TRIM20 /MEFV/Pyrin, Välimeren kuume

TRIM20 on poikkeuksellinen  TRIM. Siinä on RING- finger domaani korvautunut N-terminaalisella pyriinidomaanilla. Se nimiä ovat pyriini tai marenostriini ja sen mutaatio aiheuttaa välimerenkuumetta.
https://www.reumaliitto.fi/fi/reuma-aapinen/lastenreuma-aapinen/perinnollinen-valimerenkuume https://www.reumaliitto.fi/fi/reuma-aapinen/lastenreuma-aapinen/perinnollinen-valimerenkuume

Tämän genin mutaatioita B30.2 domaanin alueella esiintyy  systeemisessä autoinflammatorisessa oireyhtymässä familiaarinen   Välimeren kuume (Familiar Mediterranaan fever ). Tässä häiriössä esiintyy  toisuvia itsestään ohimeneviä kuumeita ja  serosisia  nivelkavotulehduksia.
IFN stimulaatio indusoi TRIM20. Se säätelee IL-1 ja NF-kB signaaliteitä.
Jokseen vaikeaa tautia aiheutuu, jos on TRIM20 geenimutaatio.  Miltei geeniterpai aihe.  Koetin ktsoa jo son geeniterapiaa, mutta en löytynyt mainintaa. Komplikaationa  taudista on amyloidoosia.
 https://www.ncbi.nlm.nih.gov/pubmed/?term=MEFV+gene+therapy

https://www.nature.com/articles/srep10819

Many tripartite motif-containing (TRIM) proteins, comprising RING-finger, B-Box, and coiled-coil domains, carry additional B30.2 domains on the C-terminus of the TRIM motif and are considered to be pattern recognition receptors involved in the detection of higher order oligomers (e.g. viral capsid proteins).
To investigate the spatial architecture of domains in TRIM proteins we determined the crystal structure of the TRIM20Δ413 fragment at 2.4 Å resolution. This structure comprises the central helical scaffold (CHS) and C-terminal B30.2 domains and reveals an anti-parallel arrangement of CHS domains placing the B-box domains 170 Å apart from each other. Small-angle X-ray scattering confirmed that the linker between CHS and B30.2 domains is flexible in solution. The crystal structure suggests an interaction between the B30.2 domain and an extended stretch in the CHS domain, which involves residues that are mutated in the inherited disease Familial Mediterranean Fever. Dimerization of B30.2 domains by means of the CHS domain is crucial for TRIM20 to bind pro-IL-1β in vitro. To exemplify how TRIM proteins could be involved in binding higher order oligomers we discuss three possible models for the TRIM5α/HIV-1 capsid interaction assuming different conformations of B30.2 domains.
...
 TRIM20 (Uniprot ID: O15553), which is also named pyrin or marenostrin, is special among other TRIM proteins, because it lacks the RING domain that confers ubiquitin ligase activity. In TRIM20 the RING domain is replaced by a PYD domain, which belongs to the death domain superfamily and is frequently involved in homotypic protein-protein interactions (reviewed in ref 3.). Depending on the splice variant of TRIM20 the PYD domain is connected to the B-box domain by either a 60 or a 280 amino acid long linker. Almost 50% of all TRIM proteins - including TRIM20 - carry a B30.2 domain immediately after the coiled-coil domain of the central TRIM motif (Fig. 1A). The B30.2 domain, which was initially called PrySpry domain, because it consists of an N-terminal Pry- and a C-terminal Spry segment, is involved in heterotypic protein-protein interactions⁴. Although TRIM proteins can be recognized by their characteristic signature sequence, their biological functions are often incompletely understood. Many TRIM proteins act as cytoplasmic pattern recognition receptors that sense higher order oligomers, e.g. a lattice of viral capsid (CA) proteins (reviewed in ref 5.).