HMGIY (High mobility group protein (non histone chromosomal) isoform I and Y)

Identity

Other names	HMG-I(Y), HMGI/Y
HGNC	HMGA1
Location	6p21.3
Location_base_pair	Starts at 34312628 and ends at 34321986 bp from pter (hg18-Mar_2006).
Local_order	centromeric to HLA-A, telomeric to D6S19

DNA/RNA

Description	10 144 bp; 8 exons, 7 introns
Transcription	HMGI and HMGY are encoded by the same gene and are generated trough alternative splicing; exons 1-4 are not transcribed, exons 5-7 encode three DNA binding domains; exon 5 contains a 33 bp segment subject to alternative splicing; exon 8 encodes the acidic carboxy-terminal end; RNA length: 1.85 kb.

Protein

Description	107 amino acids; three DNA binding domains (AT hooks)
Expression	expressed in embryonal cells; expressed in a variety of normal human adult tissues such as heart, brain, lung, skeletal muscle, kidney, pancreas, spleen, thymus, testis, ovary, small intestine, submandibular gland and leukocytes; expressed in transformed cells with a malignant phenotype and in human malignant tumors such as prostate, thyroid carcinoma and colorectal carcinomas and a subset of benign lipomas.
Localisation	nuclear
Function	architectural transcription, non histone, factor that binds to the minor groove of AT-rich DNA; alters DNA conformation by introducing bends and supercoils; HMGIY was shown to be an essential component of enhanceosome (higher order transcription enhancer complex); positive induction of several genes including IFN-b, E-selectin, interleukin-2 receptor a-chain, the chemokine MGSA/GRO, and the class II major histocompatibility complex gene HLA-DRA; negative regulation by binding the promoter regions of interleukin-4 and GP91-PHOX. the precise function remains to be elucidated; probable role in regulation of chromatin structure and gene expression, and transcriptional regulation; potential oncogenic role
Homology	member of the HMGI protein family, structural (but not expression pattern) homology with HMGIC

Mutations

Somatic

HMGIY is found involved in chromosome rearrangements in benign tumours, mainly mesenchymal tumors

Implicated in

Entity	Pulmonary chondroid hamartoma
Disease	benign tumor of the lung
Prognosis	good
Cytogenetics	the most frequent rearrangement is a reciprocal balanced translocation t(6;14) (p21.3; q24); the rearrangement between chromosomes 6 and 14 can sometimes be complex, identifiable by FISH; molecular results also suggest that the translocations might be more complex than shown by conventional cytogenetics, with the presence of additional cryptic rearrangements; translocations involving partner chromosomes other than chromosome 14, such as chromosomes 1, 3, 4, 5, 10, 12, 17 have also been reported; inversions inv(6)(p21q21) or inv(6)(p21.3q26) have been described
Hybrid/Mutated Gene	in most cases, the breakpoint was extragenic, located within a 80 kb region 3' of HMGIY; aberrant transcripts with truncation of sequences from the 3' UTR have been described; in only one case with inversion inv(6)(p21q21), a hybrid intragenic fusion has been reported: HMGIY was fused to the LAMA4 (laminin a4 chain) gene
Abnormal Protein	the HMGIY-LAMA4 resulted from the fusion of the three HMGIY DNA-binding domains with the LAMA4 EGF-like domain
Oncogenesis	the exact role of HMGI(Y)-LAMA4 fusion is not established yet
Entity	Lipomas
Disease	benign adipocyte tumors
Prognosis	good
Cytogenetics	a small subset (5-8%) of ordinary lipomas is characterized by 6p21 rearrangements, the most frequent of which being a reciprocal translocation t(3;6)(q28;p21); in contrast to other benign mesenchymal tumors with 6p21 rearrangement, there is no evidence of HMGIY rearrangements in ordinary lipomas yet; however, to be noticed, the breakpoint on 6p21 was shown to be located whithin a 80 kb region surrounding HMGIY in one lipoma case and HMGIY expression was correlated with 6p rearrangements in two ordinary lipomas and two spindle cell lipomas
Entity	Uterine leiomyoma
Disease	benign mesenchymal tumors
Prognosis	good
Cytogenetics	approximately 40% of uterine leiomyomas present structural chromosomal rearrangements, 5% of which involve 6p abnormalities; they include t(1;6)(q23;p21), t(6;14)(p21;q24) and t(6;10)(p21;q22) as well as inversions and translocations involving other chromosomal partners; the rearrangements are sometimes complex, only identifiable by FISH analysis
Hybrid/Mutated Gene	no hybrid gene has been described yet; as for other mesenchymal tumors, the breakpoint was extragenic, located within a 80 kb region 3' of HMGIY; one case of aberrant transcript with truncation of 1295 bp from the 3' UTR has been described
Abnormal Protein	HMGIY mRNA and protein levels do not always correlate, suggesting that post-transcriptional mechanisms are involved in the regulation of HMGIY
Entity	Endometrial polyps
Disease	uterine benign tumors
Prognosis	good
Cytogenetics	several chromosomal abnormalities involving the 6p21.3 region, including translocations, deletions, inversions have been described; various chromosomal partner regions, such as 14q24, 20q13, 2q35, 10q22, 8q12, 1p32, 7p15, 15q21, have been described to be associated with 6p21.3 in reciprocal translocations.
Hybrid/Mutated Gene	no hybrid gene has been described yet; as for other mesenchymal tumors, the breakpoint is extragenic, located within a 80 kb region 3' of HMGIY
Entity	Hamartoma of the breast
Disease	benign tumor-like nodule of the breast, also called adenolipoma
Prognosis	good
Cytogenetics	one case with a t(1 ;6)(p21 ;21), involving the HMGIY gene has been described
Entity	Microfollicular adenoma of the thyroid
Disease	epithelial tumors
Prognosis	favorable
Cytogenetics	one case with a t(1;6)(p35;21) correlated with an overexpression of HMGIY has been described

External links

	Nomenclature
HGNC	HMGA1   5010
Entrez_Gene	HMGA1  3159  high mobility group AT-hook 1
	Cards
Atlas	HMGIYID221
GeneCards	HMGA1
Ensembl	HMGA1 [Search_View]   ENSG00000137309 [Gene_View]
Genatlas	HMGA1
GeneLynx	HMGA1
eGenome	HMGA1
euGene	3159
	Genomic and cartography
GoldenPath	HMGA1  -  6p21.3   chr6:34312628-34321986 +  6p21   [Description]    (hg18-Mar_2006)
Ensembl	HMGA1 - 6p21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	HMGA1
	Gene and transcription
Genbank	AF176039 [ ENTREZ ]
Genbank	AK096863 [ ENTREZ ]
Genbank	AK130027 [ ENTREZ ]
Genbank	AK308245 [ ENTREZ ]
Genbank	BC004924 [ ENTREZ ]
RefSeq	NM_002131 [ SRS ]    NM_002131 [ ENTREZ ]
RefSeq	NM_145899 [ SRS ]    NM_145899 [ ENTREZ ]
RefSeq	NM_145901 [ SRS ]    NM_145901 [ ENTREZ ]
RefSeq	NM_145902 [ SRS ]    NM_145902 [ ENTREZ ]
RefSeq	NM_145903 [ SRS ]    NM_145903 [ ENTREZ ]
RefSeq	NM_145904 [ SRS ]    NM_145904 [ ENTREZ ]
RefSeq	NM_145905 [ SRS ]    NM_145905 [ ENTREZ ]
RefSeq	AC_000049 [ SRS ]    AC_000049 [ ENTREZ ]
RefSeq	AC_000138 [ SRS ]    AC_000138 [ ENTREZ ]
RefSeq	NC_000006 [ SRS ]    NC_000006 [ ENTREZ ]
RefSeq	NT_007592 [ SRS ]    NT_007592 [ ENTREZ ]
RefSeq	NW_001838980 [ SRS ]    NW_001838980 [ ENTREZ ]
RefSeq	NW_923073 [ SRS ]    NW_923073 [ ENTREZ ]
AceView	HMGA1 AceView - NCBI
Unigene	Hs.703764 [ SRS ]    Hs.703764 [ NCBI ]     HS703764 [ spliceNest ]
Fast-db	8121 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P17096 [ SRS]    P17096 [ EXPASY ]     P17096 [ INTERPRO ]     P17096 [ UNIPROT ]
Prosite	PS00354 HMGI_Y [ SRS ]    PS00354 HMGI_Y [ Expasy ]
Interpro	IPR000637 AT_hook_DNA_bd [ SRS ]    IPR000637 AT_hook_DNA_bd [ EBI ]
Interpro	IPR000116 Highmoblty_IY [ SRS ]    IPR000116 Highmoblty_IY [ EBI ]
CluSTr	P17096
Pfam	PF02178 AT_hook [ SRS ]    PF02178 AT_hook [ Sanger ]    pfam02178 [ NCBI-CDD ]
Smart	SM00384 AT_hook [EMBL]
Prodom	PD005593 Highmoblty_IY[INRA-Toulouse]
Prodom	P17096 HMGA1_HUMAN [ Domain structure ]   P17096 HMGA1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P17096
PDB	2EZD [ SRS ]    2EZD [ PdbSum ],   2EZD [ IMB ]   2EZD [ RSDB ]
PDB	2EZE [ SRS ]    2EZE [ PdbSum ],   2EZE [ IMB ]   2EZE [ RSDB ]
PDB	2EZF [ SRS ]    2EZF [ PdbSum ],   2EZF [ IMB ]   2EZF [ RSDB ]
PDB	2EZG [ SRS ]    2EZG [ PdbSum ],   2EZG [ IMB ]   2EZG [ RSDB ]
HPRD	02829
	Protein Interaction databases
DIP	P17096
IntAct	P17096
	Polymorphism : SNP, mutations, diseases
OMIM	600701    [ map ]
GENECLINICS	600701
SNP	HMGA1 [dbSNP-NCBI]
SNP	NM_002131 [SNP-NCI]
SNP	NM_145899 [SNP-NCI]
SNP	NM_145901 [SNP-NCI]
SNP	NM_145902 [SNP-NCI]
SNP	NM_145903 [SNP-NCI]
SNP	NM_145904 [SNP-NCI]
SNP	NM_145905 [SNP-NCI]
SNP	HMGA1 [GeneSNPs - Utah]  HMGA1] [HGBASE - SRS]
HAPMAP	HMGA1 [HAPMAP]
COSMIC	HMGA1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	HMGA1 [Translocation breakpoints In Cancer]
HGMD	HMGA1
	General knowledge
Family Browser	HMGA1 [UCSC Family Browser]
SOURCE	NM_002131
SOURCE	NM_145899
SOURCE	NM_145901
SOURCE	NM_145902
SOURCE	NM_145903
SOURCE	NM_145904
SOURCE	NM_145905
SMD	Hs.703764
SAGE	Hs.703764
GO	chromatin [Amigo]  chromatin
GO	DNA binding [Amigo]  DNA binding
GO	AT DNA binding [Amigo]  AT DNA binding
GO	transcription factor activity [Amigo]  transcription factor activity
GO	nucleus [Amigo]  nucleus
GO	transcription factor complex [Amigo]  transcription factor complex
GO	chromosome [Amigo]  chromosome
GO	cytosol [Amigo]  cytosol
GO	DNA unwinding during replication [Amigo]  DNA unwinding during replication
GO	nucleosome disassembly [Amigo]  nucleosome disassembly
GO	loss of chromatin silencing [Amigo]  loss of chromatin silencing
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	protein complex assembly [Amigo]  protein complex assembly
GO	transmembrane receptor protein tyrosine kinase signaling pathway [Amigo]  transmembrane receptor protein tyrosine kinase signaling pathway
GO	provirus integration [Amigo]  provirus integration
GO	initiation of viral infection [Amigo]  initiation of viral infection
GO	ligand-dependent nuclear receptor transcription coactivator activity [Amigo]  ligand-dependent nuclear receptor transcription coactivator activity
GO	peroxisome proliferator activated receptor binding [Amigo]  peroxisome proliferator activated receptor binding
GO	interspecies interaction between organisms [Amigo]  interspecies interaction between organisms
GO	positive regulation of transcription [Amigo]  positive regulation of transcription
GO	retinoid X receptor binding [Amigo]  retinoid X receptor binding
PubGene	HMGA1
TreeFam	HMGA1
CTD	3159 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	HMGA1 Related clones (RZPD - Berlin)
	PubMed
PubMed	86 Pubmed reference(s) in Entrez

