FKBP5_HUMAN
ID FKBP5_HUMAN Reviewed; 457 AA.
AC Q13451; F5H7R1; Q59EB8; Q5TGM6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP5;
DE Short=PPIase FKBP5;
DE EC=5.2.1.8 {ECO:0000269|PubMed:11350175};
DE AltName: Full=51 kDa FK506-binding protein;
DE Short=51 kDa FKBP;
DE Short=FKBP-51;
DE AltName: Full=54 kDa progesterone receptor-associated immunophilin;
DE AltName: Full=Androgen-regulated protein 6;
DE AltName: Full=FF1 antigen;
DE AltName: Full=FK506-binding protein 5;
DE Short=FKBP-5;
DE AltName: Full=FKBP54;
DE Short=p54;
DE AltName: Full=HSP90-binding immunophilin;
DE AltName: Full=Rotamase;
GN Name=FKBP5; Synonyms=AIG6, FKBP51 {ECO:0000303|PubMed:28147277};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thymus;
RX PubMed=9125197; DOI=10.1006/bbrc.1997.6307;
RA Baughman G., Wiederrecht G.J., Chang F., Martin M.M., Bourgeois S.;
RT "Tissue distribution and abundance of human FKBP51, an FK506-binding
RT protein that can mediate calcineurin inhibition.";
RL Biochem. Biophys. Res. Commun. 232:437-443(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhang J.S., Smith D.I.;
RT "Identification of AIG6 as an androgen response gene in human prostate
RT cancer cell line LNCaP.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Aortic endothelium;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-457 (ISOFORM 1).
RX PubMed=9001212; DOI=10.1128/mcb.17.2.594;
RA Nair S.C., Rimerman R.A., Toran E.J., Chen S., Prapapanich V., Butts R.N.,
RA Smith D.F.;
RT "Molecular cloning of human FKBP51 and comparisons of immunophilin
RT interactions with Hsp90 and progesterone receptor.";
RL Mol. Cell. Biol. 17:594-603(1997).
RN [9]
RP SUBUNIT.
RX PubMed=7693698; DOI=10.1016/s0021-9258(20)80520-1;
RA Smith D.F., Albers M.W., Schreiber S.L., Leach K.L., Deibel M.R. Jr.;
RT "FKBP54, a novel FK506-binding protein in avian progesterone receptor
RT complexes and HeLa extracts.";
RL J. Biol. Chem. 268:24270-24273(1993).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11350175; DOI=10.1006/jmbi.2001.4595;
RA Pirkl F., Buchner J.;
RT "Functional analysis of the Hsp90-associated human peptidyl prolyl
RT cis/trans isomerases FKBP51, FKBP52 and Cyp40.";
RL J. Mol. Biol. 308:795-806(2001).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-445, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20]
RP FUNCTION, AND INTERACTION WITH IKBKB AND IKBKE.
RX PubMed=26101251; DOI=10.1093/nar/gkv615;
RA Romano S., Xiao Y., Nakaya M., D'Angelillo A., Chang M., Jin J., Hausch F.,
RA Masullo M., Feng X., Romano M.F., Sun S.C.;
RT "FKBP51 employs both scaffold and isomerase functions to promote NF-kappaB
RT activation in melanoma.";
RL Nucleic Acids Res. 43:6983-6993(2015).
RN [21]
RP FUNCTION, INTERACTION WITH AKT1 AND PHLPP1, ACETYLATION AT LYS-28 AND
RP LYS-155, AND MUTAGENESIS OF LYS-28 AND LYS-155.
RX PubMed=28147277; DOI=10.1016/j.celrep.2017.01.009;
RA Yu J., Qin B., Wu F., Qin S., Nowsheen S., Shan S., Zayas J., Pei H.,
RA Lou Z., Wang L.;
RT "Regulation of serine-threonine kinase Akt activation by NAD+-dependent
RT deacetylase SIRT7.";
RL Cell Rep. 18:1229-1240(2017).
RN [22]
RP FUNCTION, AND INTERACTION WITH IFI44L; IKBKB AND IKBKE.
