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 c ...

of regulated secretory

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

s ubiquitously found in the cores of amine and peptide

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

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 comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the ...

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 p ...

paracrine Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse ove ...

, and

activities have been demonstrated

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

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, and ...

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

catecholamines A catecholamine (; abbreviated CA) 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. Catechol can be either a free molecule or a subst ...

(

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 and ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

) 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 br ...

cells.

Structure

Apart from their subcellular location and the abundance of acidic residues (

Asp Asp may refer to: Places * Asp, part of Densbüren, Aargau, Switzerland * Aspe (''Asp'' in Valencian), Alicante, Spain * Asp Lake, a lake in Minnesota Animals * Asp (fish) * Asp (snake), in antiquity, one of several venomous snakes ** ''Cera ...

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, 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 the protein is ...

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 formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, s ...

residues involved in a

disulfide bond In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups ...

. 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 (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 an ...

(SgVII), and ProSAAS (SgVIII).

References

External links

* {{Nerve tissue protein Protein structural motifs