2G2F,1OPK,2FO0,2HYY,2G2I,1OPJ,2G1T,3PYY


Conserved Protein Domain Family
PTKc_Abl

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cd05052: PTKc_Abl 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl 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: 270645
Aligned: 23 rows
Threshold Bit Score: 544.708
Created: 17-Jul-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 18 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
  • Structure:2G2F; Human Abl tyr kinase binds peptide substrate and thiophosphoric acid; defined at 3.5A contacts.
  • Structure:2G1T; Human Abl tyr kinase binds peptide substrate analog and thiophosphoric acid; defined at 3.5A contacts.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                      # ###                # #                                           
2G2F_A         10 WEMERTDITMKHKLGGGQYGEVYEGVWKKYsLTVAVKTLKEDTmeVEEFLKEAAVMKEIKHPNLVQLLGVCTrepPFYII 89   human
P03949        304 WELDRSEIIMHNKLGGGQYGDVYEGYWKRHdCTIAVKALKEDAmpLHEFLAEAAIMKDLHHKNLVRLLGVCTheaPFYII 383  nematode
P00522        364 WEICRTDIMMKHKLGGGQYGEVYEAVWKRYgNTVAVKTLKEDTmaLKDFLEEAAIMKEMKHPNLVQLIGVCTrepPFYII 443  fruit fly
3PYY_A         21 WEMERTDITMKHKLGGGQYGEVYEGVWKKYsLTVAVKTLKEDTmeVEEFLKEAAVMKEIKHPNLVQLLGVCTrepPFYII 100  human
EFX83371        7 WEIERTDIAMKQKLGGGQYGDVYEAMWKRYnMTVAVKTLKEDTmaLKDFLEEAAIMKEMKHPNLVQLLGVCTrepPFYIV 86   common water ...
JAA64456      230 WEIDRTDIVMKHRLGGGQYGDVYEALWKRYnLTVAVKTLKEDTmaLKDFLEEAAIMKEMKHPNLVQLIGVCTrepPFYII 309  Rhipicephalus...
XP_002733964  254 WEIERTEIVMKHKLGGGQYGEVYEAIWKKHnKTIAVKTLKEETmqVEEFLKEASVMKEIKHPNLVQLLGVCTrepPFYII 333  Saccoglossus ...
XP_001639258    7 WEIERTEIAMKHKLGGGQYGEVYEGTWKKYnKTVAVKTLREETmeVEEFLKEASVMKGIKHQNLVQLLGVCTrepPFYII 86   starlet sea a...
XP_002124117  195 WEIDRSEIHMKQRLGGGQYGDVYEAVWKRYnKTIAVKTFREDTtnTEEFLKEAAVMKSIKHPNLVQLLGVCTrepPFYIV 274  Ciona intesti...
XP_001199130  259 WEIERTDISMKNKLGGGQYGEVYEAIWKKHnKIVAVKTLREENmrVDEFLREAAVMKNVKHPNLVQLLGVCTrepPFYIV 338  purple urchin
Feature 1          # #   #                                               #          #             
2G2F_A         90 TEFMTYGNLLDYLRECnrqeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTY 168  human
P03949        384 TEFMCNGNLLEYLRRTdkslLPPIILVQMASQIASGMSYLEARHFIHRDLAARNCLVSEHNIVKIADFGLARFM-KEDTY 462  nematode
P00522        444 TEFMSHGNLLDFLRSAgretLDAVALLYMATQIASGMSYLESRNYIHRDLAARNCLVGDNKLVKVADFGLARLM-RDDTY 522  fruit fly
3PYY_A        101 TEFMTYGNLLDYLRECnrqeVNAVVLLYMATQISSAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLM-TGDTY 179  human
EFX83371       87 TEFMSRGNLLDYLRRAnreeIDAIVLLYMATQVAAAMSYLESRNFIHRDLAARNCLVGENHLVKVADFGLARLM-RDDTY 165  common water ...
