ID   FKBP4_BOVIN             Reviewed;         459 AA.
AC   Q9TRY0; A5D9B2; Q3T0C4; Q9TRX9;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   27-MAR-2024, entry version 147.
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=FK506-binding protein 4;
DE            Short=FKBP-4;
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;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA   Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA   Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT   "Characterization of 954 bovine full-CDS cDNA sequences.";
RL   BMC Genomics 6:166-166(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PROTEIN SEQUENCE OF 2-28; 75-83; 89-98; 122-137; 164-175; 214-222; 245-250;
RP   277-282; 345-354; 410-424 AND 427-440.
RC   TISSUE=Thymus;
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   [4]
RP   PROTEIN SEQUENCE OF 2-18 AND 121-137.
RC   TISSUE=Thymus;
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).
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). May play a role in the intracellular trafficking of
CC       heterooligomeric forms of steroid hormone receptors between cytoplasm
CC       and nuclear compartments (By similarity). The isomerase activity
CC       controls neuronal growth cones via regulation of TRPC1 channel opening
CC       (By similarity). Acts also as a regulator of microtubule dynamics by
CC       inhibiting MAPT/TAU ability to promote microtubule assembly. May have a
CC       protective role against oxidative stress in mitochondria (By
CC       similarity). {ECO:0000250}.
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. Associates with tubulin. Interacts with MAPT/TAU. Interacts
CC       (via 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 with
CC       dynein; causes partially NR3C1 transport to the nucleus (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q02790,
CC       ECO:0000250|UniProtKB:Q9QVC8}.
CC   -!- INTERACTION:
CC       Q9TRY0; P02639: S100A1; NbExp=2; IntAct=EBI-6477371, EBI-6477285;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Mitochondrion
CC       {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm, cytoskeleton
CC       {ECO:0000250}. Note=Shuttles from mitochondria to nucleus; colocalizes
CC       in mitochondria with the glucocorticoid receptor. {ECO:0000250}.
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       {ECO:0000250}.
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DR   EMBL; BT030531; ABQ12971.1; -; mRNA.
DR   EMBL; BC102456; AAI02457.1; -; mRNA.
DR   PIR; A42576; A42576.
DR   PIR; B42576; B42576.
DR   RefSeq; NP_001029494.1; NM_001034322.2.
DR   AlphaFoldDB; Q9TRY0; -.
DR   SMR; Q9TRY0; -.
DR   IntAct; Q9TRY0; 1.
DR   STRING; 9913.ENSBTAP00000009998; -.
DR   PaxDb; 9913-ENSBTAP00000009998; -.
DR   PeptideAtlas; Q9TRY0; -.
DR   GeneID; 508535; -.
DR   KEGG; bta:508535; -.
DR   CTD; 2288; -.
DR   eggNOG; KOG0543; Eukaryota.
DR   InParanoid; Q9TRY0; -.
DR   OrthoDB; 25281at2759; -.
DR   Proteomes; UP000009136; Unplaced.
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:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR   GO; GO:0061077; P:chaperone-mediated protein folding; ISS:UniProtKB.
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   Gene3D; 3.10.50.40; -; 2.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
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; PTHR46512; PEPTIDYLPROLYL ISOMERASE; 1.
DR   PANTHER; PTHR46512:SF9; TETRATRICOPEPTIDE REPEAT DOMAIN 9; 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; Chaperone; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW   Isomerase; Methylation; Microtubule; Mitochondrion; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Rotamase; TPR repeat.
FT   CHAIN           1..459
FT                   /note="Peptidyl-prolyl cis-trans isomerase FKBP4"
FT                   /id="PRO_0000391467"
FT   INIT_MET        1
FT                   /note="Removed; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q02790"
FT   CHAIN           2..459
FT                   /note="Peptidyl-prolyl cis-trans isomerase FKBP4, N-
FT                   terminally processed"
FT                   /id="PRO_0000075317"
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          354..386
FT                   /note="TPR 3"
FT   REGION          1..22
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..459
FT                   /note="Disordered"
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"
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   CONFLICT        428
FT                   /note="T -> L (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   459 AA;  51529 MW;  2A0A25B737BC9A7B CRC64;
     MTAEETKAAE SGAQSAPLRL EGVDISPKQD EGVLKVIKRE GTGTETPMIG DRVFVHYTGW
     LLDGTKFDSS LDRKDRFSFD LGKGEVIKAW DIAVATMKVG EVCHITCKPE YAYGLAGSPP
     KIPPNATLVF EVELFEFKGE DLTEEEDGGI IRRIRTRGEG YAKPNEGALV EVALEGYFKD
     QVFDRRELRF EVGEGESMDL PCGLEKAIQR MEKGEHSIVY LKPRYAFGSA GKEKFQIPPN
     AELKYEIHLK SFEKAKESWE MSSEEKLEQS TIVKERGTVY FKEGKYKQAV LQYKKIVSWL
     EYESSFSDED AEKAQALRLA SHLNLAMCHL KLQAFSAAIE NCNKALELDS NNEKGLFRRG
     EAHLAVNDFD LARADFQKVL QLYPSNKAAK AQLVVCQQRI RKQLEKEKKL YANMFERLAE
     EETKAKATVA AGDQPADAEM RDEPKNDVAG GQPQVEAEA
//