Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Binds also to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-alpha-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation. Interacts with TRAF1 AND TRAF2 as well as with JUN. Forms a multimeric complex with RUNX2 and E3 ubiquitin ligase WWP1. Expressed in macrophages, lymphocytes, brain, thymus, spleen and bone marrow. Expressed in osteoblasts, whole bone and, to a lesser extent, in osteoclasts. Expressed in the thymus with increasing level, approximately 4-fold, from 15.5 dpc to 16.5 dpc, constant level from 16.5 dpc to birth, then decrease to a low level by P30. Expressed at 13.5 dpc in the dorsal root ganglia of the peripheral nervous system and the trigeminal ganglion of the metencephalon and at relatively low levels in the cerebral cortex; no significant expression was observed prior to 13.5 dpc. Expressed in the spinal cord at 19 dpc, but weakly detected in the lung and the liver. Upon CD3/CD28 stimulation in CD4 T-cells. Induced by LPS in pre-B-cells. ZAS2 domain binds DNA as dimers, tetramers, and multiple of tetramers and readily forms highly ordered DNA-protein structures. Phosphorylated on threonine and serine residues. Phosphorylation by cyclin-dependent kinase CDK1 decreases HIVEP3 DNA binding affinity, and by epidermal growth factor receptor kinase increases its DNA binding affinity. Mice display adult-onset osteosclerosis with increased bone mass due to increased osteoblast activity; the osteoblasts contain elevated levels of Runx2. Hivep3 gene expression is probably controlled by a combination of differential promoter usage, alternative splicing, and possible intergenic splicing. Truncated N-terminus.