ID   FKB35_PLAF7             Reviewed;         304 AA.
AC   Q8I4V8;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Peptidyl-prolyl cis-trans isomerase FKBP35 {ECO:0000305};
DE            EC=5.2.1.8 {ECO:0000255|PROSITE-ProRule:PRU00277, ECO:0000269|PubMed:15664653, ECO:0000269|PubMed:15850699, ECO:0000269|PubMed:23974147};
DE   AltName: Full=PfFKBP35 {ECO:0000303|PubMed:15664653};
GN   Name=FKBP35 {ECO:0000303|PubMed:15664653};
GN   ORFNames=PF3D7_1247400 {ECO:0000312|EMBL:CZT99629.1};
OS   Plasmodium falciparum (isolate 3D7).
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX   NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN   [1] {ECO:0000312|Proteomes:UP000001450}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX   PubMed=12368864; DOI=10.1038/nature01097;
RA   Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA   Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA   Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA   Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA   Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA   Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA   Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA   Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT   "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL   Nature 419:498-511(2002).
RN   [2] {ECO:0000305}
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND DOMAIN.
RX   PubMed=15664653; DOI=10.1016/j.molbiopara.2004.10.007;
RA   Monaghan P., Bell A.;
RT   "A Plasmodium falciparum FK506-binding protein (FKBP) with peptidyl-prolyl
RT   cis-trans isomerase and chaperone activities.";
RL   Mol. Biochem. Parasitol. 139:185-195(2005).
RN   [3] {ECO:0000305}
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH HSP90,
RP   SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DOMAIN.
RX   PubMed=15850699; DOI=10.1016/j.molbiopara.2005.02.007;
RA   Kumar R., Adams B., Musiyenko A., Shulyayeva O., Barik S.;
RT   "The FK506-binding protein of the malaria parasite, Plasmodium falciparum,
RT   is a FK506-sensitive chaperone with FK506-independent calcineurin-
RT   inhibitory activity.";
RL   Mol. Biochem. Parasitol. 141:163-173(2005).
RN   [4] {ECO:0000305}
RP   FUNCTION, AND SUBUNIT.
RX   PubMed=17289400; DOI=10.1016/j.pep.2006.12.019;
RA   Yoon H.R., Kang C.B., Chia J., Tang K., Yoon H.S.;
RT   "Expression, purification, and molecular characterization of Plasmodium
RT   falciparum FK506-binding protein 35 (PfFKBP35).";
RL   Protein Expr. Purif. 53:179-185(2007).
RN   [5] {ECO:0007744|PDB:2VN1}
RP   X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 1-127 IN COMPLEX WITH INHIBITOR
RP   FK506.
RX   PubMed=18465874; DOI=10.1021/bi800004u;
RA   Kotaka M., Ye H., Alag R., Hu G., Bozdech Z., Preiser P.R., Yoon H.S.,
RA   Lescar J.;
RT   "Crystal structure of the FK506 binding domain of Plasmodium falciparum
RT   FKBP35 in complex with FK506.";
RL   Biochemistry 47:5951-5961(2008).
RN   [6] {ECO:0007744|PDB:2OFN}
RP   STRUCTURE BY NMR OF 1-127.
RX   PubMed=17876830; DOI=10.1002/prot.21623;
RA   Kang C.B., Ye H., Yoon H.R., Yoon H.S.;
RT   "Solution structure of FK506 binding domain (FKBD) of Plasmodium falciparum
RT   FK506 binding protein 35 (PfFKBP35).";
RL   Proteins 70:300-302(2008).
RN   [7] {ECO:0007744|PDB:2FBN}
RP   X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 128-304, INTERACTION WITH HSP90,
RP   AND MUTAGENESIS OF LYS-148; ASN-152; ASN-199; LYS-229 AND LYS-233.
RX   PubMed=19691130; DOI=10.1002/pro.226;
RA   Alag R., Bharatham N., Dong A., Hills T., Harikishore A., Widjaja A.A.,
RA   Shochat S.G., Hui R., Yoon H.S.;
RT   "Crystallographic structure of the tetratricopeptide repeat domain of
RT   Plasmodium falciparum FKBP35 and its molecular interaction with Hsp90 C-
RT   terminal pentapeptide.";
RL   Protein Sci. 18:2115-2124(2009).
RN   [8] {ECO:0007744|PDB:4J4N}
RP   X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-127 WITH INHIBITOR D44,
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=23974147; DOI=10.1038/srep02501;
RA   Harikishore A., Niang M., Rajan S., Preiser P.R., Yoon H.S.;
RT   "Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria
RT   agent.";
RL   Sci. Rep. 3:2501-2501(2013).
RN   [9] {ECO:0007744|PDB:4QT2, ECO:0007744|PDB:4QT3}
RP   X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 5-127 IN COMPLEX WITH INHIBITOR
RP   RAPAMYCIN.
RX   PubMed=26057671; DOI=10.1107/s1399004715006239;
RA   Bianchin A., Allemand F., Bell A., Chubb A.J., Guichou J.F.;
RT   "Two crystal structures of the FK506-binding domain of Plasmodium
RT   falciparum FKBP35 in complex with rapamycin at high resolution.";
RL   Acta Crystallogr. D 71:1319-1327(2015).
