.
DR PhosphoSitePlus; Q18PE1; -.
DR BioMuta; DOK7; -.
DR DMDM; 115311705; -.
DR jPOST; Q18PE1; -.
DR MassIVE; Q18PE1; -.
DR PaxDb; Q18PE1; -.
DR PeptideAtlas; Q18PE1; -.
DR PRIDE; Q18PE1; -.
DR ProteomicsDB; 19148; -.
DR ProteomicsDB; 61176; -. [Q18PE1-1]
DR ProteomicsDB; 61177; -. [Q18PE1-2]
DR ProteomicsDB; 61178; -. [Q18PE1-3]
DR Antibodypedia; 55035; 450 antibodies from 28 providers.
DR DNASU; 285489; -.
DR Ensembl; ENST00000340083.6; ENSP00000344432.5; ENSG00000175920.18. [Q18PE1-1]
DR Ensembl; ENST00000507039.5; ENSP00000423614.1; ENSG00000175920.18. [Q18PE1-4]
DR GeneID; 285489; -.
DR KEGG; hsa:285489; -.
DR MANE-Select; ENST00000340083.6; ENSP00000344432.5; NM_173660.5; NP_775931.3.
DR UCSC; uc003ghd.4; human. [Q18PE1-1]
DR CTD; 285489; -.
DR DisGeNET; 285489; -.
DR GeneCards; DOK7; -.
DR GeneReviews; DOK7; -.
DR HGNC; HGNC:26594; DOK7.
DR HPA; ENSG00000175920; Tissue enhanced (heart muscle, skeletal muscle).
DR MalaCards; DOK7; -.
DR MIM; 254300; phenotype.
DR MIM; 610285; gene.
DR MIM; 618389; phenotype.
DR neXtProt; NX_Q18PE1; -.
DR OpenTargets; ENSG00000175920; -.
DR Orphanet; 994; Fetal akinesia deformation sequence.
DR Orphanet; 98913; Postsynaptic congenital myasthenic syndromes.
DR PharmGKB; PA162384035; -.
DR VEuPathDB; HostDB:ENSG00000175920; -.
DR eggNOG; ENOG502QQBI; Eukaryota.
DR GeneTree; ENSGT00390000015386; -.
DR HOGENOM; CLU_095366_0_0_1; -.
DR InParanoid; Q18PE1; -.
DR OMA; GSEYQIP; -.
DR OrthoDB; 317220at2759; -.
DR PhylomeDB; Q18PE1; -.
DR TreeFam; TF332288; -.
DR PathwayCommons; Q18PE1; -.
DR SignaLink; Q18PE1; -.
DR SIGNOR; Q18PE1; -.
DR BioGRID-ORCS; 285489; 4 hits in 1061 CRISPR screens.
DR ChiTaRS; DOK7; human.
DR GenomeRNAi; 285489; -.
DR Pharos; Q18PE1; Tbio.
DR PRO; PR:Q18PE1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q18PE1; protein.
DR Bgee; ENSG00000175920; Expressed in apex of heart and 117 other tissues.
DR ExpressionAtlas; Q18PE1; baseline and differential.
DR Genevisible; Q18PE1; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0007528; P:neuromuscular junction development; IBA:GO_Central.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR CDD; cd14677; PH_DOK7; 1.
DR CDD; cd13165; PTB_DOK7; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR037746; Dok-7.
DR InterPro; IPR037747; Dok-7_PH.
DR InterPro; IPR037748; Dok-7_PTB.
DR InterPro; IPR002404; IRS_PTB.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR21636; PTHR21636; 1.
DR Pfam; PF02174; IRS; 1.
DR SMART; SM00233; PH; 1.
DR PROSITE; PS51064; IRS_PTB; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Congenital myasthenic syndrome;
KW Disease variant; Lipid-binding; Membrane; Reference proteome; Synapse.
