FKBP5 Antibody [J11H16] Datasheet

Biological Description

Specificity	FKBP5 Antibody [J11H16] detects endogenous levels of total FKBP5 protein.
Background	FKBP5, also termed FKBP51, is an immunophilin family member with peptidyl‑prolyl isomerase activity and co‑chaperone functions that modulate steroid hormone receptor signaling, stress‑axis regulation, and kinase pathways at the interface of endocrine and inflammatory control. The protein contains an N‑terminal FK1 domain with cis–trans prolyl isomerase and FK506/rapamycin‑binding activity, an FK2‑like domain with mainly scaffolding function, and a C‑terminal region bearing tetratricopeptide repeat motifs that mediate binding to HSP90 and assembly into multichaperone complexes with glucocorticoid, progesterone, androgen, and mineralocorticoid receptors. FKBP5 associates with HSP90‑bound glucocorticoid receptor (GR) complexes and reduces ligand affinity and efficiency of GR nuclear translocation, resulting in a receptor state with lower hormone sensitivity; GR activation then induces FKBP5 transcription via intronic glucocorticoid response elements, creating an ultra‑short negative feedback loop on GR signaling and hypothalamic–pituitary–adrenal (HPA) axis feedback. This autoregulatory circuit influences systemic cortisol dynamics, as alleles associated with stronger FKBP5 upregulation after GR activation correlate with increased GR resistance, reduced feedback inhibition, and prolonged stress‑hormone elevation in humans. FKBP5 also functions as a scaffold in kinase signaling: it binds AKT through its FK1 domain and the phosphatase PHLPP via TPR motifs, promotes their interaction, and facilitates dephosphorylation of AKT at Ser473, thereby constraining AKT activity and linking FKBP5 abundance to PI3K–Akt pathway output and cell survival signaling. At the level of inflammatory and cardiovascular control, FKBP5 expression is epigenetically and transcriptionally upregulated by aging and chronic stress, enhances NF‑κB–related signaling, and associates with a pro‑inflammatory profile and increased cardiovascular risk, indicating that FKBP5 connects stress endocrine mechanisms to innate immune activation and vascular pathology. Genetic and epigenetic variation at the FKBP5 locus, including functional polymorphisms and stress‑responsive DNA methylation changes, associates with altered FKBP5 inducibility, HPA‑axis reactivity, and susceptibility to major depression, post‑traumatic stress disorder, bipolar disorder, and related stress‑induced psychiatric conditions, and these same variants can influence response rates to antidepressant therapy.

Specificity

FKBP5 Antibody [J11H16] detects endogenous levels of total FKBP5 protein.

Background

FKBP5, also termed FKBP51, is an immunophilin family member with peptidyl‑prolyl isomerase activity and co‑chaperone functions that modulate steroid hormone receptor signaling, stress‑axis regulation, and kinase pathways at the interface of endocrine and inflammatory control. The protein contains an N‑terminal FK1 domain with cis–trans prolyl isomerase and FK506/rapamycin‑binding activity, an FK2‑like domain with mainly scaffolding function, and a C‑terminal region bearing tetratricopeptide repeat motifs that mediate binding to HSP90 and assembly into multichaperone complexes with glucocorticoid, progesterone, androgen, and mineralocorticoid receptors. FKBP5 associates with HSP90‑bound glucocorticoid receptor (GR) complexes and reduces ligand affinity and efficiency of GR nuclear translocation, resulting in a receptor state with lower hormone sensitivity; GR activation then induces FKBP5 transcription via intronic glucocorticoid response elements, creating an ultra‑short negative feedback loop on GR signaling and hypothalamic–pituitary–adrenal (HPA) axis feedback. This autoregulatory circuit influences systemic cortisol dynamics, as alleles associated with stronger FKBP5 upregulation after GR activation correlate with increased GR resistance, reduced feedback inhibition, and prolonged stress‑hormone elevation in humans. FKBP5 also functions as a scaffold in kinase signaling: it binds AKT through its FK1 domain and the phosphatase PHLPP via TPR motifs, promotes their interaction, and facilitates dephosphorylation of AKT at Ser473, thereby constraining AKT activity and linking FKBP5 abundance to PI3K–Akt pathway output and cell survival signaling. At the level of inflammatory and cardiovascular control, FKBP5 expression is epigenetically and transcriptionally upregulated by aging and chronic stress, enhances NF‑κB–related signaling, and associates with a pro‑inflammatory profile and increased cardiovascular risk, indicating that FKBP5 connects stress endocrine mechanisms to innate immune activation and vascular pathology. Genetic and epigenetic variation at the FKBP5 locus, including functional polymorphisms and stress‑responsive DNA methylation changes, associates with altered FKBP5 inducibility, HPA‑axis reactivity, and susceptibility to major depression, post‑traumatic stress disorder, bipolar disorder, and related stress‑induced psychiatric conditions, and these same variants can influence response rates to antidepressant therapy.

Usage Information

Application

WB, IP

Dilution

WB	IP
1:1000	1:50

Reactivity

Human, Mouse, Rat, Monkey

Source

Rabbit Monoclonal Antibody

MW

51 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/19560279/
https://pubmed.ncbi.nlm.nih.gov/26250598/

FKBP5 Antibody [J11H16]

Biological Description

Usage Information

References

Application Data