P24 protein family is a group of transmembrane proteins that are major components of

COPI COPI is a coatomer, a protein complex that coats vesicle (biology), vesicles transporting proteins from the ''cis'' end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally Translation (genetics), synthesi ...

and

COPII The coat protein complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. Thi ...

-coated vesicles. The family is also known as EMP24/GP25L/p24 family and TMP21-like proteins. The latter naming was after transmembrane emp24 domain-containing protein 10 that was found in the

human brain The human brain is the central organ (anatomy), organ of the nervous system, and with the spinal cord, comprises the central nervous system. It consists of the cerebrum, the brainstem and the cerebellum. The brain controls most of the activi ...

. It was claimed to block the

beta-amyloid Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor pro ...

peptide, which is implicated in the pathogenesis of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

Function

p24 family proteins localize to the major

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

s of the early secretory pathway: the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

and the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

, where they seem to be involved in trafficking between the two compartments. In yeast, all p24 family proteins can be removed, causing only a mild phenotype. However, in mammals at least some p24 proteins are essential for survival, e.g. removal of p24δ1 is lethal in mice. p24 family members have been implicated in the biogenesis of

and

-coated vesicles, transporting membrane-bound proteins through the secretory system, and forming the structure of the endoplasmic reticulum and Golgi.

Distribution

Most p24 family proteins are widely expressed in various tissues. They are highly expressed in

secretory cell Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

types.

Structure

p24 family proteins are type 1 transmembrane proteins with a single transmembrane domain. Most of the protein is in the lumen of the endoplasmic reticulum or Golgi save for a 13–20

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

ic tail at the protein's

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 ...

. The N-terminus has a GOLD domain (for "Golgi Dynamics") which may be involved in cargo recognition, followed by a

coiled coil A coiled coil is a structural motif in proteins in which two to seven alpha-helices are coiled together like the strands of a rope. ( Dimers and trimers are the most common types.) They have been found in roughly 5-10% of proteins and have a ...

domain involved in the oligomerization of p24 family members. The cytosolic tail is involved in binding COPI and COPII proteins for sorting into vesicles within the secretory system.

Evolution

p24 family proteins are divided based on their sequence into four families: called α, β, γ, and δ. Most vertebrates have three α family members, one β, five γ, and two δ; while yeast have three α, a β, three γ, and one δ. Plants have only the β and δ subfamilies.

Family members

Vertebrates have three α family members: p24α1 (Erp1p in yeast), p24α2 (Erp5p), and p24α3 (Erp6p); one β member p24β1 (Emp24p in yeast); five γ members: p24γ1, p24γ2 (Erp2p in yeast), p24γ3 (Erp3p), p24γ4 (Erp4p), and p24γ5; and two δ members: p24δ1 (Erv25p in yeast) and p24δ2.

History

p24 proteins were originally named based on their apparently molecular weight of around 24

kilodalton The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

s, giving rise to names p23, p24, et al. As further family members were discovered, they were given names that fit the pattern – p26, p27, and p28 – even though they too were around 24 kilodaltons. In 1998, a more systematic nomenclature was proposed with all proteins called "p24", the Greek letter for their sub-family, and then numbered in the order of their discovery.

References

{{DEFAULTSORT:Tpm21 Single-pass transmembrane proteins