A protein is considered a transcription factor (TF) if it is listed in the TF reference set published in Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM: A census of human transcription factors: function, expression and evolution. Nat Rev Genet. 2009 Apr;10(4):252-63..
(This constitues a set of all proteins that possess a sequence specific DNA binding domain, which was manually curated for TFs.)
Additionally a human protein can enter into our set of TFs if it is contained in TRANSFAC and passed a manual curation step. In total there are only 70 proteins that are TFs in TRANSFAC, but are not in above reference list, 19 of which were included into our list of TFs.
Finally a human protein can enter into our set of TFs if the mouse ortholog of the gene that codes for this protein is contained in TFCAT. The protein also needs to pass a manual curation step. We included 8 proteins from TFCAT.

A protein is considered a transcription co-factor (TcoF) if it satisfies all of these conditions:

• It is not a member of above specified list of transcription factors.
• It is shown to bind to a transcription factor from the above list. This binding was demonstrated by experiment and is referenced in scientific literature.
• It is annotated in Gene Ontology with GO:0030528 ('transcription regulator activity') or one of its descendent terms or with GO:0045449 ('regulation of transcription') or one of its descendent terms
• It is annotated in Gene Ontology with GO:0005634 ('nucleus')

Transcription co-factors are grouped into four different classes according to the type of evidence that was presented for their annotation in Gene Ontology (see bottom 2 conditions above).
These classes are:

• Class 1: All TcoFs that have experimental evidence for both, involvement in transcription regulation and for occurrence in the cell nucleus.
• Class 2: All TcoFs that have experimental evidence for involvement in transcription regulation, but only non-experimental evidence (e.g. 'Inferred from Electronic Annotation') for occurrence in the cell nucleus.
• Class 3: All TcoFs that have experimental evidence for occurrence in the cell nucleus, but only non-experimental evidence (e.g. 'Inferred from Electronic Annotation') for involvement in transcription regulation.
• Class 4: All TcoFs that have only non-experimental evidence (e.g. 'Inferred from Electronic Annotation') for both, involvement in transcription regulation and for occurrence in the cell nucleus.