ID   FKBP4_RAT               Reviewed;         458 AA.
AC   Q9QVC8; A6IM14; Q8K3U8;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   13-OCT-2009, sequence version 3.
DT   02-SEP-2026, entry version 169.
DE   RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP4;
DE            Short=PPIase FKBP4;
DE            EC=5.2.1.8;
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 2-25.
RC   TISSUE=Leukemia;
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   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 57-458.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RA   Desai B.J., McKinney K.Q., Meyer M.H., Bahrani-Mostafavi Z.,
RA   Meyer R.A. Jr.;
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TUBULIN.
RX   PubMed=17435176; DOI=10.1096/fj.06-7667com;
RA   Chambraud B., Belabes H., Fontaine-Lenoir V., Fellous A., Baulieu E.E.;
RT   "The immunophilin FKBP52 specifically binds to tubulin and prevents
RT   microtubule formation.";
RL   FASEB J. 21:2787-2797(2007).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP   MAPT.
RX   PubMed=20133804; DOI=10.1073/pnas.0914957107;
RA   Chambraud B., Sardin E., Giustiniani J., Dounane O., Schumacher M.,
RA   Goedert M., Baulieu E.E.;
RT   "A role for FKBP52 in Tau protein function.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:2658-2663(2010).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RA   Maurya D.K., Bhargava P.;
RL   Submitted (JAN-2009) to UniProtKB.
CC   -!- FUNCTION: Immunophilin protein with PPIase and co-chaperone activities
CC       (By similarity). Component of unligated steroid receptors
CC       heterocomplexes through interaction with heat-shock protein 90 (HSP90)
CC       (By similarity). Plays a role in the intracellular trafficking of
CC       heterooligomeric forms of steroid hormone receptors between cytoplasm
CC       and nuclear compartments. May have a protective role against oxidative
CC       stress in mitochondria (By similarity). Also acts as a regulator of
CC       microtubule dynamics by inhibiting MAPT/TAU ability to promote
CC       microtubule assembly. The PPIase activity controls neuronal growth
CC       cones via regulation of TRPC1 channel opening. {ECO:0000250,
CC       ECO:0000269|PubMed:17435176, ECO:0000269|PubMed:20133804}.
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:0000250}.
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with GLMN. Associates
CC       with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also
CC       interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH).
CC       Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90
CC       complex (By similarity). Associates with tubulin (PubMed:17435176).
CC       Interacts with MAPT/TAU (PubMed:20133804). 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 (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:Q02790, ECO:0000269|PubMed:17435176,
CC       ECO:0000269|PubMed:20133804}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17435176,
CC       ECO:0000269|PubMed:20133804}. Mitochondrion
CC       {ECO:0000250|UniProtKB:Q02790}. Nucleus {ECO:0000250|UniProtKB:P30416}.
CC       Cytoplasm, cytoskeleton {ECO:0000269|PubMed:17435176}. Cell projection,
CC       axon {ECO:0000269|PubMed:20133804}. Note=Shuttles from mitochondria to
CC       nucleus; co-localizes in mitochondria with the glucocorticoid receptor
CC       (By similarity). Colocalized with MAPT/TAU in the distal part of the
CC       primary cortical neurons (PubMed:20133804).
CC       {ECO:0000250|UniProtKB:Q02790, ECO:0000269|PubMed:20133804}.
CC   -!- TISSUE SPECIFICITY: Widely detected in the brain (at protein level).
CC       {ECO:0000269|PubMed:20133804}.
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.
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       {ECO:0000250}.
CC   -!- PTM: Phosphorylation by CK2 results in loss of HSP90 binding activity.
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";
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DR   EMBL; CH473964; EDM01775.1; -; Genomic_DNA.
DR   EMBL; AF531427; AAM95632.1; -; mRNA.
DR   RefSeq; NP_001178792.1; NM_001191863.1.
DR   AlphaFoldDB; Q9QVC8; -.
DR   SMR; Q9QVC8; -.
DR   BioGRID; 251740; 5.
DR   DIP; DIP-59214N; -.
DR   FunCoup; Q9QVC8; 2706.
DR   IntAct; Q9QVC8; 2.
DR   MINT; Q9QVC8; -.
DR   STRING; 10116.ENSRNOP00000008737; -.
DR   GlyGen; Q9QVC8; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9QVC8; -.
DR   PhosphoSitePlus; Q9QVC8; -.
DR   jPOST; Q9QVC8; -.
DR   PaxDb; 10116-ENSRNOP00000008737; -.
DR   Ensembl; ENSRNOT00000008737.8; ENSRNOP00000008737.6; ENSRNOG00000006444.8.
DR   Ensembl; ENSRNOT00055018859; ENSRNOP00055015217; ENSRNOG00055011116.
DR   Ensembl; ENSRNOT00060031627; ENSRNOP00060025692; ENSRNOG00060018406.
