PRL1_LEIMA
ID PRL1_LEIMA Reviewed; 175 AA.
AC Q4QEZ7;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Protein tyrosine phosphatase PRL-1 {ECO:0000305};
DE EC=3.1.3.48 {ECO:0000269|PubMed:28507071};
DE Flags: Precursor;
GN Name=PRL-1 {ECO:0000303|PubMed:28507071};
GN ORFNames=LMJF_16_0230 {ECO:0000312|EMBL:CAJ03450.1};
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664 {ECO:0000312|Proteomes:UP000000542};
RN [1] {ECO:0000312|Proteomes:UP000000542}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/IL/81/Friedlin;
RX PubMed=16020728; DOI=10.1126/science.1112680;
RA Ivens A.C., Peacock C.S., Worthey E.A., Murphy L., Aggarwal G.,
RA Berriman M., Sisk E., Rajandream M.A., Adlem E., Aert R., Anupama A.,
RA Apostolou Z., Attipoe P., Bason N., Bauser C., Beck A., Beverley S.M.,
RA Bianchettin G., Borzym K., Bothe G., Bruschi C.V., Collins M., Cadag E.,
RA Ciarloni L., Clayton C., Coulson R.M.R., Cronin A., Cruz A.K., Davies R.M.,
RA De Gaudenzi J., Dobson D.E., Duesterhoeft A., Fazelina G., Fosker N.,
RA Frasch A.C., Fraser A., Fuchs M., Gabel C., Goble A., Goffeau A.,
RA Harris D., Hertz-Fowler C., Hilbert H., Horn D., Huang Y., Klages S.,
RA Knights A., Kube M., Larke N., Litvin L., Lord A., Louie T., Marra M.,
RA Masuy D., Matthews K., Michaeli S., Mottram J.C., Mueller-Auer S.,
RA Munden H., Nelson S., Norbertczak H., Oliver K., O'neil S., Pentony M.,
RA Pohl T.M., Price C., Purnelle B., Quail M.A., Rabbinowitsch E.,
RA Reinhardt R., Rieger M., Rinta J., Robben J., Robertson L., Ruiz J.C.,
RA Rutter S., Saunders D., Schaefer M., Schein J., Schwartz D.C., Seeger K.,
RA Seyler A., Sharp S., Shin H., Sivam D., Squares R., Squares S., Tosato V.,
RA Vogt C., Volckaert G., Wambutt R., Warren T., Wedler H., Woodward J.,
RA Zhou S., Zimmermann W., Smith D.F., Blackwell J.M., Stuart K.D.,
RA Barrell B.G., Myler P.J.;
RT "The genome of the kinetoplastid parasite, Leishmania major.";
RL Science 309:436-442(2005).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISULFIDE BOND,
RP ISOPRENYLATION AT CYS-172, AND MUTAGENESIS OF CYS-53; CYS-114 AND CYS-172.
RX PubMed=28507071; DOI=10.1128/iai.00084-17;
RA Leitherer S., Clos J., Liebler-Tenorio E.M., Schleicher U., Bogdan C.,
RA Soulat D.;
RT "Characterization of the protein tyrosine phosphatase LmPRL-1 secreted by
RT Leishmania major via the exosome pathway.";
RL Infect. Immun. 0:0-0(2017).
RN [3] {ECO:0007744|PDB:3S4O}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 4-165 IN COMPLEX WITH SUBSTRATE
RP ANALOG THIOSULFATE, AND DISULFIDE BONDS.
RA Merritt E.A., Arakaki T., Neely H., Phizicky E., Quartley E.,
RA Van Voorhis W.C., Buckner F.S., Fan E., Zucker F., Verlinde C.L.M.J.,
RA Hol W.G.J.;
RT "Protein tyrosine phosphatase from Leishmania major.";
RL Submitted (MAY-2011) to the PDB data bank.
CC -!- FUNCTION: Has protein tyrosine phosphatase activity and may act as a
CC virulence factor to support intracellular survival in host macrophages.
CC {ECO:0000269|PubMed:28507071}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC Evidence={ECO:0000269|PubMed:28507071};
CC -!- ACTIVITY REGULATION: Activated in a reduced environment which promotes
CC the reduction of the disulfide bond between the regulatory Cys-53 and
CC catalytic Cys-114 residues. {ECO:0000269|PubMed:28507071}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6. {ECO:0000269|PubMed:28507071};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28507071}.
CC Mitochondrion matrix, kinetoplast {ECO:0000269|PubMed:28507071}.
CC Secreted, extracellular exosome {ECO:0000269|PubMed:28507071}. Secreted
CC {ECO:0000269|PubMed:28507071}. Note=Enriched around the kinetoplast.
