About TF family
In AnimalTFDB4.0, the TF family classifications are consistent with AnimalTFDB3.0. Because we use the latest version of Ensembl fasta files and gtf files, we adjusted the thresholds for some families. For example, the Fork_head and MYB family thresholds are adjusted to 1e-2, and the threshold for Homeobox family is adjusted to 1e-3.
In most cases, a TF only has one kind of DBD; thus, it is easy to correctly assign it to one certain family. However, in some cases, a TF may have more than one kind of DBD. In order to classify them into a correct family, we checked all the TFs of human and mouse which contained multiple kinds of DBDs and then set up three rules. First, if a superfamily has several subfamilies, we classified the TFs based on the subfamily DBD. For example, the Homeobox superfamily has four subfamilies: Pou, CUT, TF_Otx and other Homeobox. In this superfamily, all TFs have a Homeobox domain, and some of them have one of the Pou, CUT, and TF_Otx subfamily signature domains. We assigned them to a specific family based on their subfamily signature domain. The second rule is that if a TF has more than one unrelated DBD, we will classify it into the family based on the DBD with the smallest E-value. The third rule is that if a TF family contains a non-TF gene (such as an enzyme gene) and cannot be rejected by changing the cutoff, we will remove the non-TF gene based on the prediction result of the other non-TF gene domain. There are three domains of enzyme genes (PLU-1, MOZ_SAS and TRAM_LAG1_CLN8) and three domains (TIP_N, SNF2_N, EP400_N ) act as non-TF gene domains in our prediction process. The thresholds of PLU-1, MOZ_SAS, TRAM_LAG1_CLN8 and TIP_N are 1e-2, and the thresholds of SNF2_N and EP400_N are 1e-60. We checked all the human and mouse classification results and found our method was reasonable. The self-build Hmm files are available here
| Family | DNA-binding domain | Pfam ID or InterPro ID | Cutoff | Rules | ||
| AF-4 | AF-4 | PF05110 | 1E-04 | AF-4 domain | ||
| AP-2 | TF_AP-2 | PF03299 | 1E-04 | TF_AP-2 domain | ||
| ARID | ARID | PF01388 | 1E-04 | ARID domain, no PLU-1 domain | ||
| bHLH | HLH | PF00010 | 1E-02 | HLH domain | ||
| CBF | CBF_beta | PF02312 | 1E-04 | CBF_beta domain | ||
| CSL | BTD | PF09270 | 1E-04 | BTD domain | ||
| NF-Y | NF-YA | CBFB_NFYA | PF02045 | 1E-04 | CBFB_NFYA domain | |
| NF-YB | NF-YB | self-build | 1E-04 | NF-YB domain | ||
| NF-YC | NF-YC | self-build | 1E-04 | NF-YC domain | ||
| CG-1 | CG-1 | PF03859 | 1E-04 | CG-1 domain | ||
| CP2 | CP2 | PF04516 | 1E-04 | CP2 domain | ||
| CSD | CSD | PF00313 | 1E-04 | CSD domain | ||
| CSRNP_N | CSRNP_N | PF16019 | 1E-04 | CSRNP_N domain | ||
| DACH | DACH | self-build | 1E-04 | DACH domain | ||
| E2F | E2F_TDP | PF02319 | 1E-04 | E2F_TDP domain | ||
| ETS | Ets | PF00178 | 1E-04 | Ets domain | ||
| Fork_head | Fork_head | PF00250 | 1E-03 | Fork_head domain | ||
| GCM | GCM | PF03615 | 1E-04 | GCM domain | ||
| GTF2I | GTF2I | PF02946 | 1E-04 | GTF2I domain | ||
| HMG | HMG_box | PF00505 | 1E-03 | HMG_box domain | ||
| HMGA | HMGA | self-build | 1E-04 | HMGA domain | ||
| HSF | HSF_DNA-bind | PF00447 | 1E-04 | HSF_DNA-bind domain | ||
