Descriptions

Muscle, skeletal receptor tyrosine-protein kinase (MuSK) RTK(receptor tyrosine kinase) that is expressed exclusively in muscle cells, and is essential for the formation of neuromuscular synapses because of its key role in clustering acetylcholine receptors. Mutation of the MUSK juxtamembrane Tyr residue results in the loss of ligand (agrin)-stimulated receptor autophosphorylation in muscle cells. However, the soluble cytoplasmic domain of MUSK bearing a Tyr553Phe substitution undergoes activation-segment autophosphorylation and kinase activation in vitro. MUSK is subject to strong activation-segment autoinhibition.

Autoinhibitory domains (AIDs)

Target domain

574-855 (Protein kinase domain)

Relief mechanism

Others

Assay

Accessory elements

741-766 (Activation loop from InterPro)

Target domain

574-855 (Protein kinase domain)

Relief mechanism

Assay

741-766 (Activation loop from InterPro)

Target domain

574-855 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

4 structures for Q62838

Entry ID Method Resolution Chain Position Source
1LUF X-ray 205 A A 529-868 PDB
2IEP X-ray 221 A A/B 22-212 PDB
3HKL X-ray 210 A A/B 313-494 PDB
AF-Q62838-F1 Predicted AlphaFoldDB

No variants for Q62838

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q62838

No associated diseases with Q62838

18 regional properties for Q62838

Type Name Position InterPro Accession
domain Protein kinase domain 574 - 855 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 575 - 855 IPR001245
domain Immunoglobulin subtype 2 40 - 106 IPR003598-1
domain Immunoglobulin subtype 2 133 - 197 IPR003598-2
domain Immunoglobulin subtype 2 224 - 289 IPR003598-3
domain Immunoglobulin subtype 34 - 118 IPR003599-1
domain Immunoglobulin subtype 127 - 209 IPR003599-2
domain Immunoglobulin subtype 218 - 300 IPR003599-3
domain Immunoglobulin-like domain 28 - 116 IPR007110-1
domain Immunoglobulin-like domain 121 - 205 IPR007110-2
domain Immunoglobulin-like domain 212 - 302 IPR007110-3
active_site Tyrosine-protein kinase, active site 720 - 732 IPR008266
domain Immunoglobulin I-set 28 - 110 IPR013098-1
domain Immunoglobulin I-set 121 - 202 IPR013098-2
domain Immunoglobulin I-set 213 - 296 IPR013098-3
binding_site Protein kinase, ATP binding site 580 - 608 IPR017441
domain Frizzled domain 312 - 450 IPR020067
domain Tyrosine-protein kinase, catalytic domain 574 - 855 IPR020635

Functions

Description
EC Number 2.7.10.1 Protein-tyrosine kinases
Subcellular Localization
  • Postsynaptic cell membrane ; Single-pass type I membrane protein
  • Localizes to the postsynaptic cell membrane of the neuromuscular junction
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
cell projection A prolongation or process extending from a cell, e.g. a flagellum or axon.
external side of plasma membrane The leaflet of the plasma membrane that faces away from the cytoplasm and any proteins embedded or anchored in it or attached to its surface.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic membrane A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane.
receptor complex Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

7 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
metal ion binding Binding to a metal ion.
PDZ domain binding Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein tyrosine kinase activity Catalysis of the reaction
transmembrane receptor protein tyrosine kinase activity Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction
Wnt-protein binding Binding to a Wnt-protein, a secreted growth factor involved in signaling.

