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Protein

Peptidyl-prolyl cis-trans isomerase FKBP5

Gene

FKBP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded.

Catalytic activityi

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

Enzyme regulationi

Inhibited by FK506 but not cyclosporin.

GO - Molecular functioni

  • FK506 binding Source: GO_Central
  • heat shock protein binding Source: UniProtKB
  • peptidyl-prolyl cis-trans isomerase activity Source: UniProtKB

GO - Biological processi

  • chaperone-mediated protein folding Source: UniProtKB
  • protein folding Source: ProtInc
  • response to bacterium Source: Ensembl

Keywordsi

Molecular functionChaperone, Isomerase, Rotamase

Enzyme and pathway databases

ReactomeiR-HSA-3371497 HSP90 chaperone cycle for steroid hormone receptors (SHR)
R-HSA-8939211 ESR-mediated signaling
SIGNORiQ13451

Names & Taxonomyi

Protein namesi
Recommended name:
Peptidyl-prolyl cis-trans isomerase FKBP5 (EC:5.2.1.8)
Short name:
PPIase FKBP5
Alternative name(s):
51 kDa FK506-binding protein
Short name:
51 kDa FKBP
Short name:
FKBP-51
54 kDa progesterone receptor-associated immunophilin
Androgen-regulated protein 6
FF1 antigen
FK506-binding protein 5
Short name:
FKBP-5
FKBP54
Short name:
p54
HSP90-binding immunophilin
Rotamase
Gene namesi
Name:FKBP5
Synonyms:AIG6, FKBP51
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000096060.14
HGNCiHGNC:3721 FKBP5
MIMi602623 gene
neXtProtiNX_Q13451

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, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi2289
MalaCardsiFKBP5
OpenTargetsiENSG00000096060
PharmGKBiPA28162

Chemistry databases

ChEMBLiCHEMBL2052031

Polymorphism and mutation databases

BioMutaiFKBP5
DMDMi2851536

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753241 – 457Peptidyl-prolyl cis-trans isomerase FKBP5Add BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei13PhosphoserineCombined sources1
Modified residuei445PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13451
PaxDbiQ13451
PeptideAtlasiQ13451
PRIDEiQ13451
ProteomicsDBi59455

PTM databases

iPTMnetiQ13451
PhosphoSitePlusiQ13451
SwissPalmiQ13451

Expressioni

Tissue specificityi

Widely expressed, enriched in testis compared to other tissues.

Inductioni

By androgen.

Gene expression databases

BgeeiENSG00000096060
CleanExiHS_FKBP5
GenevisibleiQ13451 HS

Organism-specific databases

HPAiCAB009315
HPA031092
HPA031093
HPA031095

Interactioni

Subunit structurei

Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates from the complex and FKBP4 takes its place. Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.

Binary interactionsi

Show more details

GO - Molecular functioni

  • heat shock protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108579, 117 interactors
CORUMiQ13451
DIPiDIP-27597N
IntActiQ13451, 122 interactors
MINTiQ13451
STRINGi9606.ENSP00000338160

Chemistry databases

BindingDBiQ13451

Structurei

Secondary structure

1457
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi16 – 21Combined sources6
Beta strandi22 – 24Combined sources3
Beta strandi26 – 28Combined sources3
Beta strandi30 – 39Combined sources10
Beta strandi42 – 44Combined sources3
Beta strandi52 – 61Combined sources10
Beta strandi66 – 69Combined sources4
Helixi70 – 73Combined sources4
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 strandi144 – 154Combined sources11
Beta strandi167 – 176Combined sources10
Beta strandi179 – 189Combined sources11
Helixi193 – 196Combined sources4
Helixi200 – 206Combined sources7
Beta strandi214 – 219Combined sources6
Turni221 – 223Combined sources3
Helixi226 – 228Combined sources3
Helixi231 – 233Combined sources3
Beta strandi241 – 251Combined sources11
Helixi256 – 258Combined sources3
Helixi261 – 280Combined sources20
Helixi284 – 298Combined sources15
Helixi306 – 329Combined sources24
Helixi333 – 346Combined sources14
Helixi351 – 363Combined sources13
Helixi367 – 380Combined sources14
Helixi385 – 423Combined sources39

3D structure databases

ProteinModelPortaliQ13451
SMRiQ13451
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13451

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 130PPIase FKBP-type 1PROSITE-ProRule annotationAdd BLAST89
Domaini157 – 243PPIase FKBP-type 2PROSITE-ProRule annotationAdd BLAST87
Repeati268 – 301TPR 1Add BLAST34
Repeati317 – 350TPR 2Add BLAST34
Repeati351 – 384TPR 3Add BLAST34

