Stanniocalcin-2 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''STC2''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This gene encodes a secreted,

homodimeric In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ' ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

that is expressed in a wide variety of tissues and may have

autocrine Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with ...

paracrine In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication (biology), cellular communication in which a Cell (biology), cell produces a signal to induce changes in nearby cells, altering the behaviour of ...

functions. The encoded protein has 10 of its 15

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residues conserved among stanniocalcin family members and is

phosphorylate In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

d by

casein kinase 2 Casein kinase 2 ()(CK2/CSNK2) is a serine/threonine-selective protein kinase that has been implicated in cell cycle control, DNA repair, regulation of the circadian rhythm, and other cellular processes. De-regulation of CK2 has been linked to tumor ...

exclusively on its serine residues. Its

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

contains a cluster of

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

residues which may interact with

metal ion A metal () is a material that, when polished or fractured, shows a lustrous appearance, and conducts electricity and heat relatively well. These properties are all associated with having electrons available at the Fermi level, as against non ...

s. The protein may play a role in the regulation of

renal In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retrop ...

and

intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

and

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

transport,

cell metabolism ''Cell Metabolism'' is a monthly peer-reviewed scientific journal covering physiology, with an emphasis on understanding the molecular basis of how the body self-regulates in the face of change, and how disturbances in these balances can lead to di ...

, or cellular calcium/phosphate

homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...

. Constitutive overexpression of human stanniocalcin 2 in mice resulted in pre-and postnatal growth restriction, reduced bone and skeletal muscle growth, and

organomegaly Organomegaly is the abnormal enlargement of organs. For example, cardiomegaly is enlargement of the heart. Visceromegaly is the enlargement of abdominal organs. Examples of visceromegaly are enlarged liver (hepatomegaly), spleen (splenomegaly Sp ...

. Expression of this gene is induced by

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

and altered in some

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

s. Stanniocalcin reduces bone growth by modulating the activity of

IGF1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. In the 1950s IGF-1 was called " sulfa ...

. One mechanism of

regulation is through

IGFBP4 Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the ''IGFBP4'' gene. Function This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP do ...

binding it in an inactive state. The protease

PAPPA Tiberiopolis (; sometimes in sources, Tiberiapolis, and Pappa-Tiberiopolis; formerly Pappa) was a town in the Roman province of Phrygia Pacatiana, mentioned by Ptolemy, Socrates of Constantinople and Hierocles. At various times, it was considered ...

can then cleave this complex, releasing bioactive IGF1. Stanniocalcin inhibits the activity of PAPPA in releasing active IGF1 through itself binding PAPPA, thus preventing the release of active IGF1. Differences in stanniocalcin expression have been directly linked to changes in skeletal size in a variety of species. For example, laboratory mice lacking ''STC2'' are 10 to 15% larger than wild-type mice, while mice expressing STC2 at elevated levels are 45% smaller. In humans, the largest known coding variant affecting human height is a rare mutation reducing STC2 activity, yielding a 2 cm height increase in heterozygous carriers. Additionally, domestic dog size is strongly predicted by a variant immediately adjacent to ''STC2'', with almost all small dogs carrying a derived allele at this locus. A further striking example is the

stickleback The sticklebacks are a family of ray-finned fishes, the Gasterosteidae which have a Holarctic distribution in fresh, brackish and marine waters. They were thought to be related to the pipefish and seahorses but are now thought to be more close ...

, different populations of which have either increased or decreased the length of their dorsal and pelvic spines through modulation of ''STC2'' expression.

References

Further reading