Full text data of FKBP5
FKBP5
(AIG6, FKBP51)
[Confidence: low (only semi-automatic identification from reviews)]
Peptidyl-prolyl cis-trans isomerase FKBP5; PPIase FKBP5; 5.2.1.8 (51 kDa FK506-binding protein; 51 kDa FKBP; FKBP-51; 54 kDa progesterone receptor-associated immunophilin; Androgen-regulated protein 6; FF1 antigen; FK506-binding protein 5; FKBP-5; FKBP54; p54; HSP90-binding immunophilin; Rotamase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peptidyl-prolyl cis-trans isomerase FKBP5; PPIase FKBP5; 5.2.1.8 (51 kDa FK506-binding protein; 51 kDa FKBP; FKBP-51; 54 kDa progesterone receptor-associated immunophilin; Androgen-regulated protein 6; FF1 antigen; FK506-binding protein 5; FKBP-5; FKBP54; p54; HSP90-binding immunophilin; Rotamase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13451
ID FKBP5_HUMAN Reviewed; 457 AA.
AC Q13451; F5H7R1; Q59EB8; Q5TGM6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP5;
DE Short=PPIase FKBP5;
DE EC=5.2.1.8;
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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;
RA Nair S.C., Rimerman R.A., Toran E.J., Chen S., Prapapanich V.,
RA Butts R.N., 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 CHARACTERIZATION.
RX PubMed=7693698;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., 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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
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 [14]
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=12538866; DOI=10.1073/pnas.0231020100;
RA Sinars C.R., Cheung-Flynn J., Rimerman R.A., Scammell J.G.,
RA Smith D.F., 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
CC activities. Component of unligated steroid receptors
CC heterocomplexes through interaction with heat-shock protein 90
CC (HSP90). Plays a role in the intracellular trafficking of
CC heterooligomeric forms of steroid hormone receptors maintaining
CC the complex into the cytoplasm when unliganded.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by FK506 but not cyclosporin.
CC -!- SUBUNIT: Part of a heteromultimeric cytoplasmic complex with
CC HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding
CC dissociates from the complex and FKBP4 takes its place. Interacts
CC with functionally mature heterooligomeric progesterone receptor
CC complexes along with HSP90 and TEBP.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed, enriched in testis compared
CC to other tissues.
CC -!- INDUCTION: By androgen.
CC -!- SIMILARITY: Contains 2 PPIase FKBP-type domains.
CC -!- SIMILARITY: Contains 3 TPR repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93130.1; Type=Frameshift; Positions=29;
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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; CAI20256.1; -; 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 PIR; JC5422; JC5422.
DR RefSeq; NP_001139247.1; NM_001145775.1.
DR RefSeq; NP_001139248.1; NM_001145776.1.
DR RefSeq; NP_001139249.1; NM_001145777.1.
DR RefSeq; NP_004108.1; NM_004117.3.
DR UniGene; Hs.407190; -.
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 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 ProteinModelPortal; Q13451; -.
DR SMR; Q13451; 13-412.
DR DIP; DIP-27597N; -.
DR IntAct; Q13451; 15.
DR MINT; MINT-1142816; -.
DR STRING; 9606.ENSP00000338160; -.
DR ChEMBL; CHEMBL2052031; -.
DR PhosphoSite; Q13451; -.
DR DMDM; 2851536; -.
DR PaxDb; Q13451; -.
DR PRIDE; Q13451; -.
DR DNASU; 2289; -.
DR Ensembl; ENST00000357266; ENSP00000349811; ENSG00000096060.
DR Ensembl; ENST00000536438; ENSP00000444810; ENSG00000096060.
DR Ensembl; ENST00000539068; ENSP00000441205; ENSG00000096060.
DR Ensembl; ENST00000542713; ENSP00000442340; ENSG00000096060.
DR GeneID; 2289; -.
DR KEGG; hsa:2289; -.
DR UCSC; uc003okz.2; human.
DR CTD; 2289; -.
DR GeneCards; GC06M035541; -.
DR HGNC; HGNC:3721; FKBP5.
DR HPA; CAB009315; -.
DR HPA; HPA031092; -.
DR HPA; HPA031093; -.
DR MIM; 602623; gene.
DR neXtProt; NX_Q13451; -.
DR PharmGKB; PA28162; -.
DR eggNOG; COG0545; -.
DR HOGENOM; HOG000256916; -.
DR HOVERGEN; HBG051624; -.
DR InParanoid; Q13451; -.
DR KO; K09571; -.
DR OMA; HLEGCCG; -.
DR OrthoDB; EOG725DHH; -.
DR PhylomeDB; Q13451; -.
DR ChiTaRS; FKBP5; human.
DR EvolutionaryTrace; Q13451; -.
DR GeneWiki; FKBP5; -.
DR GenomeRNAi; 2289; -.
DR NextBio; 9303; -.
DR PRO; PR:Q13451; -.
