Conserved Protein Domain Family
PTKc_CSF-1R

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cd05106: PTKc_CSF-1R 
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R 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: 133237
View PSSM: cd05106
Aligned: 6 rows
Threshold Bit Score: 774.404
Threshold Setting Gi: 56118484
Created: 10-Jul-2007
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
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, as well as the structure of human c-Kit bound to MgADP.
  • Citation:PMID 9312016

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                     ## #### #                  # #     
Q00495       541 KPKYQVRWKIIERYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGk-EDAVLKVAVKMLKST 619  Norway rat
P79750       545 KPRFEIRWKIIEAREGNNYTFIDPTQLPYNEKWEFPRDKLKLGKVLGAGAFGKVVEATAFGLGedKDNTLRVAVKMLKAN 624  torafugu
CAD10625     550 KPRYEIRWKIIQASEGNNYTFIDPTQMPYNEKWEFPRDKLKLGKILGAGAFGKVVEATAYGLGe-DDNAMRVAVKMLKAR 628  rainbow trout
AAT08795     545 KPRYEIRWKIIEATNGNNYSFIDPTQLPYNEKWEFPRDKLKLGKTLGAGAFGKVVEATAYGLGk-EDNVTRVAVKMLKAS 623  goldfish
NP_001008181 523 KPKYEIRWQIIQPAEGNNYTCIDPTQLPYNDKWEFPRTNLQFGKTLGAGAFGKVMEATAVGLGn-EDSAVTVAVKMLKPS 601  western clawed...
XP_414597    538 KPKYQVRWKIIEACEGNNYIFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGk-EDSVLKVAVKMLKST 616  chicken
Feature 1                                                  # #   #                               
Q00495       620 AHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLgpsls-pgqdsEGDSSYK 698  Norway rat
P79750       625 AHSDEREALMSELKILSHLGHHQNIVNLLGACTYGGPVLVITEYCSLGDLLNFLRQKAETFVnlvmn-ipeimENSNDYK 703  torafugu
CAD10625     629 AHSDEREALMSELKILSHLGQHKNIVNLLGACTQAGPVLVITEYCSHGDLLNFLRHKQETFLnfvmn-ipavpEETSDYK 707  rainbow trout
AAT08795     624 AHPDEREALMSELKILSHLGQHKNIVNLLGACTQSGPVLVITEYCCHGDLLNFLRSKAENFLnfvm----tipNPEMDYK 699  goldfish
NP_001008181 602 AHTDEVEALMSELKILSHLGNHKNIVNLLGACTHGGPILVITEYCHYGDLLNFLRKKAQIMNemfsasleeqsSTSSDYK 681  western clawed...
XP_414597    617 ADTDEQEALMSELKIMSHLGHHANIVNLLGACTYGGPILVITEYCRYGDLLNFLRKKAEYIIiqdsa-ldtslDSTADYK 695  chicken
Feature 1                                                                                        
Q00495       699 NIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSSDSff---------kQDLDKEPSRPLELWDLLHFSSQVAQGMAFLAS 769  Norway rat
P79750       704 NICNQKWYIRSDSGISSTSSSTYLEMRPSQQSHIEAsg--------rkSLCEDNGDWPLDIDDLLRFSLQVAQGLDFLAS 775  torafugu
CAD10625     708 NLCEGKQFIRSDSGISSVCSDSYLEMRPGPQPVNSSld--------svCEDGGPDSWPLDMEDLLRFSYQVAQGLDFLAA 779  rainbow trout
AAT08795     700 NITTERMFIRSDSGISSTCSDNYLAMRPASSRPTNSaqs------sslDCEQTEDSWPLDMDDLLRFSHQVAQGLDFLAA 773  goldfish
NP_001008181 682 NMTIEHKYIKSDSGFLSKGTDSYVEMKPVSSLSSQGds--------liDEKDTDDMLPLDLYDLLSFSFQVSQGMSFLSA 753  western clawed...
XP_414597    696 NIDLEKKYIRSDSGFASQGLETYVEMRPISSSSSVSsdsaqsrgksseEDETREDLQPLNLSDLLQFSSQVAQGMAFLAS 775  chicken
Feature 1              #   ## #          #                 #####        #                        
Q00495       770 KNCIHRDVAARNVLLTSGHVAKIGDFGLARDIMNDSNYVVKGNARLPVKWMAPESILYCVYTVQSDVWSYGILLWEIFSL 849  Norway rat
P79750       776 RNCIHRDVAARNVLLTDKRVAKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSL 855  torafugu
CAD10625     780 KNCIHRDVAARNVLLTDLHVAKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCLYTVQSDVWSYGILLWEIFSL 859  rainbow trout
AAT08795     774 KNCIHRDVAARNVLLTNSRVAKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSL 853  goldfish
NP_001008181 754 KNCIHRDVAARNVLVSHGRVVKICDFGLARDIENDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEMFSL 833  western clawed...
XP_414597    776 KNCIHRDLAARNVLVSDGRVAKICDFGLARDIMNDSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSL 855  chicken
Feature 1                  #                                                     
Q00495       850 GLNPYPGILVNNKFYKLVKDGYQMAQPVFAPKNIYSIMQSCWDLEPTRRPTFQQICFLLQEQAR 913  Norway rat
P79750       856 GKSPYPSMAVDSRFYKMVKRGYQMSQPDFALPEIYMIMKMCWNLEPTERPTFSMISQMINRLLG 919  torafugu
CAD10625     860 GKSPYPSILVDTKFYNMIKCGYQMSRPDFAPPEMYTIMKMCWNLEPTERPTFSKISQLIERLLG 923  rainbow trout
AAT08795     854 GKSPYPNILVDSKFYKMIKSGYQMSRPDFASPEMYTIMKMCWNLDAAERPTFSKISQLIERMLG 917  goldfish
NP_001008181 834 GRSPYPGIMVNRKFYKMIKEGYKMDCPDYAPLEIYRIMKTCWDLEPTQRPTFNQISTLISKQIN 897  western clawed frog
XP_414597    856 GKSPYPGMAVNSKFYSMVKRGYQMARPDFAPLEMYSIMQACWSLEPTQRPTFDQICCFIQKELD 919  chicken

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