CC   -!- FUNCTION: Has peptidylprolyl isomerase (PPIase) and co-chaperone
CC       activities (PubMed:15664653, PubMed:15850699). Assists protein folding
CC       by catalyzing the peptidyl conversion of cis and trans rotamers of the
CC       prolyl amide bond of protein substrates (PubMed:15664653,
CC       PubMed:15850699, PubMed:23974147). Inhibits calcineurin phosphatase
CC       activity in vitro (PubMed:15850699, PubMed:17289400, PubMed:23974147).
CC       Plays an essential role in merozoite egress from host erythrocytes
CC       (PubMed:15664653, PubMed:23974147). {ECO:0000269|PubMed:15664653,
CC       ECO:0000269|PubMed:15850699, ECO:0000269|PubMed:17289400,
CC       ECO:0000269|PubMed:23974147}.
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; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00277, ECO:0000269|PubMed:15664653,
CC         ECO:0000269|PubMed:15850699, ECO:0000269|PubMed:23974147};
CC   -!- ACTIVITY REGULATION: Inhibited by FK506 and its derivates, such as
CC       ascomycin, and rapamycin (PubMed:15664653, PubMed:15850699). FK506 and
CC       rapamycin inhibit peptidylprolyl isomerase activity but not chaperone
CC       activity (PubMed:15664653). Inhibited by N-(2-ethyl-phenyl)-2-(3H-
CC       imidazao [4, 5-b] pyridin-2-yl-sulfanyl)-acetamide (D44)
CC       (PubMed:23974147). Not inhibited by cyclosporin A (PubMed:15664653,
CC       PubMed:15850699). Inhibition of calcineurin phosphatase activity is
CC       enhanced by FK506 (PubMed:15850699). {ECO:0000269|PubMed:15664653,
CC       ECO:0000269|PubMed:15850699, ECO:0000269|PubMed:23974147}.
CC   -!- SUBUNIT: Homodimer (PubMed:17289400). Interacts (via TPR repeats) with
CC       HSP90 (probably via MEEVD motif) (PubMed:15850699, PubMed:19691130).
CC       {ECO:0000269|PubMed:15850699, ECO:0000269|PubMed:17289400,
CC       ECO:0000269|PubMed:19691130}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15850699}. Nucleus
CC       {ECO:0000269|PubMed:15850699}. Note=During the asexual blood stage,
CC       predominantly localizes to the cytoplasm of ring stage parasites and
CC       then translocates to the nucleus during the differentiation into
CC       trophozoites and schizonts. {ECO:0000269|PubMed:15850699}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during all parasite blood stages (at
CC       protein level). {ECO:0000269|PubMed:15850699}.
CC   -!- DOMAIN: The PPIase FKBP-type domain contributes to the chaperone
CC       activity (PubMed:15664653). Required for the inhibition of calcineurin
CC       phosphatase activity (PubMed:15850699). {ECO:0000269|PubMed:15664653,
CC       ECO:0000269|PubMed:15850699}.
CC   -!- DOMAIN: The TPR repeats are important for the chaperone activity
CC       (PubMed:15664653). In another study, these repeats appear to be
CC       dispensable for chaperone activity (PubMed:15850699). Dispensable for
CC       PPIase activity (PubMed:15850699). Dispensable for the inhibition of
CC       calcineurin phosphatase activity (PubMed:15850699).
CC       {ECO:0000269|PubMed:15664653, ECO:0000269|PubMed:15850699}.
CC   -!- SIMILARITY: Belongs to the FKBP-type PPIase family. {ECO:0000305}.
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DR   EMBL; LN999947; CZT99629.1; -; Genomic_DNA.
DR   RefSeq; XP_001350859.1; XM_001350823.1.
DR   PDB; 2FBN; X-ray; 1.63 A; A/B=128-304.
DR   PDB; 2OFN; NMR; -; A=1-127.
DR   PDB; 2VN1; X-ray; 2.35 A; A/B=1-127.
DR   PDB; 4J4N; X-ray; 2.75 A; A/B/C=1-127.
DR   PDB; 4QT2; X-ray; 1.44 A; A=7-127.
DR   PDB; 4QT3; X-ray; 1.40 A; A=5-127.
DR   PDBsum; 2FBN; -.
DR   PDBsum; 2OFN; -.
DR   PDBsum; 2VN1; -.
DR   PDBsum; 4J4N; -.
DR   PDBsum; 4QT2; -.
DR   PDBsum; 4QT3; -.
DR   AlphaFoldDB; Q8I4V8; -.
DR   SMR; Q8I4V8; -.
DR   STRING; 36329.Q8I4V8; -.
DR   PaxDb; 5833-PFL2275c; -.
DR   EnsemblProtists; CZT99629; CZT99629; PF3D7_1247400.
DR   GeneID; 811507; -.
DR   KEGG; pfa:PF3D7_1247400; -.
