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Q9QVC8 (FKBP4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Peptidyl-prolyl cis-trans isomerase FKBP4

Short name=PPIase FKBP4
EC=5.2.1.8
Alternative name(s):
52 kDa FK506-binding protein
Short name=52 kDa FKBP
Short name=FKBP-52
59 kDa immunophilin
Short name=p59
FK506-binding protein 4
Short name=FKBP-4
FKBP59
HSP-binding immunophilin
Short name=HBI
Immunophilin FKBP52
Rotamase
Gene names
Name:Fkbp4
Synonyms:Fkbp52
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length458 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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) By similarity. Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. May have a protective role against oxidative stress in mitochondria By similarity. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. The PPIase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Ref.4 Ref.5

Catalytic activity

Peptidylproline (omega=180) = peptidylproline (omega=0).

Enzyme regulation

Inhibited by FK506 By similarity.

Subunit structure

Homodimer By similarity. Associates (via TPR domains) with HSP90 and HSP70 in unactivated steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH) By similarity. Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex By similarity. Associates with tubulin By similarity. Interacts with MAPT/TAU; the interaction is enhanced for phosphorylated MAPT/TAU. Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca2+ dependent By similarity. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction By similarity. Ref.4 Ref.5

Subcellular location

Cytoplasmcytosol. Mitochondrion By similarity. Nucleus By similarity. Cytoplasmcytoskeleton By similarity. Note: Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor By similarity. Colocalized with MAPT/TAU in the distal part of the primary cortical neurons. Ref.4 Ref.5

Tissue specificity

Widely detected in the brain (at protein level). Ref.5

Domain

The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA) By similarity.

The C-terminal region (AA 375-458) is required to prevent tubulin polymerization.

The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400 By similarity.

The TPR repeats mediate mitochondrial localization By similarity.

Post-translational modification

Phosphorylation by CK2 results in loss of HSP90 binding activity.

Sequence similarities

Contains 2 PPIase FKBP-type domains.

Contains 3 TPR repeats.

Ontologies

Keywords
   Cellular componentCytoplasm
Cytoskeleton
Microtubule
Mitochondrion
Nucleus
   DomainRepeat
TPR repeat
   Molecular functionChaperone
Isomerase
Rotamase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

chaperone-mediated protein folding

Inferred from sequence or structural similarity. Source: UniProtKB

copper ion transport

Inferred from mutant phenotype PubMed 15133031. Source: RGD

embryo implantation

Inferred from electronic annotation. Source: Ensembl

male sex differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of microtubule polymerization

Inferred from mutant phenotype Ref.4. Source: RGD

negative regulation of microtubule polymerization or depolymerization

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-proline modification

Inferred from Biological aspect of Ancestor. Source: RefGenome

prostate gland development

Inferred from electronic annotation. Source: Ensembl

protein complex localization

Inferred from electronic annotation. Source: Ensembl

protein peptidyl-prolyl isomerization

Inferred from Biological aspect of Ancestor. Source: GOC

steroid hormone receptor complex assembly

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxonal growth cone

Inferred from direct assay Ref.5. Source: UniProtKB

cytosol

Inferred from direct assay Ref.5. Source: UniProtKB

membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuron projection

Inferred from direct assay PubMed 20796173. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 20796173. Source: RGD

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from direct assay PubMed 20796173. Source: RGD

protein complex

Inferred from direct assay PubMed 20796173. Source: RGD

   Molecular_functionATP binding

Inferred from electronic annotation. Source: Ensembl

FK506 binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

GTP binding

Inferred from electronic annotation. Source: Ensembl

copper-dependent protein binding

Inferred from physical interaction PubMed 15133031. Source: RGD

peptidyl-prolyl cis-trans isomerase activity

Inferred from sequence or structural similarity. Source: UniProtKB

tau protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 458458Peptidyl-prolyl cis-trans isomerase FKBP4
PRO_0000391471
Initiator methionine11Removed; alternate By similarity
Chain2 – 458457Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed
PRO_0000075321

Regions

Domain50 – 13889PPIase FKBP-type 1
Domain167 – 25387PPIase FKBP-type 2
Repeat270 – 30334TPR 1
Repeat319 – 35234TPR 2
Repeat353 – 38634TPR 3
Region267 – 400134Interaction with tubulin

Amino acid modifications

Modified residue11N-acetylmethionine; in peptidyl-prolyl cis-trans isomerase FKBP4; alternate By similarity
Modified residue21N-acetylthreonine; in peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; partial By similarity
Modified residue1431Phosphothreonine; by CK2 By similarity
Modified residue2821N6-acetyllysine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9QVC8 [UniParc].

