3BBT


Conserved Protein Domain Family
PTKc_HER4

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cd05110: PTKc_HER4 
Click on image for an interactive view with Cn3D
Catalytic domain of the Protein Tyrosine Kinase, HER4
PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 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: 173655
View PSSM: cd05110
Aligned: 3 rows
Threshold Bit Score: 637.494
Threshold Setting Gi: 167745036
Created: 8-Jun-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 14 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                    ##      #                # #                    #                 
3BBT_B       9 LRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLS 88   human
ABG35747   717 LRILKETELKRIKILGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANAEFMDEALIMASMDHPHLVRLLGVSLS 796  African clawed frog
AAD31764   558 LRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLS 637  chicken
Feature 1          # ## #                                               ## #          #        
3BBT_B      89 PTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLE 168  human
ABG35747   797 PTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLE 876  African clawed frog
AAD31764   638 PTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLE 717  chicken
Feature 1                                                                                      
3BBT_B     169 GDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDV 248  human
ABG35747   877 GDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTVWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPVCTIDV 956  African clawed frog
AAD31764   718 GDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDV 797  chicken
Feature 1                                                                     
3BBT_B     249 YMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEED 311  human
ABG35747   957 YMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPNPNDSKFFKNLLNEED 1019 African clawed frog
AAD31764   798 YMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDRMKLPSPNDSKFFQNLLDEED 860  chicken

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