TRAF4

Last updated
TRAF4
Protein TRAF4 PDB 2EOD.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TRAF4 , CART1, MLN62, RNF83, TNF receptor associated factor 4
External IDs OMIM: 602464 MGI: 1202880 HomoloGene: 3173 GeneCards: TRAF4
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004295
NM_145751

NM_009423

RefSeq (protein)

NP_004286

NP_033449

Location (UCSC) Chr 17: 28.74 – 28.75 Mb Chr 11: 78.05 – 78.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

TNF receptor-associated factor 4 (TRAF4) also known as RING finger protein 83 (RNF83) is a protein that in humans is encoded by the TRAF4 gene. [5] [6] [7]

Contents

TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold proteins. [8] TRAF proteins connect IL-1R/Toll and TNF receptors with signaling factors that lead to the activation of NF-κB and mitogen-activated protein kinases. However, TRAF4 is not known to interact with TNF receptors and its cellular functions are not well understood. [9]

Protein interactions

TRAF4 has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1), [10] [11] and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one has been determined. [7]

A recent report indicates that TRAF4 binds to NOD-Like Receptors NOD1 and NOD2, and specifically inhibits activation of NF-κB by the activated NOD2-RIP2 complex [12]

Related Research Articles

<span class="mw-page-title-main">RANK</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor κ B (RANK), also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation. It is associated with bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. Osteoprotegerin (OPG) is a decoy receptor for RANKL, and regulates the stimulation of the RANK signaling pathway by competing for RANKL. The cytoplasmic domain of RANK binds TRAFs 1, 2, 3, 5, and 6 which transmit signals to downstream targets such as NF-κB and JNK.

<span class="mw-page-title-main">TRAF6</span> Protein-coding gene in the species Homo sapiens

TRAF6 is a TRAF human protein.

<span class="mw-page-title-main">TRAF2</span> Protein-coding gene in humans

TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.

<span class="mw-page-title-main">TRADD</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the TRADD gene.

<span class="mw-page-title-main">Lymphotoxin beta receptor</span>

Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release. It is a member of the tumor necrosis factor receptor superfamily.

<span class="mw-page-title-main">Janus kinase 1</span>

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.

<span class="mw-page-title-main">Tumor necrosis factor receptor 1</span> Membrane receptor protein found in humans

Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα).

<span class="mw-page-title-main">Death receptor 4</span> Protein found in humans

Death receptor 4 (DR4), also known as TRAIL receptor 1 (TRAILR1) and tumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

<span class="mw-page-title-main">Baculoviral IAP repeat-containing protein 2</span> Protein-coding gene in the species Homo sapiens

Baculoviral IAP repeat-containing protein 2 is a protein that in humans is encoded by the BIRC2 gene.

<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">TRAF5</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 5 is a protein that in humans is encoded by the TRAF5 gene.

<span class="mw-page-title-main">TRAF3</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

<span class="mw-page-title-main">TNFAIP3</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor, alpha-induced protein 3 or A20 is a protein that in humans is encoded by the TNFAIP3 gene.

<span class="mw-page-title-main">MAP3K14</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 14 also known as NF-kappa-B-inducing kinase (NIK) is an enzyme that in humans is encoded by the MAP3K14 gene.

<span class="mw-page-title-main">TANK (gene)</span> Protein-coding gene in the species Homo sapiens

TRAF family member-associated NF-kappa-B activator is a protein that in humans is encoded by the TANK gene.

Transforming growth factor-β (TGF-β) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signalling routes are also employed by this pleiotropic cytokine. For instance recently, we [?] have demonstrated that ligand-occupied TGF-β receptors can directly trigger the TRAF6-TAK1 signalling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule TTRAP as a novel component of this non-canonical TGF-β pathway. We show that the protein associates with TGF-β receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-β activated p38 and NF-κB responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-β, suggesting that the protein is an important component of the TGF-β induced apoptotic process.

<span class="mw-page-title-main">TRAP1</span> Protein-coding gene in the species Homo sapiens

Heat shock protein 75 kDa, mitochondrial is a protein that in humans is encoded by the TRAP1 gene.

<span class="mw-page-title-main">MAP4K5</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase kinase 5 is an enzyme that in humans is encoded by the MAP4K5 gene.

<span class="mw-page-title-main">TNFRSF19</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily, member 19, also known as TNFRSF19 and TROY is a human gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 2</span> Membrane receptor protein found in humans

Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000076604 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000017386 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Regnier CH, Tomasetto C, Moog-Lutz C, Chenard MP, Wendling C, Basset P, Rio MC (Dec 1995). "Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma". J Biol Chem. 270 (43): 25715–21. doi: 10.1074/jbc.270.43.25715 . PMID   7592751.
  6. Tomasetto C, Regnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC (Jan 1996). "Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17". Genomics. 28 (3): 367–76. doi:10.1006/geno.1995.1163. PMID   7490069.
  7. 1 2 "Entrez Gene: TRAF4 TNF receptor-associated factor 4".
  8. Wajant H, Henkler F, Scheurich P (June 2001). "The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators". Cell. Signal. 13 (6): 389–400. doi:10.1016/S0898-6568(01)00160-7. PMID   11384837.
  9. Kedinger V, Rio MC (2007). "TRAF4, the Unique Family Member". TNF Receptor Associated Factors (TRAFs). Advances in Experimental Medicine and Biology. Vol. 597. pp. 60–71. doi:10.1007/978-0-387-70630-6_5. ISBN   978-0-387-70629-0. PMID   17633017.
  10. Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE (October 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". J. Biol. Chem. 274 (42): 30202–8. doi: 10.1074/jbc.274.42.30202 . PMID   10514511.
  11. Krajewska M, Krajewski S, Zapata JM, Van Arsdale T, Gascoyne RD, Berern K, McFadden D, Shabaik A, Hugh J, Reynolds A, Clevenger CV, Reed JC (June 1998). "TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues". Am. J. Pathol. 152 (6): 1549–61. PMC   1858434 . PMID   9626059.
  12. Marinis JM, Homer CR, McDonald C, Abbott DW (2011). "A Novel Motif in the Crohn's Disease Susceptibility Protein, NOD2, Allows TRAF4 to Down-regulate Innate Immune Responses". J. Biol. Chem. 286 (3): 1938–1950. doi: 10.1074/jbc.M110.189308 . PMC   3023490 . PMID   21097508.

Further reading