NHR2-like (IPR014896)

Short name: NHR2

Overlapping homologous superfamilies


Domain relationships



Transcriptional activation and repression are required for control of cell proliferation and differentiation during embryonic development and homeostasis in the adult organism. Perturbations of these processes can lead to the development of cancer [PMID: 11150306]. The Eight-Twenty-One (ETO) gene product is able to form complexes with corepressors and deacetylases, such as nuclear receptor corepressor (N-CoR), which repress transcription when recruited by transcription factors [PMID: 12559562]. The ETO gene derives its name from its association with many cases of acute myelogenous leukaemia (AML), in which a reciprocal translocation, t(8;21), brings together a large portion of the ETO gene from chromosome eight and part of the AML1 gene from chromosome 21. The human ETO gene family currently comprises three major subfamilies: ETO/myeloid transforming gene on chromosome 8 (MTG8); myeloid transforming gene related protein-1 (MTGR1) and myeloid transforming gene on chromosome 16 (MTG16). ETO proteins are composed of four evolutionarily conserved domains termed nervy homology regions (NHR) 1-4. NHR1 is thought to stabilise the formation of high molecular weight complexes, but is not directly responsible for repressor activity. NHR2 and its flanking sequence comprise the core repressor domain, which mediates 50% of the wild type repressor activity. Furthermore, there is evidence that the amphipathic helical structure of NHR2 promotes the formation of ETO/AML1 homodimers [PMID: 11150306]. NHR3 and NHR4 have been shown to act in concert to bind N-CoR. NHR4 contains two zinc finger motifs, which are thought to play a role in protein interactions rather than DNA binding [PMID: 12559562].

This entry represents the NHR2 (Nervy homology 2) domain found in ETO proteins. It mediates oligomerisation and protein-protein interactions, forming an alpha-helical tetramer [PMID: 16616331].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.