Full text data of FKBP4
FKBP4
(FKBP52)
[Confidence: low (only semi-automatic identification from reviews)]
Peptidyl-prolyl cis-trans isomerase FKBP4; PPIase FKBP4; 5.2.1.8 (51 kDa FK506-binding protein; FKBP51; 52 kDa FK506-binding protein; 52 kDa FKBP; FKBP-52; 59 kDa immunophilin; p59; FK506-binding protein 4; FKBP-4; FKBP59; HSP-binding immunophilin; HBI; Immunophilin FKBP52; Rotamase; Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Peptidyl-prolyl cis-trans isomerase FKBP4; PPIase FKBP4; 5.2.1.8 (51 kDa FK506-binding protein; FKBP51; 52 kDa FK506-binding protein; 52 kDa FKBP; FKBP-52; 59 kDa immunophilin; p59; FK506-binding protein 4; FKBP-4; FKBP59; HSP-binding immunophilin; HBI; Immunophilin FKBP52; Rotamase; Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q02790
ID FKBP4_HUMAN Reviewed; 459 AA.
AC Q02790; D3DUQ1; Q9UCP1; Q9UCV7;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4;
DE Short=PPIase FKBP4;
DE EC=5.2.1.8;
DE AltName: Full=51 kDa FK506-binding protein;
DE Short=FKBP51;
DE AltName: Full=52 kDa FK506-binding protein;
DE Short=52 kDa FKBP;
DE Short=FKBP-52;
DE AltName: Full=59 kDa immunophilin;
DE Short=p59;
DE AltName: Full=FK506-binding protein 4;
DE Short=FKBP-4;
DE AltName: Full=FKBP59;
DE AltName: Full=HSP-binding immunophilin;
DE Short=HBI;
DE AltName: Full=Immunophilin FKBP52;
DE AltName: Full=Rotamase;
DE Contains:
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed;
GN Name=FKBP4; Synonyms=FKBP52;
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], FUNCTION, ENZYME REGULATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=1279700; DOI=10.1073/pnas.89.22.10974;
RA Peattie D.A., Harding M.W., Fleming M.A., Decenzo M.T., Lippke J.A.,
RA Livingston D.J., Benasutti M.;
RT "Expression and characterization of human FKBP52, an immunophilin that
RT associates with the 90-kDa heat shock protein and is a component of
RT steroid receptor complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10974-10978(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Uterus;
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 [5]
RP PROTEIN SEQUENCE OF 1-28; 40-73; 75-121; 139-152; 158-179; 187-206;
RP 211-250; 257-274; 277-313; 319-354; 359-399; 409-426 AND 446-459,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Lourenco F., Olson M.F.;
RL Submitted (JAN-2010) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 2-25, SUBUNIT, AND FUNCTION.
RC TISSUE=Thymus;
RX PubMed=1376003; DOI=10.1126/science.1376003;
RA Tai P.-K.K., Albers M.W., Chang H., Faber L.E., Schreiber S.L.;
RT "Association of a 59-kilodalton immunophilin with the glucocorticoid
RT receptor complex.";
RL Science 256:1315-1318(1992).
RN [7]
RP PROTEIN SEQUENCE OF 2-21, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Lymphocyte;
RX PubMed=2378870; DOI=10.1021/bi00473a021;
RA Sanchez E.R., Faber L.E., Henzel W.J., Pratt W.B.;
RT "The 56-59-kilodalton protein identified in untransformed steroid
RT receptor complexes is a unique protein that exists in cytosol in a
RT complex with both the 70- and 90-kilodalton heat shock proteins.";
RL Biochemistry 29:5145-5152(1990).
RN [8]
RP PROTEIN SEQUENCE OF 2-18.
RC TISSUE=T-cell;
RX PubMed=1371107;
RA Yem A.W., Tomasselli A.G., Heinrikson R.L., Zurcher-Neely H.,
RA Ruff V.A., Johnson R.A., Deibel M.R. Jr.;
RT "The Hsp56 component of steroid receptor complexes binds to
RT immobilized FK506 and shows homology to FKBP-12 and FKBP-13.";
RL J. Biol. Chem. 267:2868-2871(1992).
RN [9]
RP PROTEIN SEQUENCE OF 16-32, AND SUBUNIT.
RX PubMed=1383226;
RA Wiederrecht G., Hung S., Chan H.K., Marcy A., Martin M., Calaycay J.,
RA Boulton D., Sigal N., Kincaid R.L., Siekierka J.J.;
RT "Characterization of high molecular weight FK-506 binding activities
RT reveals a novel FK-506-binding protein as well as a protein complex.";
RL J. Biol. Chem. 267:21753-21760(1992).
RN [10]
RP TERNARY COMPLEX WITH HSP90; HSP70 AND NR3C2, AND DISSOCIATION UPON
RP ALDOSTERONE BINDING.
RX PubMed=9392437;
RA Bruner K.L., Derfoul A., Robertson N.M., Guerriero G.,
RA Fernandes-Alnemri T., Alnemri E.S., Litwack G.;
RT "The unliganded mineralocorticoid receptor is associated with heat
RT shock proteins 70 and 90 and the immunophilin FKBP-52.";
RL Recept. Signal Transduct. 7:85-98(1997).
RN [11]
RP INTERACTION WITH HSF1.
RX PubMed=11583998; DOI=10.1074/jbc.M105931200;
RA Guo Y., Guettouche T., Fenna M., Boellmann F., Pratt W.B., Toft D.O.,
RA Smith D.F., Voellmy R.;
RT "Evidence for a mechanism of repression of heat shock factor 1
RT transcriptional activity by a multichaperone complex.";
RL J. Biol. Chem. 276:45791-45799(2001).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND
RP MASS 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, AND MASS
RP SPECTROMETRY.
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [16]
RP INTERACTION WITH TRPC1, FUNCTION, AND MUTAGENESIS OF 67-PHE-ASP-68.
RX PubMed=19945390; DOI=10.1016/j.neuron.2009.09.025;
RA Shim S., Yuan J.P., Kim J.Y., Zeng W., Huang G., Milshteyn A.,
RA Kern D., Muallem S., Ming G.L., Worley P.F.;
RT "Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of
RT neuronal growth cones via regulation of TRPC1 channel opening.";
RL Neuron 64:471-483(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP INTERACTION WITH S100A1; S100A2 AND S100A6.
RX PubMed=20188096; DOI=10.1016/j.febslet.2010.02.055;
RA Shimamoto S., Kubota Y., Tokumitsu H., Kobayashi R.;
RT "S100 proteins regulate the interaction of Hsp90 with cyclophilin 40
RT and FKBP52 through their tetratricopeptide repeats.";
RL FEBS Lett. 584:1119-1125(2010).
RN [19]
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 [20]
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 [21]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH GLUCOCORTICOID
RP RECEPTOR.
