Gram domain containing 1b

There are two confirmed cytoplasmic domains within GRAMD1B. The protein gets its name from the GRAM domain, located approximately 100 amino acids from the start codon. The GRAM domain is commonly found in myotubularin family phosphatases and predominantly involved in membrane coupled processes.[9] GRAMD1B also contains the VASt (VAD1 Analog of StAR-related lipid transfer) domain. The VASt domain is predominantly associated with lipid binding domains, such as GRAM. It is most likely to function in binding large hydrophobic ligands and may be specific for sterol.[10] A C-terminal domain in GRAMD1B sits within the lumen of the ER, is predicted to have alpha-helical secondary structure,[11] and is modified by tryptophan C-mannosyaltion.[12]

There are two negative charge clusters, located from amino acids 232-267 and 348-377.[13] The first cluster is not highly conserved, nor is it located in a motif or domain. The second cluster is located directly before the VASt domain and is conserved.

There are three repeat sequence regions, all fairly conserved in orthologs.[13]

Molecular weight and isoelectric point are conserved in orthologs.

The mature protein contains two nuclear localization signals, pat4 and pat7.[16] There are four dileucine motifs, three located within or close to the GRAM domain.[16] A leucine zipper pattern extends through a majority the transmembrane region.[16] A SUMOylation site is located directly after the VASt domain.[17] The proteins secondary structure consists of alpha-helices, beta-strands and coils.[18] Beta-strands are mainly located within the two domains, while the alpha-helixes are concentrated near the transmembrane region. Three disulfide bonds are predicted throughout the protein.[19]

Predicted alpha-helix structure of GRAMD1B transmembrane region.[20]

Predicted 3D structure of GRAMD1B,[18]

GRAMD1B is predicted to localize in the nucleus and contains a transmembrane domain, most likely placing it in the membrane of the nucleus.[13]

The ortholog space for GRAMD1B spans a large portion of evolutionary time. GRAMD1B can be found in mammals, bird, fish and invertebrates. It is not present in bacteria, archaea or fungi.[7]

There are four paralogs of GRAMD1B.[7] The most closely related is GRAMD1A while the most distant ortholog is GRAMD2A/GRAMD2.

GRAMD2 diverged earliest in history while the most recent split is GRAMD1A. The GRAMD1B gene’s rate of divergence significantly faster than Fibrinogen but is not as high as Cytochrome C.

Phylogeny of GRAMD1B

Several different proteins have been experimentally confirmed or predicted to interact with GRAMD1B.[24][25]