ID FKBP5_SAIBB Reviewed; 457 AA. AC Q9XSH5; DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 117. DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP5; DE Short=PPIase FKBP5; DE EC=5.2.1.8 {ECO:0000250|UniProtKB:Q13451}; DE AltName: Full=51 kDa FK506-binding protein; DE Short=51 kDa FKBP; DE Short=FKBP-51; DE AltName: Full=FK506-binding protein 5; DE Short=FKBP-5; DE AltName: Full=Rotamase; GN Name=FKBP5; Synonyms=FKBP51; OS Saimiri boliviensis boliviensis (Bolivian squirrel monkey). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae; OC Saimiriinae; Saimiri. OX NCBI_TaxID=39432; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION. RC TISSUE=B-cell; RX PubMed=11089542; DOI=10.1210/endo.141.11.7785; RA Denny W.B., Valentine D.L., Reynolds P.D., Smith D.F., Scammell J.G.; RT "Squirrel monkey immunophilin FKBP51 is a potent inhibitor of RT glucocorticoid receptor binding."; RL Endocrinology 141:4107-4113(2000). RN [2] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 28-421, AND FUNCTION. RX PubMed=12538866; DOI=10.1073/pnas.0231020100; RA Sinars C.R., Cheung-Flynn J., Rimerman R.A., Scammell J.G., Smith D.F., RA Clardy J.; RT "Structure of the large FK506-binding protein FKBP51, an Hsp90-binding RT protein and a component of steroid receptor complexes."; RL Proc. Natl. Acad. Sci. U.S.A. 100:868-873(2003). CC -!- FUNCTION: Immunophilin protein with PPIase and co-chaperone activities. CC Component of unligated steroid receptors heterocomplexes through CC interaction with heat-shock protein 90 (HSP90) (PubMed:12538866). Plays CC a role in the intracellular trafficking of heterooligomeric forms of CC steroid hormone receptors maintaining the complex into the cytoplasm CC when unliganded (PubMed:11089542). Acts as a regulator of Akt/AKT1 CC activity by promoting the interaction between Akt/AKT1 and PHLPP1, CC thereby enhancing dephosphorylation and subsequent activation of CC Akt/AKT1. Interacts with IKBKE and IKBKB which facilitates IKK complex CC assembly leading to increased IKBKE and IKBKB kinase activity, NF- CC kappaB activation, and IFN production (By similarity). CC {ECO:0000250|UniProtKB:Q13451, ECO:0000269|PubMed:11089542, CC ECO:0000269|PubMed:12538866}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[protein]-peptidylproline (omega=180) = [protein]- CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, CC ChEBI:CHEBI:83834; EC=5.2.1.8; CC Evidence={ECO:0000250|UniProtKB:Q13451}; CC -!- ACTIVITY REGULATION: Inhibited by both FK506 and rapamycin. CC {ECO:0000250|UniProtKB:Q64378}. CC -!- SUBUNIT: Part of a heteromultimeric cytoplasmic complex with HSP90AA1, CC HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates CC from the complex and FKBP4 takes its place (By similarity). Interacts CC with functionally mature heterooligomeric progesterone receptor CC complexes along with HSP90 and TEBP (By similarity). Interacts with CC NR3C1 (By similarity). Interacts with Akt/AKT1 and PHLPP1; enhancing CC dephosphorylation and subsequent activation of Akt/AKT1 (By CC similarity). Interacts with IFI44L; this interaction modulates the CC kinase activity of IKBKB and IKBKE (By similarity). Interacts with CC IKBKB and IKBKE (By similarity). {ECO:0000250|UniProtKB:Q13451, CC ECO:0000250|UniProtKB:Q64378}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11089542}. Nucleus CC {ECO:0000250|UniProtKB:Q64378}. CC -!- PTM: Acetylation impairs ability to promote interaction between CC Akt/AKT1 and PHLPP1. Deacetylation by SIRT7 promotes interaction CC between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1 activation. CC {ECO:0000250|UniProtKB:Q13451}. CC -!- MISCELLANEOUS: The relative resistance of squirrel monkeys to CC glucocorticoids is associated with a high level of expression of FKBP5, CC but is also due to intrinsic differences between the human and the CC monkey proteins. Human FKBP5 has a much lower effect on glucocorticoid CC sensitivity. {ECO:0000269|PubMed:11089542}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF140759; AAD32678.1; -; mRNA. DR RefSeq; NP_001266943.1; NM_001280014.1. DR RefSeq; XP_010332065.1; XM_010333763.1. DR PDB; 1KT1; X-ray; 2.80 A; A=1-457. DR PDBsum; 1KT1; -. DR AlphaFoldDB; Q9XSH5; -. DR SMR; Q9XSH5; -. DR STRING; 39432.ENSSBOP00000020685; -. DR Ensembl; ENSSBOT00000037518.1; ENSSBOP00000020685.1; ENSSBOG00000026900.1. DR GeneID; 101034484; -. DR KEGG; sbq:101034484; -. DR CTD; 2289; -. DR GeneTree; ENSGT00940000158726; -. DR OrthoDB; 25281at2759; -. DR EvolutionaryTrace; Q9XSH5; -. DR Proteomes; UP000233220; Unplaced. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl. DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB. DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR Gene3D; 3.10.50.40; -; 2. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR InterPro; IPR046357; PPIase_dom_sf. DR InterPro; IPR001179; PPIase_FKBP_dom. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR001440; TPR_1. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR46512; PEPTIDYLPROLYL ISOMERASE; 1. DR PANTHER; PTHR46512:SF9; TETRATRICOPEPTIDE REPEAT DOMAIN 9; 1. DR Pfam; PF00254; FKBP_C; 2. DR Pfam; PF00515; TPR_1; 1. DR Pfam; PF13174; TPR_6; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF54534; FKBP-like; 2. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS50059; FKBP_PPIASE; 2. DR PROSITE; PS50005; TPR; 3. DR PROSITE; PS50293; TPR_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Chaperone; Cytoplasm; Isomerase; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Rotamase; TPR repeat. FT CHAIN 1..457 FT /note="Peptidyl-prolyl cis-trans isomerase FKBP5" FT /id="PRO_0000075328" FT DOMAIN 50..138 FT /note="PPIase FKBP-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT DOMAIN 165..251 FT /note="PPIase FKBP-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT REPEAT 268..301 FT /note="TPR 1" FT REPEAT 317..350 FT /note="TPR 2" FT REPEAT 351..384 FT /note="TPR 3" FT REGION 1..26 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 421..457 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..16 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:Q13451" FT MOD_RES 28 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q13451" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13451" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 52..56 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 83..86 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 88..92 FT /evidence="ECO:0007829|PDB:1KT1" FT TURN 94..96 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:1KT1" FT TURN 115..117 FT /evidence="ECO:0007829|PDB:1KT1" FT TURN 119..121 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 129..138 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 144..154 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 167..176 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 179..189 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 193..196 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 200..206 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 214..219 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:1KT1" FT TURN 231..234 FT /evidence="ECO:0007829|PDB:1KT1" FT STRAND 241..251 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 256..258 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 261..280 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 284..298 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 306..329 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 333..346 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 351..363 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 367..379 FT /evidence="ECO:0007829|PDB:1KT1" FT HELIX 385..417 FT /evidence="ECO:0007829|PDB:1KT1" SQ SEQUENCE 457 AA; 51169 MW; DFF9E1D81F7759A8 CRC64; MTTDEGAKNS RGNPAATVAE QGEDVTSKKD RGVLKIVKRV GHGEETPMIG DRVYVHYNGK LANGKKFDSS HDRNEPFVFS IGKGQVIKAW DIGVATMKKG EICHLLCKPE YAYGATGSLP KIPSNATLFF EVELLDFKGE DLLEDGGIIR RTKRRGEGYS NPNEGARVQI HLEGRCGGRV FDCRDVAFTV GEGEDHDIPI GIDKALEKMQ REEQCILHLG PRYGFGEAGK PKFGIEPNAE LIYEVTLKSF EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYVQAVIQ YGKIVSWLEM EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN EKGLYRRGEA QLLMNEFESA KGDFEKVLEV NPQNKAARLQ IFMCQKKAKE HNERDRRTYA NMFKKFAEQD AKEEANKAMS KKTSEGVTNE KLTASHAVEE EKPEGHV //