TRIM37
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTRIM37, MUL, POB1, TEF3, tripartite motif containing 37
External IDsOMIM: 605073 MGI: 2153072 HomoloGene: 9084 GeneCards: TRIM37
Orthologs
SpeciesHumanMouse
Entrez

4591

68729

Ensembl

ENSG00000108395

ENSMUSG00000018548

UniProt

O94972

Q6PCX9

RefSeq (mRNA)

NM_197987
NM_001363025
NM_001363026
NM_001363027
NM_001363028

RefSeq (protein)

NP_932104
NP_001349954
NP_001349955
NP_001349956
NP_001349957

Location (UCSC)Chr 17: 58.98 – 59.11 MbChr 11: 87.02 – 87.11 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tripartite motif-containing protein 37 is an E3 ubiquitin ligase in humans that is encoded by the TRIM37 gene.[5][6][7][8]

Function

This gene encodes a member of the tripartite motif (TRIM) family, whose members are involved in diverse cellular functions such as developmental patterning and oncogenesis. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. The RING finger and B-box domains chelate zinc and might be involved in protein–protein and/or protein–nucleic acid interactions. The gene mutations are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder that involves several tissues of mesodermal origin. Alternatively spliced transcript variants encoding the same protein have been identified.[7] It is responsible for the mono-ubiquitination of histone H2A at lysine 119, a modification commonly associated with transcriptional repression.[8][9]

Role in breast cancer

The 17q23 chromosomal region in which the TRIM37 gene is located has been shown to be amplified in up to 40% of breast cancers.[10] The TRIM37 protein is thought to play a role in breast cancer oncogenesis by ubiquitinating histone H2A in regions occupied by tumor-suppressing genes. This repression of tumor-suppressing genes increases the likelihood that a tumor will occur or that an existing tumor will be more aggressive.[8]

Interactions

TRIM37 has been shown to interact with PRC1.[11] TRIM37 has also been shown to interact with PRC2 to alter its specificity, and when TRIM37 is overexpressed, there are many changes to gene expression that lead to silencing of tumor-suppressing genes.[8] It has also been shown that TRIM37, PRC2, PRC1 work together to co-bind to target genes, resulting in their transcriptional repression. Knockdown of TRIM37 expression via RNA-interference has shown to result in H2A becoming de-ubiquitinated and the dissociation of PRC1 and PRC2 from target genes. These changes allow the target gene to become transcriptionally active.[8]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000108395 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018548 - 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. ↑ Avela K, Lipsanen-Nyman M, Perheentupa J, Wallgren-Pettersson C, Marchand S, Fauré S, et al. (April 1997). "Assignment of the mulibrey nanism gene to 17q by linkage and linkage-disequilibrium analysis". American Journal of Human Genetics. 60 (4): 896–902. PMC 1712467. PMID 9106536.
  6. ↑ Avela K, Lipsanen-Nyman M, Idänheimo N, Seemanová E, Rosengren S, Mäkelä TP, et al. (July 2000). "Gene encoding a new RING-B-box-Coiled-coil protein is mutated in mulibrey nanism". Nature Genetics. 25 (3): 298–301. doi:10.1038/77053. PMID 10888877. S2CID 24257747.
  7. 1 2 "Entrez Gene: TRIM37 tripartite motif-containing 37".
  8. 1 2 3 4 5 Bhatnagar S, Gazin C, Chamberlain L, Ou J, Zhu X, Tushir JS, et al. (December 2014). "TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein". Nature. 516 (7529): 116–20. Bibcode:2014Natur.516..116B. doi:10.1038/nature13955. PMC 4269325. PMID 25470042.
  9. ↑ Weake VM, Workman JL (March 2008). "Histone ubiquitination: triggering gene activity". Molecular Cell. 29 (6): 653–63. doi:10.1016/j.molcel.2008.02.014. PMID 18374642.
  10. ↑ Sinclair, Colleen S.; Rowley, Matthew; Naderi, Ali; Couch, Fergus J. (2003-04-01). "The 17q23 Amplicon and Breast Cancer". Breast Cancer Research and Treatment. 78 (3): 313–322. doi:10.1023/A:1023081624133. ISSN 1573-7217. PMID 12755490. S2CID 23751525.
  11. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

Further reading

  • Overview of all the structural information available in the PDB for UniProt: O94972 (E3 ubiquitin-protein ligase TRIM37) at the PDBe-KB.
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