DR   VEuPathDB; PlasmoDB:PF3D7_1247400; -.
DR   HOGENOM; CLU_013615_13_0_1; -.
DR   InParanoid; Q8I4V8; -.
DR   OMA; DMVLPMM; -.
DR   OrthoDB; 25281at2759; -.
DR   PhylomeDB; Q8I4V8; -.
DR   Reactome; R-PFA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR   EvolutionaryTrace; Q8I4V8; -.
DR   Proteomes; UP000001450; Chromosome 12.
DR   GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR   GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR   GO; GO:0005528; F:FK506 binding; IDA:GeneDB.
DR   GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; IDA:UniProtKB.
DR   GO; GO:0046983; F:protein dimerization activity; TAS:GeneDB.
DR   GO; GO:0061077; P:chaperone-mediated protein folding; IBA:GO_Central.
DR   GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:GeneDB.
DR   GO; GO:0006457; P:protein folding; IDA:GeneDB.
DR   GO; GO:0000413; P:protein peptidyl-prolyl isomerization; IDA:UniProtKB.
DR   Gene3D; 3.10.50.40; -; 1.
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; IPR019734; TPR_repeat.
DR   PANTHER; PTHR46512; PEPTIDYLPROLYL ISOMERASE; 1.
DR   PANTHER; PTHR46512:SF9; TETRATRICOPEPTIDE REPEAT DOMAIN 9; 1.
DR   Pfam; PF00254; FKBP_C; 1.
DR   SMART; SM00028; TPR; 3.
DR   SUPFAM; SSF54534; FKBP-like; 1.
DR   SUPFAM; SSF48452; TPR-like; 1.
DR   PROSITE; PS50059; FKBP_PPIASE; 1.
DR   PROSITE; PS50005; TPR; 3.
DR   PROSITE; PS50293; TPR_REGION; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Chaperone; Cytoplasm; Isomerase; Nucleus; Reference proteome;
KW   Repeat; Rotamase; TPR repeat.
FT   CHAIN           1..304
FT                   /note="Peptidyl-prolyl cis-trans isomerase FKBP35"
FT                   /id="PRO_0000451568"
FT   DOMAIN          37..126
FT                   /note="PPIase FKBP-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00277"
FT   REPEAT          144..177
FT                   /note="TPR 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT   REPEAT          194..227
FT                   /note="TPR 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT   REPEAT          228..261
FT                   /note="TPR 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00339"
FT   MUTAGEN         148
FT                   /note="K->A: Severe loss of binding to a HSP90 C-terminus
FT                   peptide (MEEVD)."
FT                   /evidence="ECO:0000269|PubMed:19691130"
FT   MUTAGEN         152
FT                   /note="N->A: Severe loss of binding to a HSP90 C-terminus
FT                   peptide (MEEVD)."
FT                   /evidence="ECO:0000269|PubMed:19691130"
FT   MUTAGEN         199
FT                   /note="N->A: Severe loss of binding to a HSP90 C-terminus
FT                   peptide (MEEVD)."
FT                   /evidence="ECO:0000269|PubMed:19691130"
FT   MUTAGEN         229
FT                   /note="K->A: Severe loss of binding to a HSP90 C-terminus
FT                   peptide (MEEVD)."
FT                   /evidence="ECO:0000269|PubMed:19691130"
FT   MUTAGEN         233
FT                   /note="K->A: Severe loss of binding to a HSP90 C-terminus
FT                   peptide (MEEVD)."
FT                   /evidence="ECO:0000269|PubMed:19691130"
FT   STRAND          7..11
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          16..24
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   HELIX           30..32
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          39..48
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   TURN            49..52
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          53..56
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          60..63
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          65..68
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          71..74
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   HELIX           76..82
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          90..95
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   HELIX           97..99
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   TURN            100..104
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   TURN            107..109
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   STRAND          116..126
FT                   /evidence="ECO:0007829|PDB:4QT3"
FT   HELIX           132..134
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           137..156
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           160..172
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   TURN            173..176
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           183..206
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           210..223
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           228..241
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           244..257
FT                   /evidence="ECO:0007829|PDB:2FBN"
FT   HELIX           262..279
FT                   /evidence="ECO:0007829|PDB:2FBN"
SQ   SEQUENCE   304 AA;  34827 MW;  72DBA2427DDF50DE CRC64;
     MTTEQEFEKV ELTADGGVIK TILKKGDEGE ENIPKKGNEV TVHYVGKLES TGKVFDSSFD
     RNVPFKFHLE QGEVIKGWDI CVSSMRKNEK CLVRIESMYG YGDEGCGESI PGNSVLLFEI
     ELLSFREAKK SIYDYTDEEK VQSAFDIKEE GNEFFKKNEI NEAIVKYKEA LDFFIHTEEW
     DDQILLDKKK NIEISCNLNL ATCYNKNKDY PKAIDHASKV LKIDKNNVKA LYKLGVANMY
     FGFLEEAKEN LYKAASLNPN NLDIRNSYEL CVNKLKEARK KDKLTFGGMF DKGPLYEEKK
     NSAN
//