GRAM

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins

• SMART accession number: SM00568
• Interpro abstract (IPR004182):

  The GRAM domain is found in glucosyltransferases, myotubularins and other putative membrane-associated proteins. It is normally about 70 amino acids in length. It is thought to be an intracellular protein-binding or lipid-binding signalling domain, which has an important function in membrane-associated processes. Mutations in the GRAM domain of myotubularins cause a muscle disease, which suggests that the domain is essential for the full function of the enzyme [(PUBMED:11050430)]. Myotubularin-related proteins are a large subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids [(PUBMED:14690594)].

There are 1265 GRAM domains in 1057 proteins in SMART's nrdb database.

Disease (disease genes where sequence variants are found in this domain)

SwissProt sequences and OMIM curated human diseases associated with missense mutations within the GRAM domain.

Protein	Disease
Myotubularin (Q13496) (SMART)	OMIM:310400: Myotubular myopathy, X-linked

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
20.00	map00740	Riboflavin metabolism
20.00	map00530	Aminosugars metabolism
20.00	map00730	Thiamine metabolism
20.00	map00051	Fructose and mannose metabolism
20.00	map00760	Nicotinate and nicotinamide metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GRAM domain which could be assigned to a KEGG orthologous group, and not all proteins containing GRAM domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of GRAM domains in PDB

PDB code	Title
1lw3	Crystal structure of myotubularin-related protein 2 complexed with phosphate
1m7r	Crystal structure of myotubularin-related protein-2 (mtmr2) complexed with phosphate
1zsq	Crystal structure of mtmr2 in complex with phosphatidylinositol 3-phosphate
1zvr	Crystal structure of mtmr2 in complex with phosphatidylinositol 3,5-bisphosphate

Links (links to other resources describing this domain)

• INTERPRO: IPR004182