https://www.ncbi.nlm.nih.gov/pubmed/16547521
- Summary:The protein encoded by this gene is a member of the
Kelch-like gene family, whose members contain a BTB/POZ domain, a BACK
domain, and several Kelch domains. The encoded protein possesses six
Kelch domains and localizes to the endoplasmic reticulum, where it
interacts with torsin-1A. [provided by RefSeq, Sep 2015]
- ExpressionBiased expression in thyroid (RPKM 4.4), spleen (RPKM 2.8) and 10 other tissues See more
- Preferred Names
- kelch-like protein 14
- Names
- kelch-like 14
- printor
- protein interactor of Torsin-1A
- ( Torsin-1A? https://www.ncbi.nlm.nih.gov/pubmed/26092934.TorsinA (also known as torsin-1A)
is a membrane-embedded AAA+ ATPase that has an important role in the
nuclear envelope lumen. However, most torsinA is localized in the
peripheral endoplasmic reticulum (ER) lumen where it has a slow mobility
that is incompatible with free equilibration between ER subdomains. We
now find that nuclear-envelope-localized torsinA is present on the inner
nuclear membrane (INM) and ask how torsinA reaches this subdomain. The
ER system contains two transmembrane proteins, LAP1 and LULL1 (also
known as TOR1AIP1 and TOR1AIP2, respectively), that reversibly
co-assemble with and activate torsinA. Whereas LAP1 localizes on the
INM, we show that LULL1 is in the peripheral ER and does not enter the
INM. Paradoxically, interaction between torsinA and LULL1 in the ER
targets torsinA to the INM. Native gel electrophoresis reveals torsinA
oligomeric complexes that are destabilized by LULL1. Mutations in
torsinA or LULL1 that inhibit ATPase activity reduce the access of
torsinA to the INM. Furthermore, although LULL1 binds torsinA in the ER
lumen, its effect on torsinA localization requires
cytosolic-domain-mediated oligomerization. These data suggest that LULL1
oligomerizes to engage and transiently disassemble torsinA oligomers,
and is thereby positioned to transduce cytoplasmic signals to the INM
through torsinA).
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The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing.
Vater I, et al. Leukemia, 2015 Mar. PMID 25189415 https://www.ncbi.nlm.nih.gov/pubmed/25189415 To decipher the mutational pattern of primary CNS lymphoma (PCNSL), we
performed whole-exome sequencing to a median coverage of 103 × followed
by mutation verification in 9 PCNSL and validation using Sanger
sequencing in 22 PCNSL. We identified a median of 202 (range: 139-251)
potentially somatic single nucleotide variants (SNV) and 14 small indels
(range: 7-22) with potentially protein-changing features per PCNSL.
Mutations affected the B-cell receptor, toll-like receptor(TLR), and NF-κB
and genes involved in chromatin structure and modifications, cell-cycle
regulation, and immune recognition. A median of 22.2% (range:
20.0-24.7%) of somatic SNVs in 9 PCNSL overlaps with the RGYW motif
targeted by somatic hypermutation (SHM); a median of 7.9% (range:
6.2-12.6%) affects its hotspot position suggesting a major impact of SHM
on PCNSL pathogenesis. In addition to the well-known targets of
aberrant SHM (aSHM) (PIM1), our data suggest new targets of aSHM
(KLHL14, OSBPL10, and SUSD2). Among the four most frequently mutated
genes was ODZ4 showing protein-changing mutations in 4/9 PCNSL. Together
with mutations affecting CSMD2, CSMD3, and PTPRD, these findings may
suggest that alterations in genes having a role in CNS development may
facilitate diffuse large B-cell lymphoma manifestation in the CNS. This
may point to intriguing mechanisms of CNS tropism in PCNSL.
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Printor, a novel torsinA-interacting protein implicated in dystonia pathogenesis.
