Q9QVC8 (FKBP4_RAT) 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:	Fkbp52

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 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	Cytoplasm › cytosol. Mitochondrion By similarity. Nucleus By similarity. Cytoplasm › cytoskeleton 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 component	Cytoplasm Cytoskeleton Microtubule Mitochondrion Nucleus
Domain	Repeat TPR repeat
Molecular function	Chaperone Isomerase Rotamase
PTM	Acetylation Phosphoprotein
Technical term	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 copper ion transport Inferred from mutant phenotype PubMed 15133031. Source: RGD embryo implantation Inferred from electronic annotation. Source: Compara male sex differentiation Inferred from electronic annotation. Source: Compara negative regulation of microtubule polymerization Inferred from mutant phenotype Ref.4. Source: RGD negative regulation of neuron projection development Inferred from sequence or structural similarity. 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 direct assay Ref.5. Source: UniProtKB cytosol Inferred from direct assay Ref.5. Source: UniProtKB microtubule Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell 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_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_0000391471
	Initiator methionine	1	1	Removed; alternate By similarity
	Chain	2 – 458	457	Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed		PRO_0000075321
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
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 By similarity
	Modified residue	282	1	N6-acetyllysine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q9QVC8 [UniParc]. Last modified October 13, 2009. Version 3. Checksum: 5701387E5DC991C8	FASTA	458	51,450
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00358443.
RefSeq	NP_001178792.1. NM_001191863.1.
UniGene	Rn.233747.
3D structure databases
ProteinModelPortal	Q9QVC8.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59214N.
PTM databases
PhosphoSite	Q9QVC8.
Proteomic databases
PaxDb	Q9QVC8.
PRIDE	Q9QVC8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000008737; ENSRNOP00000008737; ENSRNOG00000006444.
GeneID	260321.
KEGG	rno:260321.
UCSC	RGD:628729. rat.
Organism-specific databases
CTD	2288.
RGD	628729. Fkbp4.
Phylogenomic databases
eggNOG	COG0545.
GeneTree	ENSGT00550000074272.
HOGENOM	HOG000256916.
HOVERGEN	HBG051624.
InParanoid	Q8K3U8.
KO	K09571.
OrthoDB	EOG49GKGJ.
Gene expression databases
Genevestigator	Q9QVC8.
GermOnline	ENSRNOG00000006444. Rattus norvegicus.
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. 1 hit. [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
NextBio	624351.

Entry information

Entry name

FKBP4_RAT

Accession

Primary (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:	May 29, 2013
This is version 91 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program