Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

HMGA1 (High mobility group protein (non histone chromosomal) isoform I and Y)

Identity

Other namesHMG-I(Y), HMGI/Y
HGNC (Hugo) HMGA1
LocusID (NCBI) 3159
Location 6p21.31
Location_base_pair Starts at 34204577 and ends at 34214008 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order centromeric to HLA-A, telomeric to D6S19
 
  Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

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
      

    Other Leukemias implicated (Data extracted from papers in the Atlas)

    Leukemias 11q23ChildAMLID1615 11q23ID1030 11q23secondLeukID1131

    Other Solid tumors implicated (Data extracted from papers in the Atlas)

    Solid Tumors AmeloblastomID5945 MedulloblastomaID5065 rhab5004

    External links

    Nomenclature
    HGNC (Hugo)HMGA1   5010
    Cards
    AtlasHMGIYID221
    Entrez_Gene (NCBI)HMGA1  3159  high mobility group AT-hook 1
    GeneCards (Weizmann)HMGA1
    Ensembl (Hinxton)ENSG00000137309 [Gene_View]  chr6:34204577-34214008 [Contig_View]  HMGA1 [Vega]
    ICGC DataPortalENSG00000137309
    AceView (NCBI)HMGA1
    Genatlas (Paris)HMGA1
    WikiGenes3159
    SOURCE (Princeton)NM_002131 NM_145899 NM_145901 NM_145902 NM_145903 NM_145904 NM_145905
    Genomic and cartography
    GoldenPath (UCSC)HMGA1  -  6p21.31   chr6:34204577-34214008 +  6p21   [Description]    (hg19-Feb_2009)
    EnsemblHMGA1 - 6p21 [CytoView]
    Mapping of homologs : NCBIHMGA1 [Mapview]
    OMIM125853   600701   
    Gene and transcription
    Genbank (Entrez)AF176039 AK096863 AK130027 AK301434 AK308245
    RefSeq transcript (Entrez)NM_002131 NM_145899 NM_145901 NM_145902 NM_145903 NM_145904 NM_145905
    RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_029020 NT_007592 NW_001838980 NW_004929326
    Consensus coding sequences : CCDS (NCBI)HMGA1
    Cluster EST : UnigeneHs.703764 [ NCBI ]
    CGAP (NCI)Hs.703764
    Alternative Splicing : Fast-db (Paris)GSHG0025660
    Alternative Splicing GalleryENSG00000137309
    Gene ExpressionHMGA1 [ NCBI-GEO ]     HMGA1 [ SEEK ]   HMGA1 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP17096 (Uniprot)
    NextProtP17096  [Medical]
    With graphics : InterProP17096
    Splice isoforms : SwissVarP17096 (Swissvar)
    Domaine pattern : Prosite (Expaxy)HMGI_Y (PS00354)   
    Domains : Interpro (EBI)AT_hook-like    AT_hook_DNA-bd_motif    HMGI/HMGY    HMGI/Y_DNA-bd_CS   
    Related proteins : CluSTrP17096
    Domain families : Pfam (Sanger)AT_hook (PF02178)   
    Domain families : Pfam (NCBI)pfam02178   
    Domain families : Smart (EMBL)AT_hook (SM00384)  
    DMDM Disease mutations3159
    Blocks (Seattle)P17096
    PDB (SRS)2EZD    2EZE    2EZF    2EZG   
    PDB (PDBSum)2EZD    2EZE    2EZF    2EZG   
    PDB (IMB)2EZD    2EZE    2EZF    2EZG   
    PDB (RSDB)2EZD    2EZE    2EZF    2EZG   
    Human Protein AtlasENSG00000137309
    Peptide AtlasP17096
    HPRD02829
    IPIIPI00179700   IPI00177716   IPI00746310   IPI00744851   IPI00450855   IPI00442843   
    Protein Interaction databases
    DIP (DOE-UCLA)P17096
    IntAct (EBI)P17096
    FunCoupENSG00000137309
    BioGRIDHMGA1
    IntegromeDBHMGA1
    STRING (EMBL)HMGA1
    Ontologies - Pathways
    QuickGOP17096
