FKBP5_CHLAE
ID FKBP5_CHLAE Reviewed; 457 AA.
AC Q95L05;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 97.
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 Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Denny W.B., Scammell J.G.;
RT "African green monkey immunophilin FKBP51.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
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 Acts as a regulator of Akt/AKT1 activity by promoting the interaction
CC between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and
CC subsequent activation of Akt/AKT1. Interacts with IKBKE and IKBKB which
CC facilitates IKK complex assembly leading to increased IKBKE and IKBKB
CC kinase activity, NF-kappaB activation, and IFN production.
CC {ECO:0000250|UniProtKB:Q13451}.
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 ---------------------------------------------------------------------------
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; AY044168; AAK95405.1; -; mRNA.
DR AlphaFoldDB; Q95L05; -.
DR SMR; Q95L05; -.
DR PRIDE; Q95L05; -.
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_0000075323"
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..22
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 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13451"
FT MOD_RES 28
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13451"
FT MOD_RES 155
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; 51095 MW; 9CB4CA338CF75144 CRC64;
MTTDEGAKNS GESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG DKVYVHYKGK
LSNGKKFNSS HDRNEPFVFS LGKSQVIKAW DIGVATMKKG EICHLLCKPE YAYGSAGSVP
KIPSNATLFF EIELLDFKGE DLLEDGGIIR RTKRKGEGYS NPNEGATVEI HLEGRCGERM
FDCRDVAFTV GEGEDHDIPI GIDKALEKMQ REEQCILYLG PRYGFGEAGK PKFGIEPNAE
LIYEVTLKSF EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYMRAVIQ YGKIVSWLEM
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN EKGLYRRGEA
QLLMNEFESA KGDFEKVLEV NPQNKAARLQ ISMCQKKAKE HNERDRRIYA NMFKKFAEQD
AKEEANKAMG KKTSEGVTNE KGTDSSAVEE EKAEGHV
