TRAF6 is a
TRAF
TNF receptor associated factors (TRAFs) are a family of proteins primarily involved in the regulation of inflammation, antiviral responses and apoptosis.
Currently, seven TRAF proteins have been characterized in mammals: TRAF1, TRAF2, TRAF3, TRAF4 ...
human protein.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including
IRAK1/IRAK,
SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are
ubiquitin
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fo ...
conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.
Interactions
TRAF6 has been shown to
interact
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with:
*
ASK1
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and ...
,
*
CD40
Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on T helper cell, TH cells to CD40 activates antigen presenting cells and induces a ...
,
*
FHL2
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.
Function
FHL-2 is thought to have a ...
,
*
HSPB2
Heat shock protein beta-2 is a protein that in humans is encoded by the ''HSPB2'' gene.
Interactions
HSPB2 has been shown to interact with:
* CRYAB,
* HSPB8,
* Myotonic dystrophy protein kinase and
* TRAF6
TRAF6 is a TRAF human protein.
...
,
*
IKBKG
NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the ''IKBKG'' gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB ...
,
IRAK1
Interleukin-1 receptor-associated kinase 1 (IRAK-1) is an enzyme in humans encoded by the ''IRAK1'' gene. IRAK-1 plays an important role in the regulation of the expression of inflammatory genes by immune cells, such as monocytes and macrophages, ...
,TAB1
Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the ''TAB1'' gene.
Function
The protein encoded by this gene was identified as a regulator of the MAP kinase kinase kinase MAP3K7/ ...
,MAP3K7IP2
Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the ''MAP3K7IP2'' gene.
The protein encoded by this gene is an activator of MAP3K7/ TAK1, which is required for the IL-1 induced act ...
,MAP3K7
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the ''MAP3K7'' gene.
Structure
TAK1 is an evolutionarily conserved kinase in the MAP3 K family and clusters with the tyro ...
PPP4C
Serine/threonine-protein phosphatase 4 catalytic subunit is an enzyme that in humans is encoded by the ''PPP4C'' gene.
Interactions
PPP4C has been shown to interact with:
* CCDC6,
* CCT2,
* CCT3,
* CCT4,
* CCT5,
* CCT6A,
* CCT7,
* IG ...
,RANK
Rank is the relative position, value, worth, complexity, power, importance, authority, level, etc. of a person or object within a ranking, such as:
Level or position in a hierarchical organization
* Academic rank
* Diplomatic rank
* Hierarchy
* H ...
,SDCBP
Syntenin-1 is a protein that in humans is encoded by the ''SDCBP'' gene.
Function
The protein encoded by this gene was initially identified as a molecule linking syndecan-mediated signaling to the cytoskeleton. The syntenin protein contains ta ...
,SIGIRR
Single Ig IL-1-related receptor (SIGIRR), also called Toll/Interleukin-1 receptor 8 (TIR8) or Interleukin-1 receptor 8 (IL-1R8), is transmembrane protein encoded by gene ''SIGIRR'', which modulate inflammation, immune response, and tumorigenesis o ...
,Sequestosome 1
Sequestosome-1 is a protein that in humans is encoded by the ''SQSTM1'' gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacti ...
,TAX1BP1
Tax1-binding protein 1 is a protein that in humans is encoded by the ''TAX1BP1'' gene.
Interactions
TAX1BP1 has been shown to interact with TNFAIP3 and TRAF6. TAX1BP1 binds to TNFAIP3
Tumor necrosis factor, alpha-induced protein 3 or A20 i ...
,[
* ]TNFAIP3
Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the ''TNFAIP3'' gene.
This gene was identified as a gene whose expression is rapidly induced by the tumor necrosis factor (TNF). The protein encoded ...
,TNFRSF13B
Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.
TNFRSF13B is a transmembrane protein of the TNF re ...
,UBE2N
Ubiquitin-conjugating enzyme E2 N is a protein that in humans is encoded by the ''UBE2N'' gene.
Function
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradat ...
,Ubiquitin C
Polyubiquitin-C is a protein encoded by the ''UBC'' gene in humans. Polyubiquitin-C is one of the sources of ubiquitin, along with UBB, UBA52, and RPS27A.
''UBC'' gene is one of the two stress-regulated polyubiquitin genes (''UBB'' and ''UBC'') ...
.
Model organisms
Model organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...
s have been used in the study of TRAF6 function. A conditional knockout mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...
line called ''Traf6tm2a(EUCOMM)Wtsi'' was generated at the Wellcome Trust Sanger Institute
The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.
It is located on the Wellcome G ...
.phenotypic screen
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
References
Further reading
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External links
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{{Cytokine receptor modulators