Human Gene FKBP4 (ENST00000001008.6) from GENCODE V44
Description: Homo sapiens FKBP prolyl isomerase 4 (FKBP4), mRNA. (from RefSeq NM_002014) RefSeq Summary (NM_002014): The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene 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. The human genome contains several non-transcribed pseudogenes similar to this gene. [provided by RefSeq, Sep 2008]. Gencode Transcript: ENST00000001008.6 Gencode Gene: ENSG00000004478.8 Transcript (Including UTRs) Position: hg38 chr12:2,794,970-2,805,423 Size: 10,454 Total Exon Count: 10 Strand: + Coding Region Position: hg38 chr12:2,795,140-2,803,258 Size: 8,119 Coding Exon Count: 10
ID:FKBP4_HUMAN DESCRIPTION: RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4; Short=PPIase FKBP4; EC=5.2.1.8; AltName: Full=51 kDa FK506-binding protein; Short=FKBP51; AltName: Full=52 kDa FK506-binding protein; Short=52 kDa FKBP; Short=FKBP-52; AltName: Full=59 kDa immunophilin; Short=p59; AltName: Full=FK506-binding protein 4; Short=FKBP-4; AltName: Full=FKBP59; AltName: Full=HSP-binding immunophilin; Short=HBI; AltName: Full=Immunophilin FKBP52; AltName: Full=Rotamase; Contains: RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; FUNCTION: Immunophilin protein with PPIase and co-chaperone activities (By similarity). Component of unligated 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 (By similarity). 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. CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline (omega=0). ENZYME REGULATION: Inhibited by FK506. SUBUNIT: Homodimer. Associates with HSP90 and HSP70 in unactivated steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with HSF1 in the HSP90 complex. Associates with tubulin (By similarity). Interacts with MAPT/TAU (By similarity). Interacts with NR3C1 and dynein (By similarity). Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity). Nucleus. Cytoplasm, cytoskeleton (By similarity). TISSUE SPECIFICITY: Widely expressed. DOMAIN: The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA) (By similarity). DOMAIN: The C-terminal region (AA 375-458) is required to prevent tubulin polymerization (By similarity). DOMAIN: The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400 (By similarity). PTM: Phosphorylation by CK2 results in loss of HSP90 binding activity (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR. SIMILARITY: Contains 2 PPIase FKBP-type domains. SIMILARITY: Contains 3 TPR repeats. WEB RESOURCE: Name=Protein Spotlight; Note=A mind astray - Issue 118 of June 2010; URL="http://web.expasy.org/spotlight/back_issues/sptlt118.shtml";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q02790
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000413 protein peptidyl-prolyl isomerization GO:0006457 protein folding GO:0006463 steroid hormone receptor complex assembly GO:0006825 copper ion transport GO:0007566 embryo implantation GO:0010977 negative regulation of neuron projection development GO:0030521 androgen receptor signaling pathway GO:0030850 prostate gland development GO:0031111 negative regulation of microtubule polymerization or depolymerization GO:0031115 negative regulation of microtubule polymerization GO:0031503 protein complex localization GO:0046661 male sex differentiation GO:0048608 reproductive structure development GO:0061077 chaperone-mediated protein folding GO:1900034 regulation of cellular response to heat