28 GO annotations of biological process

Name Definition
cell differentiation The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
cochlea development The progression of the cochlea over time from its formation to the mature structure. The cochlea is the snail-shaped portion of the inner ear that is responsible for the detection of sound.
enzyme-linked receptor protein signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell, where the receptor possesses catalytic activity or is closely associated with an enzyme such as a protein kinase, and ending with the regulation of a downstream cellular process, e.g. transcription.
long-term synaptic potentiation A process that modulates synaptic plasticity such that synapses are changed resulting in the increase in the rate, or frequency of synaptic transmission at the synapse.
memory The activities involved in the mental information processing system that receives (registers), modifies, stores, and retrieves informational stimuli. The main stages involved in the formation and retrieval of memory are encoding (processing of received information by acquisition), storage (building a permanent record of received information as a result of consolidation) and retrieval (calling back the stored information and use it in a suitable way to execute a given task).
motor neuron apoptotic process Any apoptotic process in a motor neuron, an efferent neuron that passes from the central nervous system or a ganglion toward or to a muscle and conducts an impulse that causes movement.
negative regulation of gene expression Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
neuromuscular junction development A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a neuromuscular junction.
phosphorylation The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
positive regulation of gene expression Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of motor neuron apoptotic process Any process that activates or increases the frequency, rate or extent of motor neuron apoptotic process.
positive regulation of neuron projection development Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
positive regulation of peptidyl-tyrosine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-tyrosine.
positive regulation of protein geranylgeranylation Any process that activates or increases the frequency, rate or extent of protein geranylgeranylation.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of Rac protein signal transduction Any process that activates or increases the frequency, rate or extent of Rac protein signal transduction.
positive regulation of skeletal muscle acetylcholine-gated channel clustering Any process that activates or increases the frequency, rate or extent of skeletal muscle acetylcholine-gated channel clustering.
positive regulation of synaptic assembly at neuromuscular junction Any process that activates or increases the frequency, rate or extent of synaptic assembly at neuromuscular junction.
positive regulation of synaptic transmission, cholinergic Any process that activates, maintains or increases the frequency, rate or extent of cholinergic synaptic transmission, the process of communication from a neuron to another neuron across a synapse using the neurotransmitter acetylcholine.
receptor clustering The receptor metabolic process that results in grouping of a set of receptors at a cellular location, often to amplify the sensitivity of a signaling response.
regulation of DNA-templated transcription Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
regulation of synaptic assembly at neuromuscular junction Any process that modulates the frequency, rate or extent of synaptic assembly at neuromuscular junctions.
response to axon injury Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an axon injury stimulus.
response to electrical stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an electrical stimulus.
response to muscle activity Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a muscle activity stimulus.
retina development in camera-type eye The process whose specific outcome is the progression of the retina over time, from its formation to the mature structure. The retina is the innermost layer or coating at the back of the eyeball, which is sensitive to light and in which the optic nerve terminates.
skeletal muscle acetylcholine-gated channel clustering The accumulation of acetylcholine-gated cation channels in a narrow, central region of muscle fibers, in apposition to nerve terminals.
transmembrane receptor protein tyrosine kinase signaling pathway The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.

