Transmembrane Proteins

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Annotating Transmembrane Proteins

  • Subcellular localization of transmembrane proteins is often determined by methods that do not specifically address the precise topology of the protein.
  • For example, immunofluorescence experiments using fusion proteins or antibodies, as well as experiments that label and detect cell surface proteins, may be used to confirm localization of a transmembrane protein to a plasma, or organellar, membrane.
  • For GO Cellular Component curation, it is acceptable to annotate a protein containing a predicted transmembrane domain to the appropriate child of GO:0016021, 'integral to membrane' using such experiments as supporting evidence if the following conditions are met:
    • Sequence analyses of the protein being annotated support the existence of one or more transmembrane domains
      • InterPro mappings between InterPro domains and GO:0016021, 'integral to membrane' or a child term; currently, there are over >1200 such mappings
      • Caution should be taken with proteins that contain a single predicted transmembrane domain at the N-terminus of the protein, as this sequence could be functioning as a signal sequence that would result in secretion and therefore an annotation to an extracellular CC term
    • The experiments clearly demonstrate localization to the plasma membrane or the membrane of a subcellular organelle

Legacy Transmembrane Protein Annotations

  • As the decision to allow annotations to GO:0016021, 'integral to membrane' based on experiments described above was made after a number of manual annotations to more general parent terms, e.g. GO:0005886, 'plasma membrane' had been made, the following strategy was proposed for bringing existing annotations inline with current guidelines:
    • For all annotations that currently have:
  1. An experimental annotations to a child of GO:0016020, 'membrane' that is not also a child of GO:0016021, 'integral to membrane'
  2. A sequence-based annotation to GO:0016021, 'integral to membrane' or a child term
  • The GO_Central pipeline may/will automatically convert the original annotation to the corresponding 'integral to X membrane' annotation, maintaining the original evidence code.

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