PROSITE documentation PDOC51968
Grh/CP2 DNA-binding (DB) domain profile


Grh/CP2 transcription factors (TFs) are highly conserved in multicellular organisms as key regulators of epithelial differentiation, organ development and skin barrier formation. Members of this TF family are widely found in diverse taxa, ranging from fungi to animals. The Grh/CP2 family of TFs comprises two distinct divisions, CP2 (CCAAT box-binding protein 2) and Grh (grainyhead). Phylogenetic analysis indicates that the Grh/CP2 family originated prior to the metazoan-fungal divergence and the diversification of the two subfamilies probably occurred in an ancient animal lineage. Proteins of the CP2 subfamily are generally expressed ubiquitously, while the expression pattern of the Grh subfamily is rather tissue- and developmental stage specific. All Grh/CP2 family members share a common domain architecture characterized by an intrinsically unstructured N-terminal transactivation domain (TAD), a conserved DNA-binding domain (DBD), also termed CP2 binding domain, and a C-terminal dimerization domain (DD) [1,2,3].

The Grh/CP2 DB domain contains an immunoglobulin (Ig)-like core with two long, twisted antiparallel β sheets of five (β1, β3, β8, β5 and β11) and six (β2, β4, β6, β7, β9 and β10) strands, respectively. This core is decorated by three α helices and a series of surface loops (see <PDB:5MPH>) [3].

The profile we developed covers the entire Grh/CP2 DB domain.

Last update:

March 2021 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GRH_CP2_DB, PS51968; Grh/CP2 DNA-binding (DB) domain profile  (MATRIX)


1AuthorsWang S. Samakovlis C.
TitleGrainy head and its target genes in epithelial morphogenesis and wound healing.
SourceCurr. Top. Dev. Biol. 98:35-63(2012).
PubMed ID22305158

2AuthorsPare A. Kim M. Juarez M.T. Brody S. McGinnis W.
TitleThe functions of grainy head-like proteins in animals and fungi and the evolution of apical extracellular barriers.
SourcePLoS One. 7:E36254-E36254(2012).
PubMed ID22590528

3AuthorsMing Q. Roske Y. Schuetz A. Walentin K. Ibraimi I. Schmidt-Ott K.M. Heinemann U.
TitleStructural basis of gene regulation by the Grainyhead/CP2 transcription factor family.
SourceNucleic. Acids. Res. 46:2082-2095(2018).
PubMed ID29309642

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