TRIM37

Tripartite motif-containing protein 37 is an E3 ubiquitin ligase in humans that is encoded by the TRIM37 gene.

TRIM37
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3LRQ
Identifiers
Aliases	TRIM37, MUL, POB1, TEF3, tripartite motif containing 37
External IDs	OMIM: 605073; MGI: 2153072; HomoloGene: 9084; GeneCards: TRIM37; OMA:TRIM37 - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17q22 Start 58,982,638 bp End 59,106,921 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 C Start 87,017,903 bp End 87,111,509 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell secondary oocyte sperm Brodmann area 23 middle temporal gyrus postcentral gyrus pons Brodmann area 46 superior frontal gyrus frontal pole Top expressed in spermatocyte spermatid medial vestibular nucleus pontine nuclei primary motor cortex deep cerebellar nuclei medial dorsal nucleus inferior colliculi seminiferous tubule central gray substance of midbrain More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity ubiquitin protein ligase activity zinc ion binding chromatin binding metal ion binding ubiquitin-protein transferase activity protein binding tumor necrosis factor receptor binding ubiquitin protein ligase binding transferase activity Cellular component cytosol ESC/E(Z) complex intracellular anatomical structure aggresome perinuclear region of cytoplasm peroxisome cytoplasm Biological process negative regulation of centriole replication positive regulation of DNA-binding transcription factor activity negative regulation of transcription by RNA polymerase II transcription, DNA-templated positive regulation of NF-kappaB transcription factor activity protein ubiquitination negative regulation of NF-kappaB transcription factor activity aggresome assembly protein autoubiquitination histone H2A monoubiquitination histone H2A-K119 monoubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4591 68729 Ensembl ENSG00000108395 ENSMUSG00000018548 UniProt O94972 Q6PCX9 RefSeq (mRNA) NM_001005207 NM_015294 NM_001320987 NM_001320988 NM_001320989 NM_001320990 NM_001353082 NM_001353083 NM_001353084 NM_001353085 NM_001353086 NM_197987 NM_001363025 NM_001363026 NM_001363027 NM_001363028 RefSeq (protein) NP_001005207 NP_001307916 NP_001307917 NP_001307918 NP_001307919 NP_056109 NP_001340011 NP_001340012 NP_001340013 NP_001340014 NP_001340015 NP_932104 NP_001349954 NP_001349955 NP_001349956 NP_001349957 Location (UCSC) Chr 17: 58.98 – 59.11 Mb Chr 11: 87.02 – 87.11 Mb PubMed search
Wikidata
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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. It is responsible for the mono-ubiquitination of histone H2A at lysine 119, a modification commonly associated with transcriptional repression.

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. 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.

Interactions

TRIM37 has been shown to interact with PRC1. 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. 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.

See also

• Mulibrey nanism

Further reading

• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, et al. (December 1998). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
• Zapata JM, Pawlowski K, Haas E, Ware CF, Godzik A, Reed JC (June 2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". The Journal of Biological Chemistry. 276 (26): 24242–52. doi:10.1074/jbc.M100354200. PMID 11279055.
• Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.
• Lehesjoki AE, Reed VA, Mark Gardiner R, Greene ND (October 2001). "Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in human and mouse embryogenesis". Mechanisms of Development. 108 (1–2): 221–5. doi:10.1016/S0925-4773(01)00491-9. PMID 11578880. S2CID 15474684.
• Kallijärvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki AE (May 2002). "The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder". American Journal of Human Genetics. 70 (5): 1215–28. doi:10.1086/340256. PMC 447596. PMID 11938494.
• Jagiello P, Hammans C, Wieczorek S, Arning L, Stefanski A, Strehl H, et al. (June 2003). "A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity". Human Mutation. 21 (6): 630–5. doi:10.1002/humu.10220. PMID 12754710. S2CID 24074182.
• Hämäläinen RH, Avela K, Lambert JA, Kallijärvi J, Eyaid W, Gronau J, et al. (May 2004). "Novel mutations in the TRIM37 gene in Mulibrey Nanism". Human Mutation. 23 (5): 522. doi:10.1002/humu.9233. PMID 15108285. S2CID 22994120.
• Kallijärvi J, Lahtinen U, Hämäläinen R, Lipsanen-Nyman M, Palvimo JJ, Lehesjoki AE (August 2005). "TRIM37 defective in mulibrey nanism is a novel RING finger ubiquitin E3 ligase". Experimental Cell Research. 308 (1): 146–55. doi:10.1016/j.yexcr.2005.04.001. PMID 15885686.
• 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.
• Karlberg N, Jalanko H, Kallijärvi J, Lehesjoki AE, Lipsanen-Nyman M (December 2005). "Insulin resistance syndrome in subjects with mutated RING finger protein TRIM37". Diabetes. 54 (12): 3577–81. doi:10.2337/diabetes.54.12.3577. PMID 16306379.
• Hämäläinen RH, Joensuu T, Kallijärvi J, Lehesjoki AE (January 2006). "Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing". Gene. 366 (1): 180–8. doi:10.1016/j.gene.2005.08.008. PMID 16310976.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Hämäläinen RH, Mowat D, Gabbett MT, O'brien TA, Kallijärvi J, Lehesjoki AE (December 2006). "Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism". Clinical Genetics. 70 (6): 473–9. doi:10.1111/j.1399-0004.2006.00700.x. PMID 17100991. S2CID 20007234.
• Doğanc T, Yüksel Konuk BE, Alpan N, Konuk O, Hämäläinen RH, Lehesjoki AE, Tekin M (July 2007). "A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy". Clinical Dysmorphology. 16 (3): 173–6. doi:10.1097/MCD.0b013e3280f6d00b. PMID 17551331. S2CID 45965305.

External links

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