HMGA1

HMGA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EZD, 2EZE, 2EZF, 2EZG
Identifiers
Aliases	HMGA1, HMG-R, HMGA1A, HMGIY, high mobility group AT-hook 1
External IDs	MGI: 96160 HomoloGene: 128226 GeneCards: HMGA1
Gene ontology Molecular function • retinoid X receptor binding • retinoic acid receptor binding • enzyme binding • peroxisome proliferator activated receptor binding • DNA binding • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding • ligand-dependent nuclear receptor transcription coactivator activity • protein binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • 5'-deoxyribose-5-phosphate lyase activity • DNA-(apurinic or apyrimidinic site) lyase activity • AT DNA binding • transcription factor binding Cellular component • nucleus • nucleoplasm • cytosol • senescence-associated heterochromatin focus • chromosome • focal adhesion • transcription factor complex • chromatin • RNA polymerase II transcription factor complex Biological process • negative regulation of cell proliferation • oncogene-induced cell senescence • base-excision repair • establishment of integrated proviral latency • nucleosome disassembly • regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • positive regulation of cellular senescence • senescence-associated heterochromatin focus assembly • negative regulation of transcription, DNA-templated • response to virus • negative regulation of chromatin silencing • DNA unwinding involved in DNA replication • transcription, DNA-templated • protein complex assembly • transcription from RNA polymerase II promoter • nuclear transport • viral process Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3159	15361
Ensembl	ENSG00000137309	ENSMUSG00000046711
UniProt	P17096	P17095
RefSeq (mRNA)	NM_002131 NM_145899 NM_145901 NM_145902 NM_145903 NM_145904 NM_145905 NM_001319077 NM_001319078 NM_001319079 NM_001319080 NM_001319081 NM_001319082	NM_001025427 NM_001039356 NM_001166535 NM_001166536 NM_001166537 NM_001166539 NM_001166540 NM_001166541 NM_001166542 NM_001166543 NM_001166544 NM_001166545 NM_001166546 NM_016660
RefSeq (protein)	NP_002122.1 NP_665906.1 NP_665908.1 NP_665909.1 NP_665910.1 NP_665912.1 NP_001306006.1 NP_001306007.1 NP_001306008.1 NP_001306009.1 NP_001306010.1 NP_001306011.1	NP_001020598.1 NP_001034445.1 NP_001159948.1 NP_001159949.1 NP_001160007.1 NP_001160008.1 NP_001160009.1 NP_001160011.1 NP_001160012.1 NP_001160013.1 NP_001160014.1 NP_057869.2
Location (UCSC)	Chr 6: 34.24 – 34.25 Mb	Chr 17: 27.56 – 27.56 Mb
PubMed search	[1]	[2]
Wikidata

High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.^[3][4]

Function

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.^[5]

At least seven transcript variants encoding two different isoforms (HMGA1a, HMGA1b) have been found for this gene.^[6] 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.^[7]

Interactions

HMGA1 has been shown to interact with CEBPB^[8] and Sp1 transcription factor.^[8]

See also

• HMGA
• AT-hook

References

Further reading

External links

• HMGA1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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