RX PubMed=21730050; DOI=10.1074/jbc.M111.256610;
RA Gallo L.I., Lagadari M., Piwien-Pilipuk G., Galigniana M.D.;
RT "The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is
RT a mitochondrial protein that translocates to the nucleus to protect
RT cells against oxidative stress.";
RL J. Biol. Chem. 286:30152-30160(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2-139.
RX PubMed=12499534;
RA Li P., Ding Y., Wu B., Shu C., Shen B., Rao Z.;
RT "Structure of the N-terminal domain of human FKBP52.";
RL Acta Crystallogr. D 59:16-22(2003).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-458 IN COMPLEX WITH HSP90,
RP AND SUBUNIT.
RX PubMed=15159550; DOI=10.1073/pnas.0305969101;
RA Wu B., Li P., Liu Y., Lou Z., Ding Y., Shu C., Ye S., Bartlam M.,
RA Shen B., Rao Z.;
RT "3D structure of human FK506-binding protein 52: implications for the
RT assembly of the glucocorticoid receptor/Hsp90/immunophilin
RT heterocomplex.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8348-8353(2004).
CC -!- FUNCTION: Immunophilin protein with PPIase and co-chaperone
CC activities. Component of steroid receptors heterocomplexes through
CC interaction with heat-shock protein 90 (HSP90). May play a role in
CC the intracellular trafficking of heterooligomeric forms of steroid
CC hormone receptors between cytoplasm and nuclear compartments. The
CC isomerase activity controls neuronal growth cones via regulation
CC of TRPC1 channel opening. Acts also as a regulator of microtubule
CC dynamics by inhibiting MAPT/TAU ability to promote microtubule
CC assembly. May have a protective role against oxidative stress in
CC mitochondria.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by FK506.
CC -!- SUBUNIT: Homodimer (By similarity). Associates with HSP90AA1 and
CC HSP70 in steroid hormone receptor complexes. Also interacts with
CC peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with
CC NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex.
CC Associates with tubulin. Interacts with MAPT/TAU. Interacts (via
CC TPR domain) with S100A1, S100A2 and S100A6; the interaction is
CC Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with
CC S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts
CC with dynein; causes partially NR3C1 transport to the nucleus.
CC -!- INTERACTION:
CC P07900:HSP90AA1; NbExp=8; IntAct=EBI-1047444, EBI-296047;
CC P35467:S100a1 (xeno); NbExp=7; IntAct=EBI-1047444, EBI-6477109;
CC P29034:S100A2; NbExp=3; IntAct=EBI-1047444, EBI-752230;
CC P06703:S100A6; NbExp=3; IntAct=EBI-1047444, EBI-352877;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity).
CC Mitochondrion. Nucleus. Cytoplasm, cytoskeleton (By similarity).
CC Note=Shuttles from mitochondria to nucleus; co-localizes in
CC mitochondria with the glucocorticoid receptor.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The PPIase activity is mainly due to the fisrt PPIase
CC FKBP-type domain (1-138 AA) (By similarity).
CC -!- DOMAIN: The C-terminal region (AA 375-458) is required to prevent
CC tubulin polymerization (By similarity).
CC -!- DOMAIN: The chaperone activity resides in the C-terminal region,
CC mainly between amino acids 264 and 400 (By similarity).
CC -!- DOMAIN: The TPR repeats mediate mitochondrial localization.
CC -!- PTM: Phosphorylation by CK2 results in loss of HSP90 binding
CC activity (By similarity).
CC -!- SIMILARITY: Contains 2 PPIase FKBP-type domains.
CC -!- SIMILARITY: Contains 3 TPR repeats.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A mind astray - Issue
CC 118 of June 2010;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt118.shtml";
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DR EMBL; M88279; AAA36111.1; -; mRNA.
DR EMBL; AC005841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88889.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88890.1; -; Genomic_DNA.
DR EMBL; BC001786; AAH01786.1; -; mRNA.
DR EMBL; BC007924; AAH07924.1; -; mRNA.
DR PIR; A46372; A46372.
DR RefSeq; NP_002005.1; NM_002014.3.
DR UniGene; Hs.524183; -.
DR UniGene; Hs.713721; -.
DR PDB; 1N1A; X-ray; 2.40 A; A/B=2-139.
DR PDB; 1P5Q; X-ray; 2.80 A; A/B/C=146-458.
DR PDB; 1Q1C; X-ray; 1.90 A; A=2-259.
DR PDB; 1QZ2; X-ray; 3.00 A; A/B/C=145-458.
DR PDB; 4DRJ; X-ray; 1.80 A; A=1-140.
DR PDB; 4LAV; X-ray; 1.80 A; A/B=15-260.
DR PDB; 4LAW; X-ray; 2.40 A; A/B=15-260.
DR PDB; 4LAX; X-ray; 2.01 A; A=16-260.
DR PDB; 4LAY; X-ray; 1.70 A; A=1-260.
DR PDBsum; 1N1A; -.
DR PDBsum; 1P5Q; -.
DR PDBsum; 1Q1C; -.
DR PDBsum; 1QZ2; -.
DR PDBsum; 4DRJ; -.
DR PDBsum; 4LAV; -.
DR PDBsum; 4LAW; -.
DR PDBsum; 4LAX; -.
DR PDBsum; 4LAY; -.
DR ProteinModelPortal; Q02790; -.
DR SMR; Q02790; 21-427.
DR DIP; DIP-50866N; -.
DR IntAct; Q02790; 22.
DR MINT; MINT-3024864; -.
DR STRING; 9606.ENSP00000001008; -.
DR BindingDB; Q02790; -.
DR ChEMBL; CHEMBL4050; -.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR PhosphoSite; Q02790; -.
DR DMDM; 399866; -.
DR REPRODUCTION-2DPAGE; IPI00219005; -.
DR PaxDb; Q02790; -.
DR PeptideAtlas; Q02790; -.
DR PRIDE; Q02790; -.
DR DNASU; 2288; -.
DR Ensembl; ENST00000001008; ENSP00000001008; ENSG00000004478.
DR GeneID; 2288; -.
DR KEGG; hsa:2288; -.
DR UCSC; uc001qkz.3; human.
DR CTD; 2288; -.
DR GeneCards; GC12P002904; -.
DR H-InvDB; HIX0010330; -.
DR HGNC; HGNC:3720; FKBP4.
DR HPA; CAB017441; -.
DR HPA; HPA006148; -.
DR MIM; 600611; gene.
DR neXtProt; NX_Q02790; -.
DR PharmGKB; PA28161; -.
DR eggNOG; COG0545; -.
DR HOGENOM; HOG000256916; -.
DR HOVERGEN; HBG051624; -.
DR InParanoid; Q02790; -.
DR KO; K09571; -.
DR OMA; KVFVHYV; -.
DR PhylomeDB; Q02790; -.
DR ChiTaRS; FKBP4; human.
DR EvolutionaryTrace; Q02790; -.
DR GeneWiki; FKBP52; -.
DR GenomeRNAi; 2288; -.
DR NextBio; 9299; -.
