EKS-HOS-00081

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00081

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Musk	626.5	2.8E-188	575	855	281

Status

Reviewed

Ensembl Protein

ENSP00000363571

UniProt Accession

O15146; Q32MJ8; Q32MJ9; Q5VZW7; Q5VZW8;

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

MUSK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000030304	ENSP00000393608	ENST00000416899
ENSG00000030304	ENSP00000189978	ENST00000189978
ENSG00000030304	ENSP00000363562	ENST00000374439
ENSG00000030304	ENSP00000363561	ENST00000374438
ENSG00000030304	ENSP00000363563	ENST00000374440
ENSG00000030304	ENSP00000363571	ENST00000374448

Organism

Homo sapiens

Functional Description

Receptor tyrosine kinase which plays a central role inthe formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. 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).

Protein Length

869

Protein 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 869

Nucleotide Sequence
(FASTA)

ATGAGAGAGC TCGTCAACAT TCCACTGGTA CATATTCTTA CTCTGGTTGC CTTCAGCGGA 60

ACTGAGAAAC TTCCAAAAGC TCCTGTCATC ACCACTCCTC TTGAAACAGT GGATGCCTTA 120

GTTGAAGAAG TGGCTACTTT CATGTGTGCA GTGGAATCCT ACCCCCAGCC TGAGATTTCC 180

TGGACTAGAA ATAAAATTCT CATTAAACTC TTTGACACCC GGTACAGCAT CCGGGAGAAT 240

GGGCAGCTCC TCACCATCCT GAGTGTGGAA GACAGTGATG ATGGCATTTA CTGCTGCACG 300

GCCAACAATG GTGTGGGAGG AGCTGTGGAG AGTTGTGGAG CCCTGCAAGT GAAGATGAAA 360

CCTAAAATAA CTCGTCCTCC CATAAATGTG AAAATAATAG AGGGATTAAA AGCAGTCCTA 420

CCATGTACTA CAATGGGTAA TCCCAAACCA TCAGTGTCTT GGATAAAGGG AGACAGCCCT 480

CTCAGGGAAA ATTCCCGAAT TGCAGTTCTT GAATCTGGGA GCTTGAGGAT TCATAACGTA 540

CAAAAGGAAG ATGCAGGACA GTATCGATGT GTGGCAAAAA ACAGCCTCGG GACAGCATAT 600

TCCAAAGTGG TGAAGCTGGA AGTTGAGGTT TTTGCCAGGA TCCTGCGGGC TCCTGAATCC 660

CACAATGTCA CCTTTGGCTC CTTTGTGACC CTGCACTGTA CAGCAACAGG CATTCCTGTC 720

CCCACCATCA CCTGGATTGA AAACGGAAAT GCTGTTTCTT CTGGGTCCAT TCAAGAGAGT 780

GTGAAAGACC GAGTGATTGA CTCAAGACTG CAGCTGTTTA TCACCAAGCC AGGACTCTAC 840

ACATGCATAG CTACCAATAA GCATGGGGAG AAGTTCAGTA CTGCCAAGGC TGCAGCCACC 900

ATCAGCATAG CAGAATGGAG TAAACCACAG AAAGATAACA AAGGCTACTG CGCCCAGTAC 960

AGAGGGGAGG TGTGTAATGC AGTCCTGGCA AAAGATGCTC TTGTTTTTCT CAACACCTCC 1020

TATGCGGACC CTGAGGAGGC CCAAGAGCTA CTGGTCCACA CGGCCTGGAA TGAACTGAAA 1080

GTAGTGAGCC CAGTCTGCCG GCCAGCTGCT GAGGCTTTGT TGTGTAACCA CATCTTCCAG 1140

GAGTGCAGTC CTGGAGTAGT GCCTACTCCT ATTCCCATTT GCAGAGAGTA CTGCTTGGCA 1200

GTAAAGGAGC TCTTCTGCGC AAAAGAATGG CTGGTAATGG AAGAGAAGAC CCACAGAGGA 1260

CTCTACAGAT CCGAGATGCA TTTGCTGTCC GTGCCAGAAT GCAGCAAGCT TCCCAGCATG 1320

CATTGGGACC CCACGGCCTG TGCCAGACTG CCACATCTAG ATTATAACAA AGAAAACCTA 1380

AAAACATTCC CACCAATGAC GTCCTCAAAG CCAAGTGTGG ACATTCCAAA TCTGCCTTCC 1440

TCCTCCTCTT CTTCCTTCTC TGTCTCACCT ACATACTCCA TGACTGTAAT AATCTCCATC 1500

ATGTCCAGCT TTGCAATATT TGTGCTTCTT ACCATAACTA CTCTCTATTG CTGCCGAAGA 1560

AGAAAACAAT GGAAAAATAA GAAAAGAGAA TCAGCAGCAG TAACCCTCAC CACACTGCCT 1620

TCTGAGCTCT TACTAGATAG ACTTCATCCC AACCCCATGT ACCAGAGGAT GCCGCTCCTT 1680

CTGAACCCCA AATTGCTCAG CCTGGAGTAT CCAAGGAATA ACATTGAATA TGTGAGAGAC 1740

ATCGGAGAGG GAGCGTTTGG AAGGGTGTTT CAAGCAAGGG CACCAGGCTT ACTTCCCTAT 1800

GAACCTTTCA CTATGGTGGC AGTAAAGATG CTCAAAGAAG AAGCCTCGGC AGATATGCAA 1860

GCGGACTTTC AGAGGGAGGC AGCCCTCATG GCAGAATTTG ACAACCCTAA CATTGTGAAG 1920

CTATTAGGAG TGTGTGCTGT CGGGAAGCCA ATGTGCCTGC TCTTTGAATA CATGGCCTAT 1980

GGTGACCTCA ATGAGTTCCT CCGCAGCATG TCCCCTCACA CCGTGTGCAG CCTCAGTCAC 2040

AGTGACTTGT CTATGAGGGC TCAGGTCTCC AGCCCTGGGC CCCCACCCCT CTCCTGTGCT 2100

GAGCAGCTTT GCATTGCCAG GCAGGTGGCA GCTGGCATGG CTTACCTCTC AGAACGTAAG 2160