DR ArrayExpress; Q13451; -.
DR Bgee; Q13451; -.
DR CleanEx; HS_FKBP5; -.
DR Genevestigator; Q13451; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005528; F:FK506 binding; IBA:RefGenome.
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 Gene3D; 1.10.150.160; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR023114; Elongated_TPR_rpt_dom.
DR InterPro; IPR023566; PPIase_FKBP.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR013026; TPR-contain_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10516; PTHR10516; 1.
DR Pfam; PF00254; FKBP_C; 2.
DR Pfam; PF00515; TPR_1; 2.
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;
KW Complete proteome; Cytoplasm; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Rotamase; TPR repeat.
FT CHAIN 1 457 Peptidyl-prolyl cis-trans isomerase
FT FKBP5.
FT /FTId=PRO_0000075324.
FT DOMAIN 42 130 PPIase FKBP-type 1.
FT DOMAIN 157 243 PPIase FKBP-type 2.
FT REPEAT 268 301 TPR 1.
FT REPEAT 317 350 TPR 2.
FT REPEAT 351 384 TPR 3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 445 445 Phosphoserine.
FT VAR_SEQ 223 268 YGFGEAGKPKFGIEPNAELIYEVTLKSFEKAKESWEMDTKE
FT KLEQA -> PKNPGRWIPKKNWSRLPLSKRREPYTSRCVSP
FT YAILSISKNLFKCW (in isoform 2).
FT /FTId=VSP_044820.
FT VAR_SEQ 269 457 Missing (in isoform 2).
FT /FTId=VSP_044821.
FT HELIX 16 21
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 30 39
FT STRAND 42 44
FT STRAND 52 61
FT STRAND 66 69
FT HELIX 70 73
FT STRAND 77 80
FT STRAND 83 86
FT HELIX 88 94
FT STRAND 102 107
FT HELIX 109 111
FT TURN 112 116
FT TURN 119 121
FT STRAND 128 138
FT STRAND 144 154
FT STRAND 167 176
FT STRAND 179 189
FT HELIX 193 196
FT HELIX 200 206
FT STRAND 214 219
FT HELIX 221 223
FT HELIX 231 233
FT STRAND 241 251
FT HELIX 256 258
FT HELIX 261 280
FT HELIX 284 298
FT HELIX 306 329
FT HELIX 333 346
FT HELIX 351 363
FT HELIX 367 378
FT HELIX 387 411
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
//
ID FKBP5_HUMAN Reviewed; 457 AA.
AC Q13451; F5H7R1; Q59EB8; Q5TGM6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 2.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP5;
DE Short=PPIase FKBP5;
DE EC=5.2.1.8;
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA 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.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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;
RA Nair S.C., Rimerman R.A., Toran E.J., Chen S., Prapapanich V.,
RA Butts R.N., 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 CHARACTERIZATION.
RX PubMed=7693698;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., 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 [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
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 [14]
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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.,
RA Buerckstuemmer T., 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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RX PubMed=12538866; DOI=10.1073/pnas.0231020100;
RA Sinars C.R., Cheung-Flynn J., Rimerman R.A., Scammell J.G.,
RA Smith D.F., 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
CC activities. Component of unligated steroid receptors
CC heterocomplexes through interaction with heat-shock protein 90
CC (HSP90). Plays a role in the intracellular trafficking of
CC heterooligomeric forms of steroid hormone receptors maintaining
CC the complex into the cytoplasm when unliganded.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by FK506 but not cyclosporin.
CC -!- SUBUNIT: Part of a heteromultimeric cytoplasmic complex with
CC HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding
CC dissociates from the complex and FKBP4 takes its place. Interacts
CC with functionally mature heterooligomeric progesterone receptor
CC complexes along with HSP90 and TEBP.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
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 Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Widely expressed, enriched in testis compared
CC to other tissues.
CC -!- INDUCTION: By androgen.
CC -!- SIMILARITY: Contains 2 PPIase FKBP-type domains.
CC -!- SIMILARITY: Contains 3 TPR repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD93130.1; Type=Frameshift; Positions=29;
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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; CAI20256.1; -; 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 PIR; JC5422; JC5422.
DR RefSeq; NP_001139247.1; NM_001145775.1.
DR RefSeq; NP_001139248.1; NM_001145776.1.
DR RefSeq; NP_001139249.1; NM_001145777.1.
DR RefSeq; NP_004108.1; NM_004117.3.
DR UniGene; Hs.407190; -.
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 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 ProteinModelPortal; Q13451; -.
DR SMR; Q13451; 13-412.
DR DIP; DIP-27597N; -.
DR IntAct; Q13451; 15.
DR MINT; MINT-1142816; -.
DR STRING; 9606.ENSP00000338160; -.
DR ChEMBL; CHEMBL2052031; -.
DR PhosphoSite; Q13451; -.
DR DMDM; 2851536; -.
DR PaxDb; Q13451; -.
