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Protein

Peptidyl-prolyl cis-trans isomerase FKBP4

Gene

Fkbp4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications

Catalytic activityi

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

Enzyme regulationi

Inhibited by FK506.By similarity

GO - Molecular functioni

  • ATP binding Source: Ensembl
  • copper-dependent protein binding Source: RGD
  • FK506 binding Source: GO_Central
  • GTP binding Source: Ensembl
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  • poly(A) RNA binding Source: Ensembl
  • tau protein binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase, Rotamase

Enzyme and pathway databases

ReactomeiR-RNO-3371568. Attenuation phase.

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP4 (EC:5.2.1.8)
Short name:
PPIase FKBP4
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:
Gene namesi
Name:Fkbp4
Synonyms:Fkbp52
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi628729. Fkbp4.

Subcellular locationi

GO - Cellular componenti

  • axonal growth cone Source: UniProtKB
  • cytosol Source: UniProtKB
  • endoplasmic reticulum membrane Source: GO_Central
  • extracellular exosome Source: Ensembl
  • microtubule Source: UniProtKB-KW
  • mitochondrion Source: UniProtKB-SubCell
  • neuronal cell body Source: RGD
  • neuron projection Source: RGD
  • nucleoplasm Source: Ensembl
  • perinuclear region of cytoplasm Source: RGD
  • protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Microtubule, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003914711 – 458Peptidyl-prolyl cis-trans isomerase FKBP4Add BLAST458
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00000753212 – 458Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processedAdd BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; in peptidyl-prolyl cis-trans isomerase FKBP4; alternateBy similarity1
Modified residuei2N-acetylthreonine; in peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; partialBy similarity1
Modified residuei143Phosphothreonine; by CK2By similarity1
Modified residuei220PhosphotyrosineBy similarity1
Modified residuei282N6-acetyllysineBy similarity1
Modified residuei373Omega-N-methylarginineBy similarity1
Modified residuei436PhosphothreonineBy similarity1
Cross-linki441Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity

Post-translational modificationi

Phosphorylation by CK2 results in loss of HSP90 binding activity.

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9QVC8.
PRIDEiQ9QVC8.

PTM databases

iPTMnetiQ9QVC8.
PhosphoSitePlusiQ9QVC8.

Expressioni

Tissue specificityi

Widely detected in the brain (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000006444.
GenevisibleiQ9QVC8. RN.

Interactioni

Subunit structurei

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).By similarity

GO - Molecular functioni

  • copper-dependent protein binding Source: RGD
  • tau protein binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-59214N.
STRINGi10116.ENSRNOP00000008737.

Structurei

3D structure databases

ProteinModelPortaliQ9QVC8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini50 – 138PPIase FKBP-type 1PROSITE-ProRule annotationAdd BLAST89
Domaini167 – 253PPIase FKBP-type 2PROSITE-ProRule annotationAdd BLAST87
Repeati270 – 303TPR 1Add BLAST34
Repeati319 – 352TPR 2Add BLAST34
Repeati353 – 386TPR 3Add BLAST34

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni267 – 400Interaction with tubulinAdd BLAST134

Domaini

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

Sequence similaritiesi

Contains 2 PPIase FKBP-type domains.PROSITE-ProRule annotation
Contains 3 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000256916.
HOVERGENiHBG051624.
InParanoidiQ9QVC8.
KOiK09571.
OMAiHPTDTEM.
OrthoDBiEOG091G07OA.
PhylomeDBiQ9QVC8.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR031212. FKBP4.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR001440. TPR_1.
IPR013105. TPR_2.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 2 hits.
PTHR10516:SF25. PTHR10516:SF25. 2 hits.
PfamiPF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 1 hit.
PF07719. TPR_2. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9QVC8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAEEMKVAE NGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETAMIG
60 70 80 90 100
DRVFVHYTGW LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG
110 120 130 140 150
EVCHITCKPE YAYGSAGSPP KIPPNATLVF EVELFEFKGE DLTEDEDGGI
160 170 180 190 200
IRRIRTRGEG YARPNDGAMV EVALEGYYND RLFDQRELCF EVGEGESLDL
210 220 230 240 250
PCGLEEAIQR MEKGEHSIVY LKPSYAFGSV GKERFQIPPH AELRYEVHLK
260 270 280 290 300
SFEKAKASWE MNSEEKLEQS NIVKERGTVY FKEGKYKQAL LQYKKIVSWL
310 320 330 340 350
EYESSFSGEE MQKVHALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS
360 370 380 390 400
NNEKGLFRRG EAHLAVNDFD LARADFQKVL QLYPSNKAAK TQLAVCQQRT
410 420 430 440 450
RRQLAREKKL YANMFERLAE EEHKAKTEVA AGDHPTDAEM KGEPNNVAGN

QAQVKTEA
Length:458
Mass (Da):51,450
Last modified:October 13, 2009 - v3
Checksum:i5701387E5DC991C8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473964 Genomic DNA. Translation: EDM01775.1.
AF531427 mRNA. Translation: AAM95632.1.
RefSeqiNP_001178792.1. NM_001191863.1.
UniGeneiRn.23741.

Genome annotation databases

EnsembliENSRNOT00000008737; ENSRNOP00000008737; ENSRNOG00000006444.
GeneIDi260321.
KEGGirno:260321.
UCSCiRGD:628729. rat.

Cross-referencesi

Web resourcesi

Protein Spotlight

A mind astray - Issue 118 of June 2010

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CH473964 Genomic DNA. Translation: EDM01775.1.
AF531427 mRNA. Translation: AAM95632.1.
RefSeqiNP_001178792.1. NM_001191863.1.
UniGeneiRn.23741.

3D structure databases

ProteinModelPortaliQ9QVC8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59214N.
STRINGi10116.ENSRNOP00000008737.

PTM databases

iPTMnetiQ9QVC8.
PhosphoSitePlusiQ9QVC8.

Proteomic databases

PaxDbiQ9QVC8.
PRIDEiQ9QVC8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008737; ENSRNOP00000008737; ENSRNOG00000006444.
GeneIDi260321.
KEGGirno:260321.
UCSCiRGD:628729. rat.

Organism-specific databases

CTDi2288.
RGDi628729. Fkbp4.

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000256916.
HOVERGENiHBG051624.
InParanoidiQ9QVC8.
KOiK09571.
OMAiHPTDTEM.
OrthoDBiEOG091G07OA.
PhylomeDBiQ9QVC8.

Enzyme and pathway databases

ReactomeiR-RNO-3371568. Attenuation phase.

Miscellaneous databases

PROiQ9QVC8.

Gene expression databases

BgeeiENSRNOG00000006444.
GenevisibleiQ9QVC8. RN.

Family and domain databases

Gene3Di1.25.40.10. 1 hit.
InterProiIPR031212. FKBP4.
IPR023566. PPIase_FKBP.
IPR001179. PPIase_FKBP_dom.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR001440. TPR_1.
IPR013105. TPR_2.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10516. PTHR10516. 2 hits.
PTHR10516:SF25. PTHR10516:SF25. 2 hits.
PfamiPF00254. FKBP_C. 2 hits.
PF00515. TPR_1. 1 hit.
PF07719. TPR_2. 1 hit.
[Graphical view]
SMARTiSM00028. TPR. 3 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 1 hit.
PROSITEiPS50059. FKBP_PPIASE. 2 hits.
PS50005. TPR. 3 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFKBP4_RAT
AccessioniPrimary (citable) accession number: Q9QVC8
Secondary accession number(s): A6IM14, Q8K3U8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: October 13, 2009
Last modified: November 2, 2016
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.