DR PRO; PR:Q02790; -.
DR ArrayExpress; Q02790; -.
DR Bgee; Q02790; -.
DR CleanEx; HS_FKBP4; -.
DR Genevestigator; Q02790; -.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:RefGenome.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR GO; GO:0005528; F:FK506 binding; TAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein binding, bridging; TAS:ProtInc.
DR GO; GO:0030521; P:androgen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0006825; P:copper ion transport; IEA:Ensembl.
DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR GO; GO:0046661; P:male sex differentiation; IEA:Ensembl.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IEA:Ensembl.
DR GO; GO:0031111; P:negative regulation of microtubule polymerization or depolymerization; ISS:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0031503; P:protein complex localization; IEA:Ensembl.
DR GO; GO:0006463; P:steroid hormone receptor complex assembly; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 1.
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; 3.
DR SMART; SM00028; TPR; 3.
DR PROSITE; PS50059; FKBP_PPIASE; 2.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chaperone; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Isomerase; Microtubule;
KW Mitochondrion; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Rotamase; TPR repeat.
FT CHAIN 1 459 Peptidyl-prolyl cis-trans isomerase
FT FKBP4.
FT /FTId=PRO_0000391468.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 459 Peptidyl-prolyl cis-trans isomerase
FT FKBP4, N-terminally processed.
FT /FTId=PRO_0000075318.
FT DOMAIN 50 138 PPIase FKBP-type 1.
FT DOMAIN 167 253 PPIase FKBP-type 2.
FT REPEAT 270 303 TPR 1.
FT REPEAT 319 352 TPR 2.
FT REPEAT 353 386 TPR 3.
FT REGION 267 400 Interaction with tubulin (By similarity).
FT MOD_RES 1 1 N-acetylmethionine; in peptidyl-prolyl
FT cis-trans isomerase FKBP4; alternate.
FT MOD_RES 2 2 N-acetylthreonine; in peptidyl-prolyl
FT cis-trans isomerase FKBP4, N-terminally
FT processed; partial.
FT MOD_RES 143 143 Phosphothreonine; by CK2 (By similarity).
FT MOD_RES 282 282 N6-acetyllysine.
FT MOD_RES 451 451 Phosphoserine.
FT MOD_RES 453 453 Phosphoserine.
FT VARIANT 436 436 T -> P (in dbSNP:rs1042228).
FT /FTId=VAR_050624.
FT MUTAGEN 67 68 FD->DV: Decreased catalytic activity
FT toward TRPC1.
FT STRAND 22 24
FT STRAND 30 39
FT STRAND 42 44
FT STRAND 52 61
FT STRAND 66 70
FT STRAND 73 75
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 148 156
FT STRAND 159 161
FT STRAND 169 178
FT STRAND 181 191
FT TURN 192 194
FT HELIX 195 198
FT HELIX 202 208
FT STRAND 216 221
FT HELIX 223 225
FT TURN 226 230
FT HELIX 233 235
FT STRAND 243 253
FT HELIX 258 260
FT HELIX 263 283
FT HELIX 286 299
FT TURN 300 302
FT HELIX 309 331
FT HELIX 335 348
FT HELIX 353 365
FT HELIX 369 382
FT HELIX 387 424
SQ SEQUENCE 459 AA; 51805 MW; 6A498105418D9435 CRC64;
MTAEEMKATE SGAQSAPLPM EGVDISPKQD EGVLKVIKRE GTGTEMPMIG DRVFVHYTGW
LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAIATMKVG EVCHITCKPE YAYGSAGSPP
KIPPNATLVF EVELFEFKGE DLTEEEDGGI IRRIQTRGEG YAKPNEGAIV EVALEGYYKD
KLFDQRELRF EIGEGENLDL PYGLERAIQR MEKGEHSIVY LKPSYAFGSV GKEKFQIPPN
AELKYELHLK SFEKAKESWE MNSEEKLEQS TIVKERGTVY FKEGKYKQAL LQYKKIVSWL
EYESSFSNEE AQKAQALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS NNEKGLFRRG
EAHLAVNDFE LARADFQKVL QLYPNNKAAK TQLAVCQQRI RRQLAREKKL YANMFERLAE
EENKAKAEAS SGDHPTDTEM KEEQKSNTAG SQSQVETEA
//
ID FKBP4_HUMAN Reviewed; 459 AA.
AC Q02790; D3DUQ1; Q9UCP1; Q9UCV7;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 159.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4;
DE Short=PPIase FKBP4;
DE EC=5.2.1.8;
DE AltName: Full=51 kDa FK506-binding protein;
DE Short=FKBP51;
DE AltName: Full=52 kDa FK506-binding protein;
DE Short=52 kDa FKBP;
DE Short=FKBP-52;
DE AltName: Full=59 kDa immunophilin;
DE Short=p59;
DE AltName: Full=FK506-binding protein 4;
DE Short=FKBP-4;
DE AltName: Full=FKBP59;
DE AltName: Full=HSP-binding immunophilin;
DE Short=HBI;
DE AltName: Full=Immunophilin FKBP52;
DE AltName: Full=Rotamase;
DE Contains:
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4, N-terminally processed;
GN Name=FKBP4; Synonyms=FKBP52;
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], FUNCTION, ENZYME REGULATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=1279700; DOI=10.1073/pnas.89.22.10974;
RA Peattie D.A., Harding M.W., Fleming M.A., Decenzo M.T., Lippke J.A.,
RA Livingston D.J., Benasutti M.;
RT "Expression and characterization of human FKBP52, an immunophilin that
RT associates with the 90-kDa heat shock protein and is a component of
RT steroid receptor complexes.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:10974-10978(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, and Uterus;
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 [5]
RP PROTEIN SEQUENCE OF 1-28; 40-73; 75-121; 139-152; 158-179; 187-206;
RP 211-250; 257-274; 277-313; 319-354; 359-399; 409-426 AND 446-459,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, AND
RP MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Lourenco F., Olson M.F.;
RL Submitted (JAN-2010) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 2-25, SUBUNIT, AND FUNCTION.
RC TISSUE=Thymus;
RX PubMed=1376003; DOI=10.1126/science.1376003;
RA Tai P.-K.K., Albers M.W., Chang H., Faber L.E., Schreiber S.L.;
RT "Association of a 59-kilodalton immunophilin with the glucocorticoid
RT receptor complex.";
RL Science 256:1315-1318(1992).
RN [7]
RP PROTEIN SEQUENCE OF 2-21, FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Lymphocyte;
RX PubMed=2378870; DOI=10.1021/bi00473a021;
RA Sanchez E.R., Faber L.E., Henzel W.J., Pratt W.B.;
RT "The 56-59-kilodalton protein identified in untransformed steroid
RT receptor complexes is a unique protein that exists in cytosol in a
RT complex with both the 70- and 90-kilodalton heat shock proteins.";
RL Biochemistry 29:5145-5152(1990).
RN [8]
RP PROTEIN SEQUENCE OF 2-18.
