HMGA1

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

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; OMA:HMGA1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human) Band 6p21.31 Start 34,236,873 bp End 34,246,231 bp
Gene location (Mouse) Chr. Chromosome 17 (mouse) Band 17 A3.3|17 14.5 cM Start 27,775,471 bp End 27,782,648 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue embryo mucosa of pharynx ganglionic eminence skin of abdomen thymus mucosa of transverse colon skin of leg nipple appendix Top expressed in epiblast tail of embryo yolk sac genital tubercle embryo embryo secondary oocyte zygote lip ventricular zone 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
Wikidata
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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.

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, show a cardiac hypertrophy and express low levels of the insulin receptor.

Interactions

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

See also

• HMGA
• AT-hook

Further reading

• Hui H, Perfetti R (Feb 2002). "Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood". European Journal of Endocrinology. 146 (2): 129–41. doi:10.1530/eje.0.1460129. PMID 11834421.
• Van Maele B, Debyser Z (2005). "HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins". AIDS Reviews. 7 (1): 26–43. PMID 15875659.
• Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z (Feb 2006). "Cellular co-factors of HIV-1 integration". Trends in Biochemical Sciences. 31 (2): 98–105. doi:10.1016/j.tibs.2005.12.002. PMID 16403635.
• Reeves R, Nissen MS (May 1990). "The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure". The Journal of Biological Chemistry. 265 (15): 8573–82. doi:10.1016/S0021-9258(19)38926-4. PMID 1692833.
• Nissen MS, Langan TA, Reeves R (Oct 1991). "Phosphorylation by cdc2 kinase modulates DNA binding activity of high mobility group I nonhistone chromatin protein". The Journal of Biological Chemistry. 266 (30): 19945–52. doi:10.1016/S0021-9258(18)54874-2. PMID 1939057.
• Eckner R, Birnstiel ML (Aug 1989). "Cloning of cDNAs coding for human HMG I and HMG Y proteins: both are capable of binding to the octamer sequence motif". Nucleic Acids Research. 17 (15): 8637–59. doi:10.1093/nar/17.15.8637. PMC 318252. PMID 2505228.
• Johnson KR, Lehn DA, Reeves R (May 1989). "Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y". Molecular and Cellular Biology. 9 (5): 2114–23. doi:10.1128/mcb.9.5.2114. PMC 363005. PMID 2701943.
• Palvimo J, Linnala-Kankkunen A (Oct 1989). "Identification of sites on chromosomal protein HMG-I phosphorylated by casein kinase II". FEBS Letters. 257 (1): 101–4. Bibcode:1989FEBSL.257..101P. doi:10.1016/0014-5793(89)81796-X. PMID 2806554. S2CID 7960951.
• Karlson JR, Mørk E, Holtlund J, Laland SG, Lund T (Feb 1989). "The amino acid sequence of the chromosomal protein HMG-Y, its relation to HMG-I and possible domains for the preferential binding of the proteins to stretches of A-T base pairs". Biochemical and Biophysical Research Communications. 158 (3): 646–51. doi:10.1016/0006-291X(89)92770-8. PMID 2920035.
• Lund T, Dahl KH, Mørk E, Holtlund J, Laland SG (Jul 1987). "The human chromosomal protein HMG I contains two identical palindrome amino acid sequences". Biochemical and Biophysical Research Communications. 146 (2): 725–30. doi:10.1016/0006-291X(87)90589-4. PMID 3619901.
• Leger H, Sock E, Renner K, Grummt F, Wegner M (Jul 1995). "Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y". Molecular and Cellular Biology. 15 (7): 3738–47. doi:10.1128/mcb.15.7.3738. PMC 230612. PMID 7791781.
• John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ (Mar 1995). "Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins". Molecular and Cellular Biology. 15 (3): 1786–96. doi:10.1128/mcb.15.3.1786. PMC 230403. PMID 7862168.
• Farnet CM, Bushman FD (Feb 1997). "HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro". Cell. 88 (4): 483–92. doi:10.1016/S0092-8674(00)81888-7. PMID 9038339. S2CID 14476092.
• Miller MD, Farnet CM, Bushman FD (Jul 1997). "Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition". Journal of Virology. 71 (7): 5382–90. doi:10.1128/JVI.71.7.5382-5390.1997. PMC 191777. PMID 9188609.
• Huth JR, Bewley CA, Nissen MS, Evans JN, Reeves R, Gronenborn AM, Clore GM (Aug 1997). "The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif". Nature Structural Biology. 4 (8): 657–65. doi:10.1038/nsb0897-657. PMID 9253416. S2CID 2183841.
• Currie RA (Dec 1997). "Functional interaction between the DNA binding subunit trimerization domain of NF-Y and the high mobility group protein HMG-I(Y)". The Journal of Biological Chemistry. 272 (49): 30880–8. doi:10.1074/jbc.272.49.30880. PMID 9388234.
• Chin MT, Pellacani A, Wang H, Lin SS, Jain MK, Perrella MA, Lee ME (Apr 1998). "Enhancement of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y)". The Journal of Biological Chemistry. 273 (16): 9755–60. doi:10.1074/jbc.273.16.9755. PMID 9545312.
• Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martinez-Tello FJ, Pentimalli F, de Nigris F, Mastro A, Botti G, Fedele M, Berger N, Santoro M, Giancotti V, Fusco A (Sep 1998). "Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma". Cancer Research. 58 (18): 4193–8. PMID 9751634.
• Vogel B, Löschberger A, Sauer M, Hock R (Sep 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.

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.