FKBP5_MOUSE
ID FKBP5_MOUSE Reviewed; 456 AA.
AC Q64378;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7479941; DOI=10.1073/pnas.92.24.11081;
RA Yeh W.-C., Li T.-K., Bierer B.E., McKnight S.L.;
RT "Identification and characterization of an immunophilin expressed during
RT the clonal expansion phase of adipocyte differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:11081-11085(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ACTIVITY REGULATION.
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=7542743; DOI=10.1128/mcb.15.8.4395;
RA Baughman G., Wiederrecht G.J., Campbell N.F., Martin M.M., Bourgeois S.;
RT "FKBP51, a novel T-cell-specific immunophilin capable of calcineurin
RT inhibition.";
RL Mol. Cell. Biol. 15:4395-4402(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION IN A COMPLEX WITH HSP90AA1 AND NR3C1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=11751894; DOI=10.1074/jbc.c100531200;
RA Davies T.H., Ning Y.M., Sanchez E.R.;
RT "A new first step in activation of steroid receptors: hormone-induced
RT switching of FKBP51 and FKBP52 immunophilins.";
RL J. Biol. Chem. 277:4597-4600(2002).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INTERACTION WITH NR3C1.
RX PubMed=21994940; DOI=10.1074/jbc.m111.311662;
RA Hinds T.D. Jr., Stechschulte L.A., Cash H.A., Whisler D., Banerjee A.,
RA Yong W., Khuder S.S., Kaw M.K., Shou W., Najjar S.M., Sanchez E.R.;
RT "Protein phosphatase 5 mediates lipid metabolism through reciprocal control
RT of glucocorticoid receptor and peroxisome proliferator-activated receptor-?
RT (PPAR?).";
RL J. Biol. Chem. 286:42911-42922(2011).
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:0000269|PubMed:7542743}.
CC -!- SUBUNIT: Part of a heteromultimeric cytoplasmic complex with HSP90AA1,
CC HSPA1A/HSPA1B and steroid receptors (PubMed:11751894). Upon ligand
CC binding dissociates from the complex and FKBP4 takes its place
CC (PubMed:11751894). Interacts with functionally mature heterooligomeric
CC progesterone receptor complexes along with HSP90 and TEBP (By
CC similarity). Interacts with NR3C1 (PubMed:21994940). Interacts with
CC Akt/AKT1 and PHLPP1; enhancing dephosphorylation and subsequent
CC activation of Akt/AKT1 (By similarity). Interacts with IFI44L; this
CC interaction modulates the kinase activity of IKBKB AND IKBKE (By
CC similarity). Interacts with IKBKB and IKBKE (By similarity).
CC {ECO:0000250|UniProtKB:Q13451, ECO:0000269|PubMed:11751894,
CC ECO:0000269|PubMed:21994940}.
CC -!- INTERACTION:
CC Q64378; P06537: Nr3c1; NbExp=2; IntAct=EBI-492796, EBI-492753;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11751894}. Nucleus
CC {ECO:0000269|PubMed:11751894}.
CC -!- TISSUE SPECIFICITY: Widely expressed, highest levels found in the
CC liver, skeletal muscle, kidney and thymus. Expression is regulated
CC during adipocyte differentiation. {ECO:0000269|PubMed:7479941}.
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}.
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DR EMBL; U36220; AAA89162.1; -; mRNA.
DR EMBL; U16959; AAA86983.1; -; mRNA.
DR EMBL; BC015260; AAH15260.1; -; mRNA.
DR CCDS; CCDS37528.1; -.
DR RefSeq; NP_034350.1; NM_010220.4.
DR AlphaFoldDB; Q64378; -.
DR SMR; Q64378; -.
DR BioGRID; 199686; 8.
DR CORUM; Q64378; -.
DR IntAct; Q64378; 8.
DR STRING; 10090.ENSMUSP00000078382; -.
DR ChEMBL; CHEMBL3792270; -.
DR iPTMnet; Q64378; -.
DR PhosphoSitePlus; Q64378; -.
DR CPTAC; non-CPTAC-4036; -.
DR EPD; Q64378; -.
DR jPOST; Q64378; -.
DR MaxQB; Q64378; -.
DR PaxDb; Q64378; -.
DR PRIDE; Q64378; -.
DR ProteomicsDB; 271699; -.
DR Antibodypedia; 3988; 473 antibodies from 36 providers.
DR DNASU; 14229; -.
DR Ensembl; ENSMUST00000079413; ENSMUSP00000078382; ENSMUSG00000024222.
DR Ensembl; ENSMUST00000114792; ENSMUSP00000110440; ENSMUSG00000024222.
DR Ensembl; ENSMUST00000177939; ENSMUSP00000136245; ENSMUSG00000024222.
DR Ensembl; ENSMUST00000233102; ENSMUSP00000156418; ENSMUSG00000024222.
DR GeneID; 14229; -.
DR KEGG; mmu:14229; -.
DR UCSC; uc008bqz.3; mouse.
DR CTD; 2289; -.
DR MGI; MGI:104670; Fkbp5.
DR VEuPathDB; HostDB:ENSMUSG00000024222; -.
DR eggNOG; KOG0543; Eukaryota.
DR GeneTree; ENSGT00940000158726; -.
DR HOGENOM; CLU_013615_13_1_1; -.
DR InParanoid; Q64378; -.
DR OMA; KYDKAAD; -.
DR OrthoDB; 897391at2759; -.
DR PhylomeDB; Q64378; -.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-8939211; ESR-mediated signaling.
DR BioGRID-ORCS; 14229; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Fkbp5; mouse.
DR PRO; PR:Q64378; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q64378; protein.
DR Bgee; ENSMUSG00000024222; Expressed in stroma of bone marrow and 263 other tissues.
DR ExpressionAtlas; Q64378; baseline and differential.
DR Genevisible; Q64378; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005528; F:FK506 binding; IEA:InterPro.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
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; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEP:MGI.
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 Acetylation; Chaperone; Cytoplasm; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Rotamase; TPR repeat.
FT CHAIN 1..456
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP5"
FT /id="PRO_0000075325"
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..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 421..456
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 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 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13451"
SQ SEQUENCE 456 AA; 50966 MW; 8FD0C9B61478EB46 CRC64;
MTTDEGTSNN GENPAATMTE QGEDITTKKD RGVLKIVKRV GTSDEAPMFG DKVYVHYKGM
LSDGKKFDSS HDRKKPFAFS LGQGQVIKAW DIGVSTMKKG EICHLLCKPE YAYGSAGHLQ
KIPSNATLFF EIELLDFKGE DLFEDSGVIR RIKRKGEGYS NPNEGATVKV HLEGCCGGRT
FDCRDVVFVV GEGEDHDIPI GIDKALVKMQ REEQCILYLG PRYGFGEAGK PKFGIDPNAE
LMYEVTLKSF EKAKESWEMD TKEKLTQAAI VKEKGTVYFK GGKYTQAVIQ YRKIVSWLEM
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYNKAVECC DKALGLDSAN EKGLYRRGEA
QLLMNDFESA KGDFEKVLAV NPQNRAARLQ ISMCQRKAKE HNERDRRVYA NMFKKFAERD
AKEEASKAGS KKAVEGAAGK QHESQAMEEG KAKGHV
