FKBP4_HUMAN
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 03-AUG-2022, entry version 234.
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 Acts also 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=4; IntAct=EBI-1047444, EBI-726150;
CC Q02790; P07900: HSP90AA1; NbExp=8; 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; 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://web.expasy.org/spotlight/back_issues/118";
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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 CCDS; CCDS8512.1; -.
DR PIR; A46372; A46372.
DR RefSeq; NP_002005.1; NM_002014.3.
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 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 AlphaFoldDB; Q02790; -.
DR SMR; Q02790; -.
DR BioGRID; 108578; 181.
DR DIP; DIP-50866N; -.
DR IntAct; Q02790; 98.
DR MINT; Q02790; -.
DR STRING; 9606.ENSP00000001008; -.
DR BindingDB; Q02790; -.
DR ChEMBL; CHEMBL4050; -.
DR DrugCentral; Q02790; -.
DR GuidetoPHARMACOLOGY; 3176; -.
DR GlyGen; Q02790; 1 site, 1 O-linked glycan (1 site).
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 EPD; Q02790; -.
DR jPOST; Q02790; -.
DR MassIVE; Q02790; -.
DR MaxQB; Q02790; -.
DR PaxDb; Q02790; -.
DR PeptideAtlas; Q02790; -.
DR PRIDE; Q02790; -.
DR ProteomicsDB; 58125; -.
DR Antibodypedia; 1205; 665 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 CTD; 2288; -.
DR DisGeNET; 2288; -.
DR GeneCards; FKBP4; -.
DR HGNC; HGNC:3720; FKBP4.
DR HPA; ENSG00000004478; Tissue enhanced (brain).
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; NLELISW; -.
DR OrthoDB; 897391at2759; -.
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 1081 CRISPR screens.
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 208 other tissues.
DR ExpressionAtlas; Q02790; baseline and differential.
DR Genevisible; Q02790; HS.
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: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:0000413; P:protein peptidyl-prolyl isomerization; IBA:GO_Central.
DR GO; GO:0031503; P:protein-containing complex localization; IEA:Ensembl.
DR GO; GO:0006463; P:steroid hormone receptor complex assembly; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 2.
DR IDEAL; IID00068; -.
DR InterPro; IPR031212; FKBP4.
DR InterPro; IPR046357; PPIase_dom_sf.
DR InterPro; IPR001179; PPIase_FKBP_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR001440; TPR_1.
DR InterPro; IPR013105; TPR_2.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10516:SF25; PTHR10516:SF25; 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; SSF48452; SSF48452; 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 Reference proteome; Repeat; Rotamase; 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 421..444
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 445..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 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
