| LMO2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | LMO2 , RBTN2, RBTNL1, RHOM2, TTG2, LIM domain only 2, LMO-2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 180385; MGI: 102811; HomoloGene: 4072; GeneCards: LMO2; OMA:LMO2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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LIM domain only 2 (rhombotin-like 1), also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene. [5]
LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis. [6] The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved.
Aberrant LMO2 expression is a significant feature of T cell acute lymphoblastic leukaemia with multiple described mechanisms of activation. [5] [7] The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number of T-cell acute lymphoblastic leukemia-specific translocations occur. [8] An upstream noncoding DNA element is also the site of recurrent mutations in T cell acute lymphoblastic leukaemia, leading the recruitment of the transcription factor MYB and significant H3K27ac enrichment and thus the formation of an aberrant enhancer which up-regulates the expression of LMO2 [9] Furthermore, recurrent and somatically acquired mutations of LMO2 intron 1 lead to its over-expression in both adult and paediatric T cell acute lymphoblastic leukaemia. [10] These mutations introduce new transcription factor binding sites for MYB, ETS1 and RUNX1 allowing for the formation of an aberrant promoter which drives LMO2 expression.
LMO2 has been shown to interact with:
GATA-binding factor 1 or GATA-1 is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the GATA1 and Gata1 genes, respectively. These genes are located on the X chromosome in both species.
ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.
T-cell acute lymphocytic leukemia protein 1 is a protein that in humans is encoded by the TAL1 gene.
Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene.
Transcription factor 3, also known as TCF3, is a protein that in humans is encoded by the TCF3 gene. TCF3 has been shown to directly enhance Hes1 expression.
Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.
Friend leukemia integration 1 transcription factor (FLI1), also known as transcription factor ERGB, is a protein that in humans is encoded by the FLI1 gene, which is a proto-oncogene.
GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of blood-forming, lympathic system-forming, and other tissue-forming stem cells. GATA2 is encoded by the GATA2 gene, a gene which often suffers germline and somatic mutations which lead to a wide range of familial and sporadic diseases, respectively. The gene and its product are targets for the treatment of these diseases.
Histone-lysine N-methyltransferase 2A, also known as acute lymphoblastic leukemia 1 (ALL-1), myeloid/lymphoid or mixed-lineage leukemia1 (MLL1), or zinc finger protein HRX (HRX), is an enzyme that in humans is encoded by the KMT2A gene.
LIM domain-binding protein 1 is a protein that in humans is encoded by the LDB1 gene.
Hepatic leukemia factor is a protein that in humans is encoded by the HLF gene.
T-cell leukemia homeobox protein 1 is a protein that in humans is encoded by the TLX1 gene, which was initially named HOX11.
Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the KDM5A gene.
Rhombotin-1 is a protein that in humans is encoded by the LMO1 gene.
T-cell leukemia homeobox protein 3 is a protein that in humans is encoded by the TLX3 gene.
Protein lyl-1 is a protein that in humans is encoded by the LYL1 gene.
Protein ENL is a protein that in humans is encoded by the MLLT1 gene.
Ankyrin repeat and sterile alpha motif domain-containing protein 1B is a protein that in humans is encoded by the ANKS1B gene.
T-cell acute lymphocytic leukemia 2, also known as TAL2, is a protein which in humans is encoded by the TAL2 gene.
In molecular biology MicroRNA-223 (miR-223) is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms. miR-223 is a hematopoietic specific microRNA with crucial functions in myeloid lineage development. It plays an essential role in promoting granulocytic differentiation while also being associated with the suppression of erythrocytic differentiation. miR-223 is commonly repressed in hepatocellular carcinoma and leukemia. Higher expression levels of miRNA-223 are associated with extranodal marginal-zone lymphoma of mucosa-associated lymphoid tissue of the stomach and recurrent ovarian cancer. In some cancers the microRNA-223 down-regulation is correlated with higher tumor burden, disease aggressiveness, and poor prognostic factors. MicroRNA-223 is also associated with rheumatoid arthritis, fibromyalgia, sepsis, type 2 diabetes, and hepatic ischemia.
