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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
which in humans is encoded by the ''LMO2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
LMO2 encodes a cysteine-rich, two
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 ...
protein that is required for yolk sac
erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "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 stimulated by decrea ...
.
The LMO2 protein has a central and crucial role in
hematopoietic
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
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 regul ...
element is also the site of recurrent mutations in
T cell acute lymphoblastic leukaemia, leading the recruitment of the transcription factor
MYB
MyB (Hangul: 마이비) was a South Korean girl group formed by Maroo Entertainment. The group debuted on August 25, 2015 with ''My Oh My'' and made a comeback on November 13, 2015 with ''Ddoddo'', before the group officially disbanded on December ...
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., gene. ...
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) is a protein that in humans is encoded by the ''RUNX1'' gene.
RUNX1 is a transcription factor that re ...
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 using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
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 by ...
,
*
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 bl ...
,
[
* ]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 ...
,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-lo ...
References
Further reading
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External links
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* {{PDBe-KB2, P25801, Mouse Rhombotin-2