DR PRIDE; Q13451; -.
DR DNASU; 2289; -.
DR Ensembl; ENST00000357266; ENSP00000349811; ENSG00000096060.
DR Ensembl; ENST00000536438; ENSP00000444810; ENSG00000096060.
DR Ensembl; ENST00000539068; ENSP00000441205; ENSG00000096060.
DR Ensembl; ENST00000542713; ENSP00000442340; ENSG00000096060.
DR GeneID; 2289; -.
DR KEGG; hsa:2289; -.
DR UCSC; uc003okz.2; human.
DR CTD; 2289; -.
DR GeneCards; GC06M035541; -.
DR HGNC; HGNC:3721; FKBP5.
DR HPA; CAB009315; -.
DR HPA; HPA031092; -.
DR HPA; HPA031093; -.
DR MIM; 602623; gene.
DR neXtProt; NX_Q13451; -.
DR PharmGKB; PA28162; -.
DR eggNOG; COG0545; -.
DR HOGENOM; HOG000256916; -.
DR HOVERGEN; HBG051624; -.
DR InParanoid; Q13451; -.
DR KO; K09571; -.
DR OMA; HLEGCCG; -.
DR OrthoDB; EOG725DHH; -.
DR PhylomeDB; Q13451; -.
DR ChiTaRS; FKBP5; human.
DR EvolutionaryTrace; Q13451; -.
DR GeneWiki; FKBP5; -.
DR GenomeRNAi; 2289; -.
DR NextBio; 9303; -.
DR PRO; PR:Q13451; -.
DR ArrayExpress; Q13451; -.
DR Bgee; Q13451; -.
DR CleanEx; HS_FKBP5; -.
DR Genevestigator; Q13451; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IBA:RefGenome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005528; F:FK506 binding; IBA:RefGenome.
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 Gene3D; 1.10.150.160; -; 1.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR023114; Elongated_TPR_rpt_dom.
DR InterPro; IPR023566; PPIase_FKBP.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR013026; TPR-contain_dom.
DR InterPro; IPR011990; TPR-like_helical.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10516; PTHR10516; 1.
DR Pfam; PF00254; FKBP_C; 2.
DR Pfam; PF00515; TPR_1; 2.
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;
KW Complete proteome; Cytoplasm; Isomerase; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Rotamase; TPR repeat.
FT CHAIN 1 457 Peptidyl-prolyl cis-trans isomerase
FT FKBP5.
FT /FTId=PRO_0000075324.
FT DOMAIN 42 130 PPIase FKBP-type 1.
FT DOMAIN 157 243 PPIase FKBP-type 2.
FT REPEAT 268 301 TPR 1.
FT REPEAT 317 350 TPR 2.
FT REPEAT 351 384 TPR 3.
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 445 445 Phosphoserine.
FT VAR_SEQ 223 268 YGFGEAGKPKFGIEPNAELIYEVTLKSFEKAKESWEMDTKE
FT KLEQA -> PKNPGRWIPKKNWSRLPLSKRREPYTSRCVSP
FT YAILSISKNLFKCW (in isoform 2).
FT /FTId=VSP_044820.
FT VAR_SEQ 269 457 Missing (in isoform 2).
FT /FTId=VSP_044821.
FT HELIX 16 21
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 30 39
FT STRAND 42 44
FT STRAND 52 61
FT STRAND 66 69
FT HELIX 70 73
FT STRAND 77 80
FT STRAND 83 86
FT HELIX 88 94
FT STRAND 102 107
FT HELIX 109 111
FT TURN 112 116
FT TURN 119 121
FT STRAND 128 138
FT STRAND 144 154
FT STRAND 167 176
FT STRAND 179 189
FT HELIX 193 196
FT HELIX 200 206
FT STRAND 214 219
FT HELIX 221 223
FT HELIX 231 233
FT STRAND 241 251
FT HELIX 256 258
FT HELIX 261 280
FT HELIX 284 298
FT HELIX 306 329
FT HELIX 333 346
FT HELIX 351 363
FT HELIX 367 378
FT HELIX 387 411
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
//
MIM
602623
*RECORD*
*FIELD* NO
602623
*FIELD* TI
*602623 FK506-BINDING PROTEIN 5; FKBP5
;;FK506-BINDING PROTEIN, 51-KD; FKBP51;;
FKBP54
read more*FIELD* TX
For background information on FK506-binding proteins (FKBPs), see FKBP1A
(186945).
CLONING
Nair et al. (1997) cloned a cDNA for human FKBP51 from a HeLa cell cDNA
library. The FKBP51 cDNA encodes a predicted 457-amino acid polypeptide
with 90% identity to mouse fkbp51 and 55% identity to FKBP52 (600611).
Baughman et al. (1997) cloned a cDNA encoding human FKBP51 by screening
a human thymus cDNA library with a fragment of the murine Fkbp51 cDNA.
