Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid[5]) noncollagenous protein hormone found in bone and dentin, first identified as a calcium-binding protein in chick bone.[6]
Because osteocalcin has gla domains, its synthesis is vitamin K dependent. In humans, osteocalcin is encoded by the BGLAP gene.[7][8] Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor.[9][10]
| Identifiers | |||
|---|---|---|---|
| Aliases | BGLAP, BGP, OC, OCN, bone gamma-carboxyglutamate protein, Osteocalcin | ||
Osteopontin (OPN), also known as bone sialoprotein I (BSP-1 or BNSP), early T-lymphocyte activation (ETA-1), secreted phosphoprotein 1 (SPP1), 2ar and Rickettsia resistance (Ric),[5] is a protein that in humans is encoded by the SPP1 gene (secreted phosphoprotein 1). The murine ortholog is Spp1. Osteopontin is a SIBLING (glycoprotein) that was first identified in 1986 in osteoblasts.
The prefix osteo- indicates that the protein is expressed in bone, although it is also expressed in other tissues. The suffix -pontin is derived from "pons," the Latin word for bridge, and signifies osteopontin's role as a linking protein. Osteopontin is an extracellular structural protein and therefore an organic component of bone. Synonyms for this protein include sialoprotein I and 44K BPP (bone phosphoprotein).
The gene has 7 exons, spans 5 kilobases in length and in humans it is located on the long arm of chromosome 4 region 22 (4q1322.1). The protein is composed of ~300 amino acids residues and has ~30 carbohydrate residues attached, including 10 sialic acid residues, which are attached to the protein during post-translational modification in the Golgi apparatus. The protein is rich in acidic residues: 30-36% are either aspartic or glutamic acid.
Isoforms[edit]
Full-length OPN (OPN-FL) can be modified by thrombin cleavage, which exposes a cryptic sequence, SVVYGLR on the cleaved form of the protein known as OPN-R (Fig. 1). This thrombin-cleaved OPN (OPN-R) exposes an epitope for integrin receptors of α4β1, α9β1, and α9β4.[11][12] These integrin receptors are present on a number of immune cells such as mast cells,[13] neutrophils,[14] and T cells. It is also expressed by monocytes and macrophages.[15] Upon binding these receptors, cells use several signal transduction pathways to elicit immune responses in these cells. OPN-R can be further cleaved by Carboxypeptidase B (CPB) by removal of C-terminal arginine and become OPN-L. The function of OPN-L is largely unknown.
It appears an intracellular variant of OPN (iOPN) is involved in a number of cellular processes including migration, fusion and motility.[16][17][18][19] Intracellular OPN is generated using an alternative translation start site on the same mRNA species used to generate the extracellular isoform.[20] This alternative translation start site is downstream of the N-terminal endoplasmic reticulum-targeting signal sequence, thus allowing cytoplasmic translation of OPN.
Various human cancers, including breast cancer, have been observed to express splice variants of OPN.[21][22] The cancer-specific splice variants are osteopontin-a, osteopontin-b, and osteopontin-c. Exon 5 is lacking from osteopontin-b, whereas osteopontin-c lacks exon 4.[21] Osteopontin-c has been suggested to facilitate the anchorage-independent phenotype of some human breast cancer cells due to its inability to associate with the extracellular matrix.[21]
Biosynthesis[edit]
Osteopontin is biosynthesized by a variety of tissue types including cardiac fibroblasts,[23]preosteoblasts, osteoblasts, osteocytes, odontoblasts, some bone marrow cells, hypertrophic chondrocytes, dendritic cells, macrophages,[24] smooth muscle,[25] skeletal muscle myoblasts,[26] endothelial cells, and extraosseous (non-bone) cells in the inner ear, brain, kidney, deciduum, and placenta. Synthesis of osteopontin is stimulated by calcitriol(1,25-dihydroxy-vitamin D3).