RC TISSUE=T-cell;
RX PubMed=1371107;
RA Yem A.W., Tomasselli A.G., Heinrikson R.L., Zurcher-Neely H.,
RA Ruff V.A., Johnson R.A., Deibel M.R. Jr.;
RT "The Hsp56 component of steroid receptor complexes binds to
RT immobilized FK506 and shows homology to FKBP-12 and FKBP-13.";
RL J. Biol. Chem. 267:2868-2871(1992).
RN [9]
RP PROTEIN SEQUENCE OF 16-32, AND SUBUNIT.
RX PubMed=1383226;
RA Wiederrecht G., Hung S., Chan H.K., Marcy A., Martin M., Calaycay J.,
RA Boulton D., Sigal N., Kincaid R.L., Siekierka J.J.;
RT "Characterization of high molecular weight FK-506 binding activities
RT reveals a novel FK-506-binding protein as well as a protein complex.";
RL J. Biol. Chem. 267:21753-21760(1992).
RN [10]
RP TERNARY COMPLEX WITH HSP90; HSP70 AND NR3C2, AND DISSOCIATION UPON
RP ALDOSTERONE BINDING.
RX PubMed=9392437;
RA Bruner K.L., Derfoul A., Robertson N.M., Guerriero G.,
RA Fernandes-Alnemri T., Alnemri E.S., Litwack G.;
RT "The unliganded mineralocorticoid receptor is associated with heat
RT shock proteins 70 and 90 and the immunophilin FKBP-52.";
RL Recept. Signal Transduct. 7:85-98(1997).
RN [11]
RP INTERACTION WITH HSF1.
RX PubMed=11583998; DOI=10.1074/jbc.M105931200;
RA Guo Y., Guettouche T., Fenna M., Boellmann F., Pratt W.B., Toft D.O.,
RA Smith D.F., Voellmy R.;
RT "Evidence for a mechanism of repression of heat shock factor 1
RT transcriptional activity by a multichaperone complex.";
RL J. Biol. Chem. 276:45791-45799(2001).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND
RP MASS 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, AND MASS
RP SPECTROMETRY.
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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [16]
RP INTERACTION WITH TRPC1, FUNCTION, AND MUTAGENESIS OF 67-PHE-ASP-68.
RX PubMed=19945390; DOI=10.1016/j.neuron.2009.09.025;
RA Shim S., Yuan J.P., Kim J.Y., Zeng W., Huang G., Milshteyn A.,
RA Kern D., Muallem S., Ming G.L., Worley P.F.;
RT "Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of
RT neuronal growth cones via regulation of TRPC1 channel opening.";
RL Neuron 64:471-483(2009).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [18]
RP INTERACTION WITH S100A1; S100A2 AND S100A6.
RX PubMed=20188096; DOI=10.1016/j.febslet.2010.02.055;
RA Shimamoto S., Kubota Y., Tokumitsu H., Kobayashi R.;
RT "S100 proteins regulate the interaction of Hsp90 with cyclophilin 40
RT and FKBP52 through their tetratricopeptide repeats.";
RL FEBS Lett. 584:1119-1125(2010).
RN [19]
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 [20]
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 [21]
RP SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION WITH GLUCOCORTICOID
RP RECEPTOR.
RX PubMed=21730050; DOI=10.1074/jbc.M111.256610;
RA Gallo L.I., Lagadari M., Piwien-Pilipuk G., Galigniana M.D.;
RT "The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is
RT a mitochondrial protein that translocates to the nucleus to protect
RT cells against oxidative stress.";
RL J. Biol. Chem. 286:30152-30160(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2-139.
RX PubMed=12499534;
RA Li P., Ding Y., Wu B., Shu C., Shen B., Rao Z.;
RT "Structure of the N-terminal domain of human FKBP52.";
RL Acta Crystallogr. D 59:16-22(2003).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-458 IN COMPLEX WITH HSP90,
RP AND SUBUNIT.
RX PubMed=15159550; DOI=10.1073/pnas.0305969101;
RA Wu B., Li P., Liu Y., Lou Z., Ding Y., Shu C., Ye S., Bartlam M.,
RA Shen B., Rao Z.;
RT "3D structure of human FK506-binding protein 52: implications for the
RT assembly of the glucocorticoid receptor/Hsp90/immunophilin
RT heterocomplex.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8348-8353(2004).
CC -!- FUNCTION: Immunophilin protein with PPIase and co-chaperone
CC activities. Component of steroid receptors heterocomplexes through
CC interaction with heat-shock protein 90 (HSP90). May play a role in
CC the intracellular trafficking of heterooligomeric forms of steroid
CC hormone receptors between cytoplasm and nuclear compartments. The
CC isomerase activity controls neuronal growth cones via regulation
CC of TRPC1 channel opening. Acts also as a regulator of microtubule
CC dynamics by inhibiting MAPT/TAU ability to promote microtubule
CC assembly. May have a protective role against oxidative stress in
CC mitochondria.
CC -!- CATALYTIC ACTIVITY: Peptidylproline (omega=180) = peptidylproline
CC (omega=0).
CC -!- ENZYME REGULATION: Inhibited by FK506.
CC -!- SUBUNIT: Homodimer (By similarity). Associates with HSP90AA1 and
CC HSP70 in steroid hormone receptor complexes. Also interacts with
CC peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH). Interacts with
CC NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex.
CC Associates with tubulin. Interacts with MAPT/TAU. Interacts (via
CC TPR domain) with S100A1, S100A2 and S100A6; the interaction is
CC Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with
CC S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts
CC with dynein; causes partially NR3C1 transport to the nucleus.
CC -!- INTERACTION:
CC P07900:HSP90AA1; NbExp=8; IntAct=EBI-1047444, EBI-296047;
CC P35467:S100a1 (xeno); NbExp=7; IntAct=EBI-1047444, EBI-6477109;
CC P29034:S100A2; NbExp=3; IntAct=EBI-1047444, EBI-752230;
CC P06703:S100A6; NbExp=3; IntAct=EBI-1047444, EBI-352877;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity).
CC Mitochondrion. Nucleus. Cytoplasm, cytoskeleton (By similarity).
CC Note=Shuttles from mitochondria to nucleus; co-localizes in
CC mitochondria with the glucocorticoid receptor.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The PPIase activity is mainly due to the fisrt PPIase
CC FKBP-type domain (1-138 AA) (By similarity).
CC -!- DOMAIN: The C-terminal region (AA 375-458) is required to prevent
CC tubulin polymerization (By similarity).
CC -!- DOMAIN: The chaperone activity resides in the C-terminal region,
CC mainly between amino acids 264 and 400 (By similarity).
CC -!- DOMAIN: The TPR repeats mediate mitochondrial localization.
CC -!- PTM: Phosphorylation by CK2 results in loss of HSP90 binding
CC activity (By similarity).
CC -!- SIMILARITY: Contains 2 PPIase FKBP-type domains.
