FKBP5_SAIBB
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 03-AUG-2022, entry version 112.
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}.
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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; ENSSBOP00000020685; ENSSBOG00000026900.
DR GeneID; 101034484; -.
DR KEGG; sbq:101034484; -.
DR CTD; 2289; -.
DR GeneTree; ENSGT00940000158726; -.
DR OrthoDB; 897391at2759; -.
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:0005528; F:FK506 binding; IEA:InterPro.
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:0000413; P:protein peptidyl-prolyl isomerization; IEA:InterPro.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
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; 3.
DR SUPFAM; SSF48452; SSF48452; 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
