TRIM27 (tripartite motif containing 27)

	Schematic diagram of TRIM27 protein. The domain structure of the three TRIM27 protein isoforms (i-iii) and a ribbon diagram of the structure of TRIM27 domains which represents a high confidence model generated by Phyre2 (http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index). NH2, Amino-terminal region; COOH, Carboxyl-terminal region.
Description	The longest isoform 1 of TRIM27 (protein ID ENSP00000366404) encodes a 513 amino acids protein with a molecular weight of 58 KDa; displaying the so-called tripartite/RBCC motif within its N-terminal region, composed of a RING type zinc finger (InterPro ID IPR001841) (aa 16-57), a B-box type zinc finger (InterPro ID001841) (aa 96-127) and coiled-coil domains (aa 132-172 and aa 282-311), and a B30.2/PRY-SPRY domain (InterPro ID IPR001870) within its C-terminal region (aa 298-492). The RING finger may be involved in mediating protein-protein interactions and may confer ubiquitin family ligase activity. TRIM27 can form homo and hetero-oligomeric assemblies mediated by the centrally located coiled-coil domain (Cao et al., 1997). Isoform 2 (protein ID ENSP00000366399) lacks the C-terminal SPRY domain. Isoform 3 (protein ID ENSP00000400058) encodes the B30.2/PRY-SPRY domain only. The diagram above is a scheme of the protein isoforms and their domains.
Expression	TRIM27 transcripts and protein is ubiquitous in day 10.5-13.5 mouse embryos. Expression is restricted in adult mice, with the highest level of expression in pachytene spermatocytes and round spermatids of differentiating sperm (Cao et al., 1996; Tezel et al., 1999). TRIM27 is also expressed in mouse spleen, thymus, cerebrum and cerebellum. TRIM27 is expressed in various human and rodent cell lines. Based on RNAseq., TRIM27 mRNA is detected widely in human tissues, with no evidence for absence. Expression levels between tissues are similar, including testes, with comparative expression rating of low to medium across tissues (Human Protein Atlas).
Localisation	The protein localizes to the nucleus, cytoplasm and in nuclear bodies (NB) associated with the nuclear matrix (Isomura et al., 1992). Nuclear export of RFP is dependent on a functional NES, which can be activated by protein kinase C (PKC) (Harbers et al., 2001). Hetero-oligomerization has been observed between TRIM27 and TRIM19 with the recruitment of TRIM27 to the promyelocytic leukaemia nuclear bodies (PMLs) (Cao et al., 1998). Furthermore, interaction with members of the protein inhibitors of activated STAT (PIAS) family targets TRIM27 to subnuclear compartments/NBs, involving TRIM27 sumoylation (Matsuura et al., 2005). Nuclear or cytoplasmic localisation depends on the cell type or tissue.
Function	A role for TRIM27 has been reported in transcriptional regulation through interaction with retinoblastoma protein (RB1) and the Mi-2b-containing histone deacetylase complex in the nucleus (Krutzfeldt et al., 2005; Shimono et al., 2005), in transcriptional repression through interaction with the enhancer of polycomb protein (EPC) (Shimono et al., 2000; Bloor et al., 2005) and MBD proteins (Fukushige et al., 2006), in the negative regulation of NF-kB and IFN-signaling pathways (Zha et al., 2006), in the positive regulation of apoptosis through activation of Jun N-terminal kinase (JNK) (Dho and Kwon, 2003) and augmentation of TNF alpha receptor activation (Zaman et al., 2013), and in cell cycle regulation (Patel and Ghiselli, 2005) suggesting that TRIM27 is involved in the control of multiple cellular processes. TRIM27 has been shown to confer E3 ubiquitin ligase activity with the enzymes UBE2D1 and UBE2D3 (Napolitano et al., 2011) and to possess SUMO E3 ligase activity (Chu and Yang, 2011). TRIM27 regulates innate immune responses by physical interaction with NOD2. So, TRIM27 mediates K48-linked ubiquitination and subsequent proteasomal degradation of NOD2 (Zurek et al., 2012). TRIM27 has a critical role in regulating PTEN phosphatase activity through ubiquitination which inhibits PTEN increasing AKT signalling (Lee et al., 2013). TRIM27 functions as an E3 ligase to ubiquitinate and inhibit PI3K-C2beta's kinase activity and negatively regulates CD4 T cells (Cai et al., 2011). TRIM27 also negatively regulates IgE receptor activation and downstream signalling by the same mechanism (Srivastava et al., 2012). TRIM27 interacts with MAGE-L2 protein and ubiquitination of WASH K220 by MAGE-L2-TRIM27 is required for endosomal F-actin nucleation and retrograde transport (Hao et al., 2013). MRTF-B/TRIM27 complex plays a role in the regulation of integrin b1 expression via Rho and miR-124 in Leading Cells (LCs) among migrating cancer cell groups following loss of intracellular adhension (Kato et al., 2014).
Homology	H. sapiens, TRIM27 tripartite motif containing 27, 513 aa. P. troglodytes (chimpanzee), TRIM27 tripartite motif containing 27, 513 aa (XP_001140726.2). M. mulatta, TRIM27 tripartite motif containing 27, 513 aa (XP_001094465.2). C. lupus, TRIM27 tripartite motif containing 27, 487 aa (XP_005642504.1). B. taurus, TRIM27 tripartite motif containing 27, 513 aa (XP_001069267.1). M. musculus, Trim27 tripartite motif containing 27, 513 aa (NP_033080.2). R. norvegicus, Trim27 tripartite motif containing 27, 513 aa (NP_001128446.1). G. gallus, TRIM27 tripartite motif containing 27, 505 aa (NP_001092824.1). With other RING finger/B box proteins.

	TRIM27 mutations identified in cancer.
Germinal	No germinal mutations described for TRIM27.
Somatic	TRIM27 have been identified in cancer tissues by large scale tumour genome sequencing at low frequency (see table above). COSMIC lists 26 mutations from sequence analysis of 8960 cancers (mutation rate 0.29%). Mutation spectrum: one nonrecurrent, 8 synonymous substitutions, one nonsense mutation, 16 nonsynonymous missense substitutions mostly leading to conservative aminoacid changes. Evidence is not available at present whether these observed mutations affect function of TRIM27 or confer selective advantage to tumour cells (COSMIC).

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