HMGA1

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High mobility group AT-hook 1
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols HMGA1 ; HMG-R; HMGA1A; HMGIY
External IDs OMIM600701 MGI96160 HomoloGene128226 GeneCards: HMGA1 Gene
RNA expression pattern
PBB GE HMGA1 206074 s at tn.png
PBB GE HMGA1 210457 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3159 15361
Ensembl ENSG00000137309 ENSMUSG00000046711
UniProt P17096 P17095
RefSeq (mRNA) NM_002131 NM_001025427
RefSeq (protein) NP_002122 NP_001020598
Location (UCSC) Chr 6:
34.2 – 34.21 Mb
Chr 11:
120.76 – 120.76 Mb
PubMed search [1] [2]

High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.[1][2]

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.[3]

At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene.[4] 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.[5]

Interactions[edit]

HMGA1 has been shown to interact with CEBPB[6] and Sp1 transcription factor.[6]

See also[edit]

References[edit]

  1. ^ Friedmann M, Holth LT, Zoghbi HY, Reeves R (Nov 1993). "Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene". Nucleic Acids Res 21 (18): 4259–67. doi:10.1093/nar/21.18.4259. PMC 310059. PMID 8414980. 
  2. ^ Reeves R, Beckerbauer L (Jun 2001). "HMGI/Y proteins: flexible regulators of transcription and chromatin structure". Biochim Biophys Acta 1519 (1-2): 13–29. doi:10.1016/S0167-4781(01)00215-9. PMID 11406267. 
  3. ^ Vogel, B; Löschberger, A; Sauer, M; Hock, R (Sep 1, 2011). "Cross-linking of DNA through HMGA1 suggests a DNA scaffold.". Nucleic Acids Research 39 (16): 7124–33. doi:10.1093/nar/gkr396. PMC 3167630. PMID 21596776. 
  4. ^ "Entrez Gene: HMGA1 high mobility group AT-hook 1". 
  5. ^ Robert K. Semple (2009). "From bending DNA to diabetes: the curious case of HMGA1". Journal of Biology 8 (7): 64. doi:10.1186/jbiol164. PMC 2736670. PMID 19664187. 
  6. ^ a b Foti, Daniela; Iuliano Rodolfo; Chiefari Eusebio; Brunetti Antonio (Apr 2003). "A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription". Mol. Cell. Biol. (United States) 23 (8): 2720–32. doi:10.1128/MCB.23.8.2720-2732.2003. ISSN 0270-7306. PMC 152545. PMID 12665574. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.