ID FKBP4_HUMAN Reviewed; 459 AA. AC Q02790; D3DUQ1; Q9UCP1; Q9UCV7; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 09-APR-2025, entry version 249. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY 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 steroid RT 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., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., 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., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., 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., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (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 project: RT 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, CLEAVAGE RP OF INITIATOR METHIONINE, ACETYLATION AT MET-1 AND THR-2, AND IDENTIFICATION RP BY 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 receptor RT complexes is a unique protein that exists in cytosol in a complex with both RT 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; DOI=10.1016/s0021-9258(19)50664-0; RA Yem A.W., Tomasselli A.G., Heinrikson R.L., Zurcher-Neely H., Ruff V.A., RA Johnson R.A., Deibel M.R. Jr.; RT "The Hsp56 component of steroid receptor complexes binds to immobilized RT 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; DOI=10.1016/s0021-9258(19)36676-1; 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 shock RT 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 INTERACTION WITH GLMN. RX PubMed=12604780; DOI=10.1073/pnas.0438007100; RA Krummrei U., Baulieu E.-E., Chambraud B.; RT "The FKBP-associated protein FAP48 is an antiproliferative molecule and a RT player in T cell activation that increases IL2 synthesis."; RL Proc. Natl. Acad. Sci. U.S.A. 100:2444-2449(2003). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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 phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, AND IDENTIFICATION BY RP 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 [16] 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., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [17] 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., Kern D., RA Muallem S., Ming G.L., Worley P.F.; RT "Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal RT growth cones via regulation of TRPC1 channel opening."; RL Neuron 64:471-483(2009). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-282, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA 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 [19] 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 and RT FKBP52 through their tetratricopeptide repeats."; RL FEBS Lett. 584:1119-1125(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] 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 a RT mitochondrial protein that translocates to the nucleus to protect cells RT against oxidative stress."; RL J. Biol. Chem. 286:30152-30160(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-451 AND SER-453, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-220 AND THR-436, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-441, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2-139. RX PubMed=12499534; DOI=10.1107/s0907444902017523; 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 [28] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-458 IN COMPLEX WITH HSP90, AND RP 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., Shen B., RA Rao Z.; RT "3D structure of human FK506-binding protein 52: implications for the RT assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex."; RL Proc. Natl. Acad. Sci. U.S.A. 101:8348-8353(2004). CC -!- FUNCTION: Immunophilin protein with PPIase and co-chaperone activities. CC Component of steroid receptors heterocomplexes through interaction with CC heat-shock protein 90 (HSP90). May play a role in the intracellular CC trafficking of heterooligomeric forms of steroid hormone receptors CC between cytoplasm and nuclear compartments. The isomerase activity CC controls neuronal growth cones via regulation of TRPC1 channel opening. CC Also acts as a regulator of microtubule dynamics by inhibiting MAPT/TAU CC ability to promote microtubule assembly. May have a protective role CC against oxidative stress in mitochondria. {ECO:0000269|PubMed:1279700, CC ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:19945390, CC ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[protein]-peptidylproline (omega=180) = [protein]- CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, CC ChEBI:CHEBI:83834; EC=5.2.1.8; CC -!