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Protein

Peptidyl-prolyl cis-trans isomerase FKBP4

Gene

FKBP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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).

Enzyme regulationi

Inhibited by FK506.1 Publication

GO - Molecular functioni

  • ATP binding Source: Ensembl
  • FK506 binding Source: UniProtKB
  • GTP binding Source: Ensembl
  • heat shock protein binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein binding, bridging Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase, Rotamase

Enzyme and pathway databases

BioCyciZFISH:HS00105-MONOMER.
ReactomeiR-HSA-3371568. Attenuation phase.
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

HGNCiHGNC:3720. FKBP4.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Mitochondrion 1 Publication
  • Nucleus By similarity
  • Cytoplasmcytoskeleton By similarity
  • Cell projectionaxon By similarity

  • Note: Shuttles from mitochondria to nucleus; co-localizes in mitochondria with the glucocorticoid receptor (PubMed:21730050). Colocalized with MAPT/TAU in the distal part of the primary cortical neurons (By similarity).By similarity1 Publication

GO - Cellular componenti

Complete GO annotation...

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.

2D gel databases

REPRODUCTION-2DPAGEIPI00219005.

PTM databases

iPTMnetiQ02790.
PhosphoSitePlusiQ02790.
SwissPalmiQ02790.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000004478.
CleanExiHS_FKBP4.
ExpressionAtlasiQ02790. baseline and differential.
GenevisibleiQ02790. HS.

Organism-specific databases

HPAiCAB017441.
HPA006148.
HPA062857.

Interactioni

Subunit structurei

Homodimer (By similarity). 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. 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 similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGO2Q9UKV82EBI-1047444,EBI-528269
CDC37Q165433EBI-1047444,EBI-295634
HSP90AA1P079008EBI-1047444,EBI-296047
HSPB1P047922EBI-1047444,EBI-352682
S100a1P354677EBI-1047444,EBI-6477109From a different organism.
S100A2P290343EBI-1047444,EBI-752230
S100A6P067033EBI-1047444,EBI-352877

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB
  • protein binding, bridging Source: ProtInc

Protein-protein interaction databases

BioGridi108578. 83 interactors.
DIPiDIP-50866N.
IntActiQ02790. 57 interactors.
MINTiMINT-3024864.
STRINGi9606.ENSP00000001008.

Chemistry databases

BindingDBiQ02790.

Structurei

Secondary structure

1459
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 24Combined sources3
Beta strandi30 – 39Combined sources10
Beta strandi42 – 44Combined sources3
Beta strandi52 – 61Combined sources10
Beta strandi66 – 69Combined sources4
Helixi70 – 72Combined sources3
Beta strandi73 – 75Combined sources3
Beta strandi77 – 80Combined sources4
Beta strandi83 – 86Combined sources4
Helixi88 – 94Combined sources7
Beta strandi102 – 107Combined sources6
Helixi109 – 111Combined sources3
Turni112 – 116Combined sources5
Turni119 – 121Combined sources3
Beta strandi128 – 138Combined sources11
Beta strandi147 – 156Combined sources10
Beta strandi159 – 161Combined sources3
Beta strandi169 – 178Combined sources10
Beta strandi181 – 191Combined sources11
Turni192 – 194Combined sources3
Helixi195 – 198Combined sources4
Helixi202 – 208Combined sources7
Beta strandi216 – 221Combined sources6
Helixi223 – 225Combined sources3
Turni226 – 230Combined sources5
Helixi233 – 235Combined sources3
Beta strandi243 – 253Combined sources11
Helixi258 – 260Combined sources3
Helixi263 – 283Combined sources21
Helixi286 – 299Combined sources14
Turni300 – 302Combined sources3
Helixi309 – 331Combined sources23
Helixi335 – 348Combined sources14
Helixi353 – 365Combined sources13
Helixi369 – 382Combined sources14
Helixi387 – 424Combined sources38

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...

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 fisrt 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.

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.
InParanoidiQ02790.
KOiK09571.
OMAiHPTDTEM.
OrthoDBiEOG091G07OA.
PhylomeDBiQ02790.
TreeFamiTF354214.

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.

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050624436T → P.Corresponds to variant rs1042228dbSNPEnsembl.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

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. 83 interactors.
DIPiDIP-50866N.
IntActiQ02790. 57 interactors.
MINTiMINT-3024864.
STRINGi9606.ENSP00000001008.

Chemistry databases

BindingDBiQ02790.
ChEMBLiCHEMBL4050.

PTM databases

iPTMnetiQ02790.
PhosphoSitePlusiQ02790.
SwissPalmiQ02790.

Polymorphism and mutation databases

BioMutaiFKBP4.
DMDMi399866.

2D gel databases

REPRODUCTION-2DPAGEIPI00219005.

Proteomic databases

EPDiQ02790.
MaxQBiQ02790.
PaxDbiQ02790.
PeptideAtlasiQ02790.
PRIDEiQ02790.

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.
GeneCardsiFKBP4.
H-InvDBHIX0010330.
HGNCiHGNC:3720. FKBP4.
HPAiCAB017441.
HPA006148.
HPA062857.
MIMi600611. gene.
neXtProtiNX_Q02790.
OpenTargetsiENSG00000004478.
PharmGKBiPA28161.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS00105-MONOMER.
ReactomeiR-HSA-3371568. Attenuation phase.
SIGNORiQ02790.

Miscellaneous databases

ChiTaRSiFKBP4. human.
EvolutionaryTraceiQ02790.
GeneWikiiFKBP52.
GenomeRNAii2288.
PROiQ02790.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004478.
CleanExiHS_FKBP4.
ExpressionAtlasiQ02790. baseline and differential.
GenevisibleiQ02790. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q02790
Secondary accession number(s): D3DUQ1, Q9UCP1, Q9UCV7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 191 of the entry and version 3 of the sequence. [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 chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. 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.