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4egc

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4egc, resolution 1.99Å ()
Ligands: ,
Gene: EAB1, EYA2 (Homo sapiens)
Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48


Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal Structure of MBP-fused Human Six1 Bound to Human Eya2 Eya Domain

Publication Abstract from PubMed

SIX1 interacts with EYA to form a bipartite transcription factor essential for mammalian development. Loss of function of this complex causes branchio-oto-renal (BOR) syndrome, whereas re-expression of SIX1 or EYA promotes metastasis. Here we describe the 2.0-A structure of SIX1 bound to EYA2, which suggests a new DNA-binding mechanism for SIX1 and provides a rationale for the effect of BOR syndrome mutations. The structure also reveals that SIX1 uses predominantly a single helix to interact with EYA. Substitution of a single amino acid in this helix is sufficient to disrupt SIX1-EYA interaction, SIX1-mediated epithelial-mesenchymal transition and metastasis in mouse models. Given that SIX1 and EYA are overexpressed in many tumor types, our data indicate that targeting the SIX1-EYA complex may be a potent approach to inhibit tumor progression in multiple cancer types.

Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome., Patrick AN, Cabrera JH, Smith AL, Chen XS, Ford HL, Zhao R, Nat Struct Mol Biol. 2013 Feb 24. doi: 10.1038/nsmb.2505. PMID:23435380

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Function

[MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. [EYA2_HUMAN] Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Coactivates SIX1. Seems to coactivate SIX2, SIX4 and SIX5. Together with SIX1 and DACH2 seem to be involved in myogenesis. May be involved in development of the eye. Interaction with GNAZ and GNAI2 prevents nuclear translocation and transcriptional activity.[1]

About this Structure

4egc is a 2 chain structure with sequence from [1] and Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. Krishnan N, Jeong DG, Jung SK, Ryu SE, Xiao A, Allis CD, Kim SJ, Tonks NK. Dephosphorylation of the C-terminal tyrosyl residue of the DNA damage-related histone H2A.X is mediated by the protein phosphatase eyes absent. J Biol Chem. 2009 Jun 12;284(24):16066-70. Epub 2009 Apr 7. PMID:19351884 doi:C900032200

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