FT CHAIN 1..504
FT /note="Protein Dok-7"
FT /id="PRO_0000250371"
FT DOMAIN 4..109
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 105..210
FT /note="IRS-type PTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00389"
FT REGION 210..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 249..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..300
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 328..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 421..444
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..138
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020633"
FT VAR_SEQ 139..178
FT /note="VLARDIPPAVTGQWKLSDLRRYGAVPSGFIFEGGTRCGYW -> MMSSSWPG
FT TSPRLSRGSGSCLTSGATGPCQADSSLKAGPG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_020634"
FT VAR_SEQ 175..255
FT /note="CGYWAGVFFLSSAEGEQISFLFDCIVRGISPTKGPFGLRPVLPDPSPPGPST
FT VEERVAQEALETLQLEKRLSLLSHAGRPG -> GWRLLPVLGRGGADQLPVRLHRPRHL
FT PHQGPLWAAAGSTRPKSPGTLDCGGACGPGSPGNPTAGEAAEPPLTCGQAGQWRG (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047252"
FT VAR_SEQ 256..504
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047253"
FT VAR_SEQ 500..504
FT /note="VNPPP -> GAAASAPGPATAHSGSPGPVAVDSPGPERPRGESPTYVNIPVS
FT PSSRKQLHYMGLELQEASEGVRGAGASLYAQIDIMATETAHRVGVRHARAREEQLSELE
FT QRKAAPQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_020635"
FT VARIANT 3
FT /note="E -> K (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs763233743)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068750"
FT VARIANT 31
FT /note="P -> T (in CMS10; results in a significant reduction
FT of AChR clusters)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068751"
FT VARIANT 33
FT /note="A -> V (in CMS10; results in reduced stimulation of
FT MUSK autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:17439981,
FT ECO:0000269|PubMed:20603078"
FT /id="VAR_068752"
FT VARIANT 45
FT /note="S -> L (does not affect AChR clusters number or
FT complexity; dbSNP:rs62272670)"
FT /evidence="ECO:0000269|PubMed:20012313,
FT ECO:0000269|PubMed:22661499"
FT /id="VAR_068753"
FT VARIANT 77
FT /note="T -> M (in CMS10; results in a decrease of branched,
FT c-shaped and perforated AChR clusters; dbSNP:rs940346413)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068754"
FT VARIANT 99
FT /note="A -> V (in dbSNP:rs138010842)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068755"
FT VARIANT 109
FT /note="G -> C (in CMS10; results in a significant reduction
FT of AChR clusters)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068756"
FT VARIANT 116
FT /note="V -> M (in CMS10; dbSNP:rs1429428597)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068757"
FT VARIANT 132
FT /note="H -> Q (in CMS10)"
FT /evidence="ECO:0000269|PubMed:17439981"
FT /id="VAR_068758"
FT VARIANT 139
FT /note="V -> L (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs571769859)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068759"
FT VARIANT 146
FT /note="P -> L (in CMS10; dbSNP:rs770987150)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068760"
FT VARIANT 157
FT /note="L -> R (in CMS10)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068761"
FT VARIANT 158
FT /note="R -> Q (in CMS10; reduced stimulation of MUSK
FT autophosphorylation when associated with A-174; results in
FT a significant reduction of AChR clusters;
FT dbSNP:rs754633490)"
FT /evidence="ECO:0000269|PubMed:20603078,
FT ECO:0000269|PubMed:22661499"
FT /id="VAR_031246"
FT VARIANT 161
FT /note="G -> R (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs758131044)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068762"
