ID MUSK_MOUSE Reviewed; 868 AA. AC Q61006; Q61005; Q61987; Q61988; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 14-OCT-2015, entry version 142. DE RecName: Full=Muscle, skeletal receptor tyrosine-protein kinase; DE EC=2.7.10.1; DE AltName: Full=Muscle-specific tyrosine-protein kinase receptor; DE Short=MuSK; DE Short=Muscle-specific kinase receptor; DE Flags: Precursor; GN Name=Musk; Synonyms=Nsk2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Caruso A., Morris J.C., Neben S., Finnerty H., Beier D., Turner K., RA Wood C.R.; RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4), RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY. RC TISSUE=Myoblast; RX PubMed=7624144; RA Ganju P., Walls E., Brennan J., Reith A.D.; RT "Cloning and developmental expression of Nsk2, a novel receptor RT tyrosine kinase implicated in skeletal myogenesis."; RL Oncogene 11:281-290(1995). RN [3] RP DISRUPTION PHENOTYPE, AND FUNCTION IN NEUROMUSCULAR JUNCTION RP DEVELOPMENT. RX PubMed=8653786; DOI=10.1016/S0092-8674(00)81251-9; RA DeChiara T.M., Bowen D.C., Valenzuela D.M., Simmons M.V., RA Poueymirou W.T., Thomas S., Kinetz E., Compton D.L., Rojas E., RA Park J.S., Smith C., DiStefano P.S., Glass D.J., Burden S.J., RA Yancopoulos G.D.; RT "The receptor tyrosine kinase MuSK is required for neuromuscular RT junction formation in vivo."; RL Cell 85:501-512(1996). RN [4] RP IDENTIFICATION OF AGRIN AS LIGAND, IDENTIFICATION OF THE AGRIN RP RECEPTOR COMPLEX, AND PHOSPHORYLATION. RX PubMed=8653787; DOI=10.1016/S0092-8674(00)81252-0; RA Glass D.J., Bowen D.C., Stitt T.N., Radziejewski C., Bruno J., RA Ryan T.E., Gies D.R., Shah S., Mattsson K., Burden S.J., RA DiStefano P.S., Valenzuela D.M., DeChiara T.M., Yancopoulos G.D.; RT "Agrin acts via a MuSK receptor complex."; RL Cell 85:513-523(1996). RN [5] RP FUNCTION IN ACETYLCHOLINE RECEPTOR CLUSTERING. RX PubMed=11323662; DOI=10.1038/35074025; RA Lin W., Burgess R.W., Dominguez B., Pfaff S.L., Sanes J.R., Lee K.F.; RT "Distinct roles of nerve and muscle in postsynaptic differentiation of RT the neuromuscular synapse."; RL Nature 410:1057-1064(2001). RN [6] RP INTERACTION WITH DVL1 AND PAK1. RX PubMed=12165471; DOI=10.1016/S0896-6273(02)00783-3; RA Luo Z.G., Wang Q., Zhou J.Z., Wang J., Luo Z., Liu M., He X., RA Wynshaw-Boris A., Xiong W.C., Lu B., Mei L.; RT "Regulation of AChR clustering by Dishevelled interacting with MuSK RT and PAK1."; RL Neuron 35:489-505(2002). RN [7] RP FUNCTION IN TRANSCRIPTION REGULATION. RX PubMed=12756238; DOI=10.1083/jcb.200210156; RA Lacazette E., Le Calvez S., Gajendran N., Brenner H.R.; RT "A novel pathway for MuSK to induce key genes in neuromuscular synapse RT formation."; RL J. Cell Biol. 161:727-736(2003). RN [8] RP FUNCTION IN RAC1 ACTIVATION, FUNCTION IN PHOSPHORYLATION OF FNTA, AND RP INTERACTION WITH FNTA. RX PubMed=14622576; DOI=10.1016/S0896-6273(03)00695-0; RA Luo Z.G., Je H.S., Wang Q., Yang F., Dobbins G.C., Yang Z.H., RA Xiong W.C., Lu B., Mei L.; RT "Implication of geranylgeranyltransferase I in synapse formation."; RL Neuron 40:703-717(2003). RN [9] RP INTERACTION WITH RNF31. RX PubMed=14678832; DOI=10.1016/S1567-133X(03)00146-7; RA Bromann P.A., Weiner J.A., Apel E.D., Lewis R.M., Sanes J.R.; RT "A putative ariadne-like E3 ubiquitin ligase (PAUL) that interacts RT with the muscle-specific kinase (MuSK)."; RL Gene Expr. Patterns 4:77-84(2004). RN [10] RP FUNCTION IN ACETYLCHOLINE RECEPTOR CLUSTERING. RX PubMed=15340048; DOI=10.1128/MCB.24.18.7841-7854.2004; RA Mittaud P., Camilleri A.A., Willmann R., Erb-Voegtli S., Burden S.J., RA Fuhrer C.; RT "A single pulse of agrin triggers a pathway that acts to cluster RT acetylcholine receptors."; RL Mol. Cell. Biol. 24:7841-7854(2004). RN [11] RP ENZYME REGULATION, PHOSPHORYLATION AT SER-680 AND SER-697 BY CK2, AND RP INTERACTION WITH CSNK2B. RX PubMed=16818610; DOI=10.1101/gad.375206; RA