| 释义 |
- Function
- Interactions
- See also
- References
- Further reading
- External links
{{Infobox_gene}}High-mobility group protein HMG-I/HMG-Y is a protein that in humans is encoded by the HMGA1 gene.[1][2] 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.[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 HMGA1 has been shown to interact with CEBPB[6] and Sp1 transcription factor.[6] See also References 1. ^{{cite journal | vauthors = Friedmann M, Holth LT, Zoghbi HY, Reeves R | title = Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene | journal = Nucleic Acids Research | volume = 21 | issue = 18 | pages = 4259–67 | date = Sep 1993 | pmid = 8414980 | pmc = 310059 | doi = 10.1093/nar/21.18.4259 }}
2. ^{{cite journal | vauthors = Reeves R, Beckerbauer L | title = HMGI/Y proteins: flexible regulators of transcription and chromatin structure | journal = Biochimica et Biophysica Acta | volume = 1519 | issue = 1-2 | pages = 13–29 | date = May 2001 | pmid = 11406267 | pmc = | doi = 10.1016/S0167-4781(01)00215-9 }}
3. ^{{cite journal | vauthors = Vogel B, Löschberger A, Sauer M, Hock R | title = Cross-linking of DNA through HMGA1 suggests a DNA scaffold | journal = Nucleic Acids Research | volume = 39 | issue = 16 | pages = 7124–33 | date = Sep 2011 | pmid = 21596776 | pmc = 3167630 | doi = 10.1093/nar/gkr396 }}
4. ^{{cite web | title = Entrez Gene: HMGA1 high mobility group AT-hook 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3159| accessdate = }}
5. ^{{cite journal | vauthors = Semple RK | title = From bending DNA to diabetes: the curious case of HMGA1 | journal = Journal of Biology | volume = 8 | issue = 7 | pages = 64 | year = 2009 | pmid = 19664187 | pmc = 2736670 | doi = 10.1186/jbiol164 | url = http://jbiol.com/content/8/7/64 }}
6. ^1 {{cite journal | vauthors = Foti D, Iuliano R, Chiefari E, Brunetti A | title = A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription | journal = Molecular and Cellular Biology | volume = 23 | issue = 8 | pages = 2720–32 | date = Apr 2003 | pmid = 12665574 | pmc = 152545 | doi = 10.1128/MCB.23.8.2720-2732.2003 }}
Further reading {{refbegin|33em}}- {{cite journal | vauthors = Hui H, Perfetti R | title = Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood | journal = European Journal of Endocrinology / European Federation of Endocrine Societies | volume = 146 | issue = 2 | pages = 129–41 | date = Feb 2002 | pmid = 11834421 | doi = 10.1530/eje.0.1460129 }}
- {{cite journal | vauthors = Van Maele B, Debyser Z | title = HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins | journal = AIDS Reviews | volume = 7 | issue = 1 | pages = 26–43 | year = 2005 | pmid = 15875659 | doi = }}
- {{cite journal | vauthors = Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z | title = Cellular co-factors of HIV-1 integration | journal = Trends in Biochemical Sciences | volume = 31 | issue = 2 | pages = 98–105 | date = Feb 2006 | pmid = 16403635 | doi = 10.1016/j.tibs.2005.12.002 }}
- {{cite journal | vauthors = Reeves R, Nissen MS | title = The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure | journal = The Journal of Biological Chemistry | volume = 265 | issue = 15 | pages = 8573–82 | date = May 1990 | pmid = 1692833 | doi = }}
- {{cite journal | vauthors = Nissen MS, Langan TA, Reeves R | title = Phosphorylation by cdc2 kinase modulates DNA binding activity of high mobility group I nonhistone chromatin protein | journal = The Journal of Biological Chemistry | volume = 266 | issue = 30 | pages = 19945–52 | date = Oct 1991 | pmid = 1939057 | doi = }}
- {{cite journal | vauthors = Eckner R, Birnstiel ML | title = Cloning of cDNAs coding for human HMG I and HMG Y proteins: both are capable of binding to the octamer sequence motif | journal = Nucleic Acids Research | volume = 17 | issue = 15 | pages = 5947–59 | date = Aug 1989 | pmid = 2505228 | pmc = 318252 | doi = 10.1093/nar/17.15.5947 }}
- {{cite journal | vauthors = Johnson KR, Lehn DA, Reeves R | title = Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y | journal = Molecular and Cellular Biology | volume = 9 | issue = 5 | pages = 2114–23 | date = May 1989 | pmid = 2701943 | pmc = 363005 | doi = 10.1128/mcb.9.5.2114}}
- {{cite journal | vauthors = Palvimo J, Linnala-Kankkunen A | title = Identification of sites on chromosomal protein HMG-I phosphorylated by casein kinase II | journal = FEBS Letters | volume = 257 | issue = 1 | pages = 101–4 | date = Oct 1989 | pmid = 2806554 | doi = 10.1016/0014-5793(89)81796-X }}
- {{cite journal | vauthors = Karlson JR, Mørk E, Holtlund J, Laland SG, Lund T | title = 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 | journal = Biochemical and Biophysical Research Communications | volume = 158 | issue = 3 | pages = 646–51 | date = Feb 1989 | pmid = 2920035 | doi = 10.1016/0006-291X(89)92770-8 }}
- {{cite journal | vauthors = Lund T, Dahl KH, Mørk E, Holtlund J, Laland SG | title = The human chromosomal protein HMG I contains two identical palindrome amino acid sequences | journal = Biochemical and Biophysical Research Communications | volume = 146 | issue = 2 | pages = 725–30 | date = Jul 1987 | pmid = 3619901 | doi = 10.1016/0006-291X(87)90589-4 }}
- {{cite journal | vauthors = Leger H, Sock E, Renner K, Grummt F, Wegner M | title = Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y | journal = Molecular and Cellular Biology | volume = 15 | issue = 7 | pages = 3738–47 | date = Jul 1995 | pmid = 7791781 | pmc = 230612 | doi = 10.1128/mcb.15.7.3738}}
- {{cite journal | vauthors = John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ | title = 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 | journal = Molecular and Cellular Biology | volume = 15 | issue = 3 | pages = 1786–96 | date = Mar 1995 | pmid = 7862168 | pmc = 230403 | doi = 10.1128/mcb.15.3.1786}}
- {{cite journal | vauthors = Farnet CM, Bushman FD | title = HIV-1 cDNA integration: requirement of HMG I(Y) protein for function of preintegration complexes in vitro | journal = Cell | volume = 88 | issue = 4 | pages = 483–92 | date = Feb 1997 | pmid = 9038339 | doi = 10.1016/S0092-8674(00)81888-7 }}
- {{cite journal | vauthors = Miller MD, Farnet CM, Bushman FD | title = Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition | journal = Journal of Virology | volume = 71 | issue = 7 | pages = 5382–90 | date = Jul 1997 | pmid = 9188609 | pmc = 191777 | doi = }}
- {{cite journal | vauthors = Huth JR, Bewley CA, Nissen MS, Evans JN, Reeves R, Gronenborn AM, Clore GM | title = The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif | journal = Nature Structural Biology | volume = 4 | issue = 8 | pages = 657–65 | date = Aug 1997 | pmid = 9253416 | doi = 10.1038/nsb0897-657 }}
- {{cite journal | vauthors = Currie RA | title = Functional interaction between the DNA binding subunit trimerization domain of NF-Y and the high mobility group protein HMG-I(Y) | journal = The Journal of Biological Chemistry | volume = 272 | issue = 49 | pages = 30880–8 | date = Dec 1997 | pmid = 9388234 | doi = 10.1074/jbc.272.49.30880 }}
- {{cite journal | vauthors = Chin MT, Pellacani A, Wang H, Lin SS, Jain MK, Perrella MA, Lee ME | title = Enhancement of serum-response factor-dependent transcription and DNA binding by the architectural transcription factor HMG-I(Y) | journal = The Journal of Biological Chemistry | volume = 273 | issue = 16 | pages = 9755–60 | date = Apr 1998 | pmid = 9545312 | doi = 10.1074/jbc.273.16.9755 }}
- {{cite journal | vauthors = 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 | title = 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 | journal = Cancer Research | volume = 58 | issue = 18 | pages = 4193–8 | date = Sep 1998 | pmid = 9751634 | doi = }}
- {{cite journal | vauthors = Vogel B, Löschberger A, Sauer M, Hock R | title = Cross-linking of DNA through HMGA1 suggests a DNA scaffold | journal = Nucleic Acids Research | volume = 39 | issue = 16 | pages = 7124–33 | date = Sep 2011 | pmid = 21596776 | pmc = 3167630 | doi = 10.1093/nar/gkr396 }}
{{refend}} External links - {{MeshName|HMGA1+protein,+human}}
{{NLM content}}{{Transcription factors|g0}} 1 : Transcription factors |