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LMO2

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LMO2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLMO2, RBTN2, RBTNL1, RHOM2, TTG2, LIM domain only 2, LMO-2
External IDsOMIM: 180385; MGI: 102811; HomoloGene: 4072; GeneCards: LMO2; OMA:LMO2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 2: 103.79 – 103.81 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Function

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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.

Clinical significance

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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.

Interactions

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LMO2 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135363Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032698Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Boehm T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH (May 1991). "The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13". Proceedings of the National Academy of Sciences of the United States of America. 88 (10): 4367–4371. Bibcode:1991PNAS...88.4367B. doi:10.1073/pnas.88.10.4367. PMC 51660. PMID 2034676.
  6. ^ Warren AJ, Colledge WH, Carlton MB, Evans MJ, Smith AJ, Rabbitts TH (July 1994). "The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development". Cell. 78 (1): 45–57. doi:10.1016/0092-8674(94)90571-1. PMID 8033210. S2CID 7156927.
  7. ^ Fisch P, Boehm T, Lavenir I, Larson T, Arno J, Forster A, Rabbitts TH (December 1992). "T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes". Oncogene. 7 (12): 2389–2397. PMID 1461647.
  8. ^ EntrezGene 4005
  9. ^ Abraham BJ, Hnisz D, Weintraub AS, Kwiatkowski N, Li CH, Li Z, et al. (February 2017). "Small genomic insertions form enhancers that misregulate oncogenes". Nature Communications. 8: 14385. Bibcode:2017NatCo...814385A. doi:10.1038/ncomms14385. PMC 5309821. PMID 28181482.
  10. ^ Rahman S, Magnussen M, León TE, Farah N, Li Z, Abraham BJ, et al. (June 2017). "Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia". Blood. 129 (24): 3221–3226. doi:10.1182/blood-2016-09-742148. PMC 5472898. PMID 28270453.
  11. ^ a b c Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (October 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9585–9589. Bibcode:1995PNAS...92.9585O. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
  12. ^ Mao S, Neale GA, Goorha RM (April 1997). "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene. 14 (13): 1531–1539. doi:10.1038/sj.onc.1200988. PMID 9129143. S2CID 25877540.
  13. ^ Bégay-Müller V, Ansieau S, Leutz A (June 2002). "The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene". FEBS Letters. 521 (1–3): 36–38. Bibcode:2002FEBSL.521...36B. doi:10.1016/s0014-5793(02)02814-4. PMID 12067721. S2CID 29461336.
  14. ^ Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R (October 1994). "Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia". The EMBO Journal. 13 (20): 4831–4839. doi:10.1002/j.1460-2075.1994.tb06809.x. PMC 395422. PMID 7957052.
  15. ^ Valge-Archer VE, Osada H, Warren AJ, Forster A, Li J, Baer R, Rabbitts TH (August 1994). "The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8617–8621. Bibcode:1994PNAS...91.8617V. doi:10.1073/pnas.91.18.8617. PMC 44657. PMID 8078932.
  16. ^ Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, et al. (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–366. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.

Further reading

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  • Overview of all the structural information available in the PDB for UniProt: P25791 (Human Rhombotin-2) at the PDBe-KB.
  • Overview of all the structural information available in the PDB for UniProt: P25801 (Mouse Rhombotin-2) at the PDBe-KB.