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 24-JAN-2024, entry version 140. 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 VARIANT CMS10 VAL-33, RP AND MUTAGENESIS OF SER-30; VAL-32; ARG-158 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 9. 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; 9606-ENSP00000344432; -. DR PeptideAtlas; Q18PE1; -. DR ProteomicsDB; 19148; -. DR ProteomicsDB; 61176; -. [Q18PE1-1] DR ProteomicsDB; 61177; -. [Q18PE1-2] DR ProteomicsDB; 61178; -. [Q18PE1-3] DR Antibodypedia; 55035; 502 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 AGR; HGNC:26594; -. 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; AIICRSQ; -. DR OrthoDB; 5394416at2759; -. DR PhylomeDB; Q18PE1; -. DR TreeFam; TF332288; -. DR PathwayCommons; Q18PE1; -. DR SignaLink; Q18PE1; -. DR SIGNOR; Q18PE1; -. DR BioGRID-ORCS; 285489; 5 hits in 1138 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 cell types or tissues. DR ExpressionAtlas; Q18PE1; baseline and differential. 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; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; PROTEIN DOK-7; 1. DR PANTHER; PTHR21636:SF2; PROTEIN DOK-7; 1. DR Pfam; PF02174; IRS; 1. DR SMART; SM01244; IRS; 1. DR SMART; SM00233; PH; 1. DR SUPFAM; SSF50729; PH domain-like; 2. DR PROSITE; PS51064; IRS_PTB; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR Genevisible; Q18PE1; HS. 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; results in a significant reduction FT of AChR clusters; 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:rs1487831014)" 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 158 FT /note="R->Q: Reduced stimulation of MUSK FT autophosphorylation; when associated in cis with A-174." FT /evidence="ECO:0000269|PubMed:20603078" FT MUTAGEN 174 FT /note="R->A: Reduced stimulation of MUSK FT autophosphorylation; when associated in cis 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 //