|PROSITE documentation PDOC51838 [for PROSITE entry PS51838]|
Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). NELF is a transcription factor composed of four subunits, NELF-A, -B, -C (or its variant -D), and -E, that are conserved from Drosophila to humans. Certain subunits have been implicated in numerous diseases ranging from neurological disorders to cancer. The N-terminal segment of NELF-A shows sequence similarity to the hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV) [E1]. Replication of HDV RNA appears to involve the host RNAPII and requires the presence of HDAg. HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. HDAg directly binds RNAPII and inhibits NELF-RNAPII association, possibly because HDAg competes with NELF-A for a common surface on RNAPII [1,2].
The C-terminus of the HDAg domain forms the RNAPII-binding motif conserved in humans and virus, while the NELF-C (or NELF-D)-binding region of NELF-A is localized in the middle of the HDAg domain. The region of HDAg corresponding to the NELF-C (or NELF-D)-binding region of NELF-A contains two arginine-rich motifs responsible for RNA-binding activity [1,2,3].
The HDAg domain is composed of a long N-terminal helix, interrupted by a sharp bend and continuing on into another short helix (see <PDB:1A92>) [3,4]. The middle part of the HDAg domain makes an 'extended region' that forms four helices (see <PDB:5L3X>) . The structure of the C-terminal section is not yet known.
Proteins known to contain a HDAg domain are listed below:
The profile we developed covers the entire HDAg domain.Last update:
July 2017 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Yamaguchi Y. Filipovska J. Yano K. Furuya A. Inukai N. Narita T. Wada T. Sugimoto S. Konarska M.M. Handa H.|
|Title||Stimulation of RNA polymerase II elongation by hepatitis delta antigen.|
|2||Authors||Narita T. Yamaguchi Y. Yano K. Sugimoto S. Chanarat S. Wada T. Kim D.K. Hasegawa J. Omori M. Inukai N. Endoh M. Yamada T. Handa H.|
|Title||Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.|
|Source||Mol. Cell. Biol. 23:1863-1873(2003).|
|3||Authors||Lin I.J. Lou Y.C. Pai M.T. Wu H.N. Cheng J.W.|
|Title||Solution structure and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen.|
|4||Authors||Zuccola H.J. Rozzelle J.E. Lemon S.M. Erickson B.W. Hogle J.M.|
|Title||Structural basis of the oligomerization of hepatitis delta antigen.|
|5||Authors||Vos S.M. Pollmann D. Caizzi L. Hofmann K.B. Rombaut P. Zimniak T. Herzog F. Cramer P.|
|Title||Architecture and RNA binding of the human negative elongation factor.|