The ETS family is divided into 11 subfamilies, which are listed below:
|Subfamily||Members and their homologs|
|ELF||ELF1, NERF/ELF2, MEF/ELF4|
|ERG||ERG, FLI1, FEV|
|ESE||ESE1/ESX/ELF3, ESE2/ELF5, ESE3/EHF|
|ETS||ETS1, ETS2, POINTED|
|PEA3||PEA3/E1AF/ETV4, ERM/ETV5, ER81/ETV1, ER71/ETV2|
|SPI||PU.1/SPI, SPIB, SPIC|
|TCF||ELK1, SAP1/ELK4, NET/SAP2/ELK3, LIN|
|TEL||TEL/ETV6, TEL2/ETV7, YAN|
All ETS family members are identified through a highly conserved DNA binding domain, the ETS domain, which is a winged helix-turn-helix structure that binds to DNA sites with a central GGA DNA sequence. As well as DNA-binding functions, evidence suggests that the ETS domain is also involved in protein-protein interactions. There is limited similarity outside the ETS DNA binding domain.
Other domains are also present and vary from ETS member to ETS member, including the Pointed domain, a subclass of the SAM domain family.
Multiple Ets factors have been found to be associated with cancer, such as through gene fusion. For example, the ERG ETS transcription factor is fused to the EWS gene, resulting in a condition called Ewing's sarcoma. The fusion of TEL to the JAK2 protein results in early pre-B acute lymphoid leukaemia.