Granin (chromogranin and secretogranin) is a

protein family A protein family is a group of evolutionarily related proteins. In many cases, a protein family has a corresponding gene family, in which each gene encodes a corresponding protein with a 1:1 relationship. The term "protein family" should not be ...

of regulated secretory

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 ...

s ubiquitously found in the cores of amine and peptide

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

and neurotransmitter dense-core secretory vesicles.

Function

Granins (chromogranins or secretogranins) are acidic proteins and are present in the secretory granules of a wide variety of

endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...

and neuro-endocrine cells. The exact function(s) of these proteins is not yet settled but there is evidence that granins function as pro-hormones, giving rise to an array of peptide fragments for which

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 ...

, and

activities have been demonstrated

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

and

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

. The intracellular biochemistry of granins includes binding of Ca²⁺, ATP and

catecholamines A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. ...

(

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

) within the hormone storage vesicle core. There is also evidence that CgA, and perhaps other granins, regulate the biogenesis of dense-core secretory vesicles and hormone sequestration in

neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules ( hormones) into the blood. In this way they b ...

cells.

Structure

Apart from their subcellular location and the abundance of acidic residues ( Asp and Glu), these proteins do not share many structural similarities. Only one short region, located in the

C-terminal 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 or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

section, is conserved in all these proteins. Chromogranins and secretogranins together share a C-terminal motif, whereas chromogranins A and B share a region of high similarity in their

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

section; this region includes two

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 involved in a

disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...

. There are considerable differences in the amino acid composition between different animals. Commercial assays for measuring human CGA can usually not be used for measuring CGA in samples from other species. Some specific parts of the molecule have a higher degree of amino acid homology and methods where the antibodies are directed against specific epitopes can be used to measure samples from different animals. Region-specific assays measuring defined parts of CGA, CGB and SG2 can be used for measurements in samples from cats and dogs.

Members

Chromogranins

chromogranin A Chromogranin-A (CgA) or parathyroid secretory protein 1 is encoded in the human by the gene ''CHGA''. Cga is a member of the granin family of neuroendocrine secretory proteins. As such, it is located in secretory vesicles of neurons and endocr ...

(CgA) * chromogranin B (CgB)

Secretogranins

* secretogranin II (SgII) (see also secretoneurin) * secretogranin III (SgIII) * secretogranin V (SgV)

Extended group

Some other proteins are also proposed to belong to the granins based on their physico-chemical properties. These include NESP55 (SgVI),

VGF VGF or VGF nerve growth factor inducible is a secreted protein and neuropeptide precursor that may play a role in regulating energy homeostasis, metabolism and synaptic plasticity. The protein was first discovered in 1985 by Levi ''et al''. in a ...

(SgVII), and ProSAAS (SgVIII).

References

External links

* {{Nerve tissue protein Protein structural motifs