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	OMIM: 600701 MGI: 96160 HomoloGene: 128226 GeneCards: HMGA1
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.31 Start 34,236,873 bp[1] End 34,246,231 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 A3.3|17 14.5 cM Start 27,775,471 bp[2] End 27,782,648 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in embryo ganglionic eminence skin of abdomen thymus nipple appendix human penis gastrocnemius muscle lymph node stromal cell of endometrium Top expressed in yolk sac secondary oocyte lip thymus epidermis lens neural tube mesencephalon intestine ganglionic eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function retinoid X receptor binding retinoic acid receptor binding enzyme binding peroxisome proliferator activated receptor binding DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific nuclear receptor coactivator activity protein binding chromatin binding DNA-binding transcription factor activity 5'-deoxyribose-5-phosphate lyase activity transcription factor binding DNA-(apurinic or apyrimidinic site) endonuclease activity cis-regulatory region sequence-specific DNA binding minor groove of adenine-thymine-rich DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription coactivator activity structural constituent of chromatin Cellular component nucleus nucleoplasm cytosol senescence-associated heterochromatin focus chromosome focal adhesion transcription regulator complex chromatin RNA polymerase II transcription regulator complex Biological process negative regulation of cell population proliferation oncogene-induced cell senescence establishment of integrated proviral latency nucleosome disassembly regulation of transcription, DNA-templated positive regulation of transcription, DNA-templated positive regulation of transcription by RNA polymerase II positive regulation of cellular senescence negative regulation of transcription, DNA-templated response to virus DNA unwinding involved in DNA replication transcription, DNA-templated transcription by RNA polymerase II nuclear transport viral process base-excision repair protein-containing complex assembly Sources:Amigo / QuickGO
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_001306006 NP_001306007 NP_001306008 NP_001306009 NP_001306010 NP_001306011 NP_002122 NP_665906 NP_665908 NP_665909 NP_665910 NP_665912 NP_001159948 NP_001159949 NP_001020598 NP_001034445 NP_001160007 NP_001160008 NP_001160009 NP_001160011 NP_001160012 NP_001160013 NP_001160014 NP_001160015 NP_001160016 NP_001160017 NP_001160018 NP_057869 Location (UCSC) Chr 6: 34.24 – 34.25 Mb Chr 17: 27.78 – 27.78 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.^[5][6]

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.^[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]

Interactions

HMGA1 has been shown to interact with CEBPB^[10] and Sp1 transcription factor.^[10]

See also

• HMGA
• AT-hook

References

Further reading

External links

• HMGA1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Overview of all the structural information available in the PDB for UniProt: P17096 (High mobility group protein HMG-I/HMG-Y) at the PDBe-KB.

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