P27124 (FKBP4_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Cleaved into the following chain:

1. Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed

Gene names

Name:	FKBP4
Synonyms:	P59

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	458 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes thought interaction with heat-shock protein 90 (HSP90) By similarity. 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. 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. Ref.8
Catalytic activity	Peptidylproline (omega=180) = peptidylproline (omega=0).
Enzyme regulation	Inhibited by FK506 By similarity.
Subunit structure	Homodimer By similarity. Associates 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 By similarity. 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.6 Ref.7
Subcellular location	Cytoplasm › cytosol By similarity. Mitochondrion By similarity. Nucleus. Cytoplasm › cytoskeleton 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.8 The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA). Ref.3 Ref.8 The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400. Ref.3 Ref.8 The TPR repeats mediate mitochondrial localization By similarity. Ref.3 Ref.8
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 component	Cytoplasm Cytoskeleton Microtubule Mitochondrion Nucleus
Domain	Repeat TPR repeat
Molecular function	Chaperone Isomerase Rotamase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	androgen receptor signaling pathway Inferred from electronic annotation. Source: Compara chaperone-mediated protein folding Inferred from sequence or structural similarity. Source: UniProtKB embryo implantation Inferred from electronic annotation. Source: Compara male sex differentiation Inferred from electronic annotation. Source: Compara 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: Compara protein complex localization Inferred from electronic annotation. Source: Compara steroid hormone receptor complex assembly Inferred from electronic annotation. Source: Compara
Cellular_component	axonal 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_function	ATP binding Inferred from electronic annotation. Source: Compara GTP binding Inferred from electronic annotation. Source: Compara peptidyl-prolyl cis-trans isomerase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 458

458

Peptidyl-prolyl cis-trans isomerase FKBP4

PRO_0000391470

Initiator methionine

1

1

Removed; alternate By similarity

Chain

2 – 458

457

Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed

PRO_0000075320

Regions

Domain

50 – 138

89

PPIase FKBP-type 1

Domain

167 – 253

87

PPIase FKBP-type 2

Repeat

270 – 303

34

TPR 1

Repeat

319 – 352

34

TPR 2

Repeat

353 – 386

34

TPR 3

Region

267 – 400

134

Interaction with tubulin By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine; in peptidyl-prolyl cis-trans isomerase FKBP4; alternate By similarity

Modified residue

2

1

N-acetylthreonine; in peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; partial By similarity

Modified residue

143

1

Phosphothreonine; by CK2

Modified residue

282

1

N6-acetyllysine By similarity

Modified residue

450

1

Phosphoserine By similarity

Modified residue

452

1

Phosphoserine By similarity

Experimental info

Sequence conflict

15

1

S → H AA sequence Ref.2

Sequence conflict

21 – 22

2

EG → FI AA sequence Ref.2

Sequence conflict

26

1

S → T AA sequence Ref.2

Secondary structure

1

.

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458

Helix Strand Turn

Details...

Beta strand

24 – 26

3

Turn

27 – 29

3

Beta strand

33 – 39

7

Beta strand

52 – 61

10

Turn

62 – 64

3

Beta strand

65 – 69

5

Helix

70 – 73

4

Beta strand

77 – 80

4

Turn

81 – 83

3

Helix

88 – 95

8

Beta strand

102 – 107

6

Helix

109 – 111

3

Turn

112 – 116

5

Turn

119 – 121

3

Beta strand

128 – 136

9

Sequences

	Sequence		Length	Mass (Da)
	P27124 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 2EE25D561391DFF0	FASTA	458	51,475
	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

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]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.

PIR

A42386.

RefSeq

NP_001075779.1. NM_001082310.1.

UniGene

Ocu.1944.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ROT	NMR	-	A	7-148	[»]
1ROU	NMR	-	A	7-148	[»]

ProteinModelPortal

P27124.

SMR

P27124. Positions 21-425.

ModBase

Search...

Protein-protein interaction databases

STRING

9986.ENSOCUP00000012554.

Proteomic databases

PRIDE

P27124.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

100009148.

Organism-specific databases

CTD

2288.

Phylogenomic databases

eggNOG

COG0545.

HOGENOM

HOG000256916.

HOVERGEN

HBG051624.

OrthoDB

EOG49GKGJ.

Family and domain databases

Gene3D

1.25.40.10. 1 hit.

InterPro

IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR001440. TPR-1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR10516. PTHR10516. 1 hit.

Pfam

PF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 3 hits.
[Graphical view]

SMART

SM00028. TPR. 3 hits.
[Graphical view]

PROSITE

PS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P27124.

Entry information

Entry name

FKBP4_RABIT

Accession

Primary (citable) accession number: P27124

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 123 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program