FK506-binding protein 4 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 ''FKBP4''

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 ...

Function

The protein encoded by this gene is a member of the

immunophilin In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molec ...

protein family, which play a role in immunoregulation and basic cellular processes involving

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

and trafficking. This encoded protein is a cis-trans

prolyl isomerase Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase) is an enzyme () found in both prokaryotes and eukaryotes that interconverts the ''cis'' and ''trans'' isomers of peptide bonds with the amino acid proline. Proline has an unusua ...

that binds to the

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

FK506 Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogenic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

and

rapamycin Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ rejection, organ transplant rejection, treat a rare lung disease called lymphang ...

. It has high structural and functional similarity to FK506-binding protein 1A (

FKBP1A Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins ( FKBPs). Function The protei ...

), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with

interferon regulatory factor-4 Interferon regulatory factor 4 (IRF4) also known as MUM1 is a protein that in humans is encoded by the ''IRF4'' gene. IRF4 functions as a key regulatory transcription factor in the development of human immune cells.Nam S, Lim J-S (2016). "Essentia ...

and plays an important role in immunoregulatory gene expression in B and

T lymphocyte T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s. This encoded protein is known to associate with

phytanoyl-CoA alpha-hydroxylase In enzymology, a phytanoyl-CoA dioxygenase () is an enzyme that catalysis, catalyzes the chemical reaction :phytanoyl-CoA + 2-oxoglutarate + O2 \rightleftharpoons 2-hydroxyphytanoyl-CoA + succinate + CO2 The three substrate (biochemistry), s ...

. It can also associate with two heat shock proteins (

hsp90 Hsp90 (heat shock protein 90) is a chaperone (protein), chaperone protein that assists other proteins to protein folding, fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of ...

and

hsp70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...

) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the

steroid hormone receptor Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...

s. This protein correlates strongly with

adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus '' Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in ...

type 2 vectors (AAV) resulting in a significant increase in AAV-mediated

transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...

expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

Structure

This protein contains

TPR repeats TPR may refer to: Businesses and organisations *The Pensions Regulator, UK *The Princeton Review, a US educational company * Tapestry, Inc., an American clothing company (NYSE stock ticker: TPR) *Texas Public Radio Journals *'' Town Planning ...

and has a PPlase domain.

Clinical significance

Recent research suggests that FKBP4 may play a role in preventing the

Tau protein The tau proteins (abbreviated from tubulin associated unit) form a group of six highly soluble protein isoforms produced by alternative splicing from the gene ''MAPT'' (microtubule-associated protein tau). They have roles primarily in maintainin ...

from turning pathogenic. This may prove significant for the development of new

Alzheimer's 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 ...

drugs and for detecting the disease before the onset of clinical symptoms.

Interactions

FKBP4 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

GLMN Glomulin is a protein that in humans is encoded by the ''GLMN'' gene. This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutation ...

References

External links

* {{Portal bar, Biology, border=no EC 5.2.1 Co-chaperones