61 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q91044 NTRK3 NT-3 growth factor receptor Gallus gallus (Chicken) SS
Q91987 NTRK2 BDNF/NT-3 growth factors receptor Gallus gallus (Chicken) SS
Q91009 NTRK1 High affinity nerve growth factor receptor Gallus gallus (Chicken) SS
Q8AXY6 MUSK Muscle, skeletal receptor tyrosine protein kinase Gallus gallus (Chicken) SS
Q5IS37 NTRK3 NT-3 growth factor receptor Pan troglodytes (Chimpanzee) SS
Q24488 Ror Tyrosine-protein kinase transmembrane receptor Ror Drosophila melanogaster (Fruit fly) SS
Q9V6K3 Nrk Tyrosine-protein kinase transmembrane receptor Ror2 Drosophila melanogaster (Fruit fly) SS
Q16620 NTRK2 BDNF/NT-3 growth factors receptor Homo sapiens (Human) EV
Q16288 NTRK3 NT-3 growth factor receptor Homo sapiens (Human) SS
Q01973 ROR1 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Homo sapiens (Human) PR
Q01974 ROR2 Tyrosine-protein kinase transmembrane receptor ROR2 Homo sapiens (Human) EV
P04629 NTRK1 High affinity nerve growth factor receptor Homo sapiens (Human) EV
O15146 MUSK Muscle, skeletal receptor tyrosine-protein kinase Homo sapiens (Human) EV
Q9Z138 Ror2 Tyrosine-protein kinase transmembrane receptor ROR2 Mus musculus (Mouse) SS
Q3UFB7 Ntrk1 High affinity nerve growth factor receptor Mus musculus (Mouse) SS
Q6VNS1 Ntrk3 NT-3 growth factor receptor Mus musculus (Mouse) SS
Q9Z139 Ror1 Inactive tyrosine-protein kinase transmembrane receptor ROR1 Mus musculus (Mouse) PR
P15209 Ntrk2 BDNF/NT-3 growth factors receptor Mus musculus (Mouse) SS
Q61006 Musk Muscle, skeletal receptor tyrosine-protein kinase Mus musculus (Mouse) SS
P24786 NTRK3 NT-3 growth factor receptor Sus scrofa (Pig) SS
G3V9H8 Ret Proto-oncogene tyrosine-protein kinase receptor Ret Rattus norvegicus (Rat) SS
Q63604 Ntrk2 BDNF/NT-3 growth factors receptor Rattus norvegicus (Rat) SS
P35739 Ntrk1 High affinity nerve growth factor receptor Rattus norvegicus (Rat) SS
Q03351 Ntrk3 NT-3 growth factor receptor Rattus norvegicus (Rat) SS
Q91ZT1 Flt4 Vascular endothelial growth factor receptor 3 Rattus norvegicus (Rat) SS
O08775 Kdr Vascular endothelial growth factor receptor 2 Rattus norvegicus (Rat) SS
Q64716 Insrr Insulin receptor-related protein Rattus norvegicus (Rat) SS
P24062 Igf1r Insulin-like growth factor 1 receptor Rattus norvegicus (Rat) SS
Q498D6 Fgfr4 Fibroblast growth factor receptor 4 Rattus norvegicus (Rat) PR
P57097 Mertk Tyrosine-protein kinase Mer Rattus norvegicus (Rat) SS
P97523 Met Hepatocyte growth factor receptor Rattus norvegicus (Rat) PR
Q62956 Erbb4 Receptor tyrosine-protein kinase erbB-4 Rattus norvegicus (Rat) SS
Q62799 Erbb3 Receptor tyrosine-protein kinase erbB-3 Rattus norvegicus (Rat) SS
Q05030 Pdgfrb Platelet-derived growth factor receptor beta Rattus norvegicus (Rat) SS
P20786 Pdgfra Platelet-derived growth factor receptor alpha Rattus norvegicus (Rat) SS
P15127 Insr Insulin receptor Rattus norvegicus (Rat) SS
Q63474 Ddr1 Epithelial discoidin domain-containing receptor 1 Rattus norvegicus (Rat) SS
P53767 Flt1 Vascular endothelial growth factor receptor 1 Rattus norvegicus (Rat) PR
Q04589 Fgfr1 Fibroblast growth factor receptor 1 Rattus norvegicus (Rat) SS
P06494 Erbb2 Receptor tyrosine-protein kinase erbB-2 Rattus norvegicus (Rat) SS
Q00495 Csf1r Macrophage colony-stimulating factor 1 receptor Rattus norvegicus (Rat) PR
G5EGK5 cam-1 Tyrosine-protein kinase receptor cam-1 Caenorhabditis elegans SS
O64770 At1g61490 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61490 Arabidopsis thaliana (Mouse-ear cress) SS