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0543 Eukaryota
COG0545 LUCA
GeneTreeiENSGT00760000119159
HOGENOMiHOG000256916
HOVERGENiHBG051624
InParanoidiQ13451
KOiK09571
OMAiNSEETPM
OrthoDBiEOG091G07OA
PhylomeDBiQ13451
TreeFamiTF105292

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR031210 FKBP5
IPR023566 PPIase_FKBP
IPR001179 PPIase_FKBP_dom
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR001440 TPR_1
IPR019734 TPR_repeat
PANTHERiPTHR10516 PTHR10516, 1 hit
PTHR10516:SF26 PTHR10516:SF26, 1 hit
PfamiView protein in Pfam
PF00254 FKBP_C, 2 hits
PF00515 TPR_1, 1 hit
PF13181 TPR_8, 1 hit
SMARTiView protein in SMART
SM00028 TPR, 2 hits
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50059 FKBP_PPIASE, 2 hits
PS50005 TPR, 3 hits
PS50293 TPR_REGION, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13451-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTTDEGAKNN EESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG
60 70 80 90 100
DKVYVHYKGK LSNGKKFDSS HDRNEPFVFS LGKGQVIKAW DIGVATMKKG
110 120 130 140 150
EICHLLCKPE YAYGSAGSLP KIPSNATLFF EIELLDFKGE DLFEDGGIIR
160 170 180 190 200
RTKRKGEGYS NPNEGATVEI HLEGRCGGRM FDCRDVAFTV GEGEDHDIPI
210 220 230 240 250
GIDKALEKMQ REEQCILYLG PRYGFGEAGK PKFGIEPNAE LIYEVTLKSF
260 270 280 290 300
EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYMQAVIQ YGKIVSWLEM
310 320 330 340 350
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN
360 370 380 390 400
EKGLYRRGEA QLLMNEFESA KGDFEKVLEV NPQNKAARLQ ISMCQKKAKE
410 420 430 440 450
HNERDRRIYA NMFKKFAEQD AKEEANKAMG KKTSEGVTNE KGTDSQAMEE

EKPEGHV
Length:457
Mass (Da):51,212
Last modified:July 15, 1998 - v2
Checksum:i18A86608C6891A73
GO
Isoform 2 (identifier: Q13451-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     223-268: YGFGEAGKPK...MDTKEKLEQA → PKNPGRWIPK...SISKNLFKCW
     269-457: Missing.

Note: No experimental confirmation available.
Show »
Length:268
Mass (Da):30,032
Checksum:i2B172A6E03570AAD
GO

Sequence cautioni

The sequence BAD93130 differs from that shown. Reason: Frameshift at position 29.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044820223 – 268YGFGE…KLEQA → PKNPGRWIPKKNWSRLPLSK RREPYTSRCVSPYAILSISK NLFKCW in isoform 2. 1 PublicationAdd BLAST46
Alternative sequenceiVSP_044821269 – 457Missing in isoform 2. 1 PublicationAdd BLAST189

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U71321 mRNA Translation: AAC51189.1
AF194172 mRNA Translation: AAL54872.1
AK312422 mRNA Translation: BAG35332.1
AB209893 mRNA Translation: BAD93130.1 Frameshift.
AL033519 Genomic DNA No translation available.
AL157823 Genomic DNA No translation available.
AL590400 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03842.1
BC042605 mRNA Translation: AAH42605.1
U42031 mRNA Translation: AAA86245.1
CCDSiCCDS4808.1 [Q13451-1]
CCDS54996.1 [Q13451-2]
PIRiJC5422
RefSeqiNP_001139247.1, NM_001145775.2 [Q13451-1]
NP_001139248.1, NM_001145776.1 [Q13451-1]
NP_001139249.1, NM_001145777.1 [Q13451-2]
NP_004108.1, NM_004117.3 [Q13451-1]
UniGeneiHs.407190

Genome annotation databases

EnsembliENST00000357266; ENSP00000349811; ENSG00000096060 [Q13451-1]
ENST00000536438; ENSP00000444810; ENSG00000096060 [Q13451-1]
ENST00000539068; ENSP00000441205; ENSG00000096060 [Q13451-1]
ENST00000542713; ENSP00000442340; ENSG00000096060 [Q13451-2]
GeneIDi2289
KEGGihsa:2289
UCSCiuc003okx.3 human [Q13451-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFKBP5_HUMAN
AccessioniPrimary (citable) accession number: Q13451
Secondary accession number(s): F5H7R1, Q59EB8, Q5TGM6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 15, 1998
Last modified: July 18, 2018
This is version 188 of the entry and version 2 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, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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