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Protein

Peptidyl-prolyl cis-trans isomerase FKBP4

Gene

Fkbp4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 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-MMU-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-MMU-3371568 Attenuation phase
R-MMU-8939211 ESR-mediated signaling
R-MMU-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:Fkpb52
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:95543 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

Cytoplasm, Cytoskeleton, Microtubule, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003914691 – 458Peptidyl-prolyl cis-trans isomerase FKBP4Add BLAST458
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00000753192 – 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-methylarginineCombined sources1
Modified residuei436PhosphothreonineBy similarity1
Cross-linki441Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei452PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by CK2 results in loss of HSP90 binding activity.

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30416
MaxQBiP30416
PaxDbiP30416
PeptideAtlasiP30416
PRIDEiP30416

2D gel databases

REPRODUCTION-2DPAGEiP30416

PTM databases

iPTMnetiP30416
PhosphoSitePlusiP30416
SwissPalmiP30416

Expressioni

Gene expression databases

BgeeiENSMUSG00000030357 Expressed in 301 organ(s), highest expression level in mandibular prominence
CleanExiMM_FKBP4
ExpressionAtlasiP30416 baseline and differential
GenevisibleiP30416 MM

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GLMN (By similarity). Associates with HSP90AA1 and HSPA1A/HSPA1B 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 (By similarity). 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; contributes to NR3C1 transport to the nucleus.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nr3c1P065373EBI-492746,EBI-492753

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199685, 3 interactors
IntActiP30416, 4 interactors
MINTiP30416
STRINGi10090.ENSMUSP00000032508

Structurei

3D structure databases

ProteinModelPortaliP30416
SMRiP30416
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 tubulinBy similarityAdd 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.By similarity
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
InParanoidiP30416
KOiK09571
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiP30416
TreeFamiTF354214

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P30416-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTAEEMKAAE NGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETPMIG
60 70 80 90 100
DRVFVHYTGW LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG
110 120 130 140 150
EVCHITCKPE YAYGAAGSPP KIPPNATLVF EVELFEFKGE DLTEEEDGGI
160 170 180 190 200
IRRIRTRGEG YARPNDGAMV EVALEGYHKD RLFDQRELCF EVGEGESLDL
210 220 230 240 250
PCGLEEAIQR MEKGEHSIVY LKPSYAFGSV GKERFQIPPH AELRYEVRLK
260 270 280 290 300
SFEKAKESWE MSSAEKLEQS NIVKERGTAY 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 EEHKVKAEVA AGDHPTDAEM KGERNNVAEN

QSRVETEA
Length:458
Mass (Da):51,572
Last modified:January 23, 2007 - v5
Checksum:iCFB2ED49E9B6BA7A
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6S2D5F6S2D5_MOUSE
Peptidylprolyl isomerase
Fkbp4
260Annotation score:
F7CAT1F7CAT1_MOUSE
Peptidylprolyl isomerase
Fkbp4
187Annotation score:

Sequence cautioni

The sequence CAA34914 differs from that shown. Reason: Frameshift at positions 16, 156, 204 and 265.Curated
The sequence CAA34914 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6 – 7MK → HE in CAC39452 (PubMed:8341706).Curated2
Sequence conflicti156 – 163TRGEGYAR → LGVKAMQG in CAC39452 (PubMed:8341706).Curated8
Sequence conflicti203 – 240GLEEA…QIPPH → AWRRPFSAWRKESIPSCTSN LAMLLAVWGRRGSRSHRT in CAC39452 (PubMed:8341706).CuratedAdd BLAST38
Sequence conflicti203 – 240GLEEA…QIPPH → AWRRPFSAWRKESIPSCTSN LAMLLAVWGRRGSRSHRT in CAA34914 (PubMed:8341706).CuratedAdd BLAST38
Sequence conflicti265 – 272EKLEQSNI → RSWSRATY in CAC39452 (PubMed:8341706).Curated8
Sequence conflicti315H → R in AAH03447 (PubMed:15489334).Curated1
Sequence conflicti360G → R in BAE35690 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70887 mRNA Translation: CAA50231.1
AK083912 mRNA Translation: BAC39057.1
AK160202 mRNA Translation: BAE35690.1
BC003447 mRNA Translation: AAH03447.1
X17069 mRNA Translation: CAC39452.1
X17068 mRNA Translation: CAA34914.1 Sequence problems.
CCDSiCCDS20573.1
PIRiJN0873
RefSeqiNP_034349.1, NM_010219.3
UniGeneiMm.12758

Genome annotation databases

EnsembliENSMUST00000032508; ENSMUSP00000032508; ENSMUSG00000030357
GeneIDi14228
KEGGimmu:14228
UCSCiuc009edr.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70887 mRNA Translation: CAA50231.1
AK083912 mRNA Translation: BAC39057.1
AK160202 mRNA Translation: BAE35690.1
BC003447 mRNA Translation: AAH03447.1
X17069 mRNA Translation: CAC39452.1
X17068 mRNA Translation: CAA34914.1 Sequence problems.
CCDSiCCDS20573.1
PIRiJN0873
RefSeqiNP_034349.1, NM_010219.3
UniGeneiMm.12758

3D structure databases

ProteinModelPortaliP30416
SMRiP30416
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi199685, 3 interactors
IntActiP30416, 4 interactors
MINTiP30416
STRINGi10090.ENSMUSP00000032508

PTM databases

iPTMnetiP30416
PhosphoSitePlusiP30416
SwissPalmiP30416

2D gel databases

REPRODUCTION-2DPAGEiP30416

Proteomic databases

EPDiP30416
MaxQBiP30416
PaxDbiP30416
PeptideAtlasiP30416
PRIDEiP30416

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032508; ENSMUSP00000032508; ENSMUSG00000030357
GeneIDi14228
KEGGimmu:14228
UCSCiuc009edr.1 mouse

Organism-specific databases

CTDi2288
MGIiMGI:95543 Fkbp4

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000256916
HOVERGENiHBG051624
InParanoidiP30416
KOiK09571
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiP30416
TreeFamiTF354214

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiFkbp4 mouse
PROiPR:P30416
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030357 Expressed in 301 organ(s), highest expression level in mandibular prominence
CleanExiMM_FKBP4
ExpressionAtlasiP30416 baseline and differential
GenevisibleiP30416 MM

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_MOUSE
AccessioniPrimary (citable) accession number: P30416
Secondary accession number(s): Q3TVC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 185 of the entry and version 5 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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