ECOD: identification of distant homology among multidomain and transmembrane domain proteins

BMC Mol Cell Biol. 2019 Jun 21;20(1):18. doi: 10.1186/s12860-019-0204-5.


The manual classification of protein domains is approaching its 20th anniversary. ECOD is our mixed manual-automatic domain classification. Over time, the types of proteins which require manual curation has changed. Depositions with complex multidomain and multichain arrangements are commonplace. Transmembrane domains are regularly classified. Repeatedly, domains which are initially believed to be novel are found to have homologous links to existing classified domains. Here we present a brief summary of recent manual curation efforts in ECOD generally combined with specific case studies of transmembrane and multidomain proteins wherein manual curation was useful for discovering new homologous relationships. We present a new taxonomy for the classification of ABC transporter transmembrane domains. We examine alternate topologies of the leucine-specific (LS) domain of Leucine tRNA-synthetase. Finally, we elaborate on a distant homologous links between two helical dimerization domains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • ATP-Binding Cassette Transporters / classification*
  • Carrier Proteins / chemistry
  • Cell Cycle Proteins / chemistry
  • Crystallography, X-Ray
  • Databases, Protein
  • Endopeptidases / chemistry
  • Escherichia coli / chemistry
  • Humans
  • Leucine-tRNA Ligase / chemistry
  • Membrane Proteins / chemistry
  • Organic Cation Transport Proteins / chemistry
  • Protein Domains*
  • Protein Multimerization
  • Protein Structure, Secondary
  • Structural Homology, Protein*
  • ras Proteins / chemistry


  • ATP-Binding Cassette Transporters
  • CAPRIN1 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • Organic Cation Transport Proteins
  • PAN3 protein, human
  • APH1A protein, human
  • Endopeptidases
  • ras Proteins
  • Leucine-tRNA Ligase