JAA64456      310 TEFMAHGNLLEYLRNCsreeITAVVLMYMATQIASAMSYLEARSFIHRDLAARNCLVGDCHLVKVADFGLARLM-RDDTY 388  Rhipicephalus...
XP_002733964  334 TEFMPHGNLLDYLRENneetLSAVTLMYMATQVASAMAYLEEKNFIHRDLAARNCLIGENHSVKVADFGLARLM-TGDTY 412  Saccoglossus ...
XP_001639258   87 TEFMMNGNLLDYLRSPkgkdLDAVTLMYMATQVGSAMSYLESMNFIHRDLAARNCLVGDNNLVKVADFGLSRLV-SEDIY 165  starlet sea a...
XP_002124117  275 TEFMSEGNLLEYLRRCnkveLDGVVLLHISVQVALAMEYLETRNYIHRDLAARNCLVEDNNLVKVADFGLSRLMaTGDDY 354  Ciona intesti...
XP_001199130  339 TEFMPYGNLLEYLRDNdetsLPAVTLLYMATQVAFGMSYLEKNSFIHRDLAARNCLLGEHHLLKVADFGLARMV-QGEIY 417  purple urchin
Feature 1              ### #       #                                 #   #                        
2G2F_A        169 TAPAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMR 248  human
P03949        463 TAHAGAKFPIKWTAPEGLAFNTFSSKSDVWAFGVLLWEIATYGMAPYPGVELSNVYGLLENGFRMDGPQGCPPSVYRLML 542  nematode
P00522        523 TAHAGAKFPIKWTAPEGLAYNKFSTKSDVWAFGVLLWEIATYGMSPYPAIDLTDVYHKLDKGYRMERPPGCPPEVYDLMR 602  fruit fly
3PYY_A        180 TAHAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKDYRMERPEGCPEKVYELMR 259  human
EFX83371      166 TAHAGAKFPIKWTAPEGLAYNKFSTKSDVWAFGILLWEIATYGMSPYPGIDLTDVYHTLETGYRMECPPGCPPRVYDLMQ 245  common water ...
JAA64456      389 TAHAGAKFPIKWTAPEGLAYNKFSTKSDVWAFGILLWEIATYGMSPYPGVDLTDVYHMLESGYRMECPPGCPARVYELMR 468  Rhipicephalus...
XP_002733964  413 TAQAGAKFPIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGVELTQVYEMLEKSYRMERPNGCPAEVYKLMK 492  Saccoglossus ...
XP_001639258  166 TAHQGAKFPIKWTAPEALAHNTFSIKSDVWAFGILLWELATYGMSPYPGIDLSQVYDKLDGGYRMPCPEGCPPEVYSLMQ 245  starlet sea a...
XP_002124117  355 TARAGAKFPIKWTAPESLAYNRFSTKSDVWSFGILLWEIATYGMSPYPGVDLSMVYEKLEKGYRMDSPSGCPSSVYALML 434  Ciona intesti...
XP_001199130  418 TAQAGAKFPIKWTAPESLAYYKFSSKSDVWAFGILLWEIATYGCSPYPGVDLQHVYGKLEQGYRMERPEGCPTDVYKLMH 497  purple urchin
Feature 1                                 
2G2F_A        249 ACWQWnPSDRPSFAEIHQAFETMF 272  human
P03949        543 QCWNWsPSDRPRFRDIHFNLENLI 566  nematode
P00522        603 QCWQWdATDRPTFKSIHHALEHMF 626  fruit fly
3PYY_A        260 ACWQWnPSDRPSFAEIHQAFETMF 283  human
EFX83371      246 QCWHWsANDRPTFQEIHHGLENMF 269  common water flea
JAA64456      469 QCWQWeTTDRPTFQEIHNTLENMF 492  Rhipicephalus pulchellus
XP_002733964  493 KCWKWnSSERPTFDEIHDDLNTMF 516  Saccoglossus kowalevskii
XP_001639258  246 TCWCWdPNSRPSFKEIHEKLNTMF 269  starlet sea anemone
XP_002124117  435 DCWSWdANDRPTFADIRCRLDGMF 458  Ciona intestinalis
XP_001199130  498 KCWEWrHTDRPSFTEIHEEMNNMF 521  purple urchin

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