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:

An experimental annotations to a child of GO:0016020, 'membrane' that is not also a child of GO:0016021, 'integral to membrane'
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.