DR   Ensembl; ENSRNOT00065057901; ENSRNOP00065047686; ENSRNOG00065033702.
DR   GeneID; 260321; -.
DR   KEGG; rno:260321; -.
DR   UCSC; RGD:628729; rat.
DR   AGR; RGD:628729; -.
DR   CTD; 2288; -.
DR   RGD; 628729; Fkbp4.
DR   eggNOG; KOG0543; Eukaryota.
DR   GeneTree; ENSGT00940000157200; -.
DR   HOGENOM; CLU_013615_13_1_1; -.
DR   InParanoid; Q9QVC8; -.
DR   OMA; FGAEGNE; -.
DR   OrthoDB; 433738at2759; -.
DR   PhylomeDB; Q9QVC8; -.
DR   Reactome; R-RNO-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR   Reactome; R-RNO-3371568; Attenuation phase.
DR   Reactome; R-RNO-8939211; ESR-mediated signaling.
DR   Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR   PRO; PR:Q9QVC8; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000006444; Expressed in heart and 19 other cell types or tissues.
DR   ExpressionAtlas; Q9QVC8; baseline and differential.
DR   GO; GO:0044295; C:axonal growth cone; IDA:UniProtKB.
DR   GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0005524; F:ATP binding; ISO:RGD.
DR   GO; GO:0032767; F:copper-dependent protein binding; IPI:RGD.
DR   GO; GO:0005525; F:GTP binding; ISO:RGD.
DR   GO; GO:0031072; F:heat shock protein binding; ISO:RGD.
DR   GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:RGD.
DR   GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR   GO; GO:0051219; F:phosphoprotein binding; ISO:RGD.
DR   GO; GO:0048156; F:tau protein binding; IPI:UniProtKB.
DR   GO; GO:0030521; P:androgen receptor signaling pathway; ISO:RGD.
DR   GO; GO:0006825; P:copper ion transport; IMP:RGD.
DR   GO; GO:0007566; P:embryo implantation; ISO:RGD.
DR   GO; GO:0046661; P:male sex differentiation; ISO:RGD.
DR   GO; GO:0031115; P:negative regulation of microtubule polymerization; IMP:RGD.
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; ISO:RGD.
DR   GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR   GO; GO:0031503; P:protein-containing complex localization; ISO:RGD.
DR   GO; GO:0048608; P:reproductive structure development; ISO:RGD.
DR   GO; GO:0006463; P:steroid hormone receptor complex assembly; ISO:RGD.
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   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   Acetylation; Cell projection; Chaperone; Cytoplasm; Cytoskeleton;
KW   Direct protein sequencing; Isomerase; Isopeptide bond; Methylation;
KW   Microtubule; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW   Repeat; Rotamase; TPR repeat; Ubl conjugation.
FT   CHAIN           1..458
FT                   /note="Peptidyl-prolyl cis-trans isomerase FKBP4"
FT                   /id="PRO_0000391471"
FT   INIT_MET        1
FT                   /note="Removed; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q02790"
FT   CHAIN           2..458
FT                   /note="Peptidyl-prolyl cis-trans isomerase FKBP4, N-
FT                   terminally processed"
FT                   /id="PRO_0000075321"
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          267..400
FT                   /note="Interaction with tubulin"
FT   REGION          423..458
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        447..458
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:0000250|UniProtKB:Q02790"
FT   MOD_RES         2
FT                   /note="N-acetylthreonine; in peptidyl-prolyl cis-trans
FT                   isomerase FKBP4, N-terminally processed; partial"
FT                   /evidence="ECO:0000250|UniProtKB:Q02790"
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:0000250|UniProtKB:Q02790"
FT   MOD_RES         282
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q02790"
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:0000250|UniProtKB:Q02790"
FT   CROSSLNK        441
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1)"
FT                   /evidence="ECO:0000250|UniProtKB:Q02790"
SQ   SEQUENCE   458 AA;  51450 MW;  5701387E5DC991C8 CRC64;
     MTAEEMKVAE NGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETAMIG DRVFVHYTGW
     LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG EVCHITCKPE YAYGSAGSPP
     KIPPNATLVF EVELFEFKGE DLTEDEDGGI IRRIRTRGEG YARPNDGAMV EVALEGYYND
     RLFDQRELCF EVGEGESLDL PCGLEEAIQR MEKGEHSIVY LKPSYAFGSV GKERFQIPPH
     AELRYEVHLK SFEKAKASWE MNSEEKLEQS NIVKERGTVY FKEGKYKQAL LQYKKIVSWL
     EYESSFSGEE MQKVHALRLA SHLNLAMCHL KLQAFSAAIE SCNKALELDS NNEKGLFRRG
     EAHLAVNDFD LARADFQKVL QLYPSNKAAK TQLAVCQQRT RRQLAREKKL YANMFERLAE
     EEHKAKTEVA AGDHPTDAEM KGEPNNVAGN QAQVKTEA
//