O64783 At1g61370 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61370 Arabidopsis thaliana (Mouse-ear cress) SS
O81833 SD11 G-type lectin S-receptor-like serine/threonine-protein kinase SD1-1 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWZ5 SD25 G-type lectin S-receptor-like serine/threonine-protein kinase SD2-5 Arabidopsis thaliana (Mouse-ear cress) PR
Q9LPZ9 SD113 G-type lectin S-receptor-like serine/threonine-protein kinase SD1-13 Arabidopsis thaliana (Mouse-ear cress) SS
Q9SXB5 At1g11303 G-type lectin S-receptor-like serine/threonine-protein kinase At1g11303 Arabidopsis thaliana (Mouse-ear cress) PR
Q9SYA0 At1g61500 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61500 Arabidopsis thaliana (Mouse-ear cress) SS
Q9SXB4 At1g11300 G-type lectin S-receptor-like serine/threonine-protein kinase At1g11300 Arabidopsis thaliana (Mouse-ear cress) PR
O64778 At1g61420 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61420 Arabidopsis thaliana (Mouse-ear cress) SS
O64776 At1g61440 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61440 Arabidopsis thaliana (Mouse-ear cress) SS
O64780 At1g61400 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61400 Arabidopsis thaliana (Mouse-ear cress) SS
Q9SY95 At1g61550 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61550 Arabidopsis thaliana (Mouse-ear cress) SS
O64782 SD129 G-type lectin S-receptor-like serine/threonine-protein kinase SD1-29 Arabidopsis thaliana (Mouse-ear cress) SS
O64774 At1g61460 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61460 Arabidopsis thaliana (Mouse-ear cress) PR
O64477 At2g19130 G-type lectin S-receptor-like serine/threonine-protein kinase At2g19130 Arabidopsis thaliana (Mouse-ear cress) SS
O64793 At1g67520 G-type lectin S-receptor-like serine/threonine-protein kinase At1g67520 Arabidopsis thaliana (Mouse-ear cress) PR
Q9SXB8 At1g11330 G-type lectin S-receptor-like serine/threonine-protein kinase At1g11330 Arabidopsis thaliana (Mouse-ear cress) PR
O64784 At1g61360 G-type lectin S-receptor-like serine/threonine-protein kinase At1g61360 Arabidopsis thaliana (Mouse-ear cress) SS
Q39203 SD22 G-type lectin S-receptor-like serine/threonine-protein kinase SD2-2 Arabidopsis thaliana (Mouse-ear cress) SS
10 20 30 40 50 60
MRELVNIPLL QMLTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS
70 80 90 100 110 120
WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCT ANNGVGGAVE SCGALQVKMK
130 140 150 160 170 180
PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDSA LRENSRIAVL ESGSLRIHNV
190 200 210 220 230 240
QKEDAGQYRC VAKNSLGTAY SKLVKLEVEV FARILRAPES HNVTFGSFVT LRCTAIGMPV
250 260 270 280 290 300
PTISWIENGN AVSSGSIQEN VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT
310 320 330 340 350 360
VSIAEWSKSQ KESKGYCAQY RGEVCDAVLV KDSLVFFNTS YPDPEEAQEL LIHTAWNELK
370 380 390 400 410 420
AVSPLCRPAA EALLCNHLFQ ECSPGVLPTP MPICREYCLA VKELFCAKEW LAMEGKTHRG
430 440 450 460 470 480
LYRSGMHFLP VPECSKLPSM HQDPTACTRL PYLDYKKENI TTFPSITSSK PSVDIPNLPA
490 500 510 520 530 540
STSSFAVSPA YSMTVIISIM SCFAVFALLT ITTLYCCRRR REWKNKKRES AAVTLTTLPS
550 560 570 580 590 600
ELLLDRLHPN PMYQRMPLLL NPKLLSLEYP RNNIEYVRDI GEGAFGRVFQ ARAPGLLPYE
610 620 630 640 650 660
PFTMVAVKML KEEASADMQA DFQREAALMA EFDNPNIVKL LGVCAVGKPM CLLFEYMAYG
670 680 690 700 710 720
DLNEFLRSMS PHTVCSLSHS DLSTRARVSS PGPPPLSCAE QLCIARQVAA GMAYLSERKF
730 740 750 760 770 780
VHRDLATRNC LVGENMVVKI ADFGLSRNIY SADYYKADGN DAIPIRWMPP ESIFYNRYTT
790 800 810 820 830 840
ESDVWAYGVV LWEIFSYGLQ PYYGMAHEEV IYYVRDGNIL ACPENCPLEL YNLMRLCWSK
850 860
LPADRPSFCS IHRILQRMCE RAEGTVGV