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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

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 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

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

Aberrant LMO2 expression is a significant feature of T cell acute lymphoblastic leukaemia with multiple described mechanisms of activation.[7][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:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135363 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032698 – Ensembl, 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. ^ 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. 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. ^ 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. doi:10.1073/pnas.88.10.4367. PMC 51660. PMID 2034676.
  8. ^ 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.
  9. ^ EntrezGene 4005
  10. ^ 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. doi:10.1038/ncomms14385. PMC 5309821. PMID 28181482.
  11. ^ 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.
  12. ^ 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. doi:10.1073/pnas.92.21.9585. PMC 40846. PMID 7568177.
  13. ^ 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.
  14. ^ 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. doi:10.1016/s0014-5793(02)02814-4. PMID 12067721. S2CID 29461336.
  15. ^ 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.
  16. ^ 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. doi:10.1073/pnas.91.18.8617. PMC 44657. PMID 8078932.
  17. ^ 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

  • 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.
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