Cheusova T., Khan M.A., Schubert S.W., Gavin A.C., Buchou T., RA Jacob G., Sticht H., Allende J., Boldyreff B., Brenner H.R., RA Hashemolhosseini S.; RT "Casein kinase 2-dependent serine phosphorylation of MuSK regulates RT acetylcholine receptor aggregation at the neuromuscular junction."; RL Genes Dev. 20:1800-1816(2006). RN [12] RP INTERACTION WITH DOK7, PHOSPHORYLATION AT TYR-553, AND MUTAGENESIS OF RP TYR-553. RX PubMed=16794080; DOI=10.1126/science.1127142; RA Okada K., Inoue A., Okada M., Murata Y., Kakuta S., Jigami T., RA Kubo S., Shiraishi H., Eguchi K., Motomura M., Akiyama T., Iwakura Y., RA Higuchi O., Yamanashi Y.; RT "The muscle protein Dok-7 is essential for neuromuscular RT synaptogenesis."; RL Science 312:1802-1805(2006). RN [13] RP INTERACTION WITH PDZRN3, AND UBIQUITINATION. RX PubMed=17576800; DOI=10.1083/jcb.200610060; RA Lu Z., Je H.S., Young P., Gross J., Lu B., Feng G.; RT "Regulation of synaptic growth and maturation by a synapse-associated RT E3 ubiquitin ligase at the neuromuscular junction."; RL J. Cell Biol. 177:1077-1089(2007). RN [14] RP PHOSPHORYLATION, AND INTERACTION WITH LRP4. RX PubMed=18848351; DOI=10.1016/j.cell.2008.10.002; RA Kim N., Stiegler A.L., Cameron T.O., Hallock P.T., Gomez A.M., RA Huang J.H., Hubbard S.R., Dustin M.L., Burden S.J.; RT "Lrp4 is a receptor for Agrin and forms a complex with MuSK."; RL Cell 135:334-342(2008). RN [15] RP INTERACTION WITH NSF. RX PubMed=18272689; DOI=10.1523/JNEUROSCI.4130-07.2008; RA Zhu D., Yang Z., Luo Z., Luo S., Xiong W.C., Mei L.; RT "Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine RT receptor clustering in response to agrin."; RL J. Neurosci. 28:1688-1696(2008). RN [16] RP INTERACTION WITH DNAJA3, AND SUBCELLULAR LOCATION. RX PubMed=19038220; DOI=10.1016/j.neuron.2008.09.025; RA Linnoila J., Wang Y., Yao Y., Wang Z.Z.; RT "A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, RT mediates agrin signaling at the neuromuscular junction."; RL Neuron 60:625-641(2008). RN [17] RP INTERACTION WITH CAV3. RX PubMed=19940021; DOI=10.1091/mbc.E09-05-0381; RA Hezel M., de Groat W.C., Galbiati F.; RT "Caveolin-3 promotes nicotinic acetylcholine receptor clustering and RT regulates neuromuscular junction activity."; RL Mol. Biol. Cell 21:302-310(2010). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 544-556 IN COMPLEX WITH DOK7, RP INTERACTION WITH DOK7, AND PHOSPHORYLATION AT TYR-553. 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). CC -!- FUNCTION: Receptor tyrosine kinase which plays a central role in CC the formation and the maintenance of the neuromuscular junction CC (NMJ), the synapse between the motor neuron and the skeletal CC muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex CC induces phosphorylation and activation of MUSK, the kinase of the CC complex. The activation of MUSK in myotubes regulates the CC formation of NMJs through the regulation of different processes CC including the specific expression of genes in subsynaptic nuclei, CC the reorganization of the actin cytoskeleton and the clustering of CC the acetylcholine receptors (AChR) in the postsynaptic membrane. CC May regulate AChR phosphorylation and clustering through CC activation of ABL1 and Src family kinases which in turn regulate CC MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also CC important for MUSK-dependent regulation of AChR clustering. May CC positively regulate Rho family GTPases through FNTA. Mediates the CC phosphorylation of FNTA which promotes prenylation, recruitment to CC membranes and activation of RAC1 a regulator of the actin CC cytoskeleton and of gene expression. Other effectors of the MUSK CC signaling include DNAJA3 which functions downstream of MUSK. May CC also play a role within the central nervous system by mediating CC cholinergic responses, synaptic plasticity and memory formation. CC {ECO:0000269|PubMed:11323662, ECO:0000269|PubMed:12756238, CC ECO:0000269|PubMed:14622576, ECO:0000269|PubMed:15340048, CC ECO:0000269|PubMed:8653786}. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- CC ProRule:PRU10028}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:O15146}; CC -!- ENZYME REGULATION: Positively regulated by CK2. CC {ECO:0000269|PubMed:16818610}. CC -!- SUBUNIT: Monomer. Homodimer (Probable). Interacts with LRP4; the CC heterodimer forms an AGRIN receptor complex that binds AGRIN CC resulting in activation of MUSK. Forms a heterotetramer composed CC of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans- CC autophosphorylation on tyrosine residue and activation. Interacts CC (via cytoplasmic part) with DOK7 (via IRS-type PTB domain); CC requires MUSK phosphorylation. Interacts with DVL1 (via DEP CC domain); the interaction is direct and mediates the formation of a CC DVL1, MUSK and PAK1 ternary complex involved in AChR clustering. CC Interacts with PDZRN3; this interaction is enhanced by agrin. CC Interacts with FNTA; the interaction is direct and mediates AGRIN- CC induced phosphorylation and activation of FNTA. Interacts with CC CSNK2B; mediates regulation by CK2. Interacts (via the cytoplasmic CC domain) with DNAJA3. Interacts with NSF; may regulate MUSK CC endocytosis and activity. Interacts with CAV3; may regulate MUSK CC signaling. Interacts with RNF31. {ECO:0000269|PubMed:12165471, CC ECO:0000269|PubMed:14622576, ECO:0000269|PubMed:14678832, CC ECO:0000269|PubMed:16794080, ECO:0000269|PubMed:16818610, CC ECO:0000269|PubMed:17576800, ECO:0000269|PubMed:18272689, CC ECO:0000269|PubMed:18848351, ECO:0000269|PubMed:19038220, CC ECO:0000269|PubMed:19940021, ECO:0000269|PubMed:20603078, CC ECO:0000305}. CC -!- INTERACTION: CC Q18PE0:Dok7; NbExp=3; IntAct=EBI-3989087, EBI-3989091; CC P46460:Nsf; NbExp=5; IntAct=EBI-6308424, EBI-398006; CC -!- SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell CC membrane {ECO:0000269|PubMed:19038220}; Single-pass type I CC membrane protein {ECO:0000269|PubMed:19038220}. Note=Localizes to CC the postsynaptic cell membrane of the neuromuscular junction. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=MLK2; CC IsoId=Q61006-1; Sequence=Displayed; CC Name=2; Synonyms=MLK1; CC IsoId=Q61006-2; Sequence=VSP_010784; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q61006-3; Sequence=VSP_010785; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=Q61006-4; Sequence=VSP_010786; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed preferentially in skeletal muscle. CC {ECO:0000269|PubMed:7624144}. CC -!- DEVELOPMENTAL STAGE: Skeletal myogenesis is a major site of CC expression during normal embryogenesis. In addition, the ganglia CC of the developing peripheral nervous system and various embryonic CC epithelia, including those of kidney, lung and gut are also sites CC of expression. {ECO:0000269|PubMed:7624144}. CC -!- PTM: Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis CC and lysosomal degradation. {ECO:0000269|PubMed:17576800}. CC -!- PTM: Phosphorylated (PubMed:16818610). Phosphorylation is induced CC by AGRIN (PubMed:8653787, PubMed:18848351). Autophosphorylated. CC Autophosphorylation at Tyr-553 is required for interaction with CC DOK7 which in turn stimulates the phosphorylation and the CC activation of MUSK (PubMed:16794080, PubMed:20603078). CC {ECO:0000269|PubMed:16794080, ECO:0000269|PubMed:16818610, CC ECO:0000269|PubMed:18848351, ECO:0000269|PubMed:20603078, CC ECO:0000269|PubMed:8653787}. CC -!- PTM: Neddylated. {ECO:0000250}. CC -!