HMGA

{{infobox protein

|Name=high mobility group AT-hook 1

|caption=

|image=

|width=

|HGNCid=5010

|Symbol=HMGA1

|AltSymbols=HMGIY

|EntrezGene=3159

|OMIM=600701

|RefSeq=NM_145901

|UniProt=P17096

|PDB=

|ECnumber=

|Chromosome=6

|Arm=p

|Band=21

|LocusSupplementaryData=

}}

{{infobox protein

|Name=high mobility group AT-hook 2

|caption=

|image=

|width=

|HGNCid=5009

|Symbol=HMGA2

|AltSymbols=HMGIC

|EntrezGene=8091

|OMIM=600698

|RefSeq=NM_003484

|UniProt=P52926

|PDB=

|ECnumber=

|Chromosome=12

|Arm=q

|Band=15

|LocusSupplementaryData=

}}

HMGA is a family of high mobility group proteins characterized by an AT-hook. They code for a "small, nonhistone, chromatin-associated protein that has no intrinsic transcriptional activity but can modulate transcription by altering the chromatin architecture".{{cite journal | vauthors = Mayr C, Hemann MT, Bartel DP | title = Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation | journal = Science | volume = 315 | issue = 5818 | pages = 1576–1579 | date = March 2007 | pmid = 17322030 | pmc = 2556962 | doi = 10.1126/science.1137999 | bibcode = 2007Sci...315.1576M }} Mammals have two orthologs: HMGA1 and HMGA2.

Genomic distribution

In mouse embryonic stem cells it has been demonstrated that both HMGA proteins binds uniformly to the DNA due to their AT-hook domains, with a slight preference for AT-rich regions/{{cite journal | vauthors = Colombo DF, Burger L, Baubec T, Schübeler D | title = Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content | journal = PLOS Genetics | volume = 13 | issue = 12 | pages = e1007102 | date = December 2017 | pmid = 29267285 | pmc = 5756049 | doi = 10.1371/journal.pgen.1007102 | doi-access = free }} Such regions tend to lack coding genes, an observation that argues against a direct role in transcriptional control and in agreement with previous studies, suggest that these proteins have a structural role in the chromatin, similar to histone.

Function

Normally, when cells are subjected to increased DNA damage (such as the formation of 6-O-methylguanine) this causes an increase in apoptosis (programmed cell death). However, cells with diminished activity for either proteins HMGA1 or HMGA2 (or both together) are more tolerant of such DNA damage than cells in which these proteins are not diminished.{{cite journal | vauthors = Fujikane R, Komori K, Sekiguchi M, Hidaka M | title = Function of high-mobility group A proteins in the DNA damage signaling for the induction of apoptosis | journal = Scientific Reports | volume = 6 | issue = | pages = 31714 | date = August 2016 | pmid = 27538817 | pmc = 4990841 | doi = 10.1038/srep31714 | bibcode = 2016NatSR...631714F }} Thus a normal function of the HMGA1 and HMGA2 proteins appears to be to signal the presence of DNA damage leading to induction of apoptosis.

Association with human traits

Variations in HMGA2 to have a moderate association with adult height.{{cite news |url=http://news.bbc.co.uk/1/hi/health/6975865.stm |title= Scientists discover height gene |access-date=2007-09-03 |work= BBC News| date=2007-09-03}}{{cite journal | vauthors = Weedon MN, Lettre G, Freathy RM, Lindgren CM, Voight BF, Perry JR, Elliott KS, Hackett R, Guiducci C, Shields B, Zeggini E, Lango H, Lyssenko V, Timpson NJ, Burtt NP, Rayner NW, Saxena R, Ardlie K, Tobias JH, Ness AR, Ring SM, Palmer CN, Morris AD, Peltonen L, Salomaa V, Davey Smith G, Groop LC, Hattersley AT, McCarthy MI, Hirschhorn JN, Frayling TM | display-authors = 6 | title = A common variant of HMGA2 is associated with adult and childhood height in the general population | journal = Nature Genetics | volume = 39 | issue = 10 | pages = 1245–1250 | date = October 2007 | pmid = 17767157 | pmc = 3086278 | doi = 10.1038/ng2121 | author26-link = George Davey Smith }}

References

External links

{{MeshName|HMGA+Proteins}}

Category:Transcription factors