- ACTIVITY REGULATION: Inhibited by FK506. {ECO:0000269|PubMed:1279700}. CC -!- SUBUNIT: Homodimer (By similarity). Interacts with GLMN CC (PubMed:12604780). Associates with HSP90AA1 and HSP70 in steroid CC hormone receptor complexes. Also interacts with peroxisomal phytanoyl- CC CoA alpha-hydroxylase (PHYH). Interacts with NR3C1 and dynein. CC Interacts with HSF1 in the HSP90 complex. Associates with tubulin. CC Interacts with MAPT/TAU (By similarity). Interacts (via TPR domain) CC with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. CC Interaction with S100A1 and S100A2 (but not with S100A6) leads to CC inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes CC partially NR3C1 transport to the nucleus. {ECO:0000250, CC ECO:0000250|UniProtKB:Q9QVC8, ECO:0000269|PubMed:11583998, CC ECO:0000269|PubMed:12604780, ECO:0000269|PubMed:1376003, CC ECO:0000269|PubMed:1383226, ECO:0000269|PubMed:15159550, CC ECO:0000269|PubMed:19945390, ECO:0000269|PubMed:20188096, CC ECO:0000269|PubMed:21730050, ECO:0000269|PubMed:2378870}. CC -!- INTERACTION: CC Q02790; Q9UKV8: AGO2; NbExp=2; IntAct=EBI-1047444, EBI-528269; CC Q02790; P10275: AR; NbExp=2; IntAct=EBI-1047444, EBI-608057; CC Q02790; Q16543: CDC37; NbExp=3; IntAct=EBI-1047444, EBI-295634; CC Q02790; Q92990: GLMN; NbExp=5; IntAct=EBI-1047444, EBI-726150; CC Q02790; P07900: HSP90AA1; NbExp=9; IntAct=EBI-1047444, EBI-296047; CC Q02790; P08238: HSP90AB1; NbExp=6; IntAct=EBI-1047444, EBI-352572; CC Q02790; P04792: HSPB1; NbExp=2; IntAct=EBI-1047444, EBI-352682; CC Q02790; P10636-8: MAPT; NbExp=7; IntAct=EBI-1047444, EBI-366233; CC Q02790; P29034: S100A2; NbExp=3; IntAct=EBI-1047444, EBI-752230; CC Q02790; P06703: S100A6; NbExp=3; IntAct=EBI-1047444, EBI-352877; CC Q02790; P35467: S100a1; Xeno; NbExp=7; IntAct=EBI-1047444, EBI-6477109; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:2378870}. CC Mitochondrion {ECO:0000269|PubMed:21730050}. Nucleus CC {ECO:0000250|UniProtKB:P30416}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q9QVC8}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q9QVC8}. Note=Shuttles from mitochondria to CC nucleus; co-localizes in mitochondria with the glucocorticoid receptor CC (PubMed:21730050). Colocalized with MAPT/TAU in the distal part of the CC primary cortical neurons (By similarity). CC {ECO:0000250|UniProtKB:Q9QVC8, ECO:0000269|PubMed:21730050}. CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:1279700}. CC -!- DOMAIN: The PPIase activity is mainly due to the first PPIase FKBP-type CC domain (1-138 AA). {ECO:0000250}. CC -!- DOMAIN: The C-terminal region (AA 375-458) is required to prevent CC tubulin polymerization. {ECO:0000250}. CC -!- DOMAIN: The chaperone activity resides in the C-terminal region, mainly CC between amino acids 264 and 400. {ECO:0000250}. CC -!- DOMAIN: The TPR repeats mediate mitochondrial localization. CC -!- PTM: Phosphorylation by CK2 results in loss of HSP90 binding activity. CC {ECO:0000250}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A mind astray - Issue 118 of CC June 2010; CC URL="https://www.proteinspotlight.org/back_issues/118"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 CCDS; CCDS8512.1; -. DR PIR; A46372; A46372. DR RefSeq; NP_002005.1; NM_002014.4. DR PDB; 1N1A; X-ray; 2.40 A; A/B=1-140. DR PDB; 1P5Q; X-ray; 2.80 A; A/B/C=146-459. DR PDB; 1Q1C; X-ray; 1.90 A; A=2-260. DR PDB; 1QZ2; X-ray; 3.00 A; A/B/C=145-459. DR PDB; 4DRJ; X-ray; 1.80 A; A=1-140. DR PDB; 4LAV; X-ray; 1.80 A; A/B=16-260. DR PDB; 4LAW; X-ray; 2.40 A; A/B=16-260. DR PDB; 4LAX; X-ray; 2.01 A; A=16-260. DR PDB; 4LAY; X-ray; 1.70 A; A=1-260. DR PDB; 4TW8; X-ray; 3.00 A; A/B=21-255. DR PDB; 6RCY; X-ray; 2.30 A; A=1-148. DR PDB; 8FFV; EM; 3.01 A; D=1-459. 