Bibliography

Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene.

Friedmann M, Holth LT, Zoghbi HY, Reeves R

Nucleic acids research. 1993 ; 21 (18) : 4259-4267.

PMID 8414980

High level expression of the HMGI (Y) gene during embryonic development.

Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, Trapasso F, Merciai BM, Fidanza V, Giancotti V, Santoro M, Simeone A, Fusco A

Oncogene. 1996 ; 13 (11) : 2439-2446.

PMID 8957086

Misexpression of disrupted HMGI architectural factors activates alternative pathways of tumorigenesis.

Tkachenko A, Ashar HR, Meloni AM, Sandberg AA, Chada KK

Cancer research. 1997 ; 57 (11) : 2276-2280.

PMID 9187132

Hamartoma of the breast with involvement of 6p21 and rearrangement of HMGIY.

Dal Cin P, Wanschura S, Christiaens MR, Van den Berghe I, Moerman P, Polito P, Kazmierczak B, Bullerdiek J, Van den Berghe H

Genes, chromosomes & cancer. 1997 ; 20 (1) : 90-92.

PMID 9290959

HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma.

Xiao S, Lux ML, Reeves R, Hudson TJ, Fletcher JA

The American journal of pathology. 1997 ; 150 (3) : 901-910.

PMID 9060828

Expression of HMGI-C and HMGI(Y) in ordinary lipoma and atypical lipomatous tumors: immunohistochemical reactivity correlates with karyotypic alterations.

