Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19. It is highly expressed in white adipose tissue, with lower expression in heart,

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, and brown adipose tissue. PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The ''PLIN4'' gene may be associated with

insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...

and obesity risk.

Structure

Gene

The ''PLIN4'' gene resides on chromosome 19 at the band 19p13.3 and contains 9

exon An exon is any part of a gene that will form 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 sequen ...

Protein

This protein belongs to the

perilipin Perilipin, also known as lipid droplet-associated protein, Perilipin 1, or PLIN, is a protein that, in humans, is encoded by the ''PLIN'' gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphoryla ...

family and contains 27 33- amino acid approximate tandem repeats. It is also one of the perilipin members of the PATS (

PLIN Perilipin, also known as lipid droplet-associated protein, Perilipin 1, or PLIN, is a protein that, in humans, is encoded by the ''PLIN'' gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphoryl ...

ADFP Adipose differentiation-related protein, also known as perilipin 2 , ADRP or adipophilin, is a protein which belongs from PAT family of cytoplasmic lipid droplet(CLD) binding protein. In humans it is encoded by the ''ADFP'' gene. This protein su ...

TIP47 Mannose-6-phosphate receptor binding protein 1 (M6PRBP1) is a protein which in humans is encoded by the ''M6PRBP1'' gene. Its gene product, as well as the gene itself, is commonly known as TIP47. Function Mannose 6-phosphate receptors (MPRs) ...

, S3-12) family, which is named after structural proteins that share high amino acid sequence similarity and associate with lipid droplets. It shares a conserved C-terminal of 14 amino acid residues that folds into a hydrophobic cleft with other PATS members; however, it is missing the conserved

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 ami ...

region of approximately 100 amino acid residues. Within the sequence of 33-amino acid repeats, PLIN4 contains a long stretch of imperfect 11-mer repeats predicted to form amphipathic helices with three helical turns per 11 amino acid residues. This 11-mer repeats tract is proposed to anchor the protein to the

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

monolayer of lipid droplets for its assembly, though no

targeting sequence A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-te ...

has yet been found in PLIN4.

Function

PLIN4 is a member of the

family, a group of proteins that coat lipid droplets in

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

s, the adipose tissue cells that are responsible for storing fat. Perilipin acts as a protective coating from the body’s natural

lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...

s, such as hormone-sensitive lipase, which break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis. In humans, perilipin is expressed as 5 different isoforms; it is currently understood that the level of expression for each isoform is dependent on factors such as sex, body mass index, and level of endurance exercise. PLIN4 is

hyperphosphorylated Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis. When these mechanisms fail, developmental problem ...

PKA PKA may refer to: * Professionally known as: ** Pen name ** Stage persona * p''K''a, the symbol for the acid dissociation constant at logarithmic scale * Protein kinase A, a class of cAMP-dependent enzymes * Pi Kappa Alpha, the North-American so ...

following

β-adrenergic The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...

receptor activation. Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis. Although PKA also phosphorylates hormone-sensitive lipase, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by

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 ...

) is primarily due to perilipin phosphorylation.

Clinical significance

The proteins in the Perilipin family are crucial regulators of lipid storage. PLIN4 expression is elevated in obese animals and humans. The PLIN4 gene, along with PLIN2, PLIN3, and PLIN5, have been associated with variance in body-weight regulation and may be a genetic influence on obesity risk in humans.

Interactions

PLIN4 has been shown to interact with Caspase 8 and Ubiquitin C.