TRAF4
TRAF4 (TNF receptor-associated factor 4) is an adapter protein with E3 ubiquitin ligase activity that acts in cell proliferation, migration, differentiation, DNA repair and apoptosis. It is also known as CART1, MLN62 and RNF83, and belongs to the TRAF family. Browse Assay Genie's current range of TRAF4 research reagents below, or read on for the biology behind the target.
TRAF4 is an adapter protein with E3 ligase activity that takes part in many biological processes, including cell proliferation, migration, differentiation, DNA repair, platelet activation and apoptosis. It promotes EGFR-mediated signalling by facilitating EGFR dimerisation and downstream AKT activation. It also ubiquitinates several substrates with distinct chain linkages: Lys-48-linked chains on SMURF2 target it for proteasomal degradation and support osteogenic differentiation, Lys-63-linked ubiquitination of CHK1 promotes cell cycle arrest and DNA repair, and an atypical Lys-29-linked ubiquitination of IRS1 is important for insulin-like growth factor signal transduction.
The protein regulates NF-kappa-B activation in response to Toll-like receptor signalling and is required for activation of RPS6KB1 downstream of TNF. It modulates TRAF6 function and inhibits adipogenic differentiation by activating pyruvate kinase PKM and, in turn, the beta-catenin pathway. It is required for normal skeletal development and for development of the respiratory tract. UniProt records localisation to the cytoplasm, nucleus, perinuclear region, tight junctions, cell membrane and cytoskeleton.
The TRAF4 gene encodes a member of the TNF receptor-associated factor family, B subfamily, whose proteins mediate signal transduction from TNF receptor superfamily members. HGNC classes it among RING finger E3 ubiquitin protein ligases and TRAF-type zinc fingers. TRAF4 interacts with the neurotrophin receptor p75 (NTR/NTSR1) and negatively regulates NTR-induced cell death and NF-kappa-B activation. It also binds p47phox, a regulatory component of the NAD(P)H oxidase complex, and is thought to contribute to oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed.
TRAF4 builds Lys-48, Lys-63 and atypical Lys-29 ubiquitin chains on substrates such as SMURF2, CHK1 and IRS1, making it a model for linkage-specific ubiquitination.
TRAF4 promotes EGFR dimerisation and AKT activation, and supports IGF signal transduction through IRS1, linking it to proliferation control.
Lys-63-linked ubiquitination of CHK1 by TRAF4 promotes cell cycle arrest and activation of DNA repair.
TRAF4 is required for normal skeleton and respiratory tract development and influences osteogenic and adipogenic differentiation.
TRAF4 is an adapter protein with E3 ubiquitin ligase activity. It promotes EGFR and IGF signalling, ubiquitinates substrates including SMURF2, CHK1 and IRS1, regulates NF-kappa-B downstream of Toll-like receptors, and is required for skeletal and respiratory tract development.
TRAF4 is also known as CART1, MLN62 and RNF83, and its full name is TNF receptor associated factor 4. NCBI notes that alternatively spliced transcript variants exist, although the full-length nature of only one has been determined.
TRAF4 belongs to the TNF receptor-associated factor family, B subfamily. A mouse ortholog, Traf4, is recorded for the gene. Check the datasheet of any product for its validated reactivity.
Other TRAF family members and related signalling proteins with research products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9BUZ4; product specifications from Assay Genie datasheets.