The human FKBP51 cDNA encodes a deduced 457-amino acid protein that
shows 87% sequence identity to the mouse protein. Northern blot analysis
revealed that treatment of leukemic T cells with glucocorticoids results
in a marked increase in expression of a 3.7-kb transcript. Western blot
analysis showed that unlike the predominant T-cell expression of the
mouse protein, FKBP51 is expressed as a 51-kD protein in a variety of
tissues but not in brain, colon, or lung. The expression is frequently
in molar excess of that of FKBP12 (FKBP1A; 186945), but its capacity to
inhibit calcineurin is significantly lower than that of FKBP1A.
Baughman et al. (1995) and Yeh et al. (1995) cloned and characterized
the mouse Fkbp51 gene. Baughman et al. (1995) isolated the gene based on
its induction during glucocorticoid-induced apoptosis in murine thymoma
cells. Murine Fkbp51 encodes a 456-amino acid polypeptide with a
predicted mass of 51 kD. Yeh et al. (1995) isolated the mouse gene based
on the selective accumulation of its transcript during adipocyte
differentiation. By Northern blot analysis, the gene is expressed in a
variety of tissues, with highest levels in liver, skeletal muscle, and
kidney.
MAPPING
International Radiation Hybrid Mapping Consortium mapped the FKBP51 gene
to chromosome 6 (TMAP RH47153).
GENE FUNCTION
By Western blot analysis, Baughman et al. (1995) showed that the murine
Fkbp51 gene is expressed in all tissues, most abundantly in T
lymphocytes and in the thymus. Baughman et al. (1995) showed that FKBP5
has PPIase activity and is inhibited by rapamycin and FK520, a
structural analog that is virtually identical to FK506. Yeh et al.
(1995) showed that the PPIase activity of murine Fkbp51 is inhibited by
FK506 but not by cyclosporin A.
Nair et al. (1997) showed that FKBP51 is inhibited by FK506 but not by
cyclosporine. The authors demonstrated that FKBP51 and FKBP52 bind to
Hsp90 (140571) in a competitive manner. Nair et al. (1997) also showed
that Hsp90, Hsp70 (140550), and p23 (607061), a component of the
progesterone receptor complex, bind directly or indirectly to FKBP51.
Vermeer et al. (2003) studied whether the glucocorticoid-induced
increase of the mRNA encoding FKBP5 could be used for the development of
a novel assay, ultimately to be used in native human peripheral blood
mononuclear cells (PBMCs). Glucocorticoid addition to human
lymphoblastoid cells resulted in a dose-dependent increase of FKBP5 mRNA
levels within 2 hours, followed by a further increase until 24 hours.
Northern blot analysis and real-time PCR yielded similar results.
Coincubation of glucocorticoids with the glucocorticoid receptor
(138040) antagonist ORG34116 or the protein synthesis inhibitor
cycloheximide suggested a direct, glucocorticoid receptor-mediated
upregulation of FKBP5 gene transcription. They concluded that the
induction of FKBP5 mRNA by glucocorticoids may be a suitable marker to
assess individual glucocorticoid sensitivity, the in vitro measurement
of glucocorticoid potency, and the in vivo determination of
glucocorticoid bioavailability.
Using gene expression microarrays, Woodruff et al. (2007) found that
CLCA1 (603906), periostin (POSTN; 608777), and SERPINB2 (PAI2; 173390)
were upregulated in airway epithelial cells of individuals with asthma
(see 600807), but not smokers. Corticosteroid treatment downregulated
expression of these 3 genes and upregulated expression of FKBP51. High
baseline expression of CLCA1, POSTN, and SERPINB2 was associated with a
good clinical response to corticosteroids, whereas high expression of
FKBP51 was associated with a poor response.
Tissing et al. (2007) found that 8 hours of prednisolone treatment
altered expression of 51 genes in leukemic cells from children with
precursor-B- or T-acute lymphoblastic leukemia compared with nonexposed
cells. The 3 most highly upregulated genes were FKBP5, ZBTB16 (176797),
and TXNIP (606599), which were upregulated 35.4-, 8.8-, and 3.7-fold,
respectively.
Attwood et al. (2011) demonstrated in mice that the serine protease
neuropsin (60564) is critical for stress-related plasticity in the
amygdala by regulating the dynamics of the EphB2 (600997)-NMDA receptor
interaction, the expression of Fkbp5, and anxiety-like behavior. Stress
results in neuropsin-dependent cleavage of EphB2 in the amygdala,
causing dissociation of EphB2 from the NR1 (138249) subunit of the NMDA
receptor and promoting membrane turnover of EphB2 receptors. Dynamic
EphB2-NR1 interaction enhances NMDA receptor current, induces Fkpb5 gene
expression, and enhances behavioral signatures of anxiety. On stress,
neuropsin-deficient mice do not show EphB2 cleavage and its dissociation
from NR1, resulting in a static EphB2-NR1 interaction, attenuated
induction of the Fkbp5 gene, and low anxiety. The behavioral response to
stress can be restored by intraamygdala injection of neuropsin into
neuropsin-deficient mice and disrupted by the injection of either
anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of
wildtype mice. Attwood et al. (2011) concluded that their findings
established a novel neuronal pathway linking stress-induced proteolysis
of EphB2 in the amygdala to anxiety.