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 PDBsum; 4TW8; -. DR PDBsum; 6RCY; -. DR PDBsum; 8FFV; -. DR AlphaFoldDB; Q02790; -. DR EMDB; EMD-29068; -. DR SMR; Q02790; -. DR BioGRID; 108578; 299. DR DIP; DIP-50866N; -. DR IntAct; Q02790; 117. DR MINT; Q02790; -. DR STRING; 9606.ENSP00000001008; -. DR BindingDB; Q02790; -. DR ChEMBL; CHEMBL4050; -. DR DrugCentral; Q02790; -. DR GuidetoPHARMACOLOGY; 3176; -. DR GlyGen; Q02790; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q02790; -. DR MetOSite; Q02790; -. DR PhosphoSitePlus; Q02790; -. DR SwissPalm; Q02790; -. DR BioMuta; FKBP4; -. DR DMDM; 399866; -. DR REPRODUCTION-2DPAGE; IPI00219005; -. DR CPTAC; CPTAC-202; -. DR CPTAC; CPTAC-203; -. DR jPOST; Q02790; -. DR MassIVE; Q02790; -. DR PaxDb; 9606-ENSP00000001008; -. DR PeptideAtlas; Q02790; -. DR ProteomicsDB; 58125; -. DR Pumba; Q02790; -. DR Antibodypedia; 1205; 787 antibodies from 44 providers. DR DNASU; 2288; -. DR Ensembl; ENST00000001008.6; ENSP00000001008.4; ENSG00000004478.8. DR GeneID; 2288; -. DR KEGG; hsa:2288; -. DR MANE-Select; ENST00000001008.6; ENSP00000001008.4; NM_002014.4; NP_002005.1. DR UCSC; uc001qkz.4; human. DR AGR; HGNC:3720; -. DR CTD; 2288; -. DR DisGeNET; 2288; -. DR GeneCards; FKBP4; -. DR HGNC; HGNC:3720; FKBP4. DR HPA; ENSG00000004478; Low tissue specificity. DR MIM; 600611; gene. DR neXtProt; NX_Q02790; -. DR OpenTargets; ENSG00000004478; -. DR PharmGKB; PA28161; -. DR VEuPathDB; HostDB:ENSG00000004478; -. DR eggNOG; KOG0543; Eukaryota. DR GeneTree; ENSGT00940000157200; -. DR HOGENOM; CLU_013615_13_1_1; -. DR InParanoid; Q02790; -. DR OMA; RLSCNLN; -. DR OrthoDB; 433738at2759; -. DR PhylomeDB; Q02790; -. DR TreeFam; TF354214; -. DR PathwayCommons; Q02790; -. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-3371568; Attenuation phase. DR Reactome; R-HSA-8939211; ESR-mediated signaling. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR SignaLink; Q02790; -. DR SIGNOR; Q02790; -. DR BioGRID-ORCS; 2288; 16 hits in 1157 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; FKBP4; human. DR EvolutionaryTrace; Q02790; -. DR GeneWiki; FKBP52; -. DR GenomeRNAi; 2288; -. DR Pharos; Q02790; Tchem. DR PRO; PR:Q02790; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q02790; protein. DR Bgee; ENSG00000004478; Expressed in right hemisphere of cerebellum and 210 other cell types or tissues. DR ExpressionAtlas; Q02790; baseline and differential. DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. 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:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:Ensembl. DR GO; GO:0032767; F:copper-dependent protein binding; IEA:Ensembl. DR GO; GO:0005528; F:FK506 binding; TAS:UniProtKB. DR GO; GO:0005525; F:GTP binding; IEA:Ensembl. DR GO; GO:0031072; F:heat shock protein binding; IPI:UniProtKB. DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IEA:Ensembl. DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB. DR GO; GO:0051219; F:phosphoprotein binding; IEA:Ensembl. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:ProtInc. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0140839; F:RNA polymerase II CTD heptapeptide repeat P3 isomerase activity; IEA:UniProtKB-EC. DR GO; GO:0140840; F:RNA polymerase II CTD heptapeptide repeat P6 isomerase activity; IEA:UniProtKB-EC. DR GO; GO:0048156; F:tau protein binding; IEA:Ensembl. 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:0006457; P:protein folding; TAS:ProtInc. DR GO; GO:0031503; P:protein-containing complex localization; IEA:Ensembl. DR GO; GO:0006463; P:steroid hormone receptor complex assembly; IEA:Ensembl. DR FunFam; 1.25.40.10:FF:000008; Peptidylprolyl isomerase; 1. DR FunFam; 3.10.50.40:FF:000011; Peptidylprolyl isomerase; 1. DR FunFam; 3.10.50.40:FF:000013; Peptidylprolyl isomerase; 1. DR Gene3D; 3.10.50.40; -; 2. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1. DR IDEAL; IID00068; -. DR InterPro; IPR050754; FKBP4/5/8-like. DR InterPro; IPR046357; PPIase_dom_sf. DR InterPro; IPR001179; PPIase_FKBP_dom. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR013105; TPR_2. DR InterPro; IPR019734; TPR_rpt. DR PANTHER; PTHR46512; PEPTIDYLPROLYL ISOMERASE; 1. DR PANTHER; PTHR46512:SF9; PEPTIDYLPROLYL ISOMERASE; 1. DR Pfam; PF00254; FKBP_C; 2. DR Pfam; PF00515; TPR_1; 1. DR Pfam; PF07719; TPR_2; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF54534; FKBP-like; 2. DR SUPFAM; SSF48452; TPR-like; 1. 