Giles LM, et al. J Biol Chem, 2009 Aug 7. PMID 19535332, Free PMC Article Early onset generalized dystonia (DYT1) is an autosomal dominant
neurological disorder caused by deletion of a single glutamate residue
(torsinA DeltaE) in the C-terminal region of the AAA(+) (ATPases
associated with a variety of cellular activities) protein torsinA. The
pathogenic mechanism by which torsinA DeltaE mutation leads to dystonia
remains unknown. Here we report the identification and characterization
of a 628-amino acid novel protein, printor (KLHL14), that interacts with torsinA.
Printor co-distributes with torsinA in multiple brain regions and
co-localizes with torsinA in the endoplasmic reticulum. Interestingly,
printor selectively binds to the ATP-free form but not to the ATP-bound
form of torsinA, supporting a role for printor as a cofactor rather than
a substrate of torsinA. The interaction of printor with torsinA is
completely abolished by the dystonia-associated torsinA DeltaE mutation.
Our findings suggest that printor is a new component of the DYT1
pathogenic pathway and provide a potential molecular target for
therapeutic intervention in dystonia.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755898/figure/F1/
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Regulation of Torsin ATPases by LAP1 and LULL1.
Zhao C, et al. Proc Natl Acad Sci U S A, 2013 Apr 23. PMID 23569223, Free PMC Article TorsinA is a membrane-associated AAA+ (ATPases associated with a variety
of cellular activities) ATPase implicated in primary dystonia, an
autosomal-dominant movement disorder. We reconstituted TorsinA and its
cofactors in vitro and show that TorsinA does not display ATPase
activity in isolation; ATP hydrolysis is induced upon association with
LAP1 and LULL1, type II transmembrane proteins residing in the nuclear
envelope and endoplasmic reticulum. This interaction requires TorsinA to
be in the ATP-bound state, and can be attributed to the luminal domains
of LAP1 and LULL1. https://iiif.elifesciences.org/lax:03239%2Felife-03239-fig5-v2.tif/full/617,/0/default.jpg This ATPase activator function controls the
activities of other members of the Torsin family in distinct fashion,
leading to an acceleration of the hydrolysis step by up to two orders of
magnitude. The dystonia-causing mutant of TorsinA is defective in this
activation mechanism, suggesting a loss-of-function mechanism for this
congenital disorder.
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Update on the Kelch-like (KLHL) gene family.
Dhanoa BS, et al. Hum Genomics, 2013 May 15. PMID 23676014, Free PMC Article
-
Prediction
of the coding sequences of unidentified human genes. XVI. The complete
sequences of 150 new cDNA clones from brain which code for large
proteins in vitro.
Nagase T, et al. DNA Res, 2000 Feb 28. PMID 10718198
-
ORIGIN
1 msrsgdrtst fdpshsdnll hglnllwrkq lfcdvtltaq gqqfhchkav lascsqyfrs
61 lfsshpplgg gvggqdglga pkdqqqppqq qpsqqqqppp qeepgtpsss pddklltspr
121 ainnlvlqgc ssiglrlvle ylytanvtls ldtveevlsv skilhipqvt klcvqflndq
181 isvqnykqvc kiaalhglee tkklankylv edvlllnfee mralldslpp pveselalfq
241 msvlwlehdr etrmqyapdl mkrlrfalip apelvervqs vdfmrtdpvc qkllldamny
301 hlmpfrqhcr qslasrirsn kkmlllvggl ppgpdrlpsn lvqyyddekk twkiltimpy
361 nsahhcvvev enflfvlgge dqwnpngkhs tnfvsrydpr fnswiqlppm qerrasfyac
421 rldkhlyvig grnetgylss vecynletne wryvsslpqp laahagavhn gkiyisggvh
481 ngeyvpwlyc ydpvmdvwar kqdmntkrai htlavmndrl yaiggnhlkg fshldvmlve
541 cydpkgdqwn ilqtpilegr sgpgcavldd siylvggysw smgaykssti cycpekgtwt
601 elegdvaepl agpacvtvil pscvpynk
- Löytyy RGYW motiiveja.
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