1LUF


Conserved Protein Domain Family
PTKc_Musk

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cd05050: PTKc_Musk 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 133181
View PSSM: cd05050
Aligned: 6 rows
Threshold Bit Score: 533.641
Threshold Setting Gi: 18150832
Created: 15-Aug-2006
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 26 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:
  • Comment:includes ATP binding and substrate binding sites
  • Comment:Based on the structures of other PTK family members bound to substrate peptides and ATP analogs.
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                   #####   #                 # #                                       
1LUF_A       43 EYPRNNIEYVRDIGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASadmQADFQREAALMAEFDNPNIVKLLGVCAvg 122
gi 27923847 435 EYPRGDIVYVRSLGQGAFGRVFQARAPGlvpdqedLLVAVKMLKDDASdqmQMDFEREACLLAEFDHPNIVRLLGVCAlg 514
gi 50401029 649 EYPRNNIEYVRDIGEGAFGRVFQARAPGllpyepfTMVAVKMLKEEASadmQADFQREAALMAEFDNPNIVKLLGVCAvg 728
gi 11877384  54 EYPRNNIEYVRDIGAGAFGRVFQARAPGllsyepfTMVAVKMLKEEASadmHADFQREAALMAEFDHPNIVKLLGVCAvg 133
gi 46981406 640 EYPRNNIEYVRDIGEGAFGRVFQARAPGllptepfTMVAVKMLKEEAStdmQNDFQREAALMSEFDHPNIVRLLGVCAvg 719
gi 18150832 611 EVDRDKVRYEGDLGQGHFGLVVKATALGvvpgrdqCIVAVKILKEGASlqtKKEFFHEAALMHSFDHPNIVKLIGVCVeq 690
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1             ####  ##                                                               #  
1LUF_A      123 kPMCLLFEYMAYGDLNEFLRSMsphtvcslshsdl-strarvsspgpppLSCAEQLCIARQVAAGMAYLSERKFVHRDLA 201
gi 27923847 515 rPMCLLFEYMAPGDLSEFLRACspyathqa------------ptqdrlqLNELHLLQMAANIAAGMLYLSERKFVHRDLA 582
gi 50401029 729 kPMCLLFEYMAYGDLNEYLRDRsprnlcslvqgg---learacllnplaLCCTSQLCIAKQVAAGMAYLSERKFVHRDLA 805
gi 11877384 134 kPMCLLFEYMAHGDLNEYLRHRspralsslshssl-aakvrlcdlnpspLSCTDQLCIAQQVAAGMAYLSERKFVHRDLA 212
gi 46981406 720 kPMCLMFEYMAYGDLNEFLRRRcatqqpslsrdtltssslvseperyppLSCQEQLSISKQVAAGMAYLSERKFVHRDLA 799
gi 18150832 691 ePLCMIFEFMQLGDLNNFLRHNspkwqessas-------cakyggpkcdITTPIQVAMSLDITAGLAYLADNHYIHRDLA 763
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1        ## #          #                 #####        #                                 
1LUF_A      202 TRNCLVGEnMVVKIADFGLSRNIYSADYYKADGNDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGLQPYYGMA 281
gi 27923847 583 TRNCLINEhMAVKIADFGLSHKIYLQDYYKGDENDFIPIRWMPLESILYNKFSLESDVWAYGICLWEVFSFALQPYFGLT 662
gi 50401029 806 TRNCLVGEnMVVKIADFGLSRNMYSADYYKANENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMA 885
gi 11877384 213 TRNCLVGEnAVVKIADFGLSRNIYSADYYKANENDAIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMA 292
gi 46981406 800 TRNCLVAEnLVVKIADFGLSRNIYAADYYKASENDAIPIRWMPPESIFYNRYTSESDVWAYGVVLWEIFSYGMQPYYGMA 879
gi 18150832 764 TRNCLVSGdLRIKISDFGLSQDIYSTDYCRLSQSELLPIRWMPPEAILFARFTTQSDVWSLGVVLWELFSYGIQPYYSMS 843
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
Feature 1       #                                                  
1LUF_A      282 HEEVIYYVRDGNILACPENCpLELYNLMRLCWSKlPADRPSFCSIHRILQR 332
gi 27923847 663 HEEVIKYIKEGNVLGCPDNTpLSVYALMRRCWNRkPSERPGFAEINHCIQH 713
gi 50401029 886 HEEVIYYVRDGNILSCPDNCpLELYNLMRLCWSKlPADRPSFASIHRILER 936
gi 11877384 293 HEEVIYYVRDGNILSCPENCpLELYNLMRLCWSKmPSDRPSFACIYRILER 343
gi 46981406 880 HEEVIYYVRDGNVLSCPENCpQELYNLMRLCWSGhPTDRPSFASIHRILER 930
gi 18150832 844 NEQVIAHVRDGNVMNCPDGCpSEIYDLMVDCWNMdPGQRPTAADVNVALQR 894

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