The G8 (for eight conserved glycine residues) domain is widely distributed, being found in proteins from various animals (from Strongylocentrotus purpuratus to Homo sapiens), lower eukaryotes (such as Dictyostelium discoideum and Tetrahymena thermophila) and bacteria (such as the α-proteobacteria Nitrobacter hamburgensis, γ-proteobacterium Hahella chejuensis and the green non-sulfur bacterium Chloroflexus aurantiacus) but absent in plants, viruses and archaea. Many G8-containing proteins are integral membrane proteins with signal peptides and/or transmembrane segments, and others lacking TM domain may be secreted. Several other protein domains frequently co-occur in proteins with a G8 domain. These include the IPT/TIG domain, the GG domain and the PbH1 repeat. Many G8-containing proteins have been associated with diseases such as polycystic kidney disease and non-syndromic hearing loss. The G8 domain may be involved in extracellular ligand binding and progress of catalysis [1].

The G8 domain is about 120 amino acids residues in length. The secondary structure prediction of the G8 domain suggests that it contains 10 β-strands and 1 helix. These strands are separated by conserved glycine residues and contain some conserved hydrophobic residues. Based on the structural prediction, the conserved glycine residues and hydrophobic residues might be important for correct folding of G8 domains, the glycine residues allowing rotation in the backbone and hydrophobic interactions among hydrophobic residues on β-strands/helix contributing to structural stabilization [1].

Some proteins known to contain a G8 domain are listed below:

• Human PKHD1 protein (also known as fibrocystin and polyductin), a large membrane protein involved in autosomal recessive polycystic kidney and hepatic disease.
• Human KIAA1199, an inner-ear-specific protein expressed in cochlea and vestibule tissues
• Human TMEM2, a protein expressed in cochlea and a variety of other tissues.

The profile we developed covers the entire G8 domain.

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