FKBP5_SAGOE
ID FKBP5_SAGOE Reviewed; 457 AA.
AC Q9XSI2;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 95.
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 Saguinus oedipus (Cotton-top tamarin).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Saguinus.
OX NCBI_TaxID=9490;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=B-cell;
RX PubMed=11703081; DOI=10.1006/gcen.2001.7696;
RA Scammell J.G., Denny W.B., Valentine D.L., Smith D.F.;
RT "Overexpression of the FK506-binding immunophilin FKBP51 is the common
RT cause of glucocorticoid resistance in three New World primates.";
RL Gen. Comp. Endocrinol. 124:152-165(2001).
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). Plays a role in the
CC intracellular trafficking of heterooligomeric forms of steroid hormone
CC receptors maintaining the complex into the cytoplasm when unliganded
CC (PubMed:11703081). Acts as a regulator of Akt/AKT1 activity by
CC promoting the interaction between Akt/AKT1 and PHLPP1, thereby
CC enhancing dephosphorylation and subsequent activation of Akt/AKT1.
CC Interacts with IKBKE and IKBKB which facilitates IKK complex assembly
CC leading to increased IKBKE and IKBKB kinase activity, NF-kappaB
CC activation, and IFN production. {ECO:0000250|UniProtKB:Q13451,
CC ECO:0000269|PubMed:11703081}.
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:0000250|UniProtKB:Q64378}. 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 New World 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:11703081}.
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; AF143809; AAD33918.2; -; mRNA.
DR AlphaFoldDB; Q9XSI2; -.
DR SMR; Q9XSI2; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005528; F:FK506 binding; IEA:InterPro.
DR GO; GO:0031072; F:heat shock protein binding; IEA:InterPro.
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:0000413; P:protein peptidyl-prolyl isomerization; IEA:InterPro.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 2.
DR InterPro; IPR031210; FKBP5.
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; PTHR10516:SF26; PTHR10516:SF26; 1.
DR Pfam; PF00254; FKBP_C; 2.
DR Pfam; PF00515; TPR_1; 1.
DR Pfam; PF13181; TPR_8; 1.
DR SMART; SM00028; TPR; 2.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS50059; FKBP_PPIASE; 2.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chaperone; Cytoplasm; Isomerase; Nucleus; Phosphoprotein;
KW Repeat; Rotamase; TPR repeat.
FT CHAIN 1..457
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP5"
FT /id="PRO_0000075327"
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..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..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"
SQ SEQUENCE 457 AA; 51116 MW; F2D4E2A2B6658302 CRC64;
MTTDEGAKSS RENPAATVAE QGEDVTSKKD RGVLKIVKRV GHGEETPMIG DKVYVHYNGK
LSNGKKFDSS HDRNEPFVFS IGKGQVIKAW DIGVSTMKKG EICHLLCKPE YAYGATGSLP
KIPSNATLFF EVELLNFKGE DLLEDGGIIR RTKRRGEGYS NPNEGARVQI HLEGRCGGRV
FDCRDVAFTV GEGEDHDIPI GIDKALEKMQ REEQCILHLG PRYGFGEAGK PKFGIEPNAE
LIYEVTLKSF EKAKESWEMD TKEKLEQAAI VKEEGTVYFK GGKYVQAVIQ YGKIVSWLEM
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYAKAVECC DKALGLDSAN EKGLYRRGEA
QLLMNEFESA KGDFEKVLEV NPQNKAARLQ IVVCQKKAKE HNERDRRIYA NMFKKFAEQD
AKEEANKAVS KKTSEGVTNE KLTVSHAVEE EKPEGHV