RX PubMed=31434731; DOI=10.1128/jvi.01159-19;
RA DeDiego M.L., Martinez-Sobrido L., Topham D.J.;
RT "Novel Functions of IFI44L as a Feedback Regulator of Host Antiviral
RT Responses.";
RL J. Virol. 93:0-0(2019).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS), 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 (PubMed:11350175). Component of unligated steroid receptors
CC heterocomplexes through interaction with heat-shock protein 90 (HSP90).
CC Plays a role in the intracellular trafficking of heterooligomeric forms
CC of steroid hormone receptors maintaining the complex into the cytoplasm
CC when unliganded (PubMed:12538866). 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 (PubMed:28147277). 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 (PubMed:26101251, PubMed:31434731). {ECO:0000269|PubMed:11350175,
CC ECO:0000269|PubMed:12538866, ECO:0000269|PubMed:26101251,
CC ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:31434731}.
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:0000269|PubMed:11350175};
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 (PubMed:7693698). Interacts with
CC NR3C1 (By similarity). Interacts with Akt/AKT1 and PHLPP1; enhancing
CC dephosphorylation and subsequent activation of Akt/AKT1
CC (PubMed:28147277). Interacts with IFI44L; this interaction modulates
CC the kinase activity of IKBKB AND IKBKE (PubMed:31434731). Interacts
CC with IKBKB and IKBKE (PubMed:26101251, PubMed:31434731).
CC {ECO:0000250|UniProtKB:Q64378, ECO:0000269|PubMed:28147277,
CC ECO:0000269|PubMed:31434731, ECO:0000269|PubMed:7693698}.
CC -!- INTERACTION:
CC Q13451; Q96Q40: CDK15; NbExp=2; IntAct=EBI-306914, EBI-1051975;
CC Q13451; P50750: CDK9; NbExp=6; IntAct=EBI-306914, EBI-1383449;
CC Q13451; O15111: CHUK; NbExp=2; IntAct=EBI-306914, EBI-81249;
CC Q13451; P07900: HSP90AA1; NbExp=8; IntAct=EBI-306914, EBI-296047;
CC Q13451; P08238: HSP90AB1; NbExp=16; IntAct=EBI-306914, EBI-352572;
CC Q13451; Q6VAB6: KSR2; NbExp=7; IntAct=EBI-306914, EBI-6424389;
CC Q13451; P10636-8: MAPT; NbExp=8; IntAct=EBI-306914, EBI-366233;
CC Q13451; Q9BTE3-2: MCMBP; NbExp=4; IntAct=EBI-306914, EBI-9384556;
CC Q13451; P00540: MOS; NbExp=3; IntAct=EBI-306914, EBI-1757866;
CC Q13451; Q15831: STK11; NbExp=6; IntAct=EBI-306914, EBI-306838;
CC Q13451; Q70CQ1: USP49; NbExp=2; IntAct=EBI-306914, EBI-2511022;
CC Q13451; PRO_0000037552 [Q9WMX2]; Xeno; NbExp=4; IntAct=EBI-306914, EBI-9005440;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q64378}. Nucleus
CC {ECO:0000250|UniProtKB:Q64378}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13451-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13451-2; Sequence=VSP_044820, VSP_044821;
CC -!- TISSUE SPECIFICITY: Widely expressed, enriched in testis compared to
CC other tissues.
CC -!- INDUCTION: By androgen.
CC -!- PTM: Acetylation impairs ability to promote interaction between
CC Akt/AKT1 and PHLPP1 (PubMed:28147277). Deacetylation by SIRT7 promotes
CC interaction between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1
CC activation (PubMed:28147277). {ECO:0000269|PubMed:28147277}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93130.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U71321; AAC51189.1; -; mRNA.
DR EMBL; AF194172; AAL54872.1; -; mRNA.
DR EMBL; AK312422; BAG35332.1; -; mRNA.
DR EMBL; AB209893; BAD93130.1; ALT_FRAME; mRNA.
DR EMBL; AL033519; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL157823; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590400; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03842.1; -; Genomic_DNA.
DR EMBL; BC042605; AAH42605.1; -; mRNA.
DR EMBL; U42031; AAA86245.1; -; mRNA.
DR CCDS; CCDS4808.1; -. [Q13451-1]
DR CCDS; CCDS54996.1; -. [Q13451-2]
DR PIR; JC5422; JC5422.
DR RefSeq; NP_001139247.1; NM_001145775.2. [Q13451-1]
DR RefSeq; NP_001139248.1; NM_001145776.1. [Q13451-1]
DR RefSeq; NP_001139249.1; NM_001145777.1. [Q13451-2]
DR RefSeq; NP_004108.1; NM_004117.3. [Q13451-1]
DR PDB; 1KT0; X-ray; 2.70 A; A=1-457.
DR PDB; 3O5D; X-ray; 4.00 A; A/B=1-260.
DR PDB; 3O5E; X-ray; 1.60 A; A=1-140.
DR PDB; 3O5F; X-ray; 1.65 A; A=1-140.
DR PDB; 3O5G; X-ray; 2.00 A; A=16-140.
DR PDB; 3O5I; X-ray; 1.80 A; A/B=16-140.
DR PDB; 3O5J; X-ray; 1.70 A; A=16-140.
DR PDB; 3O5K; X-ray; 2.70 A; A/B/C/D=16-140.
DR PDB; 3O5L; X-ray; 1.30 A; A=16-140.
DR PDB; 3O5M; X-ray; 1.60 A; A/B=16-140.
DR PDB; 3O5O; X-ray; 1.15 A; A=16-140.
DR PDB; 3O5P; X-ray; 1.00 A; A=16-140.
DR PDB; 3O5Q; X-ray; 0.96 A; A=16-140.
DR PDB; 3O5R; X-ray; 1.10 A; A=16-140.
DR PDB; 4DRH; X-ray; 2.30 A; A/D=1-140.
DR PDB; 4DRI; X-ray; 1.45 A; A=1-140.
DR PDB; 4DRK; X-ray; 1.50 A; A/B=16-140.
DR PDB; 4DRM; X-ray; 1.48 A; A=16-140.
DR PDB; 4DRN; X-ray; 1.07 A; A=16-140.
DR PDB; 4DRO; X-ray; 1.10 A; A=16-140.
DR PDB; 4DRP; X-ray; 1.80 A; A=16-140.
DR PDB; 4DRQ; X-ray; 1.00 A; A=16-140.
DR PDB; 4JFI; X-ray; 1.05 A; A=16-139.
DR PDB; 4JFJ; X-ray; 1.08 A; A=16-140.
DR PDB; 4JFK; X-ray; 1.15 A; A=16-140.
DR PDB; 4JFL; X-ray; 1.20 A; A=16-140.
DR PDB; 4JFM; X-ray; 1.02 A; A=16-140.
DR PDB; 4R0X; X-ray; 1.20 A; A=20-140.
DR PDB; 4TW6; X-ray; 1.40 A; A=16-140.
DR PDB; 4TW7; X-ray; 1.25 A; A=16-140.
DR PDB; 4TX0; X-ray; 1.03 A; A=16-140.
DR PDB; 4W9O; X-ray; 1.27 A; A/E=16-140.
DR PDB; 4W9P; X-ray; 1.50 A; A/E=16-140.
DR PDB; 4W9Q; X-ray; 1.08 A; A=16-140.
DR PDB; 5BXJ; X-ray; 1.24 A; A=16-140.
DR PDB; 5DIT; X-ray; 2.25 A; A=16-140.
DR PDB; 5DIU; X-ray; 1.30 A; A=16-140.
DR PDB; 5DIV; X-ray; 1.65 A; A=16-139.
DR PDB; 5NJX; X-ray; 2.49 A; A=1-457.
DR PDB; 5OBK; X-ray; 1.00 A; A=16-140.
DR PDB; 5OMP; X-ray; 1.88 A; A=1-457.
DR PDB; 6SAF; X-ray; 2.05 A; A=16-140.
DR PDB; 6TX4; X-ray; 1.06 A; A=16-140.
DR PDB; 6TX5; X-ray; 1.08 A; A=16-140.
DR PDB; 6TX6; X-ray; 0.98 A; A=16-140.
DR PDB; 6TX7; X-ray; 1.13 A; A=16-140.
DR PDB; 6TX8; X-ray; 1.20 A; A=16-140.
DR PDB; 6TX9; X-ray; 1.42 A; A=16-140.
DR PDB; 6TXX; X-ray; 2.10 A; A/B=16-140.
DR PDB; 7A6W; X-ray; 1.85 A; AAA/BBB=16-140.
DR PDB; 7A6X; X-ray; 1.67 A; AAA=16-140.
DR PDB; 7AOT; X-ray; 0.85 A; A=16-140.
DR PDB; 7AOU; X-ray; 1.16 A; A=16-140.
DR PDB; 7APQ; X-ray; 1.09 A; A=16-140.
DR PDB; 7APS; X-ray; 0.94 A; A/B=16-140.
DR PDB; 7APT; X-ray; 1.13 A; A=16-140.
DR PDB; 7APW; X-ray; 0.89 A; A=16-140.
DR PDB; 7AWF; X-ray; 1.40 A; A=16-140.
DR PDB; 7AWX; X-ray; 2.20 A; A/B=16-140.
DR PDB; 7B9Y; X-ray; 1.35 A; A=16-140.
DR PDB; 7B9Z; X-ray; 1.44 A; A=16-140.
DR PDB; 7BA0; X-ray; 1.14 A; A=16-140.
DR PDB; 7ETT; X-ray; 1.50 A; A=16-140.
DR PDB; 7ETU; X-ray; 1.39 A; A=16-140.
DR PDB; 7ETV; X-ray; 1.31 A; A=16-140.
DR PDB; 7L7I; EM; 3.30 A; C=1-457.
DR PDBsum; 1KT0; -.
DR PDBsum; 3O5D; -.
DR PDBsum; 3O5E; -.
DR PDBsum; 3O5F; -.
DR PDBsum; 3O5G; -.
DR PDBsum; 3O5I; -.
DR PDBsum; 3O5J; -.
DR PDBsum; 3O5K; -.
DR PDBsum; 3O5L; -.
DR PDBsum; 3O5M; -.
DR PDBsum; 3O5O; -.
DR PDBsum; 3O5P; -.
DR PDBsum; 3O5Q; -.
DR PDBsum; 3O5R; -.
DR PDBsum; 4DRH; -.
DR PDBsum; 4DRI; -.
DR PDBsum; 4DRK; -.
DR PDBsum; 4DRM; -.
DR PDBsum; 4DRN; -.
DR PDBsum; 4DRO; -.
DR PDBsum; 4DRP; -.
DR PDBsum; 4DRQ; -.
DR PDBsum; 4JFI; -.
DR PDBsum; 4JFJ; -.
DR PDBsum; 4JFK; -.
DR PDBsum; 4JFL; -.
DR PDBsum; 4JFM; -.
DR PDBsum; 4R0X; -.
DR PDBsum; 4TW6; -.
DR PDBsum; 4TW7; -.
DR PDBsum; 4TX0; -.
DR PDBsum; 4W9O; -.
DR PDBsum; 4W9P; -.
DR PDBsum; 4W9Q; -.
DR PDBsum; 5BXJ; -.
DR PDBsum; 5DIT; -.
DR PDBsum; 5DIU; -.
DR PDBsum; 5DIV; -.
DR PDBsum; 5NJX; -.
DR PDBsum; 5OBK; -.
DR PDBsum; 5OMP; -.
DR PDBsum; 6SAF; -.
DR PDBsum; 6TX4; -.
DR PDBsum; 6TX5; -.
DR PDBsum; 6TX6; -.
DR PDBsum; 6TX7; -.
DR PDBsum; 6TX8; -.
DR PDBsum; 6TX9; -.
DR PDBsum; 6TXX; -.
DR PDBsum; 7A6W; -.
DR PDBsum; 7A6X; -.
DR PDBsum; 7AOT; -.
DR PDBsum; 7AOU; -.
DR PDBsum; 7APQ; -.
DR PDBsum; 7APS; -.
DR PDBsum; 7APT; -.
DR PDBsum; 7APW; -.
DR PDBsum; 7AWF; -.
DR PDBsum; 7AWX; -.
DR PDBsum; 7B9Y; -.
DR PDBsum; 7B9Z; -.
DR PDBsum; 7BA0; -.
DR PDBsum; 7ETT; -.
DR PDBsum; 7ETU; -.
DR PDBsum; 7ETV; -.
DR PDBsum; 7L7I; -.
DR AlphaFoldDB; Q13451; -.
DR SMR; Q13451; -.
DR BioGRID; 108579; 206.
DR CORUM; Q13451; -.
DR DIP; DIP-27597N; -.
DR IntAct; Q13451; 192.
DR MINT; Q13451; -.
DR STRING; 9606.ENSP00000444810; -.
DR BindingDB; Q13451; -.
DR ChEMBL; CHEMBL2052031; -.
DR DrugCentral; Q13451; -.
DR GuidetoPHARMACOLOGY; 3175; -.
DR GlyGen; Q13451; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13451; -.
DR MetOSite; Q13451; -.
DR PhosphoSitePlus; Q13451; -.
DR SwissPalm; Q13451; -.
DR BioMuta; FKBP5; -.
DR DMDM; 2851536; -.
DR CPTAC; CPTAC-506; -.
DR CPTAC; CPTAC-507; -.
DR EPD; Q13451; -.
DR jPOST; Q13451; -.
DR MassIVE; Q13451; -.
DR MaxQB; Q13451; -.
DR PaxDb; Q13451; -.
DR PeptideAtlas; Q13451; -.
DR PRIDE; Q13451; -.
DR ProteomicsDB; 27564; -.
DR ProteomicsDB; 59455; -. [Q13451-1]
DR Antibodypedia; 3988; 473 antibodies from 36 providers.
DR DNASU; 2289; -.
DR Ensembl; ENST00000357266.9; ENSP00000349811.3; ENSG00000096060.15. [Q13451-1]
DR Ensembl; ENST00000536438.5; ENSP00000444810.1; ENSG00000096060.15. [Q13451-1]
DR Ensembl; ENST00000539068.5; ENSP00000441205.1; ENSG00000096060.15. [Q13451-1]
DR Ensembl; ENST00000542713.1; ENSP00000442340.1; ENSG00000096060.15. [Q13451-2]
DR GeneID; 2289; -.
DR KEGG; hsa:2289; -.
DR MANE-Select; ENST00000357266.9; ENSP00000349811.3; NM_004117.4; NP_004108.1.
DR UCSC; uc003okx.3; human. [Q13451-1]
DR CTD; 2289; -.
DR DisGeNET; 2289; -.
DR GeneCards; FKBP5; -.
DR HGNC; HGNC:3721; FKBP5.
DR HPA; ENSG00000096060; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; FKBP5; -.
DR MIM; 602623; gene.
DR neXtProt; NX_Q13451; -.
DR OpenTargets; ENSG00000096060; -.
DR PharmGKB; PA28162; -.
DR VEuPathDB; HostDB:ENSG00000096060; -.
DR eggNOG; KOG0543; Eukaryota.
DR GeneTree; ENSGT00940000158726; -.
DR HOGENOM; CLU_013615_13_1_1; -.
DR InParanoid; Q13451; -.
DR OMA; KYDKAAD; -.
DR OrthoDB; 897391at2759; -.
DR PhylomeDB; Q13451; -.
DR TreeFam; TF105292; -.
DR PathwayCommons; Q13451; -.
DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-HSA-8939211; ESR-mediated signaling.
DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels.
DR SignaLink; Q13451; -.
DR SIGNOR; Q13451; -.
DR BioGRID-ORCS; 2289; 13 hits in 1089 CRISPR screens.
DR ChiTaRS; FKBP5; human.
DR EvolutionaryTrace; Q13451; -.
DR GeneWiki; FKBP5; -.
DR GenomeRNAi; 2289; -.
DR Pharos; Q13451; Tchem.
DR PRO; PR:Q13451; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q13451; protein.
DR Bgee; ENSG00000096060; Expressed in mucosa of stomach and 190 other tissues.