TTTGTTCACC GAGATTTAGC CACCAGGAAC TGCCTGGTGG GCGAGAACAT GGTGGTGAAA 2220

ATTGCCGACT TTGGCCTCTC CAGGAACATC TACTCAGCAG ACTACTACAA AGCTAATGAA 2280

AACGACGCTA TCCCTATCCG TTGGATGCCA CCAGAGTCCA TTTTTTATAA CCGCTACACT 2340

ACAGAGTCTG ATGTGTGGGC CTATGGCGTG GTCCTCTGGG AGATCTTCTC CTATGGCCTG 2400

CAGCCCTACT ATGGGATGGC CCATGAGGAG GTCATTTACT ACGTGCGAGA TGGCAACATC 2460

CTCTCCTGCC CTGAGAACTG CCCCGTGGAG CTGTACAATC TCATGCGTCT ATGTTGGAGC 2520

AAGCTGCCTG CAGACAGACC CAGTTTCACC AGTATTCACC GAATTCTGGA ACGCATGTGT 2580

GAGAGGGCAG AGGGAACTGT GAGTGTCTAA 2610

Domain Profile

S: 1     ieyvrdlgegafgrvfqarapgllpyeefllvavkmlkeeasadmqadfereaallaefd  60

         ieyvrd+gegafgrvfqarapgllpye+f++vavkmlkeeasadmqadf+reaal+aefd

Q: 575   IEYVRDIGEGAFGRVFQARAPGLLPYEPFTMVAVKMLKEEASADMQADFQREAALMAEFD  634

         89**********************************************************

S: 61    npnivkllgvcavgkpmcllfeymaygdlneflrslspytvcslshsdlslraqvsspdr  120

         npnivkllgvcavgkpmcllfeymaygdlneflrs+sp+tvcslshsdls+raqvssp++

Q: 635   NPNIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRSMSPHTVCSLSHSDLSMRAQVSSPGP  694

         ************************************************************

S: 121   lplseaellciarqvaagmaylserkfvhrdlatrnclvgetmvvkiadfglsrkiysad  180

         +pls+ae+lciarqvaagmaylserkfvhrdlatrnclvge+mvvkiadfglsr+iysad

Q: 695   PPLSCAEQLCIARQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSAD  754

         ************************************************************

S: 181   yykadendaipirwmplesilynrytlesdvwaygvvlweifsyalqpyyglaheeviky  240

         yyka+endaipirwmp+esi+ynryt+esdvwaygvvlweifsy+lqpyyg+aheevi+y

Q: 755   YYKANENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMAHEEVIYY  814

         ************************************************************

S: 241   vrdgnilacpentplelyalmrlcwsklpadrpsfasihri  281

         vrdgnil+cpen+p+ely+lmrlcwsklpadrpsf+sihri

Q: 815   VRDGNILSCPENCPVELYNLMRLCWSKLPADRPSFTSIHRI  855

         ***************************************98

Domain Sequence
(FASTA)

IEYVRDIGEG AFGRVFQARA PGLLPYEPFT MVAVKMLKEE ASADMQADFQ REAALMAEFD 60

NPNIVKLLGV CAVGKPMCLL FEYMAYGDLN EFLRSMSPHT VCSLSHSDLS MRAQVSSPGP 120

PPLSCAEQLC IARQVAAGMA YLSERKFVHR DLATRNCLVG ENMVVKIADF GLSRNIYSAD 180

YYKANENDAI PIRWMPPESI FYNRYTTESD VWAYGVVLWE IFSYGLQPYY GMAHEEVIYY 240

VRDGNILSCP ENCPVELYNL MRLCWSKLPA DRPSFTSIHR I 281

Keyword

Alternative splicing; ATP-binding; Cell junction; Cell membrane; Complete proteome; Congenital myasthenic syndrome; Developmental protein; Differentiation; Disease mutation; Disulfide bond; Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Muscle protein; Nucleotide-binding; Phosphoprotein; Polymorphism; Postsynaptic cell membrane; Receptor; Reference proteome; Repeat; Signal; Synapse; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0030054	; C:cell junction
GO:0005887	; C:integral to plasma membrane
GO:0031594	; C:neuromuscular junction
GO:0045211	; C:postsynaptic membrane
GO:0005524	; F:ATP binding
GO:0004713	; F:protein tyrosine kinase activity
GO:0004714	; F:transmembrane receptor protein tyrosine kinase activity
GO:0007613	; P:memory
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-dependent
GO:0071340	; P:skeletal muscle acetylcholine-gated channel clustering
GO:0007169	; P:transmembrane receptor protein tyrosine kinase signaling pathway

KEGG

hsa:4593

;

InterPros

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

Pfam

PF01392	; Fz; 1.
PF07679	; I-set; 2.
PF07714	; Pkinase_Tyr; 1.

SMARTs

SM00408	; IGc2; 3.
SM00219	; TyrKc; 1.

Prosites

PS50038	; FZ; 1.
PS50835	; IG_LIKE; 3.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013