FKBP4_RABIT
ID FKBP4_RABIT Reviewed; 458 AA.
AC P27124;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 177.
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=P59;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=1537818; DOI=10.1016/s0021-9258(18)42827-x;
RA Lebeau M.-C., Massol N., Herrick J., Faber L.E., Renoir J.-M., Radanyi C.,
RA Baulieu E.-E.;
RT "P59, an hsp 90-binding protein. Cloning and sequencing of its cDNA and
RT preparation of a peptide-directed polyclonal antibody.";
RL J. Biol. Chem. 267:4281-4284(1992).
RN [2]
RP PROTEIN SEQUENCE OF 2-26.
RC STRAIN=New Zealand white; TISSUE=Liver;
RX PubMed=8579355; DOI=10.1006/abbi.1996.0039;
RA Deshpande K.L., Seubert P.H., Tillman D.M., Farkas W.R., Katze J.R.;
RT "Cloning and characterization of cDNA encoding the rabbit tRNA-guanine
RT transglycosylase 60-kilodalton subunit.";
RL Arch. Biochem. Biophys. 326:1-7(1996).
RN [3]
RP DOMAINS.
RX PubMed=1631118; DOI=10.1073/pnas.89.14.6270;
RA Callebaut I., Renoir J.-M., Lebeau M.-C., Massol N., Burny A.,
RA Baulieu E.-E., Mornon J.-P.;
RT "An immunophilin that binds M(r) 90,000 heat shock protein: main structural
RT features of a mammalian p59 protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6270-6274(1992).
RN [4]
RP PPIASE ACTIVITY.
RX PubMed=8216288; DOI=10.1006/bbrc.1993.2229;
RA Chambraud B., Rouviere-Fourmy N., Radanyi C., Hsiao K., Peattie D.A.,
RA Livingston D.J., Baulieu E.E.;
RT "Overexpression of p59-HBI (FKBP59), full length and domains, and
RT characterization of PPlase activity.";
RL Biochem. Biophys. Res. Commun. 196:160-166(1993).
RN [5]
RP INTERACTION WITH GLMN.
RX PubMed=8955134; DOI=10.1074/jbc.271.51.32923;
RA Chambraud B., Radanyi C., Camonis J.H., Shazand K., Rajkowski K.,
RA Baulieu E.-E.;
RT "FAP48, a new protein that forms specific complexes with both immunophilins
RT FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and
RT rapamycin.";
RL J. Biol. Chem. 271:32923-32929(1996).
RN [6]
RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND HSP90AA1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
RN [7]
RP PHOSPHORYLATION AT THR-143 BY CK2.
RX PubMed=9405642; DOI=10.1073/pnas.94.26.14500;
RA Miyata Y., Chambraud B., Radanyi C., Leclerc J., Lebeau M.-C.,
RA Renoir J.-M., Shirai R., Catelli M.-G., Yahara I., Baulieu E.-E.;
RT "Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by
RT casein kinase II: regulation of HSP90-binding activity of FKBP52.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14500-14505(1997).
RN [8]
RP INTERACTION WITH NR3C1; DYNEIN AND HSP90.
RX PubMed=10601253; DOI=10.1074/jbc.274.52.36980;
RA Silverstein A.M., Galigniana M.D., Kanelakis K.C., Radanyi C.,
RA Renoir J.-M., Pratt W.B.;
RT "Different regions of the immunophilin FKBP52 determine its association
RT with the glucocorticoid receptor, hsp90, and cytoplasmic dynein.";
RL J. Biol. Chem. 274:36980-36986(1999).
RN [9]
RP INTERACTION WITH PHYH.
RX PubMed=10051602; DOI=10.1073/pnas.96.5.2104;
RA Chambraud B., Radanyi C., Camonis J.H., Rajkowski K., Schumacher M.,
RA Baulieu E.-E.;
RT "Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme
RT phytanoyl-CoA alpha-hydroxylase is a new FKBP-associated protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2104-2109(1999).
RN [10]
RP FUNCTION AS A CO-CHAPERONE, AND DOMAINS.
RX PubMed=11473108; DOI=10.1074/jbc.m102595200;
RA Pirkl F., Fischer E., Modrow S., Buchner J.;
RT "Localization of the chaperone domain of FKBP52.";
RL J. Biol. Chem. 276:37034-37041(2001).
RN [11]
RP STRUCTURE BY NMR OF 1-149.
RX PubMed=8780506; DOI=10.1021/bi960975p;
RA Craescu C.T., Rouviere N., Popescu A., Cerpolini E., Lebeau M.-C.,
RA Baulieu E.-E., Mispelter J.;
RT "Three-dimensional structure of the immunophilin-like domain of FKBP59 in
RT solution.";
RL Biochemistry 35:11045-11052(1996).
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 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:11473108}.