DR Genevisible; Q13451; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005528; F:FK506 binding; TAS:ProtInc.
DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR DisProt; DP01845; -.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 2.
DR IDEAL; IID00073; -.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chaperone; Cytoplasm;
KW Isomerase; Nucleus; Phosphoprotein; Reference proteome; Repeat; Rotamase;
KW TPR repeat.
FT CHAIN 1..457
FT /note="Peptidyl-prolyl cis-trans isomerase FKBP5"
FT /id="PRO_0000075324"
FT DOMAIN 42..130
FT /note="PPIase FKBP-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT DOMAIN 157..243
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 420..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:0007744|PubMed:19413330"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 28
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:28147277"
FT MOD_RES 155
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:28147277"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 223..268
FT /note="YGFGEAGKPKFGIEPNAELIYEVTLKSFEKAKESWEMDTKEKLEQA -> PK
FT NPGRWIPKKNWSRLPLSKRREPYTSRCVSPYAILSISKNLFKCW (in isoform
FT 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_044820"
FT VAR_SEQ 269..457
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_044821"
FT MUTAGEN 28
FT /note="K->Q: Mimics acetylation; impaired interaction with
FT AKT1 and PHLPP1; when associated with Q-155."
FT /evidence="ECO:0000269|PubMed:28147277"
FT MUTAGEN 28
FT /note="K->R: Decreased acetylation; promotes interaction
FT with AKT1 and PHLPP1; when associated with R-155."
FT /evidence="ECO:0000269|PubMed:28147277"
FT MUTAGEN 155
FT /note="K->Q: Mimics acetylation; impaired interaction with
FT AKT1 and PHLPP1; when associated with Q-28."
FT /evidence="ECO:0000269|PubMed:28147277"
FT MUTAGEN 155
FT /note="K->R: Decreased acetylation; promotes interaction
FT with AKT1 and PHLPP1; when associated with R-28."
FT /evidence="ECO:0000269|PubMed:28147277"
FT HELIX 16..21
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:7BA0"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:4DRH"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:7APW"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:7AOT"
FT HELIX 88..94
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:7AOT"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:7AOT"
FT TURN 112..116
FT /evidence="ECO:0007829|PDB:7AOT"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 128..138
FT /evidence="ECO:0007829|PDB:7AOT"
FT STRAND 144..154
FT /evidence="ECO:0007829|PDB:5OMP"
FT STRAND 167..176
FT /evidence="ECO:0007829|PDB:5OMP"
FT STRAND 179..189
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 200..206
FT /evidence="ECO:0007829|PDB:5OMP"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:5OMP"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:5NJX"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:5OMP"
FT STRAND 241..251
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 261..280
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 284..298
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 306..329
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 333..346
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 351..363
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 367..380
FT /evidence="ECO:0007829|PDB:5OMP"
FT HELIX 385..423
FT /evidence="ECO:0007829|PDB:5OMP"
SQ SEQUENCE 457 AA; 51212 MW; 18A86608C6891A73 CRC64;
MTTDEGAKNN EESPTATVAE QGEDITSKKD RGVLKIVKRV GNGEETPMIG DKVYVHYKGK
LSNGKKFDSS HDRNEPFVFS LGKGQVIKAW DIGVATMKKG EICHLLCKPE YAYGSAGSLP
KIPSNATLFF EIELLDFKGE DLFEDGGIIR RTKRKGEGYS NPNEGATVEI HLEGRCGGRM
FDCRDVAFTV GEGEDHDIPI GIDKALEKMQ REEQCILYLG PRYGFGEAGK PKFGIEPNAE
LIYEVTLKSF EKAKESWEMD TKEKLEQAAI VKEKGTVYFK GGKYMQAVIQ YGKIVSWLEM
EYGLSEKESK ASESFLLAAF LNLAMCYLKL REYTKAVECC DKALGLDSAN EKGLYRRGEA
QLLMNEFESA KGDFEKVLEV NPQNKAARLQ ISMCQKKAKE HNERDRRIYA NMFKKFAEQD
AKEEANKAMG KKTSEGVTNE KGTDSQAMEE EKPEGHV
