PROSITE documentation PDOC51838
Hepatitis delta antigen (HDAg) domain profile


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>) [5]. The structure of the C-terminal section is not yet known.

Proteins known to contain a HDAg domain are listed below:

  • Animal NELF-A, encoded by WHSC2, a candidate gene for Wolf-Hirschhorn syndrome (WHS). This genetic disease causes a wide range of developmental defects, including some in the brain that lead to mental retardation.
  • Hepatitis Delta Antigen (HDAg), the only viral protein known to be associated with HDV. The small form (S) of HDAg functions as a trans- activator of HDV RNA replication, whereas the larger form (L) of the protein inhibits viral replication.

The profile we developed covers the entire HDAg domain.

Last update:

July 2017 / First entry.


Technical section

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

HDAG, PS51838; Hepatitis delta antigen (HDAg) domain profile  (MATRIX)


1AuthorsYamaguchi Y. Filipovska J. Yano K. Furuya A. Inukai N. Narita T. Wada T. Sugimoto S. Konarska M.M. Handa H.
TitleStimulation of RNA polymerase II elongation by hepatitis delta antigen.
SourceScience 293:124-127(2001).
PubMed ID11387440

2AuthorsNarita 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.
TitleHuman transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex.
SourceMol. Cell. Biol. 23:1863-1873(2003).
PubMed ID12612062

3AuthorsLin I.J. Lou Y.C. Pai M.T. Wu H.N. Cheng J.W.
TitleSolution structure and RNA-binding activity of the N-terminal leucine-repeat region of hepatitis delta antigen.
SourceProteins 37:121-129(1999).
PubMed ID10451556

4AuthorsZuccola H.J. Rozzelle J.E. Lemon S.M. Erickson B.W. Hogle J.M.
TitleStructural basis of the oligomerization of hepatitis delta antigen.
SourceStructure 6:821-830(1998).
PubMed ID9687364

5AuthorsVos S.M. Pollmann D. Caizzi L. Hofmann K.B. Rombaut P. Zimniak T. Herzog F. Cramer P.
TitleArchitecture and RNA binding of the human negative elongation factor.
SourceElife 5:0-0(2016).
PubMed ID27282391


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 prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)