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; rapamycin and
CC FK506 abolish the interaction with GLMN in a dose dependent manner
CC (PubMed:8955134). Associates with HSP90AA1 and HSP70 in steroid hormone
CC receptor complexes. Also interacts with peroxisomal phytanoyl-CoA
CC alpha-hydroxylase (PHYH) (PubMed:10051602). Interacts with NR3C1 and
CC dynein. Interacts with HSF1 in the HSP90 complex. Associates with
CC tubulin. Interacts with MAPT/TAU (By similarity). Interacts (via TPR
CC domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+)
CC dependent. Interaction with S100A1 and S100A2 (but not with S100A6)
CC leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein;
CC causes partially NR3C1 transport to the nucleus. {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9QVC8, ECO:0000269|PubMed:10051602,
CC ECO:0000269|PubMed:10601253, ECO:0000269|PubMed:8955134,
CC ECO:0000269|PubMed:9195923}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Mitochondrion
CC {ECO:0000250}. Nucleus. Cytoplasm, cytoskeleton {ECO:0000250}.
CC Note=Shuttles from mitochondria to nucleus; co-localizes in
CC mitochondria with the glucocorticoid receptor. {ECO:0000250}.
CC -!- DOMAIN: The C-terminal region (AA 375-458) is required to prevent
CC tubulin polymerization. {ECO:0000250}.
CC -!- DOMAIN: The PPIase activity is mainly due to the first PPIase FKBP-type
CC domain (1-138 AA).
CC -!- DOMAIN: The chaperone activity resides in the C-terminal region, mainly
CC between amino acids 264 and 400.
CC -!- DOMAIN: The TPR repeats mediate mitochondrial localization.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation by CK2 results in loss of HSP90 binding activity.
CC {ECO:0000269|PubMed:9405642}.
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DR EMBL; M84474; AAA31438.1; -; mRNA.
DR EMBL; M84988; AAA31439.1; -; mRNA.
DR PIR; A42386; A42386.
DR RefSeq; NP_001075779.1; NM_001082310.1.
DR PDB; 1ROT; NMR; -; A=4-148.
DR PDB; 1ROU; NMR; -; A=4-148.
DR PDBsum; 1ROT; -.
DR PDBsum; 1ROU; -.
DR AlphaFoldDB; P27124; -.
DR SMR; P27124; -.
DR BioGRID; 1172171; 1.
DR STRING; 9986.ENSOCUP00000012554; -.
DR iPTMnet; P27124; -.
DR Ensembl; ENSOCUT00000014603; ENSOCUP00000012554; ENSOCUG00000014603.
DR GeneID; 100009148; -.
DR KEGG; ocu:100009148; -.
DR CTD; 2288; -.
DR eggNOG; KOG0543; Eukaryota.
DR GeneTree; ENSGT00940000157200; -.
DR HOGENOM; CLU_013615_13_1_1; -.
DR InParanoid; P27124; -.
DR OMA; ELEMLGW; -.
DR OrthoDB; 897391at2759; -.
DR EvolutionaryTrace; P27124; -.
DR Proteomes; UP000001811; Chromosome 8.
DR Bgee; ENSOCUG00000014603; Expressed in testis and 17 other tissues.
DR GO; GO:0044295; C:axonal growth cone; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005528; F:FK506 binding; IEA:InterPro.
DR GO; GO:0031072; F:heat shock protein binding; IEA:InterPro.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; IPI:UniProtKB.
DR GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
DR GO; GO:0031111; P:negative regulation of microtubule polymerization or depolymerization; IDA:UniProtKB.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; IEA:InterPro.
DR Gene3D; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 2.
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; 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_0000391470"
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_0000075320"
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 423..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..448
FT /note="Basic and acidic 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:0000269|PubMed:9405642"
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 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02790"
FT MOD_RES 452
FT /note="Phosphoserine"
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"
FT CONFLICT 15
FT /note="S -> H (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 21..22
FT /note="EG -> FI (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 26
FT /note="S -> T (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1ROT"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:1ROT"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:1ROT"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:1ROT"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:1ROT"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:1ROT"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:1ROT"
FT TURN 112..116
FT /evidence="ECO:0007829|PDB:1ROT"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:1ROT"
FT STRAND 128..136
FT /evidence="ECO:0007829|PDB:1ROT"
SQ SEQUENCE 458 AA; 51475 MW; 2EE25D561391DFF0 CRC64;
MTAEEMKAAE SGAQSAPLPL EGVDISPKQD EGVLKVIKRE GTGTETPMIG DRVFVHYTGW
LLDGTKFDSS LDRKDKFSFD LGKGEVIKAW DIAVATMKVG ELCRITCKPE YAYGSAGSPP
KIPPNATLVF EVELFEFKGE DLTDDEDGGI IRRIRTRGEG YARPNDGAIV EVALEGYYKD
RLFDQRELRF EVGEGESLDL PCGLEKAIQR MEKGEHSILY LKPSYAFGNA GKEKFQIPPY
AELKYEVHLK SFEKAKESWE MSSEEKLEQS AIVKERGTVY FKEGKYKQAL LQYKKIVSWL
EYESSFSSEE VQKAQALRLA SHLNLAMCHL KLQAFSAAVE SCNKALELDS NNEKGLFRRG
EAHLAVNDFD LARADFQKVL QLYPSNKAAK AQLAVCQQRI RKQIAREKKL YANMFERLAE
EENKAKAEVA AGDHPMDTEM KDERNDVAGS QSQVETEA
