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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

which in humans is encoded by the ''LMO2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Structure

LMO2 is characterized as a small, cysteine-rich protein comprising two tandem

LIM domain LIM domains are protein structural domains, composed of two contiguous zinc fingers, separated by a two-amino acid residue hydrophobic linker. The domain name is an acronym of the three genes in which it was first identified (LIN-11, Isl-1 and M ...

s. Each LIM domain features a conserved double

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...

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 A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...

; 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.

Function

LMO2 encodes a cysteine-rich, two

protein that is required for yolk sac

erythropoiesis Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. It is s ...

. The LMO2 protein has a central and crucial role in

hematopoietic Haematopoiesis (; ; also hematopoiesis in American English, sometimes h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult human, roughly ten ...

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. 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. An upstream

noncoding DNA Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regu ...

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 H3K27ac is an epigenetic modification to the DNA packaging protein histone H3. It is a mark that indicates acetylation of the lysine residue at N-terminal position 27 of the histone H3 protein. H3K27ac is associated with the higher activation o ...

enrichment and thus the formation of an aberrant enhancer which up-regulates the expression of ''LMO2'' Furthermore, recurrent and somatically acquired mutations of ''LMO2''

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

1 lead to its over-expression in both adult and paediatric T cell acute lymphoblastic leukaemia. These mutations introduce new transcription factor binding sites for MYB,

ETS1 Protein C-ets-1 is a protein that in humans is encoded by the ''ETS1'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors. Function There are 28 ETS genes in humans and 27 in mice. They bind the DNA via ...

and

RUNX1 Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) and it is a protein that is encoded by the ''RUNX1'' gene, in humans. RUNX1 is a transcription facto ...

allowing for the formation of an aberrant promoter which drives ''LMO2'' expression.

Interactions

LMO2 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: *

GATA1 GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) 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 b ...

, *

GATA2 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 ...

, *

JARID1A Lysine-specific demethylase 5A is an enzyme that in humans is encoded by the ''KDM5A'' gene. Function The protein encoded by this gene is a ubiquitously expressed nuclear protein. It binds directly, with several other proteins, to retinoblasto ...

, *

MLLT4 Afadin is a protein that in humans is encoded by the ''AFDN'' gene. Function Afadin is a Ras (see HRAS; MIM 190020) target that regulates cell–cell adhesions downstream of Ras activation. It is fused with MLL (MIM 159555) in leukemias caused ...

, and *

TAL1 __NOTOC__ T-cell acute lymphocytic leukemia protein 1 (i.e. TAL1 but also termed stem cell leukemia/T-cell acute leukemia 1 .e. SCL/TAL1 is a protein that in humans is encoded by the ''TAL1'' gene. The protein encoded by TAL1 is a basic helix-l ...

References

External links