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 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:2,794,970-2,805,423)mRNA (may differ from genome)Protein (459 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: FKBP4
Diseases sorted by gene-association score: progesterone resistance (3), non-suppurative otitis media (2), in situ carcinoma (2), cerebellopontine angle tumor (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 70.70 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 1482.70 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -74.20170-0.436 Picture PostScript Text
3' UTR -673.502165-0.311 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR023114 - Elongated_TPR_rpt_dom
IPR023566 - PPIase_FKBP
IPR001179 - PPIase_FKBP_dom
IPR001440 - TPR-1
IPR013026 - TPR-contain_dom
IPR011990 - TPR-like_helical
IPR019734 - TPR_repeat

Pfam Domains:
PF00254 - FKBP-type peptidyl-prolyl cis-trans isomerase
PF00515 - Tetratricopeptide repeat

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1N1A - X-ray MuPIT 1P5Q - X-ray MuPIT 1Q1C - X-ray MuPIT 1QZ2 - X-ray MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsemblEnsemblWormBase 
Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence 
AlignmentAlignmentAlignmentAlignmentAlignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0003755 peptidyl-prolyl cis-trans isomerase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0005525 GTP binding
GO:0005528 FK506 binding
GO:0016853 isomerase activity
GO:0030674 protein binding, bridging
GO:0031072 heat shock protein binding
GO:0032767 copper-dependent protein binding
GO:0035259 glucocorticoid receptor binding
GO:0048156 tau protein binding
GO:0051219 phosphoprotein binding

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

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005874 microtubule
GO:0030424 axon
GO:0032991 macromolecular complex
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0044295 axonal growth cone
GO:0048471 perinuclear region of cytoplasm
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  JA482231 - Sequence 214 from Patent WO2011072091.
JE980523 - Sequence 214 from Patent EP2862929.
AK313918 - Homo sapiens cDNA, FLJ94557, highly similar to Homo sapiens FK506 binding protein 4, 59kDa (FKBP4), mRNA.
BC001786 - Homo sapiens FK506 binding protein 4, 59kDa, mRNA (cDNA clone MGC:2294 IMAGE:3542330), complete cds.
M88279 - Human immunophilin (FKBP52) mRNA, complete cds.
BC007924 - Homo sapiens FK506 binding protein 4, 59kDa, mRNA (cDNA clone MGC:14457 IMAGE:4304462), complete cds.
JD476944 - Sequence 457968 from Patent EP1572962.
CU674888 - Synthetic construct Homo sapiens gateway clone IMAGE:100018312 5' read FKBP4 mRNA.
AB385011 - Synthetic construct DNA, clone: pF1KB5006, Homo sapiens FKBP4 gene for FK506 binding protein 4, complete cds, without stop codon, in Flexi system.
DQ895800 - Synthetic construct Homo sapiens clone IMAGE:100010260; FLH187763.01L; RZPDo839C11149D FK506 binding protein 4, 59kDa (FKBP4) gene, encodes complete protein.
KJ891179 - Synthetic construct Homo sapiens clone ccsbBroadEn_00573 FKBP4 gene, encodes complete protein.
DQ893668 - Synthetic construct clone IMAGE:100006298; FLH187767.01X; RZPDo839C11150D FK506 binding protein 4, 59kDa (FKBP4) gene, encodes complete protein.
BC002887 - Homo sapiens FK506 binding protein 4, 59kDa, mRNA (cDNA clone IMAGE:3940730).
JD454374 - Sequence 435398 from Patent EP1572962.
JD214689 - Sequence 195713 from Patent EP1572962.
JD422297 - Sequence 403321 from Patent EP1572962.
JD082677 - Sequence 63701 from Patent EP1572962.
JD078032 - Sequence 59056 from Patent EP1572962.
JD459380 - Sequence 440404 from Patent EP1572962.
JD418391 - Sequence 399415 from Patent EP1572962.
JD487420 - Sequence 468444 from Patent EP1572962.
AK024694 - Homo sapiens cDNA: FLJ21041 fis, clone CAE10652.
JD383007 - Sequence 364031 from Patent EP1572962.
JD306995 - Sequence 288019 from Patent EP1572962.
JD368398 - Sequence 349422 from Patent EP1572962.
JD479790 - Sequence 460814 from Patent EP1572962.
JD192187 - Sequence 173211 from Patent EP1572962.
JD490035 - Sequence 471059 from Patent EP1572962.
JD094638 - Sequence 75662 from Patent EP1572962.
AF220048 - Homo sapiens uncharacterized hematopoietic stem/progenitor cells protein MDS028 mRNA, complete cds.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q02790 (Reactome details) participates in the following event(s):

R-HSA-5618073 FKBP4 replaces FKBP5 within HSP90:ATP:FKBP5:unfolded protein
R-HSA-5618085 FKBP4 binds HSP90:ATP:STIP1:HSP70:nascent protein
R-HSA-5324617 HSP90:FKBP4:PTGES3 binds HSF1 trimer
R-HSA-5618110 p23 (PTGES3) binds HSP90:ATP:FKBP4:nascent protein
R-HSA-5618099 SH binds SHR within the HSP90 chaperone complex
R-HSA-8939203 HSP90-dependent ATP hydrolysis promotes release of ESR:ESTG from chaperone complex
R-HSA-8939204 ESTG binds the ESR:chaperone complex
R-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-9018519 Estrogen-dependent gene expression
R-HSA-3371568 Attenuation phase
R-HSA-2262752 Cellular responses to stress
R-HSA-8939211 ESR-mediated signaling
R-HSA-3371571 HSF1-dependent transactivation
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-9006931 Signaling by Nuclear Receptors
R-HSA-3371556 Cellular response to heat stress
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: D3DUQ1, ENST00000001008.1, ENST00000001008.2, ENST00000001008.3, ENST00000001008.4, ENST00000001008.5, FKBP4_HUMAN, FKBP52, NM_002014, Q02790, Q9UCP1, Q9UCV7, uc001qkz.1, uc001qkz.2, uc001qkz.3, uc001qkz.4, uc001qkz.5
UCSC ID: ENST00000001008.6
RefSeq Accession: NM_002014
Protein: Q02790 (aka FKBP4_HUMAN or FKB4_HUMAN)
CCDS: CCDS8512.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.