CC -!- SIMILARITY: Contains 3 TPR repeats.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A mind astray - Issue
CC 118 of June 2010;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt118.shtml";
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DR EMBL; M88279; AAA36111.1; -; mRNA.
DR EMBL; AC005841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471116; EAW88889.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88890.1; -; Genomic_DNA.
DR EMBL; BC001786; AAH01786.1; -; mRNA.
DR EMBL; BC007924; AAH07924.1; -; mRNA.
DR PIR; A46372; A46372.
DR RefSeq; NP_002005.1; NM_002014.3.
DR UniGene; Hs.524183; -.
DR UniGene; Hs.713721; -.
DR PDB; 1N1A; X-ray; 2.40 A; A/B=2-139.
DR PDB; 1P5Q; X-ray; 2.80 A; A/B/C=146-458.
DR PDB; 1Q1C; X-ray; 1.90 A; A=2-259.
DR PDB; 1QZ2; X-ray; 3.00 A; A/B/C=145-458.
DR PDB; 4DRJ; X-ray; 1.80 A; A=1-140.
DR PDB; 4LAV; X-ray; 1.80 A; A/B=15-260.
DR PDB; 4LAW; X-ray; 2.40 A; A/B=15-260.
DR PDB; 4LAX; X-ray; 2.01 A; A=16-260.
DR PDB; 4LAY; X-ray; 1.70 A; A=1-260.
DR PDBsum; 1N1A; -.
DR PDBsum; 1P5Q; -.
DR PDBsum; 1Q1C; -.
DR PDBsum; 1QZ2; -.
DR PDBsum; 4DRJ; -.
DR PDBsum; 4LAV; -.
DR PDBsum; 4LAW; -.
DR PDBsum; 4LAX; -.
DR PDBsum; 4LAY; -.
DR ProteinModelPortal; Q02790; -.
DR SMR; Q02790; 21-427.
DR DIP; DIP-50866N; -.
DR IntAct; Q02790; 22.
DR MINT; MINT-3024864; -.
DR STRING; 9606.ENSP00000001008; -.
DR BindingDB; Q02790; -.
DR ChEMBL; CHEMBL4050; -.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR PhosphoSite; Q02790; -.
DR DMDM; 399866; -.
DR REPRODUCTION-2DPAGE; IPI00219005; -.
DR PaxDb; Q02790; -.
DR PeptideAtlas; Q02790; -.
DR PRIDE; Q02790; -.
DR DNASU; 2288; -.
DR Ensembl; ENST00000001008; ENSP00000001008; ENSG00000004478.
DR GeneID; 2288; -.
DR KEGG; hsa:2288; -.
DR UCSC; uc001qkz.3; human.
DR CTD; 2288; -.
DR GeneCards; GC12P002904; -.
DR H-InvDB; HIX0010330; -.
DR HGNC; HGNC:3720; FKBP4.
DR HPA; CAB017441; -.
DR HPA; HPA006148; -.
DR MIM; 600611; gene.
DR neXtProt; NX_Q02790; -.
DR PharmGKB; PA28161; -.
DR eggNOG; COG0545; -.
DR HOGENOM; HOG000256916; -.
DR HOVERGEN; HBG051624; -.
DR InParanoid; Q02790; -.
DR KO; K09571; -.
DR OMA; KVFVHYV; -.
DR PhylomeDB; Q02790; -.
DR ChiTaRS; FKBP4; human.
DR EvolutionaryTrace; Q02790; -.
DR GeneWiki; FKBP52; -.
DR GenomeRNAi; 2288; -.
DR NextBio; 9299; -.
DR PRO; PR:Q02790; -.
DR ArrayExpress; Q02790; -.
DR Bgee; Q02790; -.
DR CleanEx; HS_FKBP4; -.
DR Genevestigator; Q02790; -.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:RefGenome.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR GO; GO:0005528; F:FK506 binding; TAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein binding, bridging; TAS:ProtInc.
DR GO; GO:0030521; P:androgen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0061077; P:chaperone-mediated protein folding; IDA:UniProtKB.
DR GO; GO:0006825; P:copper ion transport; IEA:Ensembl.
DR GO; GO:0007566; P:embryo implantation; IEA:Ensembl.
DR GO; GO:0046661; P:male sex differentiation; IEA:Ensembl.
DR GO; GO:0031115; P:negative regulation of microtubule polymerization; IEA:Ensembl.
DR GO; GO:0031111; P:negative regulation of microtubule polymerization or depolymerization; ISS:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl.
DR GO; GO:0031503; P:protein complex localization; IEA:Ensembl.
DR GO; GO:0006463; P:steroid hormone receptor complex assembly; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 1.
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; 3.
DR SMART; SM00028; TPR; 3.
DR PROSITE; PS50059; FKBP_PPIASE; 2.
DR PROSITE; PS50005; TPR; 3.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chaperone; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Isomerase; Microtubule;
KW Mitochondrion; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Rotamase; TPR repeat.
FT CHAIN 1 459 Peptidyl-prolyl cis-trans isomerase
FT FKBP4.
FT /FTId=PRO_0000391468.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 459 Peptidyl-prolyl cis-trans isomerase
FT FKBP4, N-terminally processed.
FT /FTId=PRO_0000075318.
FT DOMAIN 50 138 PPIase FKBP-type 1.
FT DOMAIN 167 253 PPIase FKBP-type 2.
FT REPEAT 270 303 TPR 1.
FT REPEAT 319 352 TPR 2.
FT REPEAT 353 386 TPR 3.
FT REGION 267 400 Interaction with tubulin (By similarity).
FT MOD_RES 1 1 N-acetylmethionine; in peptidyl-prolyl
FT cis-trans isomerase FKBP4; alternate.
FT MOD_RES 2 2 N-acetylthreonine; in peptidyl-prolyl
FT cis-trans isomerase FKBP4, N-terminally
FT processed; partial.
FT MOD_RES 143 143 Phosphothreonine; by CK2 (By similarity).
FT MOD_RES 282 282 N6-acetyllysine.
FT MOD_RES 451 451 Phosphoserine.
FT MOD_RES 453 453 Phosphoserine.
FT VARIANT 436 436 T -> P (in dbSNP:rs1042228).
FT /FTId=VAR_050624.
FT MUTAGEN 67 68 FD->DV: Decreased catalytic activity
FT toward TRPC1.
FT STRAND 22 24
FT STRAND 30 39
FT STRAND 42 44
FT STRAND 52 61
FT STRAND 66 70
FT STRAND 73 75
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 148 156
FT STRAND 159 161
FT STRAND 169 178
FT STRAND 181 191
FT TURN 192 194
FT HELIX 195 198
FT HELIX 202 208
FT STRAND 216 221
FT HELIX 223 225
FT TURN 226 230
FT HELIX 233 235
FT STRAND 243 253
FT HELIX 258 260
FT HELIX 263 283
FT HELIX 286 299
FT TURN 300 302
FT HELIX 309 331
FT HELIX 335 348
FT HELIX 353 365
FT HELIX 369 382
FT HELIX 387 424
SQ SEQUENCE 459 AA; 51805 MW; 6A498105418D9435 CRC64;
MTAEEMKATE SGAQSAPLPM EGVDISPKQD EGVLKVIKRE GTGTEMPMIG DRVFVHYTGW
LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAIATMKVG EVCHITCKPE YAYGSAGSPP
KIPPNATLVF EVELFEFKGE DLTEEEDGGI IRRIQTRGEG YAKPNEGAIV EVALEGYYKD
KLFDQRELRF EIGEGENLDL PYGLERAIQR MEKGEHSIVY LKPSYAFGSV GKEKFQIPPN
AELKYELHLK SFEKAKESWE MNSEEKLEQS TIVKERGTVY FKEGKYKQAL LQYKKIVSWL
EYESSFSNEE AQKAQALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS NNEKGLFRRG
EAHLAVNDFE LARADFQKVL QLYPNNKAAK TQLAVCQQRI RRQLAREKKL YANMFERLAE
EENKAKAEAS SGDHPTDTEM KEEQKSNTAG SQSQVETEA
//
MIM
600611
*RECORD*
*FIELD* NO
600611
*FIELD* TI
*600611 FK506-BINDING PROTEIN 4; FKBP4
;;T-CELL FK506-BINDING PROTEIN, 59-KD; FKBP59; FKBP52
read more*FIELD* TX
For background information on FK506-binding proteins (FKBPs), see FKBP1A
(186945).
CLONING
Peattie et al. (1992) identified a novel FKBP using an FK506 affinity
matrix. By database analysis, 2 murine DNA sequences were identified,
and PCR primers to these were used to generate a probe for screening a
human placenta cDNA library. A translation of the human cDNA sequence
matched the original partial protein sequence, as well as primary
sequences for other FKBPs. The predicted protein, FKBP52, has a
molecular mass of 52 kD. Northern blot analysis detected FKBP52
transcripts at varying levels in all tissues examined. Peattie et al.
(1992) noted that FKBP52 is apparently identical to a 56- to 59-kD
protein referred to as p56, p59, or FKBP59 in the literature, and they
suggested that phosphorylation of FKBP52 may account for the multiple
reported isoforms.
GENE FUNCTION
Peattie et al. (1992) showed that FKBP52 associated with the 90-kD heat
shock protein (see HSP90A; 140571) in untransformed mammalian steroid
receptor complexes.
FKBP52 is a 'macro' immunophilin that shares high structural and
functional homologies in its N-terminal domain with FKBP12 (FKBP1A;
186945). Unlike FKBP12, however, it does not have immunosuppressant
activity when complexed with FK506. To investigate the physiologic
function of FKBP52, Chambraud et al. (1999) used the yeast 2-hybrid
system as an approach to find its potential protein partners and its
cellular role. They detected an FKBP-associated protein, which by
sequencing was identified as phytanoyl-CoA alpha-hydroxylase (PHYH;
602026), a peroxisomal enzyme. Inactivation of this enzyme is
responsible for Refsum disease (266500) in humans. Chambraud et al.
(1999) showed that PHYH has the physical capacity to interact with the
FKBP12-like domain of FKBP52, but not with FKBP12, suggesting that it is
a particular and specific target of FKBP52. Whereas the binding of
calcineurin (114105) to FKBP12 is potentiated by FK506, the specific
association of PHYH and FKBP52 is maintained in the presence of FK506.
These observations suggested that PHYH is a serious candidate for
studying the cellular signaling pathway(s) involving FKBP52 in the
presence of immunosuppressant drugs.
Fusco et al. (2010) demonstrated that RET51 (see 164761) activation by
both glial cell line-derived neurotrophic factor (GDNF; 600837) and NGF
(162030) triggers the formation of a RET51-FKBP52 complex. Substitution
of tyrosine-905 in RET51, a key residue phosphorylated by both GDNF and
NGF, disrupted the RET51-FKBP52 complex. NGF and GDNF have a functional
role in dopaminergic neurons, where RET51 and FKBP52 are expressed. To
clarify the contribution of the RET51-FKBP52 complex in dopaminergic
neurons, Fusco et al. (2010) screened both genes in 30 patients with
Parkinson disease (PD; 168600), in which dopaminergic neurons are
selectively lost. In 1 individual with early-onset PD, the authors found
heterozygous mutations in each gene, which together were sufficient to
disrupt the RET51-FKBP52 complex.
ANIMAL MODEL
Cheung-Flynn et al. (2005) found that male and female Fkbp52 -/- mice
were infertile. Male infertility in Fkbp52 -/- mice was due to
compromised androgen receptor (AR; 313700) function.
Tranguch et al. (2005) found that, in contrast to female progesterone
receptor (Pgr; 607311) -/- mice, female Fkbp52 -/- mice had no ovulation
defect. Gross and histopathologic analysis showed that Fkbp52 -/- uteri
were completely nonreceptive to blastocyst implantation. In situ
hybridization analysis in wildtype mice showed that Fkbp52 and Pgr
expression overlapped in uterine stroma, but Fkbp52 was also expressed
in luminal and glandular epithelium. Uterine refractoriness in Fkbp52
-/- mice was not due to altered expression of Pgr, for which Fkbp52 is a
cochaperone, or Fkbp51 (FKBP5; 602623). However, Pgr activity was not
optimal in Fkbp52 -/- mice, suggesting that the implantation defect was
due to compromised progesterone function. Northern blot and in situ
hybridization analyses showed downregulated expression of
progesterone-responsive genes in Fkbp52 -/- uteri. Tranguch et al.
(2005) concluded that FKBP52 is a critical determinant of uterine
progesterone actions in preparing the uterus for blastocyst
implantation.
Tranguch et al. (2007) demonstrated implantation failure in female
Fkbp52-null C57BL6/129 and CD1 mice. Progesterone supplementation
rescued implantation and decidualization in CD1, but not C57BL6/129,
Fkbp52-null females. Experimentally-induced decidualization in the
absence of blastocysts failed in Fkbp52-null females on either
background even with progesterone supplementation, suggesting that
embryonic signaling complements uterine signaling for this event. In
Fkbp52-null CD1 females, administration of progesterone at higher than
normal pregnancy levels was sufficient for implantation but failed to
maintain pregnancy to full term; elevating progesterone levels further
resulted in successful term pregnancy with normal litter size. Tranguch
et al. (2007) concluded that the requirement for FKBP52 in uterine
progesterone/PGR signaling is a function of genetic disparity and is
pregnancy-stage specific.
Chen et al. (2010) stated that male mice with targeted ablation of
Fkbp52 develop hypospadias. They found that Fkbp52 expression was
enriched in the ventral aspect of the developing mouse urethral
epithelium at embryonic day 18.5, when the final urethra normally forms
via closure of the enveloping epithelial layers. Scanning electron
microscopy revealed that Fkbp52 -/- males had reduced elevation of
prepucial swelling, leading to a defect in urethral seam formation. In
situ hybridization and immunohistochemical analysis suggested that
Fkbp52 mutants had a normal urethral epithelium signaling center and
epithelial differentiation, but Fkbp52 mutant ventral epithelial cells
had a reduced apoptotic cell index at the site of fusion and a defect in
genital mesenchymal cell migration in vitro. Supplementation of
gestating females with excess testosterone partially rescued the
phenotype. Chromatin immunoprecipitation analysis revealed normal
occupancy of Ar at Ar-responsive gene promoters, but reduced Ar activity
at genes controlling sexual dimorphism and cell growth was observed.
Chen et al. (2010) concluded that Fkbp52 functions downstream of Ar in
urethra morphogenesis.
*FIELD* RF
1. Chambraud, B.; Radanyi, C.; Camonis, J. H.; Rajkowski, K.; Schumacher,
M.; Baulieu, E.-E.: Immunophilins, Refsum disease, and lupus nephritis:
the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated
protein. Proc. Nat. Acad. Sci. 96: 2104-2109, 1999.
2. Chen, H.; Yong, W.; Hinds, T. D., Jr.; Yang, Z.; Zhou, Y.; Sanchez,
E. R.; Shou, W.: Fkbp52 regulates androgen receptor transactivation
activity and male urethra morphogenesis. J. Biol. Chem. 285: 27776-27784,
2010.
3. Cheung-Flynn, J.; Prapapanich, V.; Cox, M. B.; Riggs, D. L.; Suarez-Quian,
C.; Smith, D. F.: Physiological role for the cochaperone FKBP52 in
androgen receptor signaling. Molec. Endocr. 19: 1654-1666, 2005.
4. Fusco, D.; Vargiolu, M.; Vidone, M.; Mariani, E.; Pennisi, L. F.;
Bonora, E.; Capellari, S; Dirnberger, D.; Baumeister, R.; Martinelli,
P.; Romeo, G.: The RET51/FKBP52 complex and its involvement in Parkinson
disease. Hum. Molec. Genet. 19: 2804-2816, 2010.
5. Peattie, D. A.; Harding, M. W.; Fleming, M. A.; DeCenzo, M. T.;
Lippke, J. A.; Livingston, D. J.; Benasutti, M.: Expression and characterization
of human FKBP52, an immunophilin that associates with the 90-kDa heat
shock protein and is a component of steroid receptor complexes. Proc.
Nat. Acad. Sci. 89: 10974-10978, 1992.
6. Tranguch, S.; Cheung-Flynn, J.; Daikoku, T.; Prapapanich, V.; Cox,
M. B.; Xie, H.; Wang, H.; Das, S. K.; Smith, D. F.; Dey, S. K.: Cochaperone
immunophilin FKBP52 is critical to uterine receptivity for embryo
implantation. Proc. Nat. Acad. Sci. 102: 14326-14331, 2005.
7. Tranguch, S.; Wang, H.; Daikoku, T.; Xie, H.; Smith, D. F.; Dey,
S. K.: FKBP52 deficiency-conferred uterine progesterone resistance
is genetic background and pregnancy stage specific. J. Clin. Invest. 117:
1824-1834, 2007.
*FIELD* CN
George E. Tiller - updated: 8/23/2013
Patricia A. Hartz - updated: 7/5/2011
Marla J. F. O'Neill - updated: 8/2/2007
Paul J. Converse - updated: 5/3/2007
Victor A. McKusick - updated: 7/13/1999
*FIELD* CD
Alan F. Scott: 6/14/1995
*FIELD* ED
alopez: 09/04/2013
tpirozzi: 8/23/2013
mgross: 8/16/2011
terry: 7/5/2011
mgross: 3/3/2011
wwang: 8/15/2007
terry: 8/2/2007
mgross: 7/24/2007
terry: 5/3/2007
carol: 5/6/2004
jlewis: 7/28/1999
terry: 7/13/1999
alopez: 7/25/1997
mark: 4/14/1997
terry: 7/10/1995
mark: 6/14/1995
*RECORD*
*FIELD* NO
600611
*FIELD* TI
*600611 FK506-BINDING PROTEIN 4; FKBP4
;;T-CELL FK506-BINDING PROTEIN, 59-KD; FKBP59; FKBP52
read more*FIELD* TX
For background information on FK506-binding proteins (FKBPs), see FKBP1A
(186945).
CLONING
Peattie et al. (1992) identified a novel FKBP using an FK506 affinity
matrix. By database analysis, 2 murine DNA sequences were identified,
and PCR primers to these were used to generate a probe for screening a
human placenta cDNA library. A translation of the human cDNA sequence
matched the original partial protein sequence, as well as primary
sequences for other FKBPs. The predicted protein, FKBP52, has a
molecular mass of 52 kD. Northern blot analysis detected FKBP52
transcripts at varying levels in all tissues examined. Peattie et al.
(1992) noted that FKBP52 is apparently identical to a 56- to 59-kD
protein referred to as p56, p59, or FKBP59 in the literature, and they
suggested that phosphorylation of FKBP52 may account for the multiple
reported isoforms.
GENE FUNCTION
Peattie et al. (1992) showed that FKBP52 associated with the 90-kD heat
shock protein (see HSP90A; 140571) in untransformed mammalian steroid
receptor complexes.
FKBP52 is a 'macro' immunophilin that shares high structural and
functional homologies in its N-terminal domain with FKBP12 (FKBP1A;
186945). Unlike FKBP12, however, it does not have immunosuppressant
activity when complexed with FK506. To investigate the physiologic
function of FKBP52, Chambraud et al. (1999) used the yeast 2-hybrid
system as an approach to find its potential protein partners and its
cellular role. They detected an FKBP-associated protein, which by
sequencing was identified as phytanoyl-CoA alpha-hydroxylase (PHYH;
602026), a peroxisomal enzyme. Inactivation of this enzyme is
responsible for Refsum disease (266500) in humans. Chambraud et al.
(1999) showed that PHYH has the physical capacity to interact with the
FKBP12-like domain of FKBP52, but not with FKBP12, suggesting that it is
a particular and specific target of FKBP52. Whereas the binding of
calcineurin (114105) to FKBP12 is potentiated by FK506, the specific
association of PHYH and FKBP52 is maintained in the presence of FK506.
These observations suggested that PHYH is a serious candidate for
studying the cellular signaling pathway(s) involving FKBP52 in the
presence of immunosuppressant drugs.
Fusco et al. (2010) demonstrated that RET51 (see 164761) activation by
both glial cell line-derived neurotrophic factor (GDNF; 600837) and NGF
(162030) triggers the formation of a RET51-FKBP52 complex. Substitution
of tyrosine-905 in RET51, a key residue phosphorylated by both GDNF and
NGF, disrupted the RET51-FKBP52 complex. NGF and GDNF have a functional
role in dopaminergic neurons, where RET51 and FKBP52 are expressed. To
clarify the contribution of the RET51-FKBP52 complex in dopaminergic
neurons, Fusco et al. (2010) screened both genes in 30 patients with
Parkinson disease (PD; 168600), in which dopaminergic neurons are
selectively lost. In 1 individual with early-onset PD, the authors found
heterozygous mutations in each gene, which together were sufficient to
disrupt the RET51-FKBP52 complex.
ANIMAL MODEL
Cheung-Flynn et al. (2005) found that male and female Fkbp52 -/- mice
were infertile. Male infertility in Fkbp52 -/- mice was due to
compromised androgen receptor (AR; 313700) function.
Tranguch et al. (2005) found that, in contrast to female progesterone
receptor (Pgr; 607311) -/- mice, female Fkbp52 -/- mice had no ovulation
defect. Gross and histopathologic analysis showed that Fkbp52 -/- uteri
were completely nonreceptive to blastocyst implantation. In situ
hybridization analysis in wildtype mice showed that Fkbp52 and Pgr
expression overlapped in uterine stroma, but Fkbp52 was also expressed
in luminal and glandular epithelium. Uterine refractoriness in Fkbp52
-/- mice was not due to altered expression of Pgr, for which Fkbp52 is a
cochaperone, or Fkbp51 (FKBP5; 602623). However, Pgr activity was not
optimal in Fkbp52 -/- mice, suggesting that the implantation defect was
due to compromised progesterone function. Northern blot and in situ
hybridization analyses showed downregulated expression of
progesterone-responsive genes in Fkbp52 -/- uteri. Tranguch et al.
(2005) concluded that FKBP52 is a critical determinant of uterine
progesterone actions in preparing the uterus for blastocyst
implantation.
Tranguch et al. (2007) demonstrated implantation failure in female
Fkbp52-null C57BL6/129 and CD1 mice. Progesterone supplementation
rescued implantation and decidualization in CD1, but not C57BL6/129,
Fkbp52-null females. Experimentally-induced decidualization in the
absence of blastocysts failed in Fkbp52-null females on either
background even with progesterone supplementation, suggesting that
embryonic signaling complements uterine signaling for this event. In
Fkbp52-null CD1 females, administration of progesterone at higher than
normal pregnancy levels was sufficient for implantation but failed to
maintain pregnancy to full term; elevating progesterone levels further
resulted in successful term pregnancy with normal litter size. Tranguch
et al. (2007) concluded that the requirement for FKBP52 in uterine
progesterone/PGR signaling is a function of genetic disparity and is
pregnancy-stage specific.
Chen et al. (2010) stated that male mice with targeted ablation of
Fkbp52 develop hypospadias. They found that Fkbp52 expression was
enriched in the ventral aspect of the developing mouse urethral
epithelium at embryonic day 18.5, when the final urethra normally forms
via closure of the enveloping epithelial layers. Scanning electron
microscopy revealed that Fkbp52 -/- males had reduced elevation of
prepucial swelling, leading to a defect in urethral seam formation. In
situ hybridization and immunohistochemical analysis suggested that
Fkbp52 mutants had a normal urethral epithelium signaling center and
epithelial differentiation, but Fkbp52 mutant ventral epithelial cells
had a reduced apoptotic cell index at the site of fusion and a defect in
genital mesenchymal cell migration in vitro. Supplementation of
gestating females with excess testosterone partially rescued the
phenotype. Chromatin immunoprecipitation analysis revealed normal
occupancy of Ar at Ar-responsive gene promoters, but reduced Ar activity
at genes controlling sexual dimorphism and cell growth was observed.
Chen et al. (2010) concluded that Fkbp52 functions downstream of Ar in
urethra morphogenesis.
*FIELD* RF
1. Chambraud, B.; Radanyi, C.; Camonis, J. H.; Rajkowski, K.; Schumacher,
M.; Baulieu, E.-E.: Immunophilins, Refsum disease, and lupus nephritis:
the peroxisomal enzyme phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated
protein. Proc. Nat. Acad. Sci. 96: 2104-2109, 1999.
2. Chen, H.; Yong, W.; Hinds, T. D., Jr.; Yang, Z.; Zhou, Y.; Sanchez,
E. R.; Shou, W.: Fkbp52 regulates androgen receptor transactivation
activity and male urethra morphogenesis. J. Biol. Chem. 285: 27776-27784,
2010.
3. Cheung-Flynn, J.; Prapapanich, V.; Cox, M. B.; Riggs, D. L.; Suarez-Quian,
C.; Smith, D. F.: Physiological role for the cochaperone FKBP52 in
androgen receptor signaling. Molec. Endocr. 19: 1654-1666, 2005.
4. Fusco, D.; Vargiolu, M.; Vidone, M.; Mariani, E.; Pennisi, L. F.;
Bonora, E.; Capellari, S; Dirnberger, D.; Baumeister, R.; Martinelli,
P.; Romeo, G.: The RET51/FKBP52 complex and its involvement in Parkinson
disease. Hum. Molec. Genet. 19: 2804-2816, 2010.
5. Peattie, D. A.; Harding, M. W.; Fleming, M. A.; DeCenzo, M. T.;
Lippke, J. A.; Livingston, D. J.; Benasutti, M.: Expression and characterization
of human FKBP52, an immunophilin that associates with the 90-kDa heat
shock protein and is a component of steroid receptor complexes. Proc.
Nat. Acad. Sci. 89: 10974-10978, 1992.
6. Tranguch, S.; Cheung-Flynn, J.; Daikoku, T.; Prapapanich, V.; Cox,
M. B.; Xie, H.; Wang, H.; Das, S. K.; Smith, D. F.; Dey, S. K.: Cochaperone
immunophilin FKBP52 is critical to uterine receptivity for embryo
implantation. Proc. Nat. Acad. Sci. 102: 14326-14331, 2005.
7. Tranguch, S.; Wang, H.; Daikoku, T.; Xie, H.; Smith, D. F.; Dey,
S. K.: FKBP52 deficiency-conferred uterine progesterone resistance
is genetic background and pregnancy stage specific. J. Clin. Invest. 117:
1824-1834, 2007.
*FIELD* CN
George E. Tiller - updated: 8/23/2013
Patricia A. Hartz - updated: 7/5/2011
Marla J. F. O'Neill - updated: 8/2/2007
Paul J. Converse - updated: 5/3/2007
Victor A. McKusick - updated: 7/13/1999
*FIELD* CD
Alan F. Scott: 6/14/1995
*FIELD* ED
alopez: 09/04/2013
tpirozzi: 8/23/2013
mgross: 8/16/2011
terry: 7/5/2011
mgross: 3/3/2011
wwang: 8/15/2007
terry: 8/2/2007
mgross: 7/24/2007
terry: 5/3/2007
carol: 5/6/2004
jlewis: 7/28/1999
terry: 7/13/1999
alopez: 7/25/1997
mark: 4/14/1997
terry: 7/10/1995
mark: 6/14/1995