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

2000-11-01   Gilka JF Gattas , Florence Pedeutour 

Laboratoire de Génétique des Tumeurs Solides, 5öme étage, Faculté de Médecine, 28 avenue de Valombrose, 06107 Nice cedex 2, France

Identity

HGNC
LOCATION
6p21.31
IMAGE
Atlas Image
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
HMG-R,HMGA1A,HMGIY
FUSION GENES

DNA/RNA

Atlas Image

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.

Proteins

Atlas Image

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 name
    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 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
    Atlas Image
    Fusion 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 name
    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 name
    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 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
    Fusion protein
    HMGIY mRNA and protein levels do not always correlate, suggesting that post-transcriptional mechanisms are involved in the regulation of HMGIY
    Entity name
    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 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 name
    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 name
    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

    Bibliography

    Pubmed IDLast YearTitleAuthors
    94580841998Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix.Bandiera A et al
    108890432000Differential in vivo modifications of the HMGI(Y) nonhistone chromatin proteins modulate nucleosome and DNA interactions.Banks GC et al
    89570861996High level expression of the HMGI (Y) gene during embryonic development.Chiappetta G et al
    104517111999Involvement of the HMGI(Y) gene in a microfollicular adenoma of the thyroid.Dal Cin P et al
    92909591997Hamartoma of the breast with involvement of 6p21 and rearrangement of HMGIY.Dal Cin P et al
    84149801993Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene.Friedmann M et al
    94951951998Chromosomal translocations in benign tumors: the HMGI proteins.Hess JL et al
    104694501999A high frequency of tumors with rearrangements of genes of the HMGI(Y) family in a series of 191 pulmonary chondroid hamartomas.Kazmierczak B et al
    105503101999Misexpression of wild-type and truncated isoforms of the high-mobility group I proteins HMGI-C and HMGI(Y) in uterine leiomyomas.Klotzbücher M et al
    96327461998Intranuclear distribution of HMGI/Y proteins. An immunocytochemical study.Martelli AM et al
    105861081999[Genetics of uterine leiomyomata].Pedeutour F et al
    97974681998A role for the architectural transcription factors HMGI(Y) in cytokine gene transcription in T cells.Shannon MF et al
    105265291999Expression of HMGIY in three uterine leiomyomata with complex rearrangements of chromosome 6.Sornberger KS et al
    92127291997Expression of HMGI-C and HMGI(Y) in ordinary lipoma and atypical lipomatous tumors: immunohistochemical reactivity correlates with karyotypic alterations.Tallini G et al
    107440712000HMGI-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 et al
    91871321997Misexpression of disrupted HMGI architectural factors activates alternative pathways of tumorigenesis.Tkachenko A et al
    90608291997HMGI(Y) expression in human uterine leiomyomata. Involvement of another high-mobility group architectural factor in a benign neoplasm.Williams AJ et al
    90608281997HMGI(Y) activation by chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma.Xiao S et al
    103578191999The role of HMG I(Y) in the assembly and function of the IFN-beta enhanceosome.Yie J et al

    Other Information

    Locus ID:

    NCBI: 3159
    MIM: 600701
    HGNC: 5010
    Ensembl: ENSG00000137309

    Variants:

    dbSNP: 3159
    ClinVar: 3159
    TCGA: ENSG00000137309
    COSMIC: HMGA1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000137309ENST00000311487P17096
    ENSG00000137309ENST00000347617P17096
    ENSG00000137309ENST00000347617Q5T6U8
    ENSG00000137309ENST00000374116P17096
    ENSG00000137309ENST00000374116Q5T6U8
    ENSG00000137309ENST00000401473P17096
    ENSG00000137309ENST00000401473Q5T6U8
    ENSG00000137309ENST00000447654P17096

    Expression (GTEx)

    0
    100
    200
    300
    400
    500
    600
    700

    Pathways

    PathwaySourceExternal ID
    DiseaseREACTOMER-HSA-1643685
    Infectious diseaseREACTOMER-HSA-5663205
    HIV InfectionREACTOMER-HSA-162906
    HIV Life CycleREACTOMER-HSA-162587
    Early Phase of HIV Life CycleREACTOMER-HSA-162594
    Integration of provirusREACTOMER-HSA-162592
    Integration of viral DNA into host genomic DNAREACTOMER-HSA-175567
    2-LTR circle formationREACTOMER-HSA-164843
    Autointegration results in viral DNA circlesREACTOMER-HSA-177539
    Host Interactions of HIV factorsREACTOMER-HSA-162909
    Interactions of Vpr with host cellular proteinsREACTOMER-HSA-176033
    Vpr-mediated nuclear import of PICsREACTOMER-HSA-180910
    APOBEC3G mediated resistance to HIV-1 infectionREACTOMER-HSA-180689
    Cellular responses to stressREACTOMER-HSA-2262752
    Cellular SenescenceREACTOMER-HSA-2559583
    DNA Damage/Telomere Stress Induced SenescenceREACTOMER-HSA-2559586
    Formation of Senescence-Associated Heterochromatin Foci (SAHF)REACTOMER-HSA-2559584

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    References

    Pubmed IDYearTitleCitations
    182027512008The HMGA proteins: a myriad of functions (Review).117
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    232011622013MicroRNA-137, an HMGA1 target, suppresses colorectal cancer cell invasion and metastasis in mice by directly targeting FMNL2.65
    203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
    190748782008The high-mobility group A1a/signal transducer and activator of transcription-3 axis: an achilles heel for hematopoietic malignancies?56
    126655742003A nucleoprotein complex containing Sp1, C/EBP beta, and HMGI-Y controls human insulin receptor gene transcription.55
    236588262013HMGA1: a master regulator of tumor progression in triple-negative breast cancer cells.50
    270451382016In Pulmonary Arterial Hypertension, Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug.50
    192660772009Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.48
    209757072010Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes.48

    Citation

    Gilka JF Gattas ; Florence Pedeutour

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

    Atlas Genet Cytogenet Oncol Haematol. 2000-11-01

    Online version: http://atlasgeneticsoncology.org/gene/221/hmga1