Nerve growth factor IB

2QW4, 3V3E, 3V3Q, 4JGV, 4KZI, 4KZJ, 4KZM, 4RZE, 4RZF, 4RZG, 4RE8, 4REE, 4REF, 4WHF, 4WHG316415370ENSG00000123358ENSMUSG00000023034P22736P12813NM_001202233NM_001202234NM_002135NM_173157NM_173158NM_010444NP_775180.1NP_034574The nerve growth factor IB (NGFIB) also known as Nur77 or NR4A1 (nuclear receptor subfamily 4 group A member 1) is a protein that in humans is encoded by the NR4A1 gene.1cit: DNA-BINDING MECHANISM OF THE MONOMERIC ORPHAN NUCLEAR RECEPTOR NGFI-B1yje: Crystal structure of the rNGFI-B ligand-binding domain The nerve growth factor IB (NGFIB) also known as Nur77 or NR4A1 (nuclear receptor subfamily 4 group A member 1) is a protein that in humans is encoded by the NR4A1 gene. Nerve growth factor IB is a member of the Nur nuclear receptor family of intracellular transcription factors. NGFIB is involved in cell cycle mediation, inflammation and apoptosis. The NGFIB protein plays a key role in mediating inflammatory responses in macrophages. In addition, subcellular localization of the NGFIB protein appears to play a key role in the survival and death of cells. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple alternatively spliced variants, encoding the same protein, have been identified. The NR4A1 gene contains seven exons. An amino terminal transactivation domain is encoded in exon 2, a DNA-binding domain in exons 3 and 4, and dimerisation and ligand-binding domains is exons 5 to 7. The protein has an atypical ligand-binding domain that is unlike the classical ligand-binding domain in most nuclear receptors. The classical domain contains a ligand-receiving pocket and co-activator site, both of which are lacking in the NR4A family. Whereas most nuclear receptors have a hydrophobic surface that results in a cleft, NGFI-B has a hydrophilic surface. Cofactors interact with NGFI-B at a hydrophobic region between helices 11 and 12 to modulate transcription. Along with the two other Nur family members, NGFIB is expressed in macrophages following inflammatory stimuli. This process is mediated by the NF-κB (nuclear factor-kappa B) complex, a ubiquitous transcription factor involved in cellular response to stress. NGFIB can be induced by many physiological and physical stimuli. These include physiological stimuli such as 'fatty acids, stress, prostaglandins, growth factors, calcium, inflammatory cytokines, peptide hormones, phorbol esters, and neurotransmitters' and physical stimuli including 'magnetic fields, mechanical agitation (causing fluid shear stress), and membrane depolarization'. Ligands do not bind to NGFIB, so modulation occurs at the level of protein expression and posttranslational modification.Besides these, NR4A1 can mediate T cell function, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression ofNR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumor and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes.