Conserved Protein Domain Family
PTKc_Hck

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cd05073: PTKc_Hck 
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Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
Statistics
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PSSM-Id: 270658
View PSSM: cd05073
Aligned: 5 rows
Threshold Bit Score: 529.983
Threshold Setting Gi: 114794401
Created: 22-May-2007
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 11 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:2HK5; Human Hck binds Lck-targetted inhibitor Pg-1009247; defined at 3.5A contacts.
    View structure with Cn3D
  • Structure:2C0T; Human Hck binds inhibitor, A-641359; defined at 3.5A contacts.
    View structure with Cn3D
  • Comment:Also based on the binding of human Hck with the ATP analog, Amp-Pnp (1AD5).
  • Citation:PMID 9024658

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                          #  #                  #              #                        
1QCF_A       178 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTK-EP 256
2HK5_A         5 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTK-EP 83
2C0T_A       178 WEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTK-EP 256
gi 11596416  225 WEKDAWEIPRESLKLDRRLGAGQFGEVWMATYNKHTKVAVKTMKPGTMSVEAFLDEANLMKALQHDKLVRLNAVVTKeEP 304
gi 118100777 251 WEKDAWEIPRASLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVSAFLEEANLMKSLQHDKLVRLHAVVTReEP 330
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1            ## #                                              #  # #          #         
1QCF_A       257 IYIITEFMaKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIED 336
2HK5_A        84 IYIITEFMaKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIED 163
2C0T_A       257 IYIITEFMaKGSLLDFLKSDEGsKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIED 336
gi 11596416  305 IYIITEFMeKGSLLDFLKSDEGnRVQLPKLIDFSAQIAEGMAYIEQRNYIHRDLRAANILVSKALVCKIADFGLARIIED 384
gi 118100777 331 IYIITEFMeKGSLLDFLKSEEGnKQPLPKLIDFSAQIAEGMAYIEKRNYIHRDLRAANILVSAMLVCKIADFGLARIIED 410
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1QCF_A       337 NEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYN 416
2HK5_A       164 NEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYN 243
2C0T_A       337 NEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYN 416
gi 11596416  385 NEYTAREGAKFPIKWTAPEAINYGSFTIKSDVWSFGILLTEIISYGRTPYPGMTNPEVIRSLERGYRMQRTDSCPQELYD 464
gi 118100777 411 NEYVAREGAKFPIKWTAPEAINYGSFTIKSDVWSFGILLTEIVTYGRIPYPGMSSAEVIRALEHGYRMPRTESCPEELYD 490
                        250       260
                 ....*....|....*....|....*.
Feature 1                                  
1QCF_A       417 IMMRCWKNRPEERPTFEYIQSVLDDF 442
2HK5_A       244 IMMRCWKNRPEERPTFEYIQSVLDDF 269
2C0T_A       417 IMMRCWKNRPEERPTFEYIQSVLDDF 442
gi 11596416  465 VMLECWKNKPEDRPTFEYLQSVLEDF 490
gi 118100777 491 VMIRCWKTKPEDRPTFEYMQSILEDF 516

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