MOLECULAR GENETICS
The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis
has been implicated in the causality as well as the treatment of
depression (608516). To investigate a possible association between genes
regulating the HPA axis and response to antidepressants and
susceptibility for depression, Binder et al. (2004) genotyped
single-nucleotide polymorphisms (SNPs) in 8 of these genes in depressed
individuals and matched controls. They found significant associations of
response to antidepressants and the recurrence of depressive episodes
with SNPs in FKBP5, a glucocorticoid receptor-regulating cochaperone of
hsp90 (see 140571), in 2 independent samples. These SNPs were also
associated with increased intracellular FKBP5 protein expression, which
triggers adaptive changes in glucocorticoid receptor and, thereby, HPA
axis regulation. Individuals carrying the associated genotypes had less
HPA-axis hyperactivity during the depressive episode. Binder et al.
(2004) proposed that the FKBP5 variant-dependent alterations in HPA-axis
regulation could be related to the faster response to antidepressant
drug treatment and the increased recurrence of depressive episodes
observed in this group of depressed individuals. These findings
supported a central role of genes regulating the HPA axis in the
causality of depression and the mechanism of action of antidepressant
drugs.
*FIELD* AV
.0001
MAJOR DEPRESSIVE DISORDER, INCREASED RECURRENCE OF DEPRESSIVE EPISODES
IN, SUSCEPTIBILITY TO
ANTIDEPRESSANT DRUG TREATMENT, ACCELERATED RESPONSE TO, INCLUDED
FKBP5, IVS2, C-T
In 294 individuals with major depressive disorder (608516) and 339
matched controls, Binder et al. (2004) found that individuals homozygous
for the T allele of a C/T polymorphism in the FKBP5 gene, dbSNP
rs1360780, had an accelerated response to antidepressants over 5 weeks
of treatment. The responses of CT heterozygotes and CC homozygotes were
significantly slower than those of TT homozygotes and were almost
identical to each other. The authors also found that individuals with
the TT genotype had experienced more than twice as many depressive
episodes before the index episode, suggesting that these individuals
have more lifetime depressive episodes in addition to their faster
response to antidepressant drugs.
*FIELD* RF
1. Attwood, B. K.; Bourgognon, J.-M.; Patel, S.; Mucha, M.; Schiavon,
E.; Skrzypiec, A. E.; Young, K. W.; Shiosaka, S.; Korostynski, M.;
Piechota, M.; Przewlocki, R.; Pawlak, R.: Neuropsin cleaves EphB2
in the amygdala to control anxiety. Nature 473: 372-375, 2011.
2. Baughman, G.; Wiederrecht, G. J.; Campbell, N. F.; Martin, M. M.;
Bourgeois, S.: FKBP51, a novel T-cell-specific immunophilin capable
of calcineurin inhibition. Molec. Cell. Biol. 15: 4395-4402, 1995.
3. Baughman, G.; Wiederrecht, G. J.; Chang, F.; Martin, M. M.; Bourgeois,
S.: Tissue distribution and abundance of human FKBP51, an FK506-binding
protein that can mediate calcineurin inhibition. Biochem. Biophys.
Res. Commun. 232: 437-443, 1997.
4. Binder, E. B.; Salyakina, D.; Lichtner, P.; Wochnik, G. M.; Ising,
M.; Putz, B.; Papiol, S.; Seaman, S.; Lucae, S.; Kohli, M. A.; Nickel,
T.; Kunzel, H. E.; and 27 others: Polymorphisms in FKBP5 are associated
with increased recurrence of depressive episodes and rapid response
to antidepressant treatment. Nature Genet. 36: 1319-1325, 2004.
5. Nair, S. C.; Rimerman, R. A.; Toran, E. J.; Chen, S.; Prapapanich,
V.; Butts, R. N.; Smith, D. F.: Molecular cloning of human FKBP51
and comparisons of immunophilin interactions with Hsp90 and progesterone
receptor. Molec. Cell. Biol. 17: 594-603, 1997.
6. Tissing, W. J. E.; den Boer, M. L.; Meijerink, J. P. P.; Menezes,
R. X.; Swagemakers, S.; van der Spek, P. J.; Sallan, S. E.; Armstrong,
S. A.; Pieters, R.: Genomewide identification of prednisolone-responsive
genes in acute lymphoblastic leukemia cells. Blood 109: 3929-3935,
2007.
7. Vermeer, H.; Hendriks-Stegeman, B. I.; van der Burg, B.; van Buul-Offers,
S. C.; Jansen, M.: Glucocorticoid-induced increase in lymphocytic
FKBP51 messenger ribonucleic acid expression: a potential marker for
glucocorticoid sensitivity, potency, and bioavailability. J. Clin.
Endocr. Metab. 88: 277-284, 2003.
8. Woodruff, P. G.; Boushey, H. A.; Dolganov, G. M.; Barker, C. S.;
Yang, Y. H.; Donnelly, S.; Ellwanger, A.; Sidhu, S. S.; Dao-Pick,
T. P.; Pantoja, C.; Erle, D. J.; Yamamoto, K. R.; Fahy, J. V.: Genome-wide
profiling identifies epithelial cell genes associated with asthma
and with treatment response to corticosteroids. Proc. Nat. Acad.
Sci. 104: 15858-15863, 2007.
9. Yeh, W.-C.; Li, T.-K; Bierer, B. E.; McKnight, S. L.: Identification
and characterization of an immunophilin expressed during the clonal
expansion phase of adipocyte differentiation. Proc. Nat. Acad. Sci. 92:
11081-11085, 1995.
*FIELD* CN
Ada Hamosh - updated: 7/6/2011
Patricia A. Hartz - updated: 5/1/2008
Paul J. Converse - updated: 3/24/2008
Anne M. Stumpf - updated: 12/9/2004
Victor A. McKusick - updated: 12/7/2004
Joanna S. Amberger - updated: 12/3/2004
John A. Phillips, III - updated: 9/8/2004
Paul J. Converse - updated: 6/1/2000
*FIELD* CD
Jennifer P. Macke: 5/13/1998
*FIELD* ED
alopez: 07/07/2011
terry: 7/6/2011
mgross: 3/3/2011
mgross: 5/1/2008
mgross: 3/24/2008
wwang: 9/7/2007
terry: 8/2/2007
alopez: 3/11/2005
alopez: 12/9/2004
terry: 12/7/2004
alopez: 12/6/2004
joanna: 12/3/2004
alopez: 9/8/2004
mgross: 10/18/2002
carol: 6/1/2000
dholmes: 5/26/1998
*RECORD*
*FIELD* NO
602623
*FIELD* TI
*602623 FK506-BINDING PROTEIN 5; FKBP5
;;FK506-BINDING PROTEIN, 51-KD; FKBP51;;
FKBP54
read more*FIELD* TX
For background information on FK506-binding proteins (FKBPs), see FKBP1A
(186945).
CLONING
Nair et al. (1997) cloned a cDNA for human FKBP51 from a HeLa cell cDNA
library. The FKBP51 cDNA encodes a predicted 457-amino acid polypeptide
with 90% identity to mouse fkbp51 and 55% identity to FKBP52 (600611).
Baughman et al. (1997) cloned a cDNA encoding human FKBP51 by screening
a human thymus cDNA library with a fragment of the murine Fkbp51 cDNA.
The human FKBP51 cDNA encodes a deduced 457-amino acid protein that
shows 87% sequence identity to the mouse protein. Northern blot analysis
revealed that treatment of leukemic T cells with glucocorticoids results
in a marked increase in expression of a 3.7-kb transcript. Western blot
analysis showed that unlike the predominant T-cell expression of the
mouse protein, FKBP51 is expressed as a 51-kD protein in a variety of
tissues but not in brain, colon, or lung. The expression is frequently
in molar excess of that of FKBP12 (FKBP1A; 186945), but its capacity to
inhibit calcineurin is significantly lower than that of FKBP1A.
Baughman et al. (1995) and Yeh et al. (1995) cloned and characterized
the mouse Fkbp51 gene. Baughman et al. (1995) isolated the gene based on
its induction during glucocorticoid-induced apoptosis in murine thymoma
cells. Murine Fkbp51 encodes a 456-amino acid polypeptide with a
predicted mass of 51 kD. Yeh et al. (1995) isolated the mouse gene based
on the selective accumulation of its transcript during adipocyte
differentiation. By Northern blot analysis, the gene is expressed in a
variety of tissues, with highest levels in liver, skeletal muscle, and
kidney.
MAPPING
International Radiation Hybrid Mapping Consortium mapped the FKBP51 gene
to chromosome 6 (TMAP RH47153).
GENE FUNCTION
By Western blot analysis, Baughman et al. (1995) showed that the murine
Fkbp51 gene is expressed in all tissues, most abundantly in T
lymphocytes and in the thymus. Baughman et al. (1995) showed that FKBP5
has PPIase activity and is inhibited by rapamycin and FK520, a
structural analog that is virtually identical to FK506. Yeh et al.
(1995) showed that the PPIase activity of murine Fkbp51 is inhibited by
FK506 but not by cyclosporin A.
Nair et al. (1997) showed that FKBP51 is inhibited by FK506 but not by
cyclosporine. The authors demonstrated that FKBP51 and FKBP52 bind to
Hsp90 (140571) in a competitive manner. Nair et al. (1997) also showed
that Hsp90, Hsp70 (140550), and p23 (607061), a component of the
progesterone receptor complex, bind directly or indirectly to FKBP51.
