FKB35_PLAF7
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 25-MAY-2022, entry version 154.
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; 5833.PFL2275c; -.
DR PRIDE; Q8I4V8; -.
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 PhylomeDB; Q8I4V8; -.
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; 1.25.40.10; -; 1.
DR Gene3D; 3.10.50.40; -; 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 Pfam; PF00254; FKBP_C; 1.
DR Pfam; PF13181; TPR_8; 2.
DR SMART; SM00028; TPR; 3.
DR SUPFAM; SSF48452; SSF48452; 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