    Ontology : AmiGODNA catabolic process, endonucleolytic  DNA binding  AT DNA binding  sequence-specific DNA binding transcription factor activity  DNA-(apurinic or apyrimidinic site) lyase activity  protein binding  nucleus  nucleoplasm  transcription factor complex  cytosol  DNA unwinding involved in DNA replication  base-excision repair  nucleosome disassembly  transcription, DNA-templated  regulation of transcription, DNA-templated  protein complex assembly  transcription factor binding  negative regulation of cell proliferation  response to virus  viral process  enzyme binding  ligand-dependent nuclear receptor transcription coactivator activity  negative regulation of chromatin silencing  senescence-associated heterochromatin focus  senescence-associated heterochromatin focus assembly  retinoic acid receptor binding  peroxisome proliferator activated receptor binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  retinoid X receptor binding  5'-deoxyribose-5-phosphate lyase activity  establishment of integrated proviral latency  oncogene-induced cell senescence  positive regulation of cellular senescence  
    Ontology : EGO-EBIDNA catabolic process, endonucleolytic  DNA binding  AT DNA binding  sequence-specific DNA binding transcription factor activity  DNA-(apurinic or apyrimidinic site) lyase activity  protein binding  nucleus  nucleoplasm  transcription factor complex  cytosol  DNA unwinding involved in DNA replication  base-excision repair  nucleosome disassembly  transcription, DNA-templated  regulation of transcription, DNA-templated  protein complex assembly  transcription factor binding  negative regulation of cell proliferation  response to virus  viral process  enzyme binding  ligand-dependent nuclear receptor transcription coactivator activity  negative regulation of chromatin silencing  senescence-associated heterochromatin focus  senescence-associated heterochromatin focus assembly  retinoic acid receptor binding  peroxisome proliferator activated receptor binding  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  retinoid X receptor binding  5'-deoxyribose-5-phosphate lyase activity  establishment of integrated proviral latency  oncogene-induced cell senescence  positive regulation of cellular senescence  
    REACTOMEP17096 [protein]
    REACTOME PathwaysREACT_120956 Cellular responses to stress [pathway]
    REACTOME PathwaysREACT_116125 Disease [pathway]
    Protein Interaction DatabaseHMGA1
    Wikipedia pathwaysHMGA1
    Gene fusion - rearrangments
    Rearrangement : TICdbHMGA1 [6p21.31]  -  LAMA4 [19q13.32]
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)HMGA1
    SNP (GeneSNP Utah)HMGA1
    SNP : HGBaseHMGA1
    Genetic variants : HAPMAPHMGA1
    1000_GenomesHMGA1 
    ICGC programENSG00000137309 
    Cancer Gene: CensusHMGA1 
    CONAN: Copy Number AnalysisHMGA1 
    Somatic Mutations in Cancer : COSMICHMGA1 
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    DECIPHER (Syndromes)6:34204577-34214008
    Mutations and Diseases : HGMDHMGA1
    OMIM125853    600701   
    MedgenHMGA1
    GENETestsHMGA1
    Disease Genetic AssociationHMGA1
    Huge Navigator HMGA1 [HugePedia]  HMGA1 [HugeCancerGEM]
    Genomic VariantsHMGA1  HMGA1 [DGVbeta]
    Exome VariantHMGA1
    dbVarHMGA1
    ClinVarHMGA1
    snp3D : Map Gene to Disease3159
    General knowledge
    Homologs : HomoloGeneHMGA1
    Homology/Alignments : Family Browser (UCSC)HMGA1
    Phylogenetic Trees/Animal Genes : TreeFamHMGA1
    Chemical/Protein Interactions : CTD3159
    Chemical/Pharm GKB GenePA35094
    Clinical trialHMGA1
    Cancer Resource (Charite)ENSG00000137309
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Litterature
    PubMed200 Pubmed reference(s) in Entrez
    CoreMineHMGA1
    GoPubMedHMGA1
    iHOPHMGA1

    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 articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    Contributor(s)

    Written11-2000Gilka 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. 2001;5(1):3-6.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/HMGIYID221.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Nov 8 16:59:17 CET 2014

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.