- DISRUPTION PHENOTYPE: Mice die perinatally being unable to take a CC breath and to respond to tail or leg pinch. Despite the presence CC of apparently normal skeletal muscle, the absence of CC differentiated nerve terminals is sufficient to account for this CC phenotype. Every aspect of NMJ formation examined is absent in CC these mice. Branches of the main intramuscular nerve do not CC establish normal contacts with the muscle, do not form correctly CC positioned or specialized nerve terminals, and are apparently not CC given appropriate signals to stop their wandering aimlessly across CC the muscle. Furthermore, postsynaptic differentiation is absent, CC muscle-derived proteins normally localized to the synaptic basal CC lamina or the postsynaptic membrane being uniformly distributed in CC myofibers. {ECO:0000269|PubMed:8653786}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SIMILARITY: Contains 1 FZ (frizzled) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00090}. CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like) CC domains. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. 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; U37708; AAA79203.1; -; mRNA. DR EMBL; U37709; AAA79204.1; -; mRNA. DR EMBL; X86444; CAA60165.1; -; mRNA. DR EMBL; X86445; CAA60166.1; -; Genomic_DNA. DR CCDS; CCDS18210.1; -. [Q61006-2] DR CCDS; CCDS18211.1; -. [Q61006-1] DR PIR; I48696; I48696. DR PIR; I48697; I48697. DR RefSeq; NP_001032205.1; NM_001037128.1. DR RefSeq; NP_001032206.1; NM_001037129.1. DR RefSeq; NP_001032207.1; NM_001037130.1. [Q61006-2] DR RefSeq; NP_035074.2; NM_010944.2. [Q61006-1] DR UniGene; Mm.16148; -. DR PDB; 3ML4; X-ray; 2.60 A; E/F/G/H=544-556. DR PDBsum; 3ML4; -. DR ProteinModelPortal; Q61006; -. DR SMR; Q61006; 25-294, 314-454, 502-862. DR BioGrid; 201860; 5. DR IntAct; Q61006; 4. DR STRING; 10090.ENSMUSP00000095665; -. DR PhosphoSite; Q61006; -. DR PaxDb; Q61006; -. DR PRIDE; Q61006; -. DR Ensembl; ENSMUST00000084578; ENSMUSP00000081625; ENSMUSG00000057280. [Q61006-1] DR Ensembl; ENSMUST00000102893; ENSMUSP00000099957; ENSMUSG00000057280. [Q61006-2] DR GeneID; 18198; -. DR UCSC; uc033icg.1; mouse. [Q61006-1] DR CTD; 4593; -. DR MGI; MGI:103581; Musk. DR eggNOG; COG0515; -. DR GeneTree; ENSGT00760000118818; -. DR HOGENOM; HOG000044461; -. DR HOVERGEN; HBG052539; -. DR InParanoid; Q61006; -. DR OrthoDB; EOG76739G; -. DR TreeFam; TF106465; -. DR BRENDA; 2.7.10.1; 3474. DR Reactome; R-MMU-3000178; ECM proteoglycans. DR EvolutionaryTrace; Q61006; -. DR NextBio; 293560; -. DR PRO; PR:Q61006; -. DR Proteomes; UP000000589; Chromosome 4. DR Bgee; Q61006; -. DR CleanEx; MM_MUSK; -. DR ExpressionAtlas; Q61006; baseline and differential. DR Genevisible; Q61006; MM. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0031594; C:neuromuscular junction; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; ISO:MGI. DR GO; GO:0045202; C:synapse; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:MGI. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0007528; P:neuromuscular junction development; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:GOC. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:MGI. DR GO; GO:2000541; P:positive regulation of protein geranylgeranylation; IMP:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:0043113; P:receptor clustering; IMP:MGI. DR GO; GO:0008582; P:regulation of synaptic growth at neuromuscular junction; IMP:MGI. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI. DR GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; IMP:UniProtKB. DR Gene3D; 1.10.2000.10; -; 1. DR Gene3D; 2.60.40.10; -; 3. DR InterPro; IPR020067; Frizzled_dom. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR Pfam; PF01392; Fz; 1. DR Pfam; PF07679; I-set; 3. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00408; IGc2; 3. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; SSF48726; 3. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS50038; FZ; 1. DR PROSITE; PS50835; IG_LIKE; 3. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell junction; KW Cell membrane; Complete proteome; Developmental protein; KW Differentiation; Disulfide bond; Glycoprotein; Immunoglobulin domain; KW Kinase; Magnesium; Membrane; Metal-binding; Muscle protein; KW Nucleotide-binding; Phosphoprotein; Postsynaptic cell membrane; KW Receptor; Reference proteome; Repeat; Signal; Synapse; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 868 Muscle, skeletal receptor tyrosine- FT protein kinase. FT /FTId=PRO_0000024447. FT TOPO_DOM 22 494 Extracellular. {ECO:0000255}. FT TRANSMEM 495 515 Helical. {ECO:0000255}. FT TOPO_DOM 516 868 Cytoplasmic. {ECO:0000255}. FT DOMAIN 28 116 Ig-like 1. FT DOMAIN 121 205 Ig-like 2. FT DOMAIN 212 302 Ig-like 3. FT DOMAIN 312 450 FZ. {ECO:0000255|PROSITE- FT ProRule:PRU00090}. FT DOMAIN 574 855 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 580 588 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT ACT_SITE 724 724 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 608 608 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 553 553 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:16794080, FT ECO:0000269|PubMed:20603078}. FT MOD_RES 680 680 Phosphoserine; by CK2. FT {ECO:0000305|PubMed:16818610}. FT MOD_RES 697 697 Phosphoserine; by CK2. FT {ECO:0000305|PubMed:16818610}. FT MOD_RES 754 754 Phosphotyrosine; by autocatalysis. FT {ECO:0000250}. FT CARBOHYD 222 222 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 338 338 N-linked (GlcNAc...). {ECO:0000250}. FT CARBOHYD 459 459 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 49 99 {ECO:0000250}. FT DISULFID 98 112 {ECO:0000250}. FT DISULFID 142 190 {ECO:0000250}. FT DISULFID 233 282 {ECO:0000250}. FT DISULFID 317 382 {ECO:0000250}. FT DISULFID 325 375 {ECO:0000250}. FT DISULFID 366 406 {ECO:0000250}. FT DISULFID 394 447 {ECO:0000250}. FT DISULFID 398 434 {ECO:0000250}. FT VAR_SEQ 324 338 VCDAVLAKDALVFFN -> GVLMQGPGEKMLLVFLPT (in FT isoform 3). {ECO:0000303|PubMed:7624144}. FT /FTId=VSP_010785. FT VAR_SEQ 454 462 DYKKENITT -> A (in isoform 2). FT {ECO:0000303|Ref.1}. FT /FTId=VSP_010784. FT VAR_SEQ 866 868 VGV -> TDGRAHFFWPHQY (in isoform 4). FT {ECO:0000303|PubMed:7624144}. FT /FTId=VSP_010786. FT MUTAGEN 553 553 Y->F: Loss of interaction with DOK7. FT {ECO:0000269|PubMed:16794080}. FT CONFLICT 31 31 T -> A (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 169 169 V -> A (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 211 212 FA -> LG (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 235 235 A -> E (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 341 341 Y -> H (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 376 376 N -> Y (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 380 380 Q -> L (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 435 435 S -> R (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 503 503 F -> L (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT CONFLICT 512 512 A -> V (in Ref. 2; CAA60165/CAA60166). FT {ECO:0000305}. FT TURN 551 554 {ECO:0000244|PDB:3ML4}. SQ SEQUENCE 868 AA; 96693 MW; AFE4E644C6869933 CRC64; MRELVNIPLL QMLTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCI ANNGVGGAVE SCGALQVKMK PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDNA LRENSRIAVL ESGSLRIHNV QKEDAGQYRC VAKNSLGTAY SKLVKLEVEV FARILRAPES HNVTFGSFVT LRCTAIGIPV PTISWIENGN AVSSGSIQES VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT VSIAEWSKSQ KDSQGYCAQY RGEVCDAVLA KDALVFFNTS YRDPEDAQEL LIHTAWNELK AVSPLCRPAA EALLCNHLFQ ECSPGVVPTP MPICREYCLA VKELFCAKEW QAMEGKAHRG LYRSGMHLLP VPECSKLPSM HRDPTACTRL PYLDYKKENI TTFPSITSSR PSADIPNLPA STSSFAVSPA YSMTVIISIV SSFALFALLT IATLYCCRRR KEWKNKKRES TAVTLTTLPS ELLLDRLHPN PMYQRMPLLL NPKLLSLEYP RNNIEYVRDI GEGAFGRVFQ ARAPGLLPYE PFTMVAVKML KEEASADMQA DFQREAALMA EFDNPNIVKL LGVCAVGKPM CLLFEYMAYG DLNEFLRSMS PHTVCSLSHS DLSTRARVSS PGPPPLSCAE QLCIARQVAA GMAYLSERKF VHRDLATRNC LVGETMVVKI ADFGLSRNIY SADYYKADGN DAIPIRWMPP ESIFYNRYTT ESDVWAYGVV LWEIFSYGLQ PYYGMAHEEV IYYVRDGNIL ACPENCPLEL YNLMRLCWSK LPADRPSFCS IHRILQRMCE RAEGTVGV //