| HTH | HTH_psq | PF05225 | 1E-04 | HTH_psq domain | ||
| IRF | IRF | PF00605 | 1E-04 | IRF domain | ||
| MYB | Myb_DNA-bd | PF00249 | 1E-03 | Myb_DNA-binding domain,no SNF2_N and EP400_N domain | ||
| MBD | MBD | PF01429 | 1E-04 | MBD domain | ||
| NCU-G1 | NCU-G1 | PF15065 | 1E-04 | NCU-G1 domain | ||
| NDT80_PhoG | NDT80_PhoG | PF05224 | 1E-04 | NDT80_PhoG domain | ||
| Nrf1 | Nrf1_DNA-bind | PF10491 | 1E-04 | Nrf1_DNA-bind domain | ||
| PC4 | PC4 | PF02229 | 1E-04 | PC4 domain | ||
| P53 | P53 | PF00870 | 1E-04 | P53 domain | ||
| PAX | PAX | PF00292 | 1E-04 | PAX domain | ||
| HPD | HPD | PF05044 | 1E-04 | HPD domain | ||
| LRRFIP | LRRFIP | PF09738 | 1E-04 | LRRFIP domain | ||
| RFX | RFX | PF02257 | 1E-04 | RFX domain | ||
| RHD | RHD | PF00554 | 1E-04 | RHD domain | ||
| Runt | Runt | PF00853 | 1E-04 | Runt domain | ||
| SAND | SAND | PF01342 | 1E-04 | SAND domain | ||
| SRF | SRF | PF00319 | 1E-04 | SRF domain | ||
| STAT | STAT_bind | PF02864 | 1E-04 | STAT_bind domain | ||
| T-box | T-box | PF00907 | 1E-04 | T-box domain | ||
| TEA | TEA | PF01285 | 1E-04 | TEA domain | ||
| COE | COE | self-build | 1E-04 | COE domain | ||
| GCFC | GCFC | PF07842 | 1E-04 | GCFC domain, no TIP_N domain | ||
| TSC22 | TSC22 | PF01166 | 1E-04 | TSC22 domain | ||
| Tub | Tub | PF01167 | 1E-04 | Tub domain | ||
| bZIP | TF_bZIP | bZIP | self-build | 1E-04 | bZIP domain | |
| MH1 | CTF_NFI | MH1 | PF00859 | 1E-04 | CTF/NFI and MH1 domain | |
| MH1 | MH1 | PF03165 | 1E-04 | MH1 domain | ||
| Homeobox | Homeobox | Homeobox | PF00046 | 1E-02 | All TFs have a Homeobox domain, without TRAM_LAG1_CLN8 domain; some of them have one of the Pou, CUT, and TF_Otx subfamily signature domains | |
| Pou | Homeobox, Pou | PF00157 | 1E-04 | |||
| CUT | Homeobox, CUT | PF02376 | 1E-04 | |||
| TF_Otx | Homeobox, TF_Otx | PF03529 | 1E-04 | |||
| Zinc finger | zf-CCCH | zf-CCCH | PF00642 | 1E-20 | zf-CCCH domain | |
| zf-C2HC | zf-C2HC | PF01530 | 1E-04 | zf-C2HC domain, no MOZ_SAS domain | ||
| zf-GAGA | zf-GAGA | PF09237 | 1E-04 | zf-GAGA domain | ||
| zf-BED | zf-BED | PF02892 | 1E-03 | zf-BED domain | ||
| zf-C2H2 | ZBTB | zf-C2H2 | PF00651 | 1E-04 | All TFs have a zf-C2H2 domain, ZBTB family has both ZBTB and zf-C2H2 domain | |
| zf-C2H2 | zf-C2H2 | PF00096 | 1E-03 | |||
| Nuclear Receptor | Miscellaneous | zf-C4 | self-build | 1E-04 | All TFs have a zf-C4 domain; some of them have one of the Miscellaneous, THR-like, RXR-like, ESR-like, NGFIB-like, SF-like and GCNF-like subfamily signature domains | |
| THR-like | zf-C4 | self-build | 1E-04 | |||
| RXR-like | zf-C4 | self-build | 1E-04 | |||
| ESR-like | zf-C4 | self-build | 1E-04 | |||
| NGFIB-like | zf-C4 | self-build | 1E-04 | |||
| SF-like | zf-C4 | self-build | 1E-04 | |||
| GCNF-like | zf-C4 | self-build | 1E-04 | |||
| DM | DM | PF00751 | 1E-04 | DM domain | ||
| zf-GATA | zf-GATA | PF00320 | 1E-04 | zf-GATA domain | ||
| zf-LITAF-like | zf-LITAF-like | PF10601 | 1E-04 | zf-LITAF-like domain | ||
| zf-MIZ | zf-MIZ | PF02891 | 1E-04 | zf-MIZ domain | ||
| zf-NF-X1 | zf-NF-X1 | PF01422 | 1E-04 | zf-NF-X1 domain | ||
| THAP | THAP | PF05485 | 1E-04 | THAP domain | ||
| Others | 1E-04 | |||||