MUSK_CHICK
ID MUSK_CHICK Reviewed; 947 AA.
AC Q8AXY6;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 128.
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;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Myotube;
RX PubMed=11083926; DOI=10.1006/mcne.2000.0892;
RA Ip F.C.F., Glass D.G., Gies D.R., Cheung J., Lai K.-O., Fu A.K.Y.,
RA Yancopoulos G.D., Ip N.Y.;
RT "Cloning and characterization of muscle-specific kinase in chicken.";
RL Mol. Cell. Neurosci. 16:661-673(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Gies D.R., Glass D.J., Yancopoulos G.D.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor tyrosine kinase which plays a central role in the
CC formation and the maintenance of the neuromuscular junction (NMJ), the
CC synapse between the motor neuron and the skeletal muscle. Recruitment
CC of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation
CC and activation of MUSK, the kinase of the complex. The activation of
CC MUSK in myotubes regulates the formation of NMJs through the regulation
CC of different processes including the specific expression of genes in
CC subsynaptic nuclei, the reorganization of the actin cytoskeleton and
CC the clustering of the acetylcholine receptors (AChR) in the
CC postsynaptic membrane. May also play a role within the central nervous
CC system by mediating cholinergic responses, synaptic plasticity and
CC memory formation (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11083926}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (Probable). Interacts with
CC LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN
CC resulting in activation of MUSK (By similarity). {ECO:0000250,
CC ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000305}; Single-
CC pass type I membrane protein {ECO:0000305}. Note=Localizes to the
CC postsynaptic cell membrane of the neuromuscular junction.
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in muscle, but also in brain. Weakly
CC expressed in kidney, gizzard, intestine and testis.
CC {ECO:0000269|PubMed:11083926}.
CC -!- DEVELOPMENTAL STAGE: From E7.0 day, expressed in muscle but also in
CC brain and liver. Skeletal myogenesis is a major site of expression
CC during normal embryogenesis. In addition, the ganglia of the developing
CC peripheral nervous system and various embryonic epithelia, including
CC those of kidney, lung and gut are also sites of expression. Declined
CC slowly to adult. {ECO:0000269|PubMed:11083926}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AY143173; AAN05008.1; -; mRNA.
DR RefSeq; NP_989439.1; NM_204108.1.
DR AlphaFoldDB; Q8AXY6; -.
DR SMR; Q8AXY6; -.
DR STRING; 9031.ENSGALP00000025318; -.
DR PaxDb; Q8AXY6; -.
DR GeneID; 373897; -.
DR KEGG; gga:373897; -.
DR CTD; 4593; -.
DR VEuPathDB; HostDB:geneid_373897; -.
DR eggNOG; KOG1026; Eukaryota.
DR InParanoid; Q8AXY6; -.
DR OrthoDB; 471114at2759; -.
DR PhylomeDB; Q8AXY6; -.
DR PRO; PR:Q8AXY6; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; ISS:UniProtKB.
DR CDD; cd00108; KR; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR Gene3D; 2.40.20.10; -; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
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; 2.
DR Pfam; PF00051; Kringle; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00130; KR; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57440; SSF57440; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00021; KRINGLE_1; 1.
DR PROSITE; PS50070; KRINGLE_2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Developmental protein; Differentiation;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Kringle;
KW Membrane; Muscle protein; Nucleotide-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Repeat; Signal;
KW Synapse; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..947
FT /note="Muscle, skeletal receptor tyrosine protein kinase"
FT /id="PRO_0000024449"
FT TOPO_DOM 22..575
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..947
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..116
FT /note="Ig-like 1"
FT DOMAIN 121..207
FT /note="Ig-like 2"
FT DOMAIN 212..302
FT /note="Ig-like 3"
FT DOMAIN 312..451
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 464..543
FT /note="Kringle"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 655..934
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 803
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 661..669
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 689
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 833
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 460
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..99
FT /evidence="ECO:0000250"
FT DISULFID 98..112
FT /evidence="ECO:0000250"
FT DISULFID 142..190
FT /evidence="ECO:0000250"
FT DISULFID 233..282
FT /evidence="ECO:0000250"
FT DISULFID 317..382
FT /evidence="ECO:0000250"
FT DISULFID 325..375
FT /evidence="ECO:0000250"
FT DISULFID 366..407
FT /evidence="ECO:0000250"
FT DISULFID 395..448
FT /evidence="ECO:0000250"
FT DISULFID 399..435
FT /evidence="ECO:0000250"
FT DISULFID 465..543
FT /evidence="ECO:0000250"
FT DISULFID 486..526
FT /evidence="ECO:0000250"
FT DISULFID 514..538
FT /evidence="ECO:0000250"
SQ SEQUENCE 947 AA; 105589 MW; E6C3FCC5796CC8BE CRC64;
MRDLLVVPLG HVLTLAALSL AETLQKAPFI STPLETVDAL VEDVPKFVCV VESYPEPEIT
WTRNSIPIRL FDTRYSIQRN GQLLTILSVE DSDDGVYCCT ADNGVGAAAQ SCGALQVKMR
PKITRPPVNV EIIEGLKAVL PCTTMGNPKP SVSWIKGETV VKENARIAVL DSGNLRIHNV
QREDAGQYRC VAKNSLGSAY SKPATVVVEV FARILKAPES QNITFGSMVT LRCTAAGAPV
PTVTWLENGK AVSAGSIAES VKDRVVDSRL QVYVTRPGLF TCLATNKHSK TFGAAKAAAT
ISVSEWSKLY KGDAGYCSTY RGEVCSAILS RNALVFFNSS YADPEETQEL LVHTAWTELK
TVSSFCQPAA ESLLCNYIFQ ECKPSGVGPA PKPICRENCL AVKDLYCFKE WLSMEENSQR
GIYKPGLMLL ALPECNRLPS LHQDPSACTH IPFFDFKKEN ITRTCYSGNG QFYQGWANVT
ASGIPCQKWS DQAPHLHRRT PQVFPELSDA ENYCRNPGGE NERPWCYTKD PSVTWEYCSV
SPCGDASLSL GTRKPNGETQ NLPPPPSYSP TYSMNVIILI ISSFALIVIL GIITLVCCRR
RKQWKNKKRE SETPTLTTLP SELLLDRLHP NPMYQRMPLL LNPKLLSLEY PRNNIEYVRD
IGEGAFGRVF QARAPGLLPY EPFTMVAVKM LKEEASADMQ ADFQREAALM AEFDNPNIVK
LLGVCAVGKP MCLLFEYMAY GDLNEYLRDR SPRNLCSLVQ GGLEARACLL NPLALCCTSQ
LCIAKQVAAG MAYLSERKFV HRDLATRNCL VGENMVVKIA DFGLSRNMYS ADYYKANEND
AIPIRWMPPE SIFYNRYTTE SDVWAYGVVL WEIFSYGMQP YYGMAHEEVI YYVRDGNILS
CPDNCPLELY NLMRLCWSKL PADRPSFASI HRILERMYER AVASPQV
