| Literature References | 1. XUE, Z.G., GEHRING, W.J. AND LE DOURAIN, N.M.
Quox-1, A quail homeobox gene expressed in the embryonic central nervous
system, including the forebrain.
PROC.NATL.ACAD.SCI.U.S.A. 88(6) 2427-2431 (1991).
2. GEHRING, W.J.
Homeo boxes in the study of development.
SCIENCE 236 1245-1252 (1987).
3. ANGERER, L.M., DOLECKI, G.J., GAGNON, M.L., LUM, R., WANG, G., YANG, Q.,
HUMPHREYS, T. AND ANGERER, R.C.
Progressively restricted expression of a homeobox gene within the aboral
ectoderm of developing sea urchin embryos.
GENES DEV. 3(3) 370-383 (1989).
4. SASAKI, H., YOKOYAMA, E. AND KUROIWA, A.
Specific DNA-binding of the 2 chicken deformed family homeodomain proteins,
Chox-1.4 AND Chox-A.
NUCLEIC ACIDS RES. 18 1739-1747 (1990).
5. BRENNAN, R.G., TAKEDA, Y., KIM, J., ANDERSON, W.F. AND MATTHEWS, B.W.
Crystallization of a complex of cro repressor with a 17 base pair operator.
J.MOL.BIOL. 188 115-118 (1986).
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| Documentation | Organisms develop according to a precise program that specifies the body
plan in intricate detail, and also determines the timing of developmental
events [1]. The highly complex nature of these events has suggested that
the process may be regulated by proteins capable of controlling the
temporal and spatial expression of many structural genes. The genes for
this process were first discovered as homeotic mutations in Drosophila [2],
and many similar genes are now known in a wide variety of organisms.
Proteins that regulate developmental gene expression are nuclear proteins
[3] that contain a conserved domain known as the homeobox, the flanking
sequences of which differ considerably among different proteins. The homeo
domain includes the helix-turn-helix (HTH) motif, which binds to DNA in a
sequence-specific manner to exert a temporal and spatial regulation of
developmental gene expression [4]. The second helix of this motif binds
to DNA via a number of hydrogen bonds and hydrophobic interactions, which
occur between specific side chains and the exposed bases and thymine methyl
groups within the major groove. The first helix may help to stabilise the
structure [5].
Many homeodomain-containing proteins have now been sequenced and, while
the homeodomain flanking regions vary, characteristic conserved sequences
upstream of the domain allow the proteins to be grouped into 3 subfamilies:
the so-called antennapedia, engrailed and `paired box' proteins. Antenna-
pedia, which regulates the formation of leg structures in Drosophila, was
one of the first homeotic genes studied and led to the discovery of the
homeobox domain. Over expression of this gene in the wrong segment of the
fruit fly can lead to the formation of leg structures in these segments.
For example, over expression in the head segment can lead to the formation
of legs instead of antennae (hence the name antennapedia). The sequences of
the antennapedia proteins contain a conserved hexapeptide 5-16 residues
upstream of the homeobox, the specific function of which is unclear.
ANTENNAPEDIA is a 2-element fingerprint that provides a signature for the
antennapedia-type homeobox proteins. The fingerprint was derived from an
initial alignment of 10 sequences: motif 1 encodes the conserved hexa-
peptide (cf. PROSITE pattern PS00032)). Five iterations on OWL20.0 were
required to reach convergence, at which point a true set comprising 79
sequences was identified.
An update on SPTR37_9f identified a true set of 140 sequences.
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