PMID- 27854284
OWN - NLM
STAT- MEDLINE
DCOM- 20170913
LR  - 20181113
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 8
IP  - 11
DP  - 2016 Nov 15
TI  - The E3 Ubiquitin Ligase TMEM129 Is a Tri-Spanning Transmembrane Protein.
LID - 309
AB  - Misfolded proteins from the endoplasmic reticulum (ER) are transported back into 
      the cytosol for degradation via the ubiquitin-proteasome system. The human 
      cytomegalovirus protein US11 hijacks this ER-associated protein degradation 
      (ERAD) pathway to downregulate human leukocyte antigen (HLA) class I molecules in 
      virus-infected cells, thereby evading elimination by cytotoxic T-lymphocytes. 
      Recently, we identified the E3 ubiquitin ligase transmembrane protein 129 
      (TMEM129) as a key player in this process, where interference with TMEM129 
      activity in human cells completely abrogates US11-mediated class I degradation. 
      Here, we set out to further characterize TMEM129. We show that TMEM129 is a 
      non-glycosylated protein containing a non-cleaved signal anchor sequence. By 
      glycosylation scanning mutagenesis, we show that TMEM129 is a tri-spanning 
      ER-membrane protein that adopts an N(exo)-C(cyto) orientation. This insertion in 
      the ER membrane positions the C-terminal really interesting new gene (RING) 
      domain of TMEM129 in the cytosol, making it available to catalyze ubiquitination 
      reactions that are required for cytosolic degradation of secretory proteins.
FAU - van de Weijer, Michael L
AU  - van de Weijer ML
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. M.L.vandeWeijer@umcutrecht.nl.
FAU - van Muijlwijk, Guus H
AU  - van Muijlwijk GH
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. g.h.vanmuijlwijk@uu.nl.
FAU - Visser, Linda J
AU  - Visser LJ
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. L.J.Visser@uu.nl.
FAU - Costa, Ana I
AU  - Costa AI
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. A.I.CorreiadeAlmeidaCosta@umcutrecht.nl.
FAU - Wiertz, Emmanuel J H J
AU  - Wiertz EJ
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. E.Wiertz@umcutrecht.nl.
FAU - Lebbink, Robert Jan
AU  - Lebbink RJ
AD  - Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The 
      Netherlands. R.J.Lebbink-2@umcutrecht.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161115
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Membrane Proteins)
RN  - EC 2.3.2.27 (TMEM129 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Endoplasmic Reticulum/*chemistry
MH  - Humans
MH  - Intracellular Membranes/*chemistry
MH  - Membrane Proteins/*analysis/*metabolism
MH  - Models, Biological
MH  - Ubiquitin-Protein Ligases/*analysis/*metabolism
MH  - Ubiquitination
PMC - PMC5127023
OTO - NOTNLM
OT  - E3 ligase
OT  - ER-associated protein degradation
OT  - ERAD
OT  - RING domain
OT  - TMEM129
OT  - topology
OT  - transmembrane
COIS- The authors declare that there is no conflict of interest.
EDAT- 2016/11/18 06:00
MHDA- 2017/09/14 06:00
PMCR- 2016/11/01
CRDT- 2016/11/18 06:00
PHST- 2016/09/09 00:00 [received]
PHST- 2016/11/03 00:00 [revised]
PHST- 2016/11/04 00:00 [accepted]
PHST- 2016/11/18 06:00 [entrez]
PHST- 2016/11/18 06:00 [pubmed]
PHST- 2017/09/14 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - v8110309 [pii]
AID - viruses-08-00309 [pii]
AID - 10.3390/v8110309 [doi]
PST - epublish
SO  - Viruses. 2016 Nov 15;8(11):309. doi: 10.3390/v8110309.