Extracellular inorganic phosphate (ePi) has also been identified as a modulator of OPN expression.[37]
Stimulation of OPN expression also occurs upon exposure of cells to pro-inflammatory cytokines,[38] classical mediators of acute inflammation (e.g. tumour necrosis factor α [TNFα], infterleukin-1β [IL-1β]), angiotensin II, transforming growth factor β (TGFβ) and parathyroid hormone (PTH),[39][40] although a detailed mechanistic understanding of these regulatory pathways are not yet known. Hyperglycemia and hypoxia are also known to increase OPN expression.[39][41][42]
Osteopontin (OPN) expression is modulated by Schistosoma mansoni egg antigen. [34]
Schistosoma mansoni egg antigens directly stimulate the expression of the profibrogenic molecule osteopontin (OPN), and systemic OPN levels strongly correlate with disease severity, suggesting its use as a potential morbidity biomarker. Investigation into the impact of Praziquantel use on systemic OPN levels and on liver collagen deposition in chronic murine schistosomiasis revealed that Praziquantel treatment significantly reduced systemic OPN levels and liver collagen deposition, indicating that OPN could be a reliable tool for monitoring PZQ efficacy and fibrosis regression. [35][36]
https://en.wikipedia.org/wiki/Osteopontin
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized (as in the case of autoimmune diseases) are also epitopes.[1]
The epitopes of protein antigens are divided into two categories, conformational epitopes and linear epitopes, based on their structure and interaction with the paratope.[2] Conformational and linear epitopes interact with the paratope based on the 3-D conformation adopted by the epitope, which is determined by the surface features of the involved epitope residues and the shape or tertiary structure of other segments of the antigen. A conformational epitope is formed by the 3-D conformation adopted by the interaction of discontiguous amino acid residues. In contrast, a linear epitope is formed by the 3-D conformation adopted by the interaction of contiguous amino acid residues. A linear epitope is not determined solely by the primary structure of the involved amino acids. Residues that flank such amino acid residues, as well as more distant amino acid residues of the antigen affect the ability of the primary structure residues to adopt the epitope's 3-D conformation.[3][4][5][6][7] The proportion of epitopes that are conformational is unknown.[8]
https://en.wikipedia.org/wiki/Epitope
A mast cell (also known as a mastocyte or a labrocyte[1]) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877.[2] Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumours.[3][4]
The mast cell is very similar in both appearance and function to the basophil, another type of white blood cell. Although mast cells were once thought to be tissue-resident basophils, it has been shown that the two cells develop from different hematopoieticlineages and thus cannot be the same cells.[5]
https://en.wikipedia.org/wiki/Mast_cell
An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA. Just as the entire set of genes for a speciesconstitutes the genome, the entire set of exons constitutes the exome.
https://en.wikipedia.org/wiki/Exon
Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone.[1] The term "sialic acid" (from the Greek for saliva, σίαλον - sÃalon) was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this group is N-acetylneuraminic acid (Neu5Ac or NANA) found in animals and some prokaryotes.
Sialic acids are found widely distributed in animal tissues and related forms are found to a lesser extent in other organisms like in some micro-algae,[2] bacteria and archaea.[3][4][5][6] Sialic acids are commonly part of glycoproteins, glycolipids or gangliosides, where they decorate the end of sugar chains at the surface of cells or soluble proteins.[7] However, sialic acids have been also observed in Drosophila embryos and other insects.[8] Generally, plants seem not contain or display sialic acids.[9]
In humans the brain has the highest sialic acid content, where these acids play an important role in neural transmission and ganglioside structure in synaptogenesis.[7] More than 50 kinds of sialic acid are known, all of which can be obtained from a molecule of neuraminic acid by substituting its amino group of one of its hydroxyl groups.[1] In general, the amino group bears either an acetyl or a glycolyl group, but other modifications have been described. These modifications along with linkages have shown to be tissue specific and developmentally regulated expressions, so some of them are only found on certain types of glycoconjugates in specific cells.[8] The hydroxyl substituents may vary considerably; acetyl, lactyl, methyl, sulfate, and phosphate groups have been found.[10]
https://en.wikipedia.org/wiki/Sialic_acid
Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the SPARC gene.
Osteonectin is a glycoprotein in the bone that binds calcium. It is secreted by osteoblasts during bone formation, initiating mineralization and promoting mineral crystal formation. Osteonectin also shows affinity for collagen in addition to bone mineral calcium. A correlation between osteonectin over-expression and ampullary cancers and chronic pancreatitis has been found.
Not to be confused with Osteocalcin or Osteopontin.
https://en.wikipedia.org/wiki/Osteonectin
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