A FERM-adjacent (FA) region defines a subset of the 4.1 superfamily and is a potential regulator of FERM domain function

BMC Genomics. 2006 Apr 20:7:85. doi: 10.1186/1471-2164-7-85.


Background: Proteins containing FERM domains comprise a diverse group of eukaryotic proteins that bind membrane proteins and lipids. In doing so, they organise membrane microstructure, and coordinate the disposition of signalling and cell adhesion complexes. In protein 4.1R, phosphorylation adjacent to the FERM domain regulates its activity, and membrane mechanical properties.

Results: A novel sequence domain has been detected in a subset of proteins that contain FERM domains. This subset includes the true 4.1 proteins, some tyrosine phosphatases, rho-GEF proteins and type II transmembrane proteins, as well as some uncharacterised FERM proteins. This FERM-adjacent region is always closely proximate to the C-terminal of the FERM domain. This sequence is likely to be folded with elements of alpha and beta structure. The FERM-adjacent region of 4.1R contains serine residues phosphorylated by PKC and PKA; these appear conserved in about half of all other FERM-adjacent regions. Phylogenetic analyses indicate that all proteins containing a FERM-adjacent region arose from a single ancestor after FERM domains had started to proliferate in genomes of animals, plants and mycetozoa.

Conclusion: The FERM-adjacent region defines a subset of the FERM proteins in animals. The conservation of motifs in this region that are potential substrates for kinases together with the known regulatory phosphorylation of 4.1R in this region raises the possibility that the FERM-adjacent region is a regulatory adaptation in this subset of the FERM proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Blood Proteins / genetics*
  • Blood Proteins / metabolism
  • Conserved Sequence
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Evolution, Molecular
  • Gene Expression Regulation*
  • Humans
  • Membrane Proteins
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Phylogeny
  • Protein Folding
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary*
  • Sequence Alignment


  • Blood Proteins
  • Cytoskeletal Proteins
  • EPB41L4B protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • erythrocyte membrane band 4.1 protein
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C