CC {ECO:0000269|PubMed:28507071}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the promastigote life cycle stage
CC during the logarithmic growth and the stationary phase (at protein
CC level). Expressed at lower levels at the amastigote life cycle stage
CC (at protein level). {ECO:0000269|PubMed:28507071}.
CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family.
CC {ECO:0000305}.
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DR EMBL; FR796412; CAJ03450.1; -; Genomic_DNA.
DR RefSeq; XP_001682101.1; XM_001682049.1.
DR PDB; 3S4O; X-ray; 2.30 A; A/B=4-165.
DR PDBsum; 3S4O; -.
DR AlphaFoldDB; Q4QEZ7; -.
DR SMR; Q4QEZ7; -.
DR STRING; 5664.LmjF.16.0230; -.
DR EnsemblProtists; CAJ03450; CAJ03450; LMJF_16_0230.
DR GeneID; 5650568; -.
DR KEGG; lma:LMJF_16_0230; -.
DR VEuPathDB; TriTrypDB:LmjF.16.0230; -.
DR VEuPathDB; TriTrypDB:LMJLV39_160007500; -.
DR VEuPathDB; TriTrypDB:LMJSD75_160007500; -.
DR eggNOG; KOG2836; Eukaryota.
DR HOGENOM; CLU_099263_2_0_1; -.
DR InParanoid; Q4QEZ7; -.
DR OMA; NGQKNSC; -.
DR BRENDA; 3.1.3.48; 2950.
DR Proteomes; UP000000542; Chromosome 16.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:GeneDB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR GO; GO:0020023; C:kinetoplast; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016791; F:phosphatase activity; IDA:UniProtKB.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IDA:GeneDB.
DR GO; GO:0008138; F:protein tyrosine/serine/threonine phosphatase activity; IEA:InterPro.
DR GO; GO:0016311; P:dephosphorylation; IDA:UniProtKB.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR Gene3D; 3.90.190.10; -; 1.
DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like.
DR InterPro; IPR000242; PTP_cat.
DR InterPro; IPR003595; Tyr_Pase_cat.
DR InterPro; IPR000387; Tyr_Pase_dom.
DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom.
DR Pfam; PF00102; Y_phosphatase; 1.
DR SMART; SM00404; PTPc_motif; 1.
DR SUPFAM; SSF52799; SSF52799; 1.
DR PROSITE; PS50056; TYR_PHOSPHATASE_2; 1.
DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disulfide bond; Hydrolase; Kinetoplast;
KW Lipoprotein; Methylation; Mitochondrion; Prenylation; Protein phosphatase;
KW Reference proteome; Secreted; Virulence.
FT CHAIN 1..172
FT /note="Protein tyrosine phosphatase PRL-1"
FT /id="PRO_0000441637"
FT PROPEP 173..175
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000441640"
FT DOMAIN 15..172
FT /note="Tyrosine-protein phosphatase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT ACT_SITE 76
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT ACT_SITE 114
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160"
FT BINDING 116..120
FT /ligand="substrate"
FT /evidence="ECO:0000305|Ref.3"
FT MOD_RES 172
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305"
FT LIPID 172
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000305|PubMed:28507071"
FT DISULFID 53..114
FT /evidence="ECO:0000269|PubMed:28507071, ECO:0000269|Ref.3,
FT ECO:0007744|PDB:3S4O"
FT MUTAGEN 53
FT /note="C->S: Increases catalytic activity."
FT /evidence="ECO:0000269|PubMed:28507071"
FT MUTAGEN 114
FT /note="C->S: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:28507071"
FT MUTAGEN 172
FT /note="C->S: Probable loss of farnesylation. Loss of
FT kinetoplast localization. Does not affect exosome
FT localization."
FT /evidence="ECO:0000269|PubMed:28507071"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:3S4O"
FT STRAND 18..26
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 34..42
FT /evidence="ECO:0007829|PDB:3S4O"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:3S4O"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:3S4O"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3S4O"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 82..101
FT /evidence="ECO:0007829|PDB:3S4O"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:3S4O"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 120..131
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 137..147
FT /evidence="ECO:0007829|PDB:3S4O"
FT HELIX 154..162
FT /evidence="ECO:0007829|PDB:3S4O"
SQ SEQUENCE 175 AA; 19376 MW; 61E5BE241E99CE4F CRC64;
MEVNATLIDC CDPQKPSRVL FHFLILDAPS PSNLPTYIKE LQHRGVRHLV RVCGPTYDAT
LVKSRGIDVH SWPFDDGAPP TRAVLDSWLK LLDTELARQQ EDPSVPPPTI GVHCVAGLGR
APILVALALV EYGNVSALDA IALIREKRKG AINQTQMHWI TKYKRRHQGA GCVIM