Last modified October 13, 2009. Version 3.
Checksum: 5701387E5DC991C8

FASTA45851,450
        10         20         30         40         50         60 
MTAEEMKVAE NGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETAMIG DRVFVHYTGW 

        70         80         90        100        110        120 
LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG EVCHITCKPE YAYGSAGSPP 

       130        140        150        160        170        180 
KIPPNATLVF EVELFEFKGE DLTEDEDGGI IRRIRTRGEG YARPNDGAMV EVALEGYYND 

       190        200        210        220        230        240 
RLFDQRELCF EVGEGESLDL PCGLEEAIQR MEKGEHSIVY LKPSYAFGSV GKERFQIPPH 

       250        260        270        280        290        300 
AELRYEVHLK SFEKAKASWE MNSEEKLEQS NIVKERGTVY FKEGKYKQAL LQYKKIVSWL 

       310        320        330        340        350        360 
EYESSFSGEE MQKVHALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS NNEKGLFRRG 

       370        380        390        400        410        420 
EAHLAVNDFD LARADFQKVL QLYPSNKAAK TQLAVCQQRT RRQLAREKKL YANMFERLAE 

       430        440        450 
EEHKAKTEVA AGDHPTDAEM KGEPNNVAGN QAQVKTEA 

« Hide

References

« Hide 'large scale' references
[1]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex."
Tai P.-K.K., Albers M.W., Chang H., Faber L.E., Schreiber S.L.
Science 256:1315-1318(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-25.
Tissue: Leukemia.
[3]Desai B.J., McKinney K.Q., Meyer M.H., Bahrani-Mostafavi Z., Meyer R.A. Jr.
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 57-458.
Strain: Sprague-Dawley.
Tissue: Brain.
[4]"The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule formation."
Chambraud B., Belabes H., Fontaine-Lenoir V., Fellous A., Baulieu E.E.
FASEB J. 21:2787-2797(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TUBULIN.
[5]"A role for FKBP52 in Tau protein function."
Chambraud B., Sardin E., Giustiniani J., Dounane O., Schumacher M., Goedert M., Baulieu E.E.
Proc. Natl. Acad. Sci. U.S.A. 107:2658-2663(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH MAPT.
[6]Maurya D.K., Bhargava P.
Submitted (JAN-2009) to UniProtKB
Cited for: IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Web resources

Protein Spotlight

A mind astray - Issue 118 of June 2010

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CH473964 Genomic DNA. Translation: EDM01775.1.
AF531427 mRNA. Translation: AAM95632.1.
RefSeqNP_001178792.1. NM_001191863.1.
UniGeneRn.23741.

3D structure databases

ProteinModelPortalQ9QVC8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59214N.

PTM databases

PhosphoSiteQ9QVC8.

Proteomic databases

PaxDbQ9QVC8.
PRIDEQ9QVC8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000008737; ENSRNOP00000008737; ENSRNOG00000006444.
GeneID260321.
KEGGrno:260321.
UCSCRGD:628729. rat.

Organism-specific databases

CTD2288.
RGD628729. Fkbp4.

Phylogenomic databases

eggNOGCOG0545.
GeneTreeENSGT00550000074272.
HOGENOMHOG000256916.
HOVERGENHBG051624.
InParanoidQ8K3U8.
KOK09571.
OMANAELKYE.
OrthoDBEOG725DHH.
PhylomeDBQ9QVC8.

Gene expression databases

GenevestigatorQ9QVC8.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
InterProIPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR001440. TPR_1.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERPTHR10516. PTHR10516. 1 hit.
PfamPF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 1 hit.
[Graphical view]
SMARTSM00028. TPR. 3 hits.
[Graphical view]
PROSITEPS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio624351.

Entry information

Entry nameFKBP4_RAT
AccessionPrimary (citable) accession number: Q9QVC8
Secondary accession number(s): A6IM14, Q8K3U8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: October 13, 2009
Last modified: July 9, 2014
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries