Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Peptidyl-prolyl cis-trans isomerase FKBP4

Gene

FKBP4

Organism
Homo sapiens (Human)
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.5 Publications

Catalytic activityi

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

Activity regulationi

Inhibited by FK506.1 Publication

GO - Molecular functioni

  • ATP binding Source: Ensembl
  • copper-dependent protein binding Source: Ensembl
  • FK506 binding Source: GO_Central
  • glucocorticoid receptor binding Source: Ensembl
  • GTP binding Source: Ensembl
  • heat shock protein binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  • phosphoprotein binding Source: Ensembl
  • protein binding, bridging Source: ProtInc
  • RNA binding Source: UniProtKB
  • tau protein binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionChaperone, Isomerase, Rotamase

Enzyme and pathway databases

ReactomeiR-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-3371568 Attenuation phase
R-HSA-8939211 ESR-mediated signaling
R-HSA-9018519 Estrogen-dependent gene expression
SIGNORiQ02790

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP4 (EC:5.2.1.8)
Short name:
PPIase FKBP4
Alternative name(s):
51 kDa FK506-binding protein
Short name:
FKBP51
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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000004478.7
HGNCiHGNC:3720 FKBP4
MIMi600611 gene
neXtProtiNX_Q02790

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67 – 68FD → DV: Decreased catalytic activity toward TRPC1. 1 Publication2

Organism-specific databases

DisGeNETi2288
OpenTargetsiENSG00000004478
PharmGKBiPA28161

Chemistry databases

ChEMBLiCHEMBL4050

Polymorphism and mutation databases

BioMutaiFKBP4
DMDMi399866

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003914681 – 459Peptidyl-prolyl cis-trans isomerase FKBP4Add BLAST459
Initiator methionineiRemoved; alternate4 Publications
ChainiPRO_00000753182 – 459Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processedAdd BLAST458

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine; in peptidyl-prolyl cis-trans isomerase FKBP4; alternate1 Publication1
Modified residuei2N-acetylthreonine; in peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed; partial1 Publication1
Modified residuei143Phosphothreonine; by CK2By similarity1
Modified residuei220PhosphotyrosineCombined sources1
Modified residuei282N6-acetyllysineCombined sources1
Modified residuei373Omega-N-methylarginineBy similarity1
Modified residuei436PhosphothreonineCombined sources1
Cross-linki441Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Modified residuei451PhosphoserineCombined sources1
Modified residuei453PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation by CK2 results in loss of HSP90 binding activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ02790
MaxQBiQ02790
PaxDbiQ02790
PeptideAtlasiQ02790
PRIDEiQ02790
ProteomicsDBi58125

2D gel databases

REPRODUCTION-2DPAGEiIPI00219005

PTM databases

iPTMnetiQ02790
PhosphoSitePlusiQ02790
SwissPalmiQ02790

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000004478 Expressed in 237 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_FKBP4
ExpressionAtlasiQ02790 baseline and differential
GenevisibleiQ02790 HS

Organism-specific databases

HPAiCAB017441
HPA006148
HPA062857

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with GLMN (PubMed:12604780). 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. 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; causes partially NR3C1 transport to the nucleus.By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108578, 89 interactors
DIPiDIP-50866N
IntActiQ02790, 62 interactors
MINTiQ02790
STRINGi9606.ENSP00000001008

Chemistry databases

BindingDBiQ02790

Structurei

Secondary structure

1459
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ02790
SMRiQ02790
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ02790

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.

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000256916
HOVERGENiHBG051624
InParanoidiQ02790
KOiK09571
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiQ02790
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 4 potential isoforms that are computationally mapped.Show allAlign All

Q02790-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTAEEMKATE SGAQSAPLPM EGVDISPKQD EGVLKVIKRE GTGTEMPMIG
60 70 80 90 100
DRVFVHYTGW LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAIATMKVG
110 120 130 140 150
EVCHITCKPE YAYGSAGSPP KIPPNATLVF EVELFEFKGE DLTEEEDGGI
160 170 180 190 200
IRRIQTRGEG YAKPNEGAIV EVALEGYYKD KLFDQRELRF EIGEGENLDL
210 220 230 240 250
PYGLERAIQR MEKGEHSIVY LKPSYAFGSV GKEKFQIPPN AELKYELHLK
260 270 280 290 300
SFEKAKESWE MNSEEKLEQS TIVKERGTVY FKEGKYKQAL LQYKKIVSWL
310 320 330 340 350
EYESSFSNEE AQKAQALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS
360 370 380 390 400
NNEKGLFRRG EAHLAVNDFE LARADFQKVL QLYPNNKAAK TQLAVCQQRI
410 420 430 440 450
RRQLAREKKL YANMFERLAE EENKAKAEAS SGDHPTDTEM KEEQKSNTAG

SQSQVETEA
Length:459
Mass (Da):51,805
Last modified:January 23, 2007 - v3
Checksum:i6A498105418D9435
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H1U3F5H1U3_HUMAN
Peptidylprolyl isomerase
FKBP4
86Annotation score:
F5H120F5H120_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP4
51Annotation score:
H0YFG2H0YFG2_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP4
84Annotation score:
H0YG86H0YG86_HUMAN
Peptidyl-prolyl cis-trans isomerase...
FKBP4
23Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050624436T → P. Corresponds to variant dbSNP:rs1042228Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88279 mRNA Translation: AAA36111.1
AC005841 Genomic DNA No translation available.
CH471116 Genomic DNA Translation: EAW88889.1
CH471116 Genomic DNA Translation: EAW88890.1
BC001786 mRNA Translation: AAH01786.1
BC007924 mRNA Translation: AAH07924.1
CCDSiCCDS8512.1
PIRiA46372
RefSeqiNP_002005.1, NM_002014.3
UniGeneiHs.524183
Hs.713721

Genome annotation databases

EnsembliENST00000001008; ENSP00000001008; ENSG00000004478
GeneIDi2288
KEGGihsa:2288
UCSCiuc001qkz.4 human

Keywords - Coding sequence diversityi

Polymorphism

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
M88279 mRNA Translation: AAA36111.1
AC005841 Genomic DNA No translation available.
CH471116 Genomic DNA Translation: EAW88889.1
CH471116 Genomic DNA Translation: EAW88890.1
BC001786 mRNA Translation: AAH01786.1
BC007924 mRNA Translation: AAH07924.1
CCDSiCCDS8512.1
PIRiA46372
RefSeqiNP_002005.1, NM_002014.3
UniGeneiHs.524183
Hs.713721

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1N1AX-ray2.40A/B1-140[»]
1P5QX-ray2.80A/B/C146-459[»]
1Q1CX-ray1.90A2-260[»]
1QZ2X-ray3.00A/B/C145-459[»]
4DRJX-ray1.80A1-140[»]
4LAVX-ray1.80A/B16-260[»]
4LAWX-ray2.40A/B16-260[»]
4LAXX-ray2.01A16-260[»]
4LAYX-ray1.70A1-260[»]
4TW8X-ray3.00A/B21-255[»]
ProteinModelPortaliQ02790
SMRiQ02790
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108578, 89 interactors
DIPiDIP-50866N
IntActiQ02790, 62 interactors
MINTiQ02790
STRINGi9606.ENSP00000001008

Chemistry databases

BindingDBiQ02790
ChEMBLiCHEMBL4050

PTM databases

iPTMnetiQ02790
PhosphoSitePlusiQ02790
SwissPalmiQ02790

Polymorphism and mutation databases

BioMutaiFKBP4
DMDMi399866

2D gel databases

REPRODUCTION-2DPAGEiIPI00219005

Proteomic databases

EPDiQ02790
MaxQBiQ02790
PaxDbiQ02790
PeptideAtlasiQ02790
PRIDEiQ02790
ProteomicsDBi58125

Protocols and materials databases

DNASUi2288
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000001008; ENSP00000001008; ENSG00000004478
GeneIDi2288
KEGGihsa:2288
UCSCiuc001qkz.4 human

Organism-specific databases

CTDi2288
DisGeNETi2288
EuPathDBiHostDB:ENSG00000004478.7
GeneCardsiFKBP4
H-InvDBiHIX0010330
HGNCiHGNC:3720 FKBP4
HPAiCAB017441
HPA006148
HPA062857
MIMi600611 gene
neXtProtiNX_Q02790
OpenTargetsiENSG00000004478
PharmGKBiPA28161
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000256916
HOVERGENiHBG051624
InParanoidiQ02790
KOiK09571
OMAiELEMLGW
OrthoDBiEOG091G07OA
PhylomeDBiQ02790
TreeFamiTF354214

Enzyme and pathway databases

ReactomeiR-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-3371568 Attenuation phase
R-HSA-8939211 ESR-mediated signaling
R-HSA-9018519 Estrogen-dependent gene expression
SIGNORiQ02790

Miscellaneous databases

ChiTaRSiFKBP4 human
EvolutionaryTraceiQ02790
GeneWikiiFKBP52
GenomeRNAii2288
PROiPR:Q02790
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004478 Expressed in 237 organ(s), highest expression level in cerebellar hemisphere
CleanExiHS_FKBP4
ExpressionAtlasiQ02790 baseline and differential
GenevisibleiQ02790 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q02790
Secondary accession number(s): D3DUQ1, Q9UCP1, Q9UCV7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 210 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again