{PDOC51937} {PS51937; HNF_P1} {BEGIN} ********************************************** * HNF-1 dimerization (HNF-p1) domain profile * ********************************************** The homeodomain proteins hepatocyte nuclear factor (HNF)-1alpha and HNF-1beta comprise a functionnally important family in which dimerization is essential for DNA binding. HNF-1alpha and HNF-1beta regulate tissue-specific genes in liver, kidney, intestine, and pancreas. These proteins form homo- and heterodimers through an autonomously folded domain encompassing the 32 N- terminal amino acids (HNF-p1). The dimerization domain also binds the transcriptional coactivator DCoH, which stimulates HNF-1alpha activity [1,2,3,4,5]. The HNF-p1 dimer folds into an X-type, antiparallel, four-helix bundle (4HB). Each monomer consists of two helices: a longer N-terminal helix and a shorter C-terminal helix, connected by a tight turn unrelated to classical beta- or gamma-turn families (see ). The dimer contains a rigid element, the N-terminal anti-parallel mini-zipper comprising alpha-helices 1 and 1', and a plastic element, the C-terminal coiled-coil comprising alpha-helices 2 and 2' [2,3,4,5]. The profile we developed covers the entire HNF-p1 domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2020 / First entry. [ 1] Mendel D.B., Crabtree G.R. "HNF-1, a member of a novel class of dimerizing homeodomain proteins." J. Biol. Chem. 266:677-680(1991). PubMed=1985954 [ 2] Rose R.B., Bayle J.H., Endrizzi J.A., Cronk J.D., Crabtree G.R., Alber T. "Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha." Nat. Struct. Biol. 7:744-748(2000). PubMed=10966642; DOI=10.1038/78966 [ 3] Rose R.B., Endrizzi J.A., Cronk J.D., Holton J., Alber T. "High-resolution structure of the HNF-1alpha dimerization domain." Biochemistry 39:15062-15070(2000). PubMed=11106484; DOI=10.1021/bi001996t [ 4] Narayana N., Hua Q., Weiss M.A. "The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus." J. Mol. Biol. 310:635-658(2001). PubMed=11439029; DOI=10.1006/jmbi.2001.4780 [ 5] Narayana N., Phillips N.B., Hua Q.X., Jia W., Weiss M.A. "Diabetes mellitus due to misfolding of a beta-cell transcription factor: stereospecific frustration of a Schellman motif in HNF-1alpha." J. Mol. Biol. 362:414-429(2006). PubMed=16930618; DOI=10.1016/j.jmb.2006.06.086 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}