LMO2 (LIM domain only 2 (rhombotin-like 1))

2007-11-01   Pieter Van Vlierberghe  , Jean-Loup Huret  

ErasmusMC\\\/Sophia Childrens Hospital, Pediatric Oncology\\\/Hematology, Rotterdam, The Netherlands (PVV); Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH)

Identity

HGNC
LMO2
LOCATION
11p13
LOCUSID
4005
ALIAS
LMO-2,RBTN2,RBTNL1,RHOM2,TTG2
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

LMO2 belongs to a multigene family, extremely well conserved during evolution, encoding proteins containing two cystein-rich regions referred to as LIM domains: LMO1 (11p15), LMO2 (11p13), LMO3 (12p); 6 exons.

Transcription

3 transcripts: LMO2-a and LMO2-b encode the same 158-amino-acid protein; LMO2-c encodes a 151-amino-acid protein.

Proteins

Description

Small cystein rich protein with two tandemly arranged Zinc binding LIM domain motifs: named Lom2; 158 amino acids; 18 kDa; 48 % amino-acid identity with LMO1 protein.
LMO2 contains two transcription activating domains (one in N-term, in a prolin-rich 19 amino acid region, one in C-term) and two LIM domains as transcription repressing domains, selectively inhibiting the N-term activation domain (no effect on the C-term domain).

Expression

Early expressed during development, in all tissues (roughly consistent level in central nervous system, low level in thymus).
Strongly expressed in the precursors of mixed erythrocyte/macrophage/mast, erythrocyte, megakaryocyte, neutrophil and macrophage colonies, undetectable in the mature progeny.
Expressed in early B-cells, in leukemias of both the myeloid and lymphoid lineages.
Nuclear marker in normal germinal center B-cells. Also expressed in endothelial cells. High expression in the brain; expressed in the hippocampus during development.

Localisation

Nuclear.

Function

  • Hematopoiesis: LMO2 directly interacts with the basic-loop-helix protein TAL1/SCL and the GATA DNA protein GATA1. They form a transcriptional complex: LMO2 has no direct evidence in DNA binding capacity but could act as a bridging molecule bringing together different DNA binding factors (TAL1, LDB1, E12/E47, GATA1) that are essential for hematopoiesis (e.g. in the erythroid complex). This interaction is critical for the regulation of red blood cell development in early stages of hematopoiesis. TAL1 interacts specifically with the LIM domains of LMO2, which in turn binds LDB1. Because LMO2 can also bind to GATA2, a complex LMO2-GATA2 might occur at earlier stages of hematopoiesis when Gata1 is not expressed. Lmo2 has a central role in adult hematopoietic pathway regulation, on bone marrow pluripotential precursor stem cell mainly. LMO2 and TAL1 are able to partially suppress myeloid differentiation. LMO2 also interacts with retinoblastoma-binding protein 2 and elf-2 (ets transcription factor).
  • LMO2-c expression is regulated by GATA1 and PU.1; LMO2-c acts as an antagonist of LMO2-a/b, therefore blocking the transactivation of LMO2-a/b.
  • In the brain, hBEX2, LMO2, NSCL2 and LDB1 could form a similar complex.

    • Implicated in

    Entity name
    t(11;14)(p13;q11)/T-cell leukaemia --> LMO2 - TCRD-A
    Disease
    Childhood T-cell ALL ; found in 5-10% of T-cell ALL.
    Cytogenetics
    A variant translocation t(7;11)(q35;p13) has been described.
    Fusion protein
    It was previously believed that LMO2 is activated after chromosomal translocation by association either the T-cell receptor a / T-cell receptor d (14q11) or T-cell receptor b gene (7q35). Chromosome breakpoints occur 25 kb upstream LMO2 gene, in a presumed transcriptional start site, inducing truncation of the promoter/control region and leading to inappropriate Lmo2 level especially in T-cells (abnormal T-cell differentiation). However, it becomes now very likely that removal of a negative regulatory element from the LMO2 locus, rather than juxtaposition to the TCRD enhancer, is the main determinant for LMO2 activation in the majority of t(11;14)(p13;q11) translocations.
    Entity name
    del(11)(p12p13) T-cell leukaemia
    Disease
    Childhood T-cell ALL; found in about 5% of T-cell ALL.
    Cytogenetics
    Cryptic deletion that varies in size.
    Fusion protein
    LMO2 is activated through a cryptic intrachromosomal deletion, del(11)(p12p13), in which a negative regulatory element (NRE), situated upstream of the LMO2 gene, is deleted. Removal of this NRE causes activation of the proximal promoter of the LMO2 gene leading to its ectopic expression.
    Entity name
    Germinal center B-cell lymphomas
    Disease
    Diffuse large-B-cell lymphomas, follicular lymphomas, Burkitt lymphomas, less often in other haematological malignancies.
    Prognosis
    LMO2 expression, together with BCL6, FN1, CCND2, SCYA3, and BCL2 expressions, is a predictor of outcome in diffuse large-B-cell lymphoma.
    Entity name
    Prostate cancer
    Note
    Expression of LMO2 is higher in prostate tumours samples than in the normal epithelium. Moreover, overexpression of LMO2 is significantly associated with advanced tumour stage, as well as with the development of distant metastasis.
    Oncogenesis
    LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    152158942004Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.Anguita E et al
    20346761991The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.Boehm T et al
    173609392007Different chromosomal breakpoints impact the level of LMO2 expression in T-ALL.Dik WA et al
    86394171996Expression of rhombotin 2 in normal and leukaemic haemopoietic cells.Dong WF et al
    155414802005Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia.Hammond SM et al
    163143162005Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex.Han C et al
    179645432007The Lim-only protein LMO2 acts as a positive regulator of erythroid differentiation.Hansson A et al
    178781552007Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction.Lécuyer E et al
    151158292004Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes.Lossos IS et al
    171678212007The significance of LMO2 expression in the progression of prostate cancer.Ma S et al
    170385242007The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas.Natkunam Y et al
    19235111991TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11).Royer-Pokora B et al
    168736702006The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia.Van Vlierberghe P et al
    92146321997The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.Wadman IA et al
    173612242007A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2.Wang Q et al
    95204631998The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis.Yamada Y et al
    177087652007A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish.Yang Z et al

    Other Information

    Locus ID:

    NCBI: 4005
    MIM: 180385
    HGNC: 6642
    Ensembl: ENSG00000135363

    Variants:

    dbSNP: 4005
    ClinVar: 4005
    TCGA: ENSG00000135363
    COSMIC: LMO2

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000135363ENST00000257818P25791
    ENSG00000135363ENST00000395833P25791
    ENSG00000135363ENST00000411482P25791

    Expression (GTEx)

    0
    5
    10
    15
    20
    25
    30
    35
    40
    45
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Transcriptional misregulation in cancerKEGGko05202
    Transcriptional misregulation in cancerKEGGhsa05202

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    nasopharynx
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    References

    Pubmed IDYearTitleCitations
    382453452024Simulated microgravity altered the gene expression profiles and inhibited the proliferation of Kupffer cells in the early phase by downregulating LMO2 and EZH2.0
    382453452024Simulated microgravity altered the gene expression profiles and inhibited the proliferation of Kupffer cells in the early phase by downregulating LMO2 and EZH2.0
    359990962023Potential link of single nucleotide polymorphisms within LMO2 to the risk of cervical squamous-cell carcinoma in Chinese populations.0
    375191102023Value of GCET1, HGAL (GCET2), and LMO2 in the Determination of Germinal Center Phenotype in Diffuse Large B-cell Lymphoma.0
    375734052023LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1.0
    359990962023Potential link of single nucleotide polymorphisms within LMO2 to the risk of cervical squamous-cell carcinoma in Chinese populations.0
    375191102023Value of GCET1, HGAL (GCET2), and LMO2 in the Determination of Germinal Center Phenotype in Diffuse Large B-cell Lymphoma.0
    375734052023LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1.0
    350946912022Identification of LMO2 as a new marker for acinic cell carcinoma of salivary gland.0
    352868692022LMO2 plays differential roles in trophoblast subtypes and is associated with preeclampsia.0
    353221922022LMO2 expression is frequent in T-lymphoblastic leukemia and correlates with survival, regardless of T-cell stage.6
    369052682022PAK5 is a potential target in myelodysplastic syndrome through interacting with LMO2 and GATA1.0
    350946912022Identification of LMO2 as a new marker for acinic cell carcinoma of salivary gland.0
    352868692022LMO2 plays differential roles in trophoblast subtypes and is associated with preeclampsia.0
    353221922022LMO2 expression is frequent in T-lymphoblastic leukemia and correlates with survival, regardless of T-cell stage.6

    Citation

    Pieter Van Vlierberghe ; Jean-Loup Huret

    LMO2 (LIM domain only 2 (rhombotin-like 1))

    Atlas Genet Cytogenet Oncol Haematol. 2007-11-01

    Online version: http://atlasgeneticsoncology.org/gene/34/gene-fusions/teaching-explorer/favicon/favicon-16x16.png

    Historical Card

    1998-06-01 LMO2 (LIM domain only 2 (rhombotin-like 1)) by  Chrysthèle Bilhou-Nabera 

    Cytogénétique,Laboratoire dHématologie-Pr RAPHAEL, Pav BROCA - 4öme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France