FT VARIANT 166
FT /note="G -> R (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs781227659)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068763"
FT VARIANT 171
FT /note="G -> D (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs1286619522)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068764"
FT VARIANT 171
FT /note="G -> R (in CMS10)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068765"
FT VARIANT 172
FT /note="G -> R (in CMS10; dbSNP:rs768892432)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068766"
FT VARIANT 180
FT /note="G -> A (in CMS10; results in a significant reduction
FT of AChR clusters; dbSNP:rs118203994)"
FT /evidence="ECO:0000269|PubMed:16917026,
FT ECO:0000269|PubMed:22661499"
FT /id="VAR_027544"
FT VARIANT 180
FT /note="G -> V (in CMS10)"
FT /evidence="ECO:0000269|PubMed:20012313"
FT /id="VAR_068767"
FT VARIANT 197
FT /note="D -> N (in dbSNP:rs16844422)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_027545"
FT VARIANT 261
FT /note="R -> H (in dbSNP:rs16844460)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_027546"
FT VARIANT 272
FT /note="H -> Q (in dbSNP:rs115614731)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068768"
FT VARIANT 296
FT /note="Q -> R (in dbSNP:rs6811423)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:22661499"
FT /id="VAR_027547"
FT VARIANT 323
FT /note="R -> C (in dbSNP:rs150728781)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068769"
FT VARIANT 379
FT /note="G -> R (in dbSNP:rs6831659)"
FT /id="VAR_050508"
FT VARIANT 382
FT /note="E -> K (in dbSNP:rs560463670)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068770"
FT VARIANT 402
FT /note="R -> Q (in dbSNP:rs370039804)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068771"
FT VARIANT 415
FT /note="P -> S (in dbSNP:rs16844464)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_027548"
FT VARIANT 427
FT /note="G -> D (in dbSNP:rs2020433)"
FT /id="VAR_027549"
FT VARIANT 440
FT /note="A -> T (in dbSNP:rs753026831)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068772"
FT VARIANT 451
FT /note="R -> W (in dbSNP:rs16844470)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_027550"
FT VARIANT 461
FT /note="G -> D (in dbSNP:rs9684786)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:22661499"
FT /id="VAR_027551"
FT VARIANT 469
FT /note="P -> H (in CMS10; dbSNP:rs147185207)"
FT /evidence="ECO:0000269|PubMed:17439981"
FT /id="VAR_068773"
FT VARIANT 503
FT /note="P -> T (in dbSNP:rs184556570)"
FT /evidence="ECO:0000269|PubMed:22661499"
FT /id="VAR_068774"
FT MUTAGEN 30
FT /note="S->W: Reduced stimulation of MUSK
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:20603078"
FT MUTAGEN 32
FT /note="V->A: Reduced stimulation of MUSK
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:20603078"
FT MUTAGEN 174
FT /note="R->A: Reduced stimulation of MUSK
FT autophosphorylation; when associated with Q-158."
FT /evidence="ECO:0000269|PubMed:20603078"
SQ SEQUENCE 504 AA; 53097 MW; 54750E0B0BC33317 CRC64;
MTEAALVEGQ VKLRDGKKWK SRWLVLRKPS PVADCLLMLV YKDKSERIKG LRERSSLTLE
DICGLEPGLP YEGLVHTLAI VCLSQAIMLG FDSHEAMCAW DARIRYALGE VHRFHVTVAP
GTKLESGPAT LHLCNDVLVL ARDIPPAVTG QWKLSDLRRY GAVPSGFIFE GGTRCGYWAG
VFFLSSAEGE QISFLFDCIV RGISPTKGPF GLRPVLPDPS PPGPSTVEER VAQEALETLQ
LEKRLSLLSH AGRPGSGGDD RSLSSSSSEA SHLDVSASSR LTAWPEQSSS SASTSQEGPR
PAAAQAAGEA MVGASRPPPK PLRPRQLQEV GRQSSSDSGI ATGSHSSYSS SLSSYAGSSL
DVWRATDELG SLLSLPAAGA PEPSLCTCLP GTVEYQVPTS LRAHYDTPRS LCLAPRDHSP
PSQGSPGNSA ARDSGGQTSA GCPSGWLGTR RRGLVMEAPQ GSEATLPGPA PGEPWEAGGP
HAGPPPAFFS ACPVCGGLKV NPPP
