TRIM2,
NHL-TRIM2 , CMT2R, RNF86 (Kr. 4q31.3)
Tämä
TRIM2 geeni koodaa proteiinia, jossa on RBCC motiivi (RING, B-Box,
Coiled coil) . Lisäksi se omaa filamiinidomeenin ja 6
NHL-toistojaksoa . Proteiinissa on 744 aminohappoa. NHL-
toistoja ksot C-terminaalissaan omaavia TRIM-jäseniä ovat TRIM2,
-3, -32 ja -71).
TRIM2
sijaitse sytoplasmisissa filamenteissa ja on aksonissa
neuroprotektiivinen, toimii E3-ligaasina kohdeproteiineilleen.
(UBE2D1 riippuvainen E3-ubikitiiniligaasi, joka välittää NEFL:n,
kevytketjusen neurofilamentin ja fosforyloidun Bcl2L11
ubikitinaatiota. (Kts. Kuva neuronista) Saattaa osallistua neuronin
nopean iskemiavasteen toleranssiin. Mutaatiot voivat johtaa
aksonaaliseen neuropatiaan, koksa neurofilamenttai alkaa kertyä
ilman TRIM2 normaalifunktiota (Charciot Marie Tooth 2.
Proteiinihomeostaasissa TRIM2
säätyy mikroRNA miRNA-9 ja miRNA186 avulla alas. Nämä
mikroRNA:ta säätävät alas myös TGFB1, SIRT1, BTBD3). AD ja
AMD- taudeissa taas säätää juuri nämä mikroRNA:t alas.
Geenistä
pleissautuu useita variantteja. On todettu että TRIM2 geeni kuuluu
myös niihin TRIM-geeneihin, jotka ovat restriktiivisiä
endogeenisia retroviruksia kohtaan.
-
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic filaments. It plays a neuroprotective role and functions as an E3-ubiquitin ligase in proteasome-mediated degradation of target proteins. Mutations in this gene can cause early-onset axonal neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014] Broad expression in brain (RPKM 37.2), thyroid (RPKM 33.2) and 18 other
Kuva
neuronista: TRIM2 kohdemolekyyli, jonka se ubikitinoi, on NEFL ,
kevytketjuinen neurofilamentti aksonissa.
PubMed
artikkeleita:
1.
Exome
sequencing reveals homozygous TRIM2 mutation in a patient with early
onset CMT and bilateral vocal cord paralysis. Pehlivan D, et
al. Hum Genet,
2015 Jun. PMID 25893792, Free
PMC Article
2.
Differential
expression of tripartite motif-containing family in normal human
dermal fibroblasts in response to porcine endogenous retrovirus
infection. Kimsa MW, et
al. Folia Biol
(Praha), 2014. PMID 25056437 Antiretroviral restriction factors may
play an essential role in the safety of xenotransplantation.
Therefore, the present study focused on investigation of the changes
in the tripartite motif-containing family (TRIM) gene expression in
normal human dermal fibroblasts with and without lipopolysaccharide
stimulation in response to porcine endogenous retrovirus infection.
Analysis of the expression profile of TRIMs was performed using
oligonucleotide microarrays and QRT-PCR. Nine (TRIM1, TRIM2, TRIM5,
TRIM14, TRIM16, TRIM18, TRIM22, TRIM27 and TRIM31) statistically
significantly differentially expressed genes were found (P < 0.05,
one-way ANOVA). In conclusion, comprehensive analysis of retroviral
restriction factor gene expression in human dermal fibroblasts before
and after porcine endogenous retrovirus infection with and without
LPS stimulation may suggest association of the selected TRIMs with
antiretroviral activity.
3.
Expressioodular
architecture that includes N-terminal RING finger and B-box domains,
a middle coiled-coil domain and a C-terminal NHL domain. To
characterize the functional role of its NHL domain …n,
purification, crystallization and preliminary X-ray diffraction
analysis of the C-terminal NHL domain of human TRIM2. Guan X, et
al. Acta
Crystallogr F Struct Biol Commun, 2014 May. PMID 24817735, Free
PMC Article The tripartite motif-containing protein 2 (TRIM2)
functions as an E3 ubiquitin ligase. Loss of function of TRIM2 has
been shown to result in early-onset axonal neuropathy. As a member of
the TRIM-NHL family of proteins, TRIM2 has a conserved modular
architecture that includes N-terminal RING finger and B-box domains,
a middle coiled-coil domain and a C-terminal NHL domain. To
characterize the functional role of its NHL domain …
4.
Deficiency
of the E3 ubiquitin ligase TRIM2 in early-onset axonal neuropathy.
Ylikallio E, et al.
Hum Mol Genet, 2013 Aug 1. PMID 23562820
Inherited
peripheral neuropathies are a heterogeneous group of disorders that
can affect patients of all ages. Children with inherited neuropathy
often develop severe disability, but the genetic causes of recessive
early-onset axonal neuropathies are not fully known. We have taken a
whole-exome sequencing approach to identify causative disease
mutations in single patients with early-onset axonal neuropathy.
Here, we report compound heterozygous mutations in the tripartite
motif containing 2 (TRIM2) gene in a patient with childhood-onset
axonal neuropathy, low weight and small muscle mass. We show that the
patient fibroblasts are practically devoid of TRIM2, through mRNA and
protein instability caused by the mutations. TRIM2 is an E3 ubiquitin
ligase that ubiquitinates neurofilament light chain, a component of
the intermediate filament in axons. Resembling the findings in our
patient's sural nerve biopsy, Trim2-gene trap mice showed axonopathy
with accumulations of neurofilaments inside axons. Our results
suggest that loss-of-function mutations in TRIM2 are a cause of
axonal neuropathy,which we propose to develop as a consequence of
axonal accumulation of neurofilaments, secondary to lack of its
ubiquitination by TRIM2. Hum
Mol Genet. 2013 Aug 1;22(15):2975-83. doi: 10.1093/hmg/ddt149.
Epub 2013 Apr
Muistiin
28.3. 2018
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