P52926 (HMGA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
High mobility group protein HMGI-C

Alternative name(s):
High mobility group AT-hook protein 2

Gene names

Name:	HMGA2
Synonyms:	HMGIC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	109 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as a transcriptional regulator. Functions in cell cycle regulation through CCNA2. Plays an important role in chromosome condensation during the meiotic G2/M transition of spermatocytes By similarity. Ref.11
Subunit structure	Interacts with E4F1. Interacts with NEK2 By similarity. Ref.11
Subcellular location	Nucleus.
Developmental stage	Expressed predominantly during embryogenesis.
Post-translational modification	Regulated by cell cycle-dependent phosphorylation which alters its DNA binding affinity. Phosphorylated by NEK2 By similarity. Ref.13
Polymorphism	Genetic variations in HMGA2 define the stature quantitative trait locus 9 (STQTL9) [MIM:611547]. Human height is a classic, highly heritable quantitative trait.
Involvement in disease	Note=A chromosomal aberration involving HMGA2 is associated with a subclass of benign mesenchymal tumors known as lipomas. Translocation t(3;12)(q27-q28;q13-q15) with LPP is shown in lipomas. HMGA2 is also fused with a number of other genes in lipomas. Note=A chromosomal aberration involving HMGA2 is associated with pulmonary chondroid hamartomas. Translocation t(3;12)(q27-q28;q14-q15) with LPP is detected in pulmonary chondroid hamartomas. Note=A chromosomal aberration involving HMGA2 is associated with parosteal lipomas. Translocation t(3;12)(q28;q14) with LPP is also shown in one parosteal lipoma. Note=A chromosomal aberration involving HMGA2 is found in uterine leiomyoma. Translocation t(12;14)(q15;q23-24) with RAD51B. Chromosomal rearrangements involving HMGA2 do not seem to be the principle pathobiological mechanism in uterine leiomyoma.
Sequence similarities	Belongs to the HMGA family. Contains 3 A.T hook DNA-binding domains.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA condensation Growth regulation Mitosis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Domain	Repeat
Ligand	DNA-binding
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	DNA damage response, detection of DNA damage Inferred from direct assay. Source: UniProtKB base-excision repair Inferred from direct assay. Source: UniProtKB cell division Inferred from electronic annotation. Source: UniProtKB-KW chondrocyte differentiation Inferred from direct assay. Source: UniProtKB chondrocyte proliferation Inferred from direct assay. Source: UniProtKB chromosome breakage Inferred from direct assay. Source: UniProtKB chromosome condensation Inferred from electronic annotation. Source: UniProtKB-KW endodermal cell differentiation Inferred from mutant phenotype. Source: UniProtKB epithelial to mesenchymal transition Inferred from mutant phenotype. Source: UniProtKB fat cell differentiation Inferred from mutant phenotype. Source: UniProtKB histone H2A-S139 phosphorylation Inferred from direct assay. Source: UniProtKB mesodermal cell differentiation Inferred from mutant phenotype. Source: UniProtKB mesodermal-endodermal cell signaling Inferred from mutant phenotype. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW mitotic cell cycle G2/M transition DNA damage checkpoint Inferred from direct assay. Source: UniProtKB negative regulation by host of viral transcription Inferred from direct assay. Source: UniProtKB negative regulation of DNA binding Inferred from direct assay Ref.11. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay. Source: UniProtKB negative regulation of double-strand break repair via nonhomologous end joining Inferred from direct assay. Source: UniProtKB negative regulation of retroviral genome replication Inferred from direct assay. Source: UniProtKB oncogene-induced senescence Inferred from direct assay. Source: UniProtKB positive regulation of apoptotic process Inferred from direct assay. Source: UniProtKB positive regulation of cell cycle arrest Inferred from direct assay. Source: UniProtKB positive regulation of cellular response to X-ray Inferred from direct assay. Source: UniProtKB positive regulation of cellular senescence Inferred from mutant phenotype. Source: UniProtKB positive regulation of response to DNA damage stimulus Inferred from direct assay. Source: UniProtKB positive regulation of stem cell proliferation Inferred from direct assay. Source: UniProtKB positive regulation of transcription regulatory region DNA binding Inferred from direct assay. Source: UniProtKB regulation of cellular response to drug Inferred from direct assay. Source: UniProtKB regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW regulation of stem cell maintenance Inferred from mutant phenotype. Source: UniProtKB response to virus Inferred from expression pattern. Source: UniProtKB senescence-associated heterochromatin focus assembly Inferred from direct assay. Source: UniProtKB stem cell differentiation Inferred from expression pattern. Source: UniProtKB
Cellular component	SMAD protein complex Inferred from direct assay. Source: UniProtKB nuclear chromosome Inferred from sequence or structural similarity. Source: UniProtKB protein-DNA complex Inferred from direct assay. Source: UniProtKB senescence-associated heterochromatin focus Inferred from direct assay. Source: UniProtKB
Molecular function	5'-deoxyribose-5-phosphate lyase activity Inferred from direct assay. Source: UniProtKB AT DNA binding Inferred from direct assay. Source: UniProtKB C2H2 zinc finger domain binding Inferred from mutant phenotype Ref.11. Source: UniProtKB DNA binding, bending Inferred from direct assay. Source: UniProtKB DNA-(apurinic or apyrimidinic site) lyase activity Inferred from direct assay. Source: UniProtKB DNA-dependent protein kinase activity Inferred from direct assay. Source: UniProtKB MH1 domain binding Inferred from direct assay. Source: UniProtKB MH2 domain binding Inferred from direct assay. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from direct assay. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay. Source: UniProtKB SMAD binding Inferred from physical interaction. Source: UniProtKB cAMP response element binding Inferred from direct assay Ref.11. Source: UniProtKB core promoter binding Inferred from direct assay. Source: UniProtKB nucleosomal DNA binding Inferred from direct assay. Source: UniProtKB transcription factor binding Inferred from physical interaction Ref.11. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRMT6	Q96LA8	2	EBI-912511,EBI-912440

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.6
	Chain	2 – 109	108	High mobility group protein HMGI-C		PRO_0000206711
Regions
	DNA binding	24 – 34	11	A.T hook 1
	DNA binding	44 – 54	11	A.T hook 2
	DNA binding	71 – 82	12	A.T hook 3
	Region	44 – 63	20	Interaction with E4F1
Amino acid modifications
	Modified residue	2	1	N-acetylserine Ref.6
	Modified residue	14	1	Phosphoserine Ref.13
	Modified residue	40	1	Phosphothreonine Ref.13
	Modified residue	44	1	Phosphoserine Ref.13
	Modified residue	105	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P52926 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: F36BABE623DA4615	FASTA	109	11,832
	10 20 30 40 50 60 MSARGEGAGQ PSTSAQGQPA APAPQKRGRG RPRKQQQEPT GEPSPKRPRG RPKGSKNKSP 70 80 90 100 SKAAQKKAEA TGEKRPRGRP RKWPQQVVQK KPAQEETEET SSQESAEED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression and cDNA cloning of human HMGI-C phosphoprotein." Patel U.A., Bandiera A., Manfioletti G., Giancotti V., Chau K.-Y., Crane-Robinson C. Biochem. Biophys. Res. Commun. 201:63-70(1994) [PubMed: 8198613] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hepatoma.
[2]	"Recurrent rearrangements in the high mobility group protein gene, HMGI-C, in benign mesenchymal tumours." Schoenmakers E.F.P.M., Wanschura S., Mols R., Bullerdiek J., van den Berghe H., van de Ven W.J.M. Nat. Genet. 10:436-444(1995) [PubMed: 7670494] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"The gene for the human architectural transcription factor HMGI-C consists of five exons each coding for a distinct functional element." Chau K.-Y., Patel U.A., Lee K.-L.D., Lam H.-Y.P., Crane-Robinson C. Nucleic Acids Res. 23:4262-4266(1995) [PubMed: 7501444] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Genomic characterization of human HMGIC, a member of the accessory transcription factor family found at translocation breakpoints in lipomas." Ashar H.R., Cherath L., Przysybz K., Chada K. Genomics 31:207-214(1996) [PubMed: 8824803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Bienvenut W.V., Fleming J., Leug H.Y. Submitted (JAN-2010) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-27, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Hepatoma.
[7]	"Expression of reciprocal fusion transcripts of the HMGIC and LPP genes in parosteal lipoma." Petit M.M., Swarts S., Bridge J.A., Van de Ven W.J.M. Cancer Genet. Cytogenet. 106:18-23(1998) [PubMed: 9772904] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH LPP.
[8]	"Allelic knockout of novel splice variants of human recombination repair gene RAD51B in t(12;14) uterine leiomyomas." Schoenmakers E.F.P.M., Huysmans C., Van de Ven W.J.M. Cancer Res. 59:19-23(1999) [PubMed: 9892177] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH RAD51B.
[9]	"An identical HMGIC-LPP fusion transcript is consistently expressed in pulmonary chondroid hamartomas with t(3;12)(q27-28;q14-15)." Rogalla P., Lemke I., Kazmierczak B., Bullerdiek J. Genes Chromosomes Cancer 29:363-366(2000) [PubMed: 11066083] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH LPP.
[10]	"Fusion transcripts involving HMGA2 are not a common molecular mechanism in uterine leiomyomata with rearrangements in 12q15." Quade B.J., Weremowicz S., Neskey D.M., Vanni R., Ladd C., Dal Cin P., Morton C.C. Cancer Res. 63:1351-1358(2003) [PubMed: 12649198] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH RAD51B.
[11]	"Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2." Tessari M.A., Gostissa M., Altamura S., Sgarra R., Rustighi A., Salvagno C., Caretti G., Imbriano C., Mantovani R., Del Sal G., Giancotti V., Manfioletti G. Mol. Cell. Biol. 23:9104-9116(2003) [PubMed: 14645522] [Abstract] Cited for: FUNCTION, INTERACTION WITH E4F1.
[12]	"A common variant of HMGA2 is associated with adult and childhood height in the general population." The Diabetes Genetics Initiative, The Wellcome Trust case control consortium Weedon M.N., Lettre G., Freathy R.M., Lindgren C.M., Voight B.F., Perry J.R.B., Elliott K.S., Hackett R., Guiducci C., Shields B., Zeggini E., Lango H., Lyssenko V., Timpson N.J., Burtt N.P., Rayner N.W., Saxena R., Ardlie K. , Tobias J.H., Ness A.R., Ring S.M., Palmer C.N.A., Morris A.D., Peltonen L., Salomaa V., Smith G.D., Groop L.C., Hattersley A.T., McCarthy M.I., Hirschhorn J.N., Frayling T.M. Nat. Genet. 39:1245-1250(2007) [PubMed: 17767157] [Abstract] Cited for: INVOLVEMENT IN STQTL9.
[13]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; THR-40 AND SER-44, MASS SPECTROMETRY. Tissue: Embryonic kidney.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z31595 mRNA. Translation: CAA83472.1. U28749 mRNA. Translation: AAA68613.1. U28754 , U28750, U28751, U28752, U28753 Genomic DNA. Translation: AAA68614.1. L46353, L41044, L44578 Genomic DNA. Translation: AAA96484.1. X92518 mRNA. Translation: CAA63295.1. AC090673 Genomic DNA. No translation available. AC107308 Genomic DNA. No translation available.
IPI	IPI00005996.
PIR	JC2232.
RefSeq	NP_003474.1. NM_003483.4. NP_003475.1. NM_003484.1.
UniGene	Hs.505924.
3D structure databases
ProteinModelPortal	P52926.
ModBase	Search...
Protein-protein interaction databases
IntAct	P52926. 2 interactions.
STRING	P52926.
PTM databases
PhosphoSite	P52926.
Polymorphism databases
DMDM	1708263.
Proteomic databases
PRIDE	P52926.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000403681; ENSP00000384026; ENSG00000149948.
GeneID	8091.
KEGG	hsa:8091.
UCSC	uc001ssx.1. human.
Organism-specific databases
CTD	8091.
GeneCards	GC12P066218.
H-InvDB	HIX0036730.
HGNC	HGNC:5009. HMGA2.
HPA	CAB017809.
MIM	150699. phenotype. 600698. gene. 611547. phenotype.
neXtProt	NX_P52926.
Orphanet	94063. 12q14 microdeletion syndrome.
PharmGKB	PA35093.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG051913.
OMA	QEPVGPP.
OrthoDB	EOG405S2T.
Gene expression databases
ArrayExpress	P52926.
Bgee	P52926.
CleanEx	HS_HMGA2.
Genevestigator	P52926.
Family and domain databases
InterPro	IPR020478. AT_hook-like. IPR017956. AT_hook_DNA-bd_motif. IPR000116. HMGI/HMGY. IPR000637. HMGI/Y_DNA-bd_CS. [Graphical view]
KO	K09283.
Pfam	PF02178. AT_hook. 3 hits. [Graphical view]
PRINTS	PR00929. ATHOOK. PR00930. HIGHMOBLTYIY.
SMART	SM00384. AT_hook. 3 hits. [Graphical view]
PROSITE	PS00354. HMGI_Y. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	30727.
SOURCE	Search...

Entry information

Entry name

HMGA2_HUMAN

Accession

Primary (citable) accession number: P52926

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.