{PDOC00305}
{PS00353; HMG_BOX_1}
{PS50118; HMG_BOX_2}
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* HMG boxes A and B DNA-binding domains signature and profile *
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High  mobility group (HMG) chromosomal proteins are a family of relatively low
molecular  weight  non-histone  components  that  bind  DNA  without  sequence
specificity.  HMG1  (also  called HMG-T in fish) and HMG2 are related proteins
that  have  two  distinguishing  features: two HMG boxes (A and B), homologous
folded  domains  of  around  80  amino  acid  residues, and a long acidic tail
containing 20 to 30 aspartic or glutamic acid residues [1,2]. The HMG box A is
only  found  in  HMG 1 and 2 proteins whereas the HMG box B is also present in
various  transcription  factors.  HMG boxes have unusual DNA binding activity.
They bind preferentially to distorted DNAs, such as four-way junctions, kinked
cisplatin-modified  DNA,  DNA  bulges,  and have the property to bend DNA [2].
They can bind DNA without sequence specificity like in HMG1 and 2 or recognize
a specific site.

Several  structures of HMG-boxes have been solved (see <PDB:1AAB>) [3,4]. They
have a common fold consisting of three alpha helices arranged in an "L-shape".
The  HMG  box binds DNA through its concave face to the minor groove of B-form
DNA and causes bending by partial intercalation of a hydrophobic residue close
to the N-terminus of helix I [4,5].

Some proteins known to contain a HMG box are listed below:

 - Eukaryotic HMG1, HMG2 and related proteins.
 - Animal   sex   determining   region   Y   (SRY)  and  related  proteins,  a
   transcriptional   activator   which  regulates  a  genetic  switch  in male
   development.
 - Animal  SOX family of transcription factors, a conserved family of proteins
   related to the testis-determining factor SRY.
 - Mammalian  lymphoid  enhancer  binding  factor  1 (LEF1), a transcriptional
   activator which regulates a genetic switch in male development.
 - Eukaryotic   structure-specific  recognition  protein  1  (SSRP). It  binds
   specifically  to double-stranded and, at low levels, to single-stranded DNA
   which has been modified by the anticancer drug cisplatin.
 - Mitochondrial  transcription factor 1 (MTF1). It confers selective promoter
   recognition on the core subunit of the yeast mitochondrial RNA polymerase.
 - Vertebrate  nucleolar  transcription  factors  (UBF1/2). They recognize the
   ribosomal  RNA  gene  promoter  and  activate transcription mediated by RNA
   polymerase I.
 - Yeast  ARS-binding factor (ABF2). It binds specifically to the autonomously
   replicating sequence 1 (ARS1).
 - Yeast transcription factors  IXR1, ROX1, NHP6A/B, SPP41.
 - Drosophila  capicua  protein. A transcription cofactor involved in negative
   regulation of transcription.
 - Fission yeast mismatch binding protein 1 (cmb1). It binds to cytosines
   in base mismatches and opposite chemically altered guanines.
 - Tetrahymena thermophila micronuclear linker histone polyprotein (MIC LH).
 - Mammalian nuclear autoantigen Speckled 100 kDa protein (Sp-100).

The  pattern  we  developed  covers  the  second  helix  of  the HMG box A and
therefore  is  specific  for HMG1/2 proteins. We also developed a profile that
covers the whole domain and recognizes both types of HMG boxes.

-Consensus pattern: [FI]-S-[KR]-K-C-x-[EK]-R-W-K-T-[MV]
-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: December 2004 / Pattern and text revised.

[ 1] Bustin M., Lehn D.A., Landsman D.
     "Structural features of the HMG chromosomal proteins and their
     genes."
     Biochim. Biophys. Acta 1049:231-243(1990).
     PubMed=2200521
[ 2] Thomas J.O.
     "HMG1 and 2: architectural DNA-binding proteins."
     Biochem. Soc. Trans. 29:395-401(2001).
     PubMed=11497996
[ 3] Hardman C.H., Broadhurst R.W., Raine A.R., Grasser K.D., Thomas J.O.,
     Laue E.D.
     "Structure of the A-domain of HMG1 and its interaction with DNA as
     studied by heteronuclear three- and four-dimensional NMR
     spectroscopy."
     Biochemistry 34:16596-16607(1995).
     PubMed=8527432
[ 4] Werner M.H., Huth J.R., Gronenborn A.M., Clore G.M.
     "Molecular basis of human 46X,Y sex reversal revealed from the
     three-dimensional solution structure of the human SRY-DNA complex."
     Cell 81:705-714(1995).
     PubMed=7774012
[ 5] Love J.J., Li X., Case D.A., Giese K., Grosschedl R., Wright P.E.
     "Structural basis for DNA bending by the architectural transcription
     factor LEF-1."
     Nature 376:791-795(1995).
     PubMed=7651541; DOI=10.1038/376791a0

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