High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene. [5] [6]
High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene. [5] [6]
This gene encodes a non-histone chromatin protein involved in many cellular processes, including regulation of inducible gene transcription, DNA replication, heterochromatin 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-hooks with the RGRP (Arg-Gly-Arg-Pro) core motif, a novel cross-linking domain located between the second and third AT-hook, and a C-terminal 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 modifications 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 modifications 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. [7]
At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene. [8] 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, show a cardiac hypertrophy and express low levels of the insulin receptor. [9]
HMGA1 has been shown to interact with CEBPB [10] and Sp1 transcription factor. [10]
DNA-binding proteins are proteins that have DNA-binding domains and thus have a specific or general affinity for single- or double-stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that identify a base pair.
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High-Mobility Group or HMG is a group of chromosomal proteins that are involved in the regulation of DNA-dependent processes such as transcription, replication, recombination, and DNA repair.
Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene. The protein encoded by MBD1 binds to methylated sequences in DNA, and thereby influences transcription. It binds to a variety of methylated sequences, and appears to mediate repression of gene expression. It has been shown to play a role in chromatin modification through interaction with the histone H3K9 methyltransferase SETDB1. H3K9me3 is a repressive modification.
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 chromatin architecture". Mammals have two orthologs: HMGA1 and HMGA2.
High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the HMGA2 gene.
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AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ARID1A gene.
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Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.
Non-histone chromosomal protein HMG-17 is a protein that in humans is encoded by the HMGN2 gene.
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Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.
Chromobox protein homolog 5 is a protein that in humans is encoded by the CBX5 gene. It is a highly conserved, non-histone protein part of the heterochromatin family. The protein itself is more commonly called HP1α. Heterochromatin protein-1 (HP1) has an N-terminal domain that acts on methylated lysines residues leading to epigenetic repression. The C-terminal of this protein has a chromo shadow-domain (CSD) that is responsible for homodimerizing, as well as interacting with a variety of chromatin-associated, non-histone proteins.
The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG) proteins, DNA-binding proteins from plants and hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodeling complex.
H2A histone family, member B3 is a protein that in humans is encoded by the H2AFB3 gene.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.