Peptidyl-prolyl cis-trans isomerase FKBP4 (FKBP4)

The protein contains 459 amino acids for an estimated molecular weight of 51805 Da.

 

Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria. (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 100%
Model score: 61
MODL_MODELLER-9.18
MODL_I-TASSER-3.0

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs1042228

The reference OMIM entry for this protein is 600611

Fk506-binding protein 4; fkbp4
T-cell fk506-binding protein, 59-kd; fkbp59; fkbp52

For background information on FK506-binding proteins (FKBPs), see FKBP1A (186945).

CLONING

Peattie et al. (1992) identified a novel FKBP using an FK506 affinity matrix. By database analysis, 2 murine DNA sequences were identified, and PCR primers to these were used to generate a probe for screening a human placenta cDNA library. A translation of the human cDNA sequence matched the original partial protein sequence, as well as primary sequences for other FKBPs. The predicted protein, FKBP52, has a molecular mass of 52 kD. Northern blot analysis detected FKBP52 transcripts at varying levels in all tissues examined. Peattie et al. (1992) noted that FKBP52 is apparently identical to a 56- to 59-kD protein referred to as p56, p59, or FKBP59 in the literature, and they suggested that phosphorylation of FKBP52 may account for the multiple reported isoforms.

GENE FUNCTION

Peattie et al. (1992) showed that FKBP52 associated with the 90-kD heat shock protein (see HSP90A; 140571) in untransformed mammalian steroid receptor complexes. FKBP52 is a 'macro' immunophilin that shares high structural and functional homologies in its N-terminal domain with FKBP12 (FKBP1A; 186945). Unlike FKBP12, however, it does not have immunosuppressant activity when complexed with FK506. To investigate the physiologic function of FKBP52, Chambraud et al. (1999) used the yeast 2-hybrid system as an approach to find its potential protein partners and its cellular role. They detected an FKBP-associated protein, which by sequencing was identified as phytanoyl-CoA alpha-hydroxylase (PHYH; 602026), a peroxisomal enzyme. Inactivation of this enzyme is responsible for Refsum disease (266500) in humans. Chambraud et al. (1999) showed that PHYH has the physical capacity to interact with the FKBP12-like domain of FKBP52, but not with FKBP12, suggesting that it is a particular and specific target of FKBP52. Whereas the binding of calcineurin (114105) to FKBP12 is potentiated by FK506, the specific association of PHYH and FKBP52 is maintained in the presence of FK506. These observations suggested that PHYH is a serious candidate for studying the cellular signaling pathway(s) involving FKBP52 in the presence of immunosuppressant drugs. Fusco et al. (2010) demonstrated that RET51 (see 164761) activation by both glial cell line-derived neurotrophic factor (GDNF; 600837) and NGF (162030) triggers the formation of a RET51-FKBP52 complex. Substitution of tyrosine-905 in RET51, a key residue phosphorylated by both GDNF and NGF, disrupted the RET51-FKBP52 complex. NGF and GDNF have a functional role in dopaminergic neurons, where RET51 and FKBP52 are expressed. To clarify the contribution of the RET51-FKBP52 complex in dopaminergic neurons, Fusco et al. (2010) screened both genes in 30 patients with Parkinson disease (PD; 168600), in which dopaminergic neurons are selectively lost. In 1 individual with early-onset PD, the authors found heterozygous mutations in each gene, which together were sufficient to disrupt the RET51-FKBP52 complex.

ANIMAL MODEL

Cheung-Flynn et al. (2005) found that male and female Fkbp52 -/- mice were infertile. Male infertility in Fkbp52 -/- mice was due to compromised androgen receptor (AR; 313700) function. Tranguch et al. (2005) found that, in contrast to female progesterone receptor (Pgr; 607311) -/- mice, female Fkbp52 -/- mice had no ovulation defect. Gross and histopathologic analysis showed that Fkbp52 -/- uteri were complet ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600611 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed