KinaseNET

Nomenclature

Short Name:

MUSK

Full Name:

Muscle, skeletal receptor tyrosine protein kinase

Alias:

EC 2.7.10.1
MGC126323
MGC126324
Muscle specific tyrosine kinase receptor

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

Musk

SubFamily:

Specific Links

BioCarta Entry:	ach pathway
Entrez-Gene Entry:	4593
Entrez-Protein Entry:	NP_005583
GeneCards Entry:	MGC126323
KinBASE Entry:	MUSK
OMIM Entry:	601296
Pfam Entry:	O15146
PhosphoNET Entry:	O15146
Phosphosite Plus Entry:	1947
Protein Data Bank Entry:	1LUF
ScanSite Entry:	O15146
Source Entry:	MUSK
UCSD-Nature Entry:	A001567
UniProt Entry:	O15146
Kinexus Products:	MUSK Muscle, skeletal receptor tyrosine protein kinase Y756 phosphosite-specific antibody AB-PK872 Muscle, skeletal receptor tyrosine-protein kinase (S752-N759, human) pY756 phosphopeptide - Powder PE-04ABM80 Muscle, skeletal receptor tyrosine-protein kinase (R748-N759, human) pY751+pY755+pY756 phosphopeptide - Powder PE-04AWQ90

General Links

Structure

Mol. Mass (Da):

97,056

# Amino Acids:

869

# mRNA Isoforms:

mRNA Isoforms:

97,056 Da (869 AA; O15146); 87,598 Da (783 AA; O15146-2); 86,425 Da (773 AA; O15146-3)

4D Structure:

Interacts with DOK7, which probably regulates its activity By similarity. Interacts with PDZRN3; this interaction is enhanced by agrin

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

1LUF

Subfamily Alignment

Domain Distribution:

Start	End	Domain
1	21	signal_peptide
28	116	IGc2
121	205	IGc2
212	302	IGc2
312	450	Fz
496	518	TMD
575	856	TyrKc
575	858	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Muscle, skeletal receptor tyrosine protein kinase Y756 phosphosite-specific antibody AB-PK872
○	Muscle, skeletal receptor tyrosine-protein kinase (S752-N759, human) pY756 phosphopeptide - Powder PE-04ABM80
○	Muscle, skeletal receptor tyrosine-protein kinase (R748-N759, human) pY751+pY755+pY756 phosphopeptide - Powder PE-04AWQ90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

N-GlcNAcylated:

N222, N338.

Serine phosphorylated:

S293, S424, S430, S435.

Threonine phosphorylated:

T31, T294.

Tyrosine phosphorylated:

Y554+, Y577, Y751+, Y755+, Y756+, Y813.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

100

630

32

1047
3

22

18

27
5

32

14

39
33

206

123

754
50

313

33

237
0.8

5

83

5
30

192

45

414
51

320

43

453
39

248

17

201
7

44

124

74
5

31

41

35
67

421

186

456
3

17

36

20
2

13

12

15
5

30

21

29
1

7

20

10
3

20

211

20
6

37

19

40
5

30

114

27
43

274

137

275
3

20

33

22
3

18

32

17
4

25

17

23
4

26

26

22
3

21

28

24
56

352

71

404
2

14

39

11
3

20

26

23
3

20

24

26
7

45

42

45
36

228

24

228
98

618

41

867
53

333

108

905
90

570

78

494
5

31

48

18

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
25.8

42.9

93
99.2

99.5

-
-

-

94
-

-

-
81

82.6

91
-

-

-
93.1

96.4

90
93.4

96.9

93
-

-

-
82.7

90.3

-
71.4

81

70
20.2

35.5

85
59.1

70.8

-
-

-

-
29.9

45

37
33.6

48.3

-
-

-

-
22.5

40

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

MUSK	O15146	Y554	RLHPNPMYQRMPLLL	+
MUSK	O15146	Y577	YPRNNIEYVRDIGEG
MUSK	O15146	Y755	RNIYSADYYKANEND	+
MUSK	O15146	Y756	NIYSADYYKANENDA	+
MUSK	O15146	Y813	MAHEEVIYYVRDGNI

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

MUSK	O15146	Y554	RLHPNPMYQRMPLLL	+
MUSK	O15146	Y577	YPRNNIEYVRDIGEG
MUSK	O15146	Y755	RNIYSADYYKANEND	+
MUSK	O15146	Y756	NIYSADYYKANENDA	+
MUSK	O15146	Y813	MAHEEVIYYVRDGNI

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

AST-487	Kd = 3.1 nM	11409972	574738	18183025
Hesperadin	Kd < 10 nM	10142586	514409	19035792
Linifanib	Kd = 10 nM	11485656	223360	18183025
Foretinib	Kd = 13 nM	42642645	1230609	22037378
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
JAK3 Inhibitor VI	IC50 > 50 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 > 50 nM	3813	281948	22037377
Staurosporine	Kd = 86 nM	5279		18183025
AT9283	IC50 > 100 nM	24905142		19143567
Lestaurtinib	Kd = 100 nM	126565		18183025
SU14813	Kd = 100 nM	10138259	1721885	18183025
Sorafenib	Kd = 130 nM	216239	1336	18183025
ACN-S001855	IC50 > 150 nM	10377751		22037377
AS601245	IC50 > 150 nM	11422035	191384	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
SB218078	IC50 > 150 nM	447446	289422	22037377
TG003	IC50 > 150 nM	1893668	408982	22037377
Tozasertib	Kd < 150 nM	5494449	572878	19035792
KW2449	Kd = 200 nM	11427553	1908397	22037378
Crizotinib	Kd = 230 nM	11626560	601719	22037378
Gö6976	IC50 > 250 nM	3501	302449	22037377
NVP-TAE684	Kd = 260 nM	16038120	509032	22037378
Tozasertib	Kd = 300 nM	5494449	572878	18183025
BMS-777607	IC50 = 450 nM	24794418		19260711
Sunitinib	Kd = 490 nM	5329102	535	18183025
AG-E-60384	IC50 = 500 nM	6419741	413188	22037377
Aloisine A	IC50 = 500 nM	5326843	75680	22037377
BML-275	IC50 = 500 nM	11524144	478629	22037377
Flt-3 Inhibitor II	IC50 = 500 nM	11601743	377193	22037377
Gö6983	IC50 = 500 nM	3499	261491	22037377
GSK-3 Inhibitor XIII	IC50 = 500 nM	6419766	359482	22037377
N-Benzoylstaurosporine	IC50 = 500 nM	56603681	608533	22037377
PKCb Inhibitor	IC50 = 500 nM	6419755	366266	22037377
STO609	IC50 = 500 nM	51371511		22037377
TBCA	IC50 = 500 nM	1095828		22037377
Nintedanib	Kd = 590 nM	9809715	502835	22037378
Ponatinib	IC50 = 694 nM	24826799		20513156
Momelotinib	IC50 < 750 nM	25062766		19295546
TG101348	Kd = 800 nM	16722836	1287853	22037378
Dovitinib	Kd = 830 nM	57336746		18183025
1;9-Pyrazoloanthrone	IC50 > 1 µM	8515	7064	22037377
Alisertib	IC50 = 1 µM	24771867		22016509
Alsterpaullone	IC50 > 1 µM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 1 µM	16760286	260138	22037377
Bohemine	IC50 > 1 µM	2422	83980	22037377
Compound 52	IC50 > 1 µM	2856		22037377
GSK-3 Inhibitor X	IC50 > 1 µM	6538818	430226	22037377
GSK-3b Inhibitor XI	IC50 > 1 µM	10020713	272629	22037377
IDR E804	IC50 > 1 µM	6419764	1802727	22037377
IRAK-1-4 Inhibitor I	IC50 > 1 µM	11983295	379787	22037377
MK5108	IC50 > 1 µM	24748204		20053775
PKR Inhibitor; Negative Control	IC50 > 1 µM	16760619		22037377
Purvalanol A	IC50 > 1 µM	456214	23327	22037377
Quizartinib	Kd = 1 µM	24889392	576982	19654408
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SU11652	IC50 > 1 µM	24906267	13485	22037377
Tpl2 Kinase Inhibitor	IC50 > 1 µM	9549300		22037377
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Barasertib	Kd = 1.5 µM	16007391	215152	18183025
CHEMBL248757	Ki > 1.65 µM	44444843	248757	17935989
Doramapimod	Kd = 1.9 µM	156422	103667	18183025
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
JNJ-28871063	IC50 > 4 µM	17747413		17975007

Disease Linkage

General Disease Association:

Neurological, and endocrine disorders

Specific Diseases (Non-cancerous):

MUSK-related congenital myasthenic syndrome; Congenital myasthenic syndrome; Myasthenia gravis; Congenital myasthenic syndrome associated with acetylcholine receptor deficiency; Myasthenic syndrome, congenital, associated with facial dysmorphism and acetylcholine receptor deficiency; Lambert-Eaton myasthenic syndrome; Endplate acetylcholinesterase deficiency; Progressive bulbar palsy; Myasthenic syndrome, congenital, with pre- and postsynaptic defects

Comments:

Mutations of MUSK at M605I, A727V, and V790M are associated with myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD). CMS-ACHRD is a post-synaptic congenital myasthenic syndrome with inherited disorders of neuromuscular transmission.

Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for MUSK in diverse human cancers of 240, which is 48% lower than the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.09 % in 25406 diverse cancer specimens. This rate is only 22 % higher than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.55 % in 865 skin cancers tested; 0.42 % in 1329 large intestine cancers tested; 0.36 % in 603 endometrium cancers tested; 0.33 % in 589 stomach cancers tested; 0.14 % in 1956 lung cancers tested; 0.14 % in 1512 liver cancers tested; 0.08 % in 710 oesophagus cancers tested; 0.08 % in 273 cervix cancers tested; 0.08 % in 1276 kidney cancers tested; 0.07 % in 1490 breast cancers tested; 0.06 % in 833 ovary cancers tested; 0.05 % in 441 autonomic ganglia cancers tested; 0.04 % in 942 upper aerodigestive tract cancers tested; 0.04 % in 548 urinary tract cancers tested; 0.04 % in 1467 pancreas cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: E414Q (5).

Comments:

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

MUSK

OMIM Entry:

601296

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

Group:

Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

N-GlcNAcylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Kinections Map

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

General Disease Association:

Specific Diseases (Non-cancerous):

Comments:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: