A specific receptor has not been identified, but some signaling pathways involved in its bone-regenaration function has been elucidated. In blood serum it is bound to α2M along with two other binding proteins that are not clearly identified. It is found in human and rat circulation as well as regenerating bone marrow. This is converted into OGP through the cleavage of 5 amino-terminal residues. Translation is initiated at the 85th amino acid of the histone H4 mRNA, resulting in a 19-aa peptide (preOGP).

The Osteogenic Growth Peptide (OGP) is a 14-aa peptide produced from alternative translation of histone H4 mRNA, sharing the C-terminal sequence ALKRQGRTLYGFGG of histone H4. These mutations were located within either the H4 core globular domain (involved in protein-protein interaction) or C-terminal tail (involved in post-translational modification). Ten amino acids were affected, six of which were found recurrently. Pathogenic de novo missense variants have been identified in six H4 genes ( HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4I, HIST1H4J) in 33 individuals total, all presenting with neurodevelopmental features of intellectual disability and motor and/or gross developmental delay, but with variable non-neurological features. Variants in human histone H4 were only recently discovered and are very rare. There are H4 genes that are constitutively expressed throughout the cell cycle that encode for proteins that are identical in sequence to the major H4.

Histone H4 is one of the slowest evolving proteins. This tetramer further combines with two H2a-H2b dimers to form the compact Histone octamer core. Histone proteins H3 and H4 bind to form a H3-H4 dimer, two of these H3-H4 dimers combine to form a tetramer. Histone H4 is a 102 to 135 amino acid protein which shares a structural motif, known as the histone fold, formed from three a-helices connected by two loops. Most changes in histone sequences are lethal the few that are not lethal cause changes in the pattern of gene expression as well as other abnormalities. This evolutionary conservation suggests that the functions of histone proteins involve nearly all of their amino acids so that any change is deleterious to the cell. For example, the amino acid sequence of histone H4 from a pea and cow differ at only 2 out of the 102 positions. Histone proteins are among the most highly conserved eukaryotic proteins. HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4G, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L, HIST2H4A, HIST2H4B, HIST4H4. Histone H4 is encoded in multiple genes at different loci including: Histone H4 is an important protein in the structure and function of chromatin, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes. These modifications may alter expression of genes located on DNA associated with its parent histone octamer. Covalently bonded modifications include acetylation and methylation of the N-terminal tails. Histone proteins are highly post-translationally modified. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on a string' organization. Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. One of the five main histone proteins involved in the structure of chromatin H4 histone, family 3

What chromosome is SCIDS on