Tallini G, Dal Cin P, Rhoden KJ, Chiapetta G, Manfioletti G, Giancotti V, Fusco A, Van den Berghe H, Sciot R

The American journal of pathology. 1997 ; 151 (1) : 37-43.

PMID 9212729

HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.

Williams AJ, Powell WL, Collins T, Morton CC

The American journal of pathology. 1997 ; 150 (3) : 911-918.

PMID 9060829

Intranuclear distribution of HMGI/Y proteins. An immunocytochemical study.

Martelli AM, Riccio M, Bareggi R, Manfioletti G, Tabellini G, Baldini G, Narducci P, Giancotti V

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 1998 ; 46 (7) : 863-864.

PMID 9632746

A role for the architectural transcription factors HMGI(Y) in cytokine gene transcription in T cells.

Shannon MF, Himes SR, Attema J

Immunology and cell biology. 1998 ; 76 (5) : 461-466.

PMID 9797468

Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix.

Bandiera A, Bonifacio D, Manfioletti G, Mantovani F, Rustighi A, Zanconati F, Fusco A, Di Bonito L, Giancotti V

Cancer research. 1998 ; 58 (3) : 426-431.

PMID 9458084

Chromosomal translocations in benign tumors: the HMGI proteins.

Hess JL

American journal of clinical pathology. 1998 ; 109 (3) : 251-261.

PMID 9495195

HMGIY is the target of 6p21.3 rearrangements in various benign mesenchymal tumors.

Kazmierczak B, Dal Cin P, Wanschura S, Borrmann L, Fusco A, Van den Berghe H, Bullerdiek J

Genes, chromosomes & cancer. 1998 ; 23 (4) : 279-285.

PMID 9824199

A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas.

Kazmierczak B, Meyer-Bolte K, Tran KH, Wˆ�ckel W, Breightman I, Rosigkeit J, Bartnitzke S, Bullerdiek J

Genes, chromosomes & cancer. 1999 ; 26 (2) : 125-133.

PMID 10469450

[Genetics of uterine leiomyomata]

Pedeutour F, Ligon AH, Morton CC

Bulletin du cancer. 1999 ; 86 (11) : 920-928.

PMID 10586108

Misexpression of wild-type and truncated isoforms of the high-mobility group I proteins HMGI-C and HMGI(Y) in uterine leiomyomas.

Klotzbˆºcher M, Wasserfall A, Fuhrmann U

The American journal of pathology. 1999 ; 155 (5) : 1535-1542.

PMID 10550310

Expression of HMGIY in three uterine leiomyomata with complex rearrangements of chromosome 6.

Sornberger KS, Weremowicz S, Williams AJ, Quade BJ, Ligon AH, Pedeutour F, Vanni R, Morton CC

Cancer genetics and cytogenetics. 1999 ; 114 (1) : 9-16.

PMID 10526529

Involvement of the HMGI(Y) gene in a microfollicular adenoma of the thyroid.

Dal Cin P, Fusco A, Belge G, Chiappetta G, Fedele M, Pauwels P, Bullerdiek J, Van den Berghe H

Genes, chromosomes & cancer. 1999 ; 24 (3) : 286-289.

PMID 10451711

The role of HMG I(Y) in the assembly and function of the IFN-beta enhanceosome.

Yie J, Merika M, Munshi N, Chen G, Thanos D

The EMBO journal. 1999 ; 18 (11) : 3074-3089.

PMID 10357819

Differential in vivo modifications of the HMGI(Y) nonhistone chromatin proteins modulate nucleosome and DNA interactions.

Banks GC, Li Y, Reeves R

Biochemistry. 2000 ; 39 (28) : 8333-8346.

PMID 10889043

HMGI-C and HMGI(Y) immunoreactivity correlates with cytogenetic abnormalities in lipomas, pulmonary chondroid hamartomas, endometrial polyps, and uterine leiomyomas and is compatible with rearrangement of the HMGI-C and HMGI(Y) genes.

Tallini G, Vanni R, Manfioletti G, Kazmierczak B, Faa G, Pauwels P, Bullerdiek J, Giancotti V, Van Den Berghe H, Dal Cin P

Laboratory investigation; a journal of technical methods and pathology. 2000 ; 80 (3) : 359-369.

PMID 10744071

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	11-2000	Gilka JF Gattas, Florence Pedeutour
		Laboratoire de Génétique des Tumeurs Solides, 5ème étage, Faculté de Médecine, 28 avenue de Valombrose, 06107 Nice cedex 2, France

Citation

This paper should be referenced as such :

Gattas GJF, Pedeutour F . HMGIY (High mobility group protein (non histone chromosomal) isoform I and Y). Atlas Genet Cytogenet Oncol Haematol. November 2000 . URL : http://AtlasGeneticsOncology.org/Genes/HMGIYID221.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Sat Oct 11 12:52:08 2008