LMO2

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
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2XJY, 2XJZ, 2YPA, 4KFZ
Identifiers
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
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p13 Start 33,858,576 bp[1] End 33,892,076 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 E2|2 54.46 cM Start 103,788,331 bp[2] End 103,812,223 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte tendon of biceps brachii trabecular bone urethra endothelial cell vena cava inferior ganglion of vagus nerve glutes internal globus pallidus synovial membrane Top expressed in fetal liver hematopoietic progenitor cell blood spleen tibiofemoral joint human fetus external carotid artery parotid gland tail of embryo granulocyte bone marrow More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific bHLH transcription factor binding E-box binding protein binding RNA polymerase II transcription regulatory region sequence-specific DNA binding metal ion binding Cellular component nucleus transcription regulator complex nucleoplasm Biological process multicellular organism development mRNA transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II cellular response to thyroid hormone stimulus regulation of hematopoietic stem cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4005 16909 Ensembl ENSG00000135363 ENSMUSG00000032698 UniProt P25791 P25801 RefSeq (mRNA) NM_001142315 NM_001142316 NM_005574 NM_001142335 NM_001142336 NM_001142337 NM_008505 RefSeq (protein) NP_001135787 NP_001135788 NP_005565 NP_001135807 NP_001135808 NP_001135809 NP_032531 Location (UCSC) Chr 11: 33.86 – 33.89 Mb Chr 2: 103.79 – 103.81 Mb PubMed search [3] [4]
Wikidata
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Structure

LMO2 is characterized as a small, cysteine-rich protein comprising two tandem LIM domains. Each LIM domain features a conserved double zinc finger motif, wherein zinc ions are coordinated by cysteine and histidine residues. These domains are critical for LMO2's primary function as a scaffolding protein facilitating protein-protein interactions within transcriptional regulatory complexes. Notably, LMO2 lacks an intrinsic DNA-binding domain; its influence on gene expression is mediated through its recruitment into multi-protein assemblies. The inter-domain linker region contributes to the protein's overall conformational dynamics, potentially modulating its interaction with diverse binding partners. The structural integrity conferred by the zinc fingers within the LIM domains is essential for maintaining the protein's functional architecture in the context of hematopoiesis and leukemogenesis.^[6]

Function

LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis.^[7] The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved.

Clinical significance

Aberrant LMO2 expression is a significant feature of T cell acute lymphoblastic leukaemia with multiple described mechanisms of activation.^[5][8] 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.^[9] 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 ^[10] 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.^[11] 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.

Interactions

LMO2 has been shown to interact with:

• GATA1,^[12]
• GATA2,^[12]
• JARID1A,^[13]
• MLLT4,^[14] and
• TAL1^{[12][15][16][17]}