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P27124 (FKBP4_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. 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·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:P59
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

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. 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 By similarity. Ref.9

Catalytic activity

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

Enzyme regulation

Inhibited by FK506 By similarity.

Subunit structure

Homodimer By similarity. Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU. Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca2+ dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus. Ref.5 Ref.7 Ref.8

Subcellular location

Cytoplasmcytosol By similarity. Mitochondrion By similarity. Nucleus. Cytoplasmcytoskeleton By similarity. Note: Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor By similarity.

Domain

The C-terminal region (AA 375-458) is required to prevent tubulin polymerization By similarity. Ref.3 Ref.9

The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA). Ref.3 Ref.9

The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400. Ref.3 Ref.9

The TPR repeats mediate mitochondrial localization By similarity. Ref.3 Ref.9

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 term3D-structure
Complete 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

embryo implantation

Inferred from electronic annotation. Source: Ensembl

male sex differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of microtubule polymerization or depolymerization

Inferred from direct assay PubMed 20133804. Source: UniProtKB

negative regulation of neuron projection development

Inferred from direct assay PubMed 20133804. Source: UniProtKB

prostate gland development

Inferred from electronic annotation. Source: Ensembl

protein complex localization

Inferred from electronic annotation. Source: Ensembl

protein peptidyl-prolyl isomerization

Inferred from sequence or structural similarity. Source: GOC

steroid hormone receptor complex assembly

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxonal growth cone

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: Ensembl

GTP binding

Inferred from electronic annotation. Source: Ensembl

peptidyl-prolyl cis-trans isomerase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

tau protein binding

Inferred from physical interaction PubMed 20133804. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 458458Peptidyl-prolyl cis-trans isomerase FKBP4
PRO_0000391470
Initiator methionine11Removed; alternate By similarity
Chain2 – 458457Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed
PRO_0000075320

Regions

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

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
Modified residue2821N6-acetyllysine By similarity
Modified residue4501Phosphoserine By similarity
Modified residue4521Phosphoserine By similarity

Experimental info

Sequence conflict151S → H AA sequence Ref.2
Sequence conflict21 – 222EG → FI AA sequence Ref.2
Sequence conflict261S → T AA sequence Ref.2

Secondary structure

......................... 458
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P27124 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 2EE25D561391DFF0

FASTA45851,475
        10         20         30         40         50         60 
MTAEEMKAAE SGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETPMIG DRVFVHYTGW 

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

       130        140        150        160        170        180 
KIPPNATLVF EVELFEFKGE DLTDDEDGGI IRRIRTRGEG YARPNDGAIV EVALEGYYKD 

       190        200        210        220        230        240 
RLFDQRELRF EVGEGESLDL PCGLEKAIQR MEKGEHSILY LKPSYAFGNA GKEKFQIPPY 

       250        260        270        280        290        300 
AELKYEVHLK SFEKAKESWE MSSEEKLEQS AIVKERGTVY FKEGKYKQAL LQYKKIVSWL 

       310        320        330        340        350        360 
EYESSFSSEE VQKAQALRLA SHLNLAMCHL KLQAFSAAVE SCNKALELDS NNEKGLFRRG 

       370        380        390        400        410        420 
EAHLAVNDFD LARADFQKVL QLYPSNKAAK AQLAVCQQRI RKQIAREKKL YANMFERLAE 

       430        440        450 
EENKAKAEVA AGDHPMDTEM KDERNDVAGS QSQVETEA 

« Hide

References

[1]"P59, an hsp 90-binding protein. Cloning and sequencing of its cDNA and preparation of a peptide-directed polyclonal antibody."
Lebeau M.-C., Massol N., Herrick J., Faber L.E., Renoir J.-M., Radanyi C., Baulieu E.-E.
J. Biol. Chem. 267:4281-4284(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Cloning and characterization of cDNA encoding the rabbit tRNA-guanine transglycosylase 60-kilodalton subunit."
Deshpande K.L., Seubert P.H., Tillman D.M., Farkas W.R., Katze J.R.
Arch. Biochem. Biophys. 326:1-7(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-26.
Strain: New Zealand white.
Tissue: Liver.
[3]"An immunophilin that binds M(r) 90,000 heat shock protein: main structural features of a mammalian p59 protein."
Callebaut I., Renoir J.-M., Lebeau M.-C., Massol N., Burny A., Baulieu E.-E., Mornon J.-P.
Proc. Natl. Acad. Sci. U.S.A. 89:6270-6274(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAINS.
[4]"Overexpression of p59-HBI (FKBP59), full length and domains, and characterization of PPlase activity."
Chambraud B., Rouviere-Fourmy N., Radanyi C., Hsiao K., Peattie D.A., Livingston D.J., Baulieu E.E.
Biochem. Biophys. Res. Commun. 196:160-166(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PPIASE ACTIVITY.
[5]"Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin."
Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K., Chinkers M., Pratt W.B.
J. Biol. Chem. 272:16224-16230(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH NR3C1 AND HSP90AA1.
[6]"Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: regulation of HSP90-binding activity of FKBP52."
Miyata Y., Chambraud B., Radanyi C., Leclerc J., Lebeau M.-C., Renoir J.-M., Shirai R., Catelli M.-G., Yahara I., Baulieu E.-E.
Proc. Natl. Acad. Sci. U.S.A. 94:14500-14505(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CK2.
[7]"Different regions of the immunophilin FKBP52 determine its association with the glucocorticoid receptor, hsp90, and cytoplasmic dynein."
Silverstein A.M., Galigniana M.D., Kanelakis K.C., Radanyi C., Renoir J.-M., Pratt W.B.
J. Biol. Chem. 274:36980-36986(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NR3C1; DYNEIN AND HSP90.
[8]"Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein."
Chambraud B., Radanyi C., Camonis J.H., Rajkowski K., Schumacher M., Baulieu E.-E.
Proc. Natl. Acad. Sci. U.S.A. 96:2104-2109(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHYH.
[9]"Localization of the chaperone domain of FKBP52."
Pirkl F., Fischer E., Modrow S., Buchner J.
J. Biol. Chem. 276:37034-37041(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A CO-CHAPERONE, DOMAINS.
[10]"Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution."
Craescu C.T., Rouviere N., Popescu A., Cerpolini E., Lebeau M.-C., Baulieu E.-E., Mispelter J.
Biochemistry 35:11045-11052(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-149.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84474 mRNA. Translation: AAA31438.1.
M84988 mRNA. Translation: AAA31439.1.
PIRA42386.
RefSeqNP_001075779.1. NM_001082310.1.
UniGeneOcu.1944.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ROTNMR-A4-148[»]
1ROUNMR-A4-148[»]
ProteinModelPortalP27124.
SMRP27124. Positions 21-425.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid1172171. 1 interaction.
STRING9986.ENSOCUP00000012554.

Proteomic databases

PRIDEP27124.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSOCUT00000014603; ENSOCUP00000012554; ENSOCUG00000014603.
GeneID100009148.

Organism-specific databases

CTD2288.

Phylogenomic databases

eggNOGCOG0545.
GeneTreeENSGT00550000074272.
HOGENOMHOG000256916.
HOVERGENHBG051624.

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. 3 hits.
[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

EvolutionaryTraceP27124.

Entry information

Entry nameFKBP4_RABIT
AccessionPrimary (citable) accession number: P27124
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 129 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references