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; Cell projection; Chaperone; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Isomerase; Isopeptide bond; KW Methylation; Microtubule; Mitochondrion; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; Rotamase; KW TPR repeat; Ubl conjugation. FT CHAIN 1..459 FT /note="Peptidyl-prolyl cis-trans isomerase FKBP4" FT /id="PRO_0000391468" FT INIT_MET 1 FT /note="Removed; alternate" FT /evidence="ECO:0000269|PubMed:1371107, FT ECO:0000269|PubMed:1376003, ECO:0000269|PubMed:2378870, FT ECO:0000269|Ref.5" FT CHAIN 2..459 FT /note="Peptidyl-prolyl cis-trans isomerase FKBP4, N- FT terminally processed" FT /id="PRO_0000075318" FT DOMAIN 50..138 FT /note="PPIase FKBP-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT DOMAIN 167..253 FT /note="PPIase FKBP-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00277" FT REPEAT 270..303 FT /note="TPR 1" FT REPEAT 319..352 FT /note="TPR 2" FT REPEAT 353..386 FT /note="TPR 3" FT REGION 1..24 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 267..400 FT /note="Interaction with tubulin" FT /evidence="ECO:0000250" FT REGION 421..459 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 434..445 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 446..459 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine; in peptidyl-prolyl cis-trans FT isomerase FKBP4; alternate" FT /evidence="ECO:0000269|Ref.5" FT MOD_RES 2 FT /note="N-acetylthreonine; in peptidyl-prolyl cis-trans FT isomerase FKBP4, N-terminally processed; partial" FT /evidence="ECO:0000269|Ref.5" FT MOD_RES 143 FT /note="Phosphothreonine; by CK2" FT /evidence="ECO:0000250|UniProtKB:P27124" FT MOD_RES 220 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 282 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 373 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P30416" FT MOD_RES 436 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 451 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17525332, ECO:0007744|PubMed:21406692" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692" FT CROSSLNK 441 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0007744|PubMed:25114211" FT VARIANT 436 FT /note="T -> P (in dbSNP:rs1042228)" FT /id="VAR_050624" FT MUTAGEN 67..68 FT /note="FD->DV: Decreased catalytic activity toward TRPC1." FT /evidence="ECO:0000269|PubMed:19945390" FT STRAND 22..24 FT /evidence="ECO:0007829|PDB:4DRJ" FT STRAND 30..39 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 52..61 FT /evidence="ECO:0007829|PDB:4LAY" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:8FFV" FT STRAND 66..69 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 73..75 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 83..86 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 88..94 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 102..107 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:4LAY" FT TURN 112..116 FT /evidence="ECO:0007829|PDB:4LAY" FT TURN 119..121 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 128..138 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:6RCY" FT STRAND 147..156 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 169..178 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 181..191 FT /evidence="ECO:0007829|PDB:4LAY" FT TURN 192..194 FT /evidence="ECO:0007829|PDB:4LAW" FT HELIX 195..198 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 202..208 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 216..221 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 223..225 FT /evidence="ECO:0007829|PDB:4LAY" FT TURN 226..230 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:4LAY" FT STRAND 243..253 FT /evidence="ECO:0007829|PDB:4LAY" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 263..283 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 286..299 FT /evidence="ECO:0007829|PDB:1P5Q" FT TURN 300..302 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 309..331 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 335..348 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 353..365 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 369..382 FT /evidence="ECO:0007829|PDB:1P5Q" FT HELIX 387..424 FT /evidence="ECO:0007829|PDB:1P5Q" 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 //