Protein Domain GRAM

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PH: GRAM

Evolution

Structure

The GRAM domain in MTMR2 has 7 beta sheets and 1 alpha helix, resembling Pleckstrin (PH) domain [1].

Functions

Technical notes

Why build in-house profile for GRAM

The GRAM domain in MTMR2 is from 74 to 185 as shown in crystal structure [1]. However, its profiles in Pfam and SMART database are incomplete: Pfam gives 78-138 (envelope 68-139); SMART gives 71-139. The region covers beta sheets 1-5, but not beta sheet 6, 7 and alpha helix 1. We therefore built a profile to capture the full GRAM domain. Below are the sequence of GRAM domain of human MTMR2 determined by structure with 5 flanking residues at both N- and C-terminal (69-19):

KLAEMEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVSNNL

Version 1.0

Note: We tried to align the full sequences of myotubularins in phosphatome.net database. The region of GRAM domain defined by MTMR2 GRAM (74-185) does not seem well aligned.

References

  1. Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, and Stuckey JA. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell. 2003 Dec;12(6):1391-402. DOI:10.1016/s1097-2765(03)00486-6 | PubMed ID:14690594 | HubMed [Begley03]