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GRAM Domain
Class:Phospholipid binding

No ImageThe structure of Gram domain from MTMR2 shows that the Gram sequence forms 5 β strands that are part of a larger motif that structurally adopt a PH domain fold. The Gram domain plus amino acid residues immediately following it form a tertiary structure consisting of a 7 stranded β sandwich with a α-helix at the C-terminal end. The structure of the Gram domain of MTMR2 is very similar to the pleckstrin PH domain. With the high conservation of residues that form the core of the domain, all predicted Gram domains would likely share the PH domain fold.

Structure Reference:
Begley, M.J. et al. (2003) Mol. Cell. 12(6): 1391-1402. PDB: 1LW3.

Domain binding and function:
The GRAM (from glucosyltransferases, Rab-like GTPase activators and myotubularins) domain is approximately 70 amino acids in length consisting of a 7-stranded β sandwich with a α-helix at the C-terminal end. The MTMR2 GRAM domain showed an unexpectedly large fold similar to that of pleckstrin homology (PH) domain. GRAM domains are found in the myotubularin family of phosphatases and predicted to occur in ~180 proteins. Mutations have been identified in GRAM domains that lead to X-linked congenital myopathy, implicating its functional importance. Proteins that contain the GRAM domain appear to be predominately involved in membrane-coupled processes. Functional studies demonstrate that the GRAM domain is involved in PI-(3,5)P2 substrate recognition, PI-(3)-P/PI-(5)-P dependent oligomerization and PI-(5)-P specific allosteric activation of the myotubularin phosphatases.
Examples of Proteins: 
GRAM domain protein
Specific Phosphoinositide ligands
MTMR2 PI-(3,5)-P2, PI-(5)-P
MTM1 , MTMR3, and MTMR6 PI-(5)-P

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