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
Oryctolagus cuniculus (Rabbit)
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 (By similarity).By similarity1 Publication

Catalytic activityi

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

Enzyme regulationi

Inhibited by FK506.By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Isomerase, Rotamase

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:P59
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Chromosome 8

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Microtubule, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003914701 – 458Peptidyl-prolyl cis-trans isomerase FKBP4Add BLAST458
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00000753202 – 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 CK21 Publication1
Modified residuei220PhosphotyrosineBy similarity1
Modified residuei282N6-acetyllysineBy similarity1
Modified residuei373Omega-N-methylarginineBy similarity1
Cross-linki441Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Modified residuei450PhosphoserineBy similarity1
Modified residuei452PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation by CK2 results in loss of HSP90 binding activity.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP27124.

PTM databases

iPTMnetiP27124.

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 similarity3 Publications

GO - Molecular functioni

  • tau protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi1172171. 1 interactor.
STRINGi9986.ENSOCUP00000012554.

Structurei

Secondary structure

1458
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi24 – 26Combined sources3
Turni27 – 29Combined sources3
Beta strandi33 – 39Combined sources7
Beta strandi52 – 61Combined sources10
Turni62 – 64Combined sources3
Beta strandi65 – 69Combined sources5
Helixi70 – 73Combined sources4
Beta strandi77 – 80Combined sources4
Turni81 – 83Combined sources3
Helixi88 – 95Combined sources8
Beta strandi102 – 107Combined sources6
Helixi109 – 111Combined sources3
Turni112 – 116Combined sources5
Turni119 – 121Combined sources3
Beta strandi128 – 136Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ROTNMR-A4-148[»]
1ROUNMR-A4-148[»]
ProteinModelPortaliP27124.
SMRiP27124.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27124.

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 C-terminal region (AA 375-458) is required to prevent tubulin polymerization.By similarity
The PPIase activity is mainly due to the fisrt PPIase FKBP-type domain (1-138 AA).
The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400.
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.
InParanoidiP27124.
KOiK09571.
OMAiANSTVYY.
OrthoDBiEOG091G07OA.

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.

P27124-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAEEMKAAE SGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETPMIG
60 70 80 90 100
DRVFVHYTGW LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG
110 120 130 140 150
ELCRITCKPE YAYGSAGSPP KIPPNATLVF EVELFEFKGE DLTDDEDGGI
160 170 180 190 200
IRRIRTRGEG YARPNDGAIV EVALEGYYKD RLFDQRELRF EVGEGESLDL
210 220 230 240 250
PCGLEKAIQR MEKGEHSILY LKPSYAFGNA GKEKFQIPPY AELKYEVHLK
260 270 280 290 300
SFEKAKESWE MSSEEKLEQS AIVKERGTVY FKEGKYKQAL LQYKKIVSWL
310 320 330 340 350
EYESSFSSEE VQKAQALRLA SHLNLAMCHL KLQAFSAAVE SCNKALELDS
360 370 380 390 400
NNEKGLFRRG EAHLAVNDFD LARADFQKVL QLYPSNKAAK AQLAVCQQRI
410 420 430 440 450
RKQIAREKKL YANMFERLAE EENKAKAEVA AGDHPMDTEM KDERNDVAGS

QSQVETEA
Length:458
Mass (Da):51,475
Last modified:January 23, 2007 - v3
Checksum:i2EE25D561391DFF0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15S → H AA sequence (PubMed:8579355).Curated1
Sequence conflicti21 – 22EG → FI AA sequence (PubMed:8579355).Curated2
Sequence conflicti26S → T AA sequence (PubMed:8579355).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84474 mRNA. Translation: AAA31438.1.
M84988 mRNA. Translation: AAA31439.1.
PIRiA42386.
RefSeqiNP_001075779.1. NM_001082310.1.
UniGeneiOcu.1944.

Genome annotation databases

EnsembliENSOCUT00000014603; ENSOCUP00000012554; ENSOCUG00000014603.
GeneIDi100009148.
KEGGiocu:100009148.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84474 mRNA. Translation: AAA31438.1.
M84988 mRNA. Translation: AAA31439.1.
PIRiA42386.
RefSeqiNP_001075779.1. NM_001082310.1.
UniGeneiOcu.1944.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ROTNMR-A4-148[»]
1ROUNMR-A4-148[»]
ProteinModelPortaliP27124.
SMRiP27124.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi1172171. 1 interactor.
STRINGi9986.ENSOCUP00000012554.

PTM databases

iPTMnetiP27124.

Proteomic databases

PRIDEiP27124.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOCUT00000014603; ENSOCUP00000012554; ENSOCUG00000014603.
GeneIDi100009148.
KEGGiocu:100009148.

Organism-specific databases

CTDi2288.

Phylogenomic databases

eggNOGiKOG0543. Eukaryota.
COG0545. LUCA.
GeneTreeiENSGT00760000119159.
HOGENOMiHOG000256916.
HOVERGENiHBG051624.
InParanoidiP27124.
KOiK09571.
OMAiANSTVYY.
OrthoDBiEOG091G07OA.

Miscellaneous databases

EvolutionaryTraceiP27124.

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_RABIT
AccessioniPrimary (citable) accession number: P27124
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 148 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

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

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.