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Protein

Peptidyl-prolyl cis-trans isomerase FKBP4

Gene

Fkbp4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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).

Activity regulationi

Inhibited by FK506.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone, Isomerase, Rotamase

Enzyme and pathway databases

ReactomeiR-RNO-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-RNO-3371568 Attenuation phase
R-RNO-8939211 ESR-mediated signaling
R-RNO-9018519 Estrogen-dependent gene expression

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi628729 Fkbp4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 10 organ(s), highest expression level in heart
GenevisibleiQ9QVC8 RN

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GLMN. 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 (By similarity). Associates with tubulin (PubMed:17435176). Interacts with MAPT/TAU (PubMed:20133804). 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 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-59214N
IntActiQ9QVC8, 1 interactor
STRINGi10116.ENSRNOP00000008737

Structurei

3D structure databases

ProteinModelPortaliQ9QVC8
SMRiQ9QVC8
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 first 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

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000256916
HOVERGENiHBG051624
InParanoidiQ9QVC8
KOiK09571
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiQ9QVC8

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR031212 FKBP4
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR001440 TPR_1
IPR013105 TPR_2
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PTHR10516:SF25 PTHR10516:SF25, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 2 hits
PF00515 TPR_1, 1 hit
PF07719 TPR_2, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 2 hits
PS50005 TPR, 3 hits
PS50293 TPR_REGION, 2 hits

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

Similar proteinsi

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
SMRiQ9QVC8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59214N
IntActiQ9QVC8, 1 interactor
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
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiQ9QVC8

Enzyme and pathway databases

ReactomeiR-RNO-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-RNO-3371568 Attenuation phase
R-RNO-8939211 ESR-mediated signaling
R-RNO-9018519 Estrogen-dependent gene expression

Miscellaneous databases

PROiPR:Q9QVC8

Gene expression databases

BgeeiENSRNOG00000006444 Expressed in 10 organ(s), highest expression level in heart
GenevisibleiQ9QVC8 RN

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR031212 FKBP4
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR001440 TPR_1
IPR013105 TPR_2
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PTHR10516:SF25 PTHR10516:SF25, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 2 hits
PF00515 TPR_1, 1 hit
PF07719 TPR_2, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 3 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 2 hits
PS50005 TPR, 3 hits
PS50293 TPR_REGION, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiFKBP4_RAT
AccessioniPrimary (citable) accession number: Q9QVC8
Secondary accession number(s): A6IM14, Q8K3U8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: October 13, 2009
Last modified: November 7, 2018
This is version 134 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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