Vermeer et al. (2003) studied whether the glucocorticoid-induced
increase of the mRNA encoding FKBP5 could be used for the development of
a novel assay, ultimately to be used in native human peripheral blood
mononuclear cells (PBMCs). Glucocorticoid addition to human
lymphoblastoid cells resulted in a dose-dependent increase of FKBP5 mRNA
levels within 2 hours, followed by a further increase until 24 hours.
Northern blot analysis and real-time PCR yielded similar results.
Coincubation of glucocorticoids with the glucocorticoid receptor
(138040) antagonist ORG34116 or the protein synthesis inhibitor
cycloheximide suggested a direct, glucocorticoid receptor-mediated
upregulation of FKBP5 gene transcription. They concluded that the
induction of FKBP5 mRNA by glucocorticoids may be a suitable marker to
assess individual glucocorticoid sensitivity, the in vitro measurement
of glucocorticoid potency, and the in vivo determination of
glucocorticoid bioavailability.
Using gene expression microarrays, Woodruff et al. (2007) found that
CLCA1 (603906), periostin (POSTN; 608777), and SERPINB2 (PAI2; 173390)
were upregulated in airway epithelial cells of individuals with asthma
(see 600807), but not smokers. Corticosteroid treatment downregulated
expression of these 3 genes and upregulated expression of FKBP51. High
baseline expression of CLCA1, POSTN, and SERPINB2 was associated with a
good clinical response to corticosteroids, whereas high expression of
FKBP51 was associated with a poor response.
Tissing et al. (2007) found that 8 hours of prednisolone treatment
altered expression of 51 genes in leukemic cells from children with
precursor-B- or T-acute lymphoblastic leukemia compared with nonexposed
cells. The 3 most highly upregulated genes were FKBP5, ZBTB16 (176797),
and TXNIP (606599), which were upregulated 35.4-, 8.8-, and 3.7-fold,
respectively.
Attwood et al. (2011) demonstrated in mice that the serine protease
neuropsin (60564) is critical for stress-related plasticity in the
amygdala by regulating the dynamics of the EphB2 (600997)-NMDA receptor
interaction, the expression of Fkbp5, and anxiety-like behavior. Stress
results in neuropsin-dependent cleavage of EphB2 in the amygdala,
causing dissociation of EphB2 from the NR1 (138249) subunit of the NMDA
receptor and promoting membrane turnover of EphB2 receptors. Dynamic
EphB2-NR1 interaction enhances NMDA receptor current, induces Fkpb5 gene
expression, and enhances behavioral signatures of anxiety. On stress,
neuropsin-deficient mice do not show EphB2 cleavage and its dissociation
from NR1, resulting in a static EphB2-NR1 interaction, attenuated
induction of the Fkbp5 gene, and low anxiety. The behavioral response to
stress can be restored by intraamygdala injection of neuropsin into
neuropsin-deficient mice and disrupted by the injection of either
anti-EphB2 antibodies or silencing the Fkbp5 gene in the amygdala of
wildtype mice. Attwood et al. (2011) concluded that their findings
established a novel neuronal pathway linking stress-induced proteolysis
of EphB2 in the amygdala to anxiety.
MOLECULAR GENETICS
The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis
has been implicated in the causality as well as the treatment of
depression (608516). To investigate a possible association between genes
regulating the HPA axis and response to antidepressants and
susceptibility for depression, Binder et al. (2004) genotyped
single-nucleotide polymorphisms (SNPs) in 8 of these genes in depressed
individuals and matched controls. They found significant associations of
response to antidepressants and the recurrence of depressive episodes
with SNPs in FKBP5, a glucocorticoid receptor-regulating cochaperone of
hsp90 (see 140571), in 2 independent samples. These SNPs were also
associated with increased intracellular FKBP5 protein expression, which
triggers adaptive changes in glucocorticoid receptor and, thereby, HPA
axis regulation. Individuals carrying the associated genotypes had less
HPA-axis hyperactivity during the depressive episode. Binder et al.
(2004) proposed that the FKBP5 variant-dependent alterations in HPA-axis
regulation could be related to the faster response to antidepressant
drug treatment and the increased recurrence of depressive episodes
observed in this group of depressed individuals. These findings
supported a central role of genes regulating the HPA axis in the
causality of depression and the mechanism of action of antidepressant
drugs.
*FIELD* AV
.0001
MAJOR DEPRESSIVE DISORDER, INCREASED RECURRENCE OF DEPRESSIVE EPISODES
IN, SUSCEPTIBILITY TO
ANTIDEPRESSANT DRUG TREATMENT, ACCELERATED RESPONSE TO, INCLUDED
FKBP5, IVS2, C-T
In 294 individuals with major depressive disorder (608516) and 339
matched controls, Binder et al. (2004) found that individuals homozygous
for the T allele of a C/T polymorphism in the FKBP5 gene, dbSNP
rs1360780, had an accelerated response to antidepressants over 5 weeks
of treatment. The responses of CT heterozygotes and CC homozygotes were
significantly slower than those of TT homozygotes and were almost
identical to each other. The authors also found that individuals with
the TT genotype had experienced more than twice as many depressive
episodes before the index episode, suggesting that these individuals
have more lifetime depressive episodes in addition to their faster
response to antidepressant drugs.
*FIELD* RF
1. Attwood, B. K.; Bourgognon, J.-M.; Patel, S.; Mucha, M.; Schiavon,
E.; Skrzypiec, A. E.; Young, K. W.; Shiosaka, S.; Korostynski, M.;
Piechota, M.; Przewlocki, R.; Pawlak, R.: Neuropsin cleaves EphB2
in the amygdala to control anxiety. Nature 473: 372-375, 2011.
2. Baughman, G.; Wiederrecht, G. J.; Campbell, N. F.; Martin, M. M.;
Bourgeois, S.: FKBP51, a novel T-cell-specific immunophilin capable
of calcineurin inhibition. Molec. Cell. Biol. 15: 4395-4402, 1995.
3. Baughman, G.; Wiederrecht, G. J.; Chang, F.; Martin, M. M.; Bourgeois,
S.: Tissue distribution and abundance of human FKBP51, an FK506-binding
protein that can mediate calcineurin inhibition. Biochem. Biophys.
Res. Commun. 232: 437-443, 1997.
4. Binder, E. B.; Salyakina, D.; Lichtner, P.; Wochnik, G. M.; Ising,
M.; Putz, B.; Papiol, S.; Seaman, S.; Lucae, S.; Kohli, M. A.; Nickel,
T.; Kunzel, H. E.; and 27 others: Polymorphisms in FKBP5 are associated
with increased recurrence of depressive episodes and rapid response
to antidepressant treatment. Nature Genet. 36: 1319-1325, 2004.
5. Nair, S. C.; Rimerman, R. A.; Toran, E. J.; Chen, S.; Prapapanich,
V.; Butts, R. N.; Smith, D. F.: Molecular cloning of human FKBP51
and comparisons of immunophilin interactions with Hsp90 and progesterone
receptor. Molec. Cell. Biol. 17: 594-603, 1997.
6. Tissing, W. J. E.; den Boer, M. L.; Meijerink, J. P. P.; Menezes,
R. X.; Swagemakers, S.; van der Spek, P. J.; Sallan, S. E.; Armstrong,
S. A.; Pieters, R.: Genomewide identification of prednisolone-responsive
genes in acute lymphoblastic leukemia cells. Blood 109: 3929-3935,
2007.
7. Vermeer, H.; Hendriks-Stegeman, B. I.; van der Burg, B.; van Buul-Offers,
S. C.; Jansen, M.: Glucocorticoid-induced increase in lymphocytic
FKBP51 messenger ribonucleic acid expression: a potential marker for
glucocorticoid sensitivity, potency, and bioavailability. J. Clin.
Endocr. Metab. 88: 277-284, 2003.
8. Woodruff, P. G.; Boushey, H. A.; Dolganov, G. M.; Barker, C. S.;
Yang, Y. H.; Donnelly, S.; Ellwanger, A.; Sidhu, S. S.; Dao-Pick,
T. P.; Pantoja, C.; Erle, D. J.; Yamamoto, K. R.; Fahy, J. V.: Genome-wide
profiling identifies epithelial cell genes associated with asthma
and with treatment response to corticosteroids. Proc. Nat. Acad.
Sci. 104: 15858-15863, 2007.
9. Yeh, W.-C.; Li, T.-K; Bierer, B. E.; McKnight, S. L.: Identification
and characterization of an immunophilin expressed during the clonal
expansion phase of adipocyte differentiation. Proc. Nat. Acad. Sci. 92:
11081-11085, 1995.
*FIELD* CN
Ada Hamosh - updated: 7/6/2011
Patricia A. Hartz - updated: 5/1/2008
Paul J. Converse - updated: 3/24/2008
Anne M. Stumpf - updated: 12/9/2004
Victor A. McKusick - updated: 12/7/2004
Joanna S. Amberger - updated: 12/3/2004
John A. Phillips, III - updated: 9/8/2004
Paul J. Converse - updated: 6/1/2000
*FIELD* CD
Jennifer P. Macke: 5/13/1998
*FIELD* ED
alopez: 07/07/2011
terry: 7/6/2011
mgross: 3/3/2011
mgross: 5/1/2008
mgross: 3/24/2008
wwang: 9/7/2007
terry: 8/2/2007
alopez: 3/11/2005
alopez: 12/9/2004
terry: 12/7/2004
alopez: 12/6/2004
joanna: 12/3/2004
alopez: 9/8/2004
mgross: 10/18/2002
carol: 6/1/2000
dholmes: 5/26/1998