PROSITE documentation PDOC50960
Psq-type HTH domain profile


The psq-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of about 50 amino acids present in eukaryotic proteins of the Pipsqueak family. This family is named after the Drosophila pipsqueak protein, containing a DNA-binding domain that consists of four tandem repeats of the psq motif. Proteins of the Pipsqueak family occur in vertebrates, insects, nematodes, and fungi. Three subgroups of the family have been described: BTB, E93 and CENP-B. Pipsqueak and the other proteins of the BTB group (Broad-Complex, Tramtrack, Bric a brac) contain a BTB protein-protein interaction domain (see <PDOC50097>) in the N-terminal part, and the psq-type HTH domain(s) occur in the C-terminal part. Many BTB proteins are transcriptional regulators and the psq-type HTH domain of e.g. pipsqueak and bric a brac proteins binds DNA. The Drosophila cell death regulating protein E93 and e.g. human orthologs form the second subgroup and can contain the psq-type HTH at varying positions. The human centromere protein B (CENP-B) and the other members of the CENP-B group contain a psq-type DNA-binding domain in the N-terminal part and often a dimerization domain in the C-terminal part. The CENP-B group includes fungal transposases that, however, lack the N-terminal extremity of the psq-type HTH domain [1].

The NMR and crystal structures of human CENP-B show that the N-terminal part of the DNA binding domain is composed of three α-helices (see <PDB:1HLV>). The second and third helices connected via a turn comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs. In CENP-B this domain is followed by a CENPB-type HTH, which binds an adjacent DNA major groove (see <PDOC51253>).

Some proteins known to contain a psq-type HTH domain:

  • Drosophila pipsqueak protein, a developmental regulator with pleiotropic functions during oogenesis, embryonic pattern formation and adult development. The psq-type HTH domain binds to GAGA sequences [2,3].
  • Drosophila bric a brac 1 and 2 proteins, required for the development of adult ovaries, legs, antennae and abdomen.
  • Mammalian centromere protein B, associated with the centromere and specifically binding a 17 bp sequence, the CENP-B box.

The profile we developed covers the entire psq-type HTH domain.


The majority of fungal transposases lacks too many N-terminal residues in the domain and is therefore not detected by the profile.

Last update:

February 2004 / First entry.


Technical section

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

HTH_PSQ, PS50960; Psq-type HTH domain profile  (MATRIX)


1AuthorsSiegmund T. Lehmann M.
TitleThe Drosophila Pipsqueak protein defines a new family of helix-turn-helix DNA-binding proteins.
SourceDev. Genes Evol. 212:152-157(2002).
PubMed ID11976954

2AuthorsLehmann M. Siegmund T. Lintermann K.-G. Korge G.
TitleThe pipsqueak protein of Drosophila melanogaster binds to GAGA sequences through a novel DNA-binding domain.
SourceJ. Biol. Chem. 273:28504-28509(1998).
PubMed ID9774480

3AuthorsSchwendemann A. Lehmann M.
TitlePipsqueak and GAGA factor act in concert as partners at homeotic and many other loci.
SourceProc. Natl. Acad. Sci. U.S.A. 99:12883-12888(2002).
PubMed ID12271134

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