High-mobility group protein HMG-I/HMG-Y is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''HMGA1''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Function
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication,
heterochromatin
Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...
organization,
integration of retroviruses into chromosomes, and the metastatic progression of cancer cells.
HMGA1 proteins are quite small (~10-12 kDa) and basic molecules, and consist of three
AT-hook
The second AT-hook of HMGA1 (black ribbon) bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden.
The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HM ...
s with the RGRP (Arg-Gly-Arg-Pro) core
motif, a novel
cross-link
In chemistry and biology a cross-link is a bond or a short sequence of bonds that links one polymer chain to another. These links may take the form of covalent bonds or ionic bonds and the polymers can be either synthetic polymers or natural ...
ing domain located between the second and third AT-hook, and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
acidic tail characteristic for the
HMG family comprising HMGA, HMGB and HMGN proteins.
HMGA1-GFP fusion proteins are highly dynamic in vivo (determined using
FRAP analysis), but in contrast also show nanomolar affinity to AT-rich DNA in vitro (determined biochemically), which might be explained due to the extensive
post-transcriptional modification
Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, ...
s in vivo. HMGA1 preferentially binds to the minor groove of AT-rich regions in double-stranded DNA using its AT-hooks. It has little secondary structure in solution but assumes distinct conformations when bound to substrates such as DNA or other proteins. HMGA1 proteins have high amounts of diverse
posttranslational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
s and are located mainly in the nucleus, especially in heterochromatin, but also in mitochondria and the cytoplasm.
Recently it has been shown that HMGA1 proteins, HMGA1a and HMGA1b, can cross-link DNA fibers ''in vitro'' and can induce chromatin clustering ''in vivo'' suggesting a structural role of HMGA1 proteins in heterochromatin organization.
At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene.
The splice variant HMGA1c with only two AT hooks and no acidic tail is in discussion to be a real member of the HMGA family.
Mice lacking their variant of ''HMGA1'', i.e., ''Hmga1-/-'' mice, are
diabetic
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, show a cardiac hypertrophy and express low levels of the
insulin receptor
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose ho ...
.
Interactions
HMGA1 has been shown to
interact
Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...
with
CEBPB
CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the ''CEBPB'' gene.
Function
The protein encoded by this intronless gene is a bZIP transcription factor that can bind as a homodimer to certain DNA regulatory regi ...
and
Sp1 transcription factor
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.
Function
The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many pro ...
.
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See also
* HMGA
HMGA is a family of high mobility group proteins characterized by an AT-hook. They code for a "small, nonhistone, chromatin-associated protein that has no intrinsic transcriptional activity but can modulate transcription by altering the chromati ...
* AT-hook
The second AT-hook of HMGA1 (black ribbon) bound to the minor-groove of AT-rich DNA. The amino-acid side chains and nucleotides have been hidden.
The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HM ...
References
Further reading
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External links
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{{Transcription factors, g0
Transcription factors