dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000872
Uniprot Accession O15146; MUSK_HUMAN; Q32MJ8; Q32MJ9; Q5VZW7; Q5VZW8;
Genbank Protein ID NP_001159752.1; NP_001159753.1; NP_005583.1;
Genbank Nucleotide ID NM_001166280.1; NM_001166281.1; NM_005592.3;
Protein Name Muscle, skeletal receptor tyrosine-protein kinase
Protein Synonyms/Alias Muscle-specific tyrosine-protein kinase receptor;MuSK;Muscle-specific kinase receptor;
Gene Name MUSK
Gene Synonyms/Alias
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed:25537362). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity).
Phosphorylation Sites
dbPAF PTMs: 17
PositionPeptidesSourceReferences ( PMIDs )
31LPKAPVITTPLETVDPhosphoSitePlus22135298
195YRCVAKNSLGTAYSKcurated25219547
200KNSLGTAYSKVVKLEcurated25219547
201NSLGTAYSKVVKLEVcurated25219547
293NKHGEKFSTAKAAATPhosphoSitePlus22135298
294KHGEKFSTAKAAATIPhosphoSitePlus22135298
339DALVFLNTSYADPEEcurated26074081
340ALVFLNTSYADPEEAcurated26074081
424THRGLYRSEMHLLSVPhosphoSitePlus22135298
430RSEMHLLSVPECSKLPhosphoSitePlus22135298
435LLSVPECSKLPSMHWPhosphoSitePlus22135298
554RLHPNPMYQRMPLLLdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
577YPRNNIEYVRDIGEGdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
751FGLSRNIYSADYYKAdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
755RNIYSADYYKANENDdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
756NIYSADYYKANENDAdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
813MAHEEVIYYVRDGNIdbPTM 3.0;PhosphoSitePlus10781064; 16381945; 23193290; 22135298
Sequence
(Fasta)
MRELVNIPLV HILTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS 60
WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCT ANNGVGGAVE SCGALQVKMK 120
PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDSP LRENSRIAVL ESGSLRIHNV 180
QKEDAGQYRC VAKNSLGTAY SKVVKLEVEV FARILRAPES HNVTFGSFVT LHCTATGIPV 240
PTITWIENGN AVSSGSIQES VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT 300
ISIAEWSKPQ KDNKGYCAQY RGEVCNAVLA KDALVFLNTS YADPEEAQEL LVHTAWNELK 360
VVSPVCRPAA EALLCNHIFQ ECSPGVVPTP IPICREYCLA VKELFCAKEW LVMEEKTHRG 420
LYRSEMHLLS VPECSKLPSM HWDPTACARL PHLDYNKENL KTFPPMTSSK PSVDIPNLPS 480
SSSSSFSVSP TYSMTVIISI MSSFAIFVLL TITTLYCCRR RKQWKNKKRE SAAVTLTTLP 540
SELLLDRLHP NPMYQRMPLL LNPKLLSLEY PRNNIEYVRD IGEGAFGRVF QARAPGLLPY 600
EPFTMVAVKM LKEEASADMQ ADFQREAALM AEFDNPNIVK LLGVCAVGKP MCLLFEYMAY 660
GDLNEFLRSM SPHTVCSLSH SDLSMRAQVS SPGPPPLSCA EQLCIARQVA AGMAYLSERK 720
FVHRDLATRN CLVGENMVVK IADFGLSRNI YSADYYKANE NDAIPIRWMP PESIFYNRYT 780
TESDVWAYGV VLWEIFSYGL QPYYGMAHEE VIYYVRDGNI LSCPENCPVE LYNLMRLCWS 840
KLPADRPSFT SIHRILERMC ERAEGTVSV
Keyword

KW-0025--Alternative splicing
KW-0067--ATP-binding
KW-0965--Cell junction
KW-1003--Cell membrane
KW-0181--Complete proteome
KW-1004--Congenital myasthenic syndrome
KW-0217--Developmental protein
KW-0221--Differentiation
KW-0225--Disease mutation
KW-1015--Disulfide bond
KW-0325--Glycoprotein
KW-0393--Immunoglobulin domain
KW-0418--Kinase
KW-0460--Magnesium
KW-0472--Membrane
KW-0479--Metal-binding
KW-0514--Muscle protein
KW-0547--Nucleotide-binding
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-0628--Postsynaptic cell membrane
KW-0675--Receptor
KW-1185--Reference proteome
KW-0677--Repeat
KW-0732--Signal
KW-0770--Synapse
KW-0808--Transferase
KW-0812--Transmembrane
KW-1133--Transmembrane helix
KW-0829--Tyrosine-protein kinase
KW-0832--Ubl conjugation

Interpro

IPR020067--Frizzled_dom
IPR007110--Ig-like_dom
IPR013783--Ig-like_fold
IPR013098--Ig_I-set
IPR003598--Ig_sub2
IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_dom
IPR017441--Protein_kinase_ATP_BS
IPR001245--Ser-Thr/Tyr_kinase_cat_dom
IPR008266--Tyr_kinase_AS
IPR020635--Tyr_kinase_cat_dom

PROSITE

PS50038--FZ
PS50835--IG_LIKE
PS00107--PROTEIN_KINASE_ATP
PS50011--PROTEIN_KINASE_DOM
PS00109--PROTEIN_KINASE_TYR

Pfam

PF01392--Fz
PF07679--I-set
PF07714--Pkinase_Tyr

Gene Ontology

GO:0030054--C:cell junction
GO:0005887--C:integral component of plasma membrane
GO:0031594--C:neuromuscular junction
GO:0045211--C:postsynaptic membrane
GO:0043235--C:receptor complex
GO:0005524--F:ATP binding
GO:0046872--F:metal ion binding
GO:0004713--F:protein tyrosine kinase activity
GO:0004714--F:transmembrane receptor protein tyrosine kinase activity
GO:0030154--P:cell differentiation
GO:0030198--P:extracellular matrix organization
GO:0007613--P:memory
GO:0007275--P:multicellular organismal development
GO:0007528--P:neuromuscular junction development
GO:0018108--P:peptidyl-tyrosine phosphorylation
GO:0010628--P:positive regulation of gene expression
GO:0043525--P:positive regulation of neuron apoptotic process
GO:2000541--P:positive regulation of protein geranylgeranylation
GO:0001934--P:positive regulation of protein phosphorylation
GO:0046777--P:protein autophosphorylation
GO:0008582--P:regulation of synaptic growth at neuromuscular junction
GO:0006355--P:regulation of transcription, DNA-templated
GO:0071340--P:skeletal muscle acetylcholine-gated channel clustering
GO:0007169--P:transmembrane receptor protein tyrosine kinase signaling pathway