PRCMA_TRYCC
ID PRCMA_TRYCC Reviewed; 423 AA.
AC Q4DA80; Q9NCP4;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Proline racemase A;
DE EC=5.1.1.4;
DE AltName: Full=TcPA45-A;
DE AltName: Full=TcPRACA;
DE AltName: Full=rTcPA45;
DE Flags: Precursor;
GN Name=PA45-A; ORFNames=Tc00.1047053506795.80;
OS Trypanosoma cruzi (strain CL Brener).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=353153;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, FUNCTION, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RC STRAIN=CL Brener;
RX PubMed=10932226; DOI=10.1038/78651;
RA Reina-San-Martin B., Degrave W., Rougeot C., Cosson A., Chamond N.,
RA Cordeiro-da-Silva A., Arala-Chaves M., Coutinho A., Minoprio P.;
RT "A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline
RT racemase.";
RL Nat. Med. 6:890-897(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES,
RP AND MUTAGENESIS OF CYS-330.
RC STRAIN=CL Brener;
RX PubMed=12735293; DOI=10.1074/jbc.m210830200;
RA Chamond N., Gregoire C., Coatnoan N., Rougeot C., Freitas-Junior L.H.,
RA da Silveira J.F., Degrave W.M., Minoprio P.;
RT "Biochemical characterization of proline racemases from the human protozoan
RT parasite Trypanosoma cruzi and definition of putative protein signatures.";
RL J. Biol. Chem. 278:15484-15494(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 2),
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=CL Brener;
RX PubMed=16164548; DOI=10.1111/j.1365-2958.2005.04808.x;
RA Chamond N., Goytia M., Coatnoan N., Barale J.-C., Cosson A., Degrave W.M.,
RA Minoprio P.;
RT "Trypanosoma cruzi proline racemases are involved in parasite
RT differentiation and infectivity.";
RL Mol. Microbiol. 58:46-60(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CL Brener;
RX PubMed=16020725; DOI=10.1126/science.1112631;
RA El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G.,
RA Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G.,
RA Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B.,
RA Anupama A., Arner E., Aslund L., Attipoe P., Bontempi E., Bringaud F.,
RA Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H.,
RA da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G.,
RA Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y.,
RA Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J.,
RA Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y.,
RA Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M.,
RA Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L.,
RA Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J.,
RA Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C.,
RA Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D.,
RA Andersson B.;
RT "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas
RT disease.";
RL Science 309:409-415(2005).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 32-393 IN COMPLEX WITH SUBSTRATE
RP ANALOG, FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-160 AND CYS-330.
RX PubMed=16446443; DOI=10.1073/pnas.0509010103;
RA Buschiazzo A., Goytia M., Schaeffer F., Degrave W., Shepard W.,
RA Gregoire C., Chamond N., Cosson A., Berneman A., Coatnoan N., Alzari P.M.,
RA Minoprio P.;
RT "Crystal structure, catalytic mechanism, and mitogenic properties of
RT Trypanosoma cruzi proline racemase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1705-1710(2006).
CC -!- FUNCTION: Catalyzes the interconversion of L- and D-proline. Secreted
CC isoform 1 contributes to parasite immune evasion by acting as a B-cell
CC mitogen. Probably involved in parasite differentiation and infectivity.
CC {ECO:0000269|PubMed:10932226, ECO:0000269|PubMed:16164548,
CC ECO:0000269|PubMed:16446443}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-proline = D-proline; Xref=Rhea:RHEA:10680,
CC ChEBI:CHEBI:57726, ChEBI:CHEBI:60039; EC=5.1.1.4;
CC Evidence={ECO:0000269|PubMed:10932226};
CC -!- ACTIVITY REGULATION: Inhibited by maleic acid, iodoacetamide,
CC iodoacetate and, most particularly, pyrrole-2-carboxylic acid.
CC {ECO:0000269|PubMed:10932226}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29 mM for L-proline {ECO:0000269|PubMed:12735293};
CC Vmax=0.053 mmol/sec/ug enzyme {ECO:0000269|PubMed:12735293};
CC pH dependence:
CC Optimum pH is 5.5-7.0. {ECO:0000269|PubMed:12735293};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12735293,
CC ECO:0000269|PubMed:16446443}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted
CC {ECO:0000269|PubMed:16164548}. Membrane {ECO:0000269|PubMed:16164548}.
CC Note=Membrane-bound and secreted upon differentiation of the parasite
CC into non-dividing infective forms, suggesting that isoform 1 appears
CC upon differentiation (PubMed:16164548).
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:10932226, ECO:0000269|PubMed:16164548}.
CC Note=Cytoplasmic in replicative non-infective forms (PubMed:16164548).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q4DA80-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q4DA80-2; Sequence=VSP_025849;
CC -!- SIMILARITY: Belongs to the proline racemase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAN89436.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF195522; AAF97423.1; -; Genomic_DNA.
DR EMBL; AAHK01000747; EAN89436.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_811287.1; XM_806194.1.
DR PDB; 1W61; X-ray; 2.10 A; A/B=32-423.
DR PDB; 1W62; X-ray; 2.50 A; A/B=32-423.
DR PDB; 6HJE; X-ray; 2.00 A; A/B=32-423.
DR PDB; 6HJF; X-ray; 1.70 A; A/B=32-423.
DR PDB; 6HJG; X-ray; 1.90 A; A/B=32-423.
DR PDBsum; 1W61; -.
DR PDBsum; 1W62; -.
DR PDBsum; 6HJE; -.
DR PDBsum; 6HJF; -.
DR PDBsum; 6HJG; -.
DR AlphaFoldDB; Q4DA80; -.
DR SMR; Q4DA80; -.
DR DIP; DIP-61100N; -.
DR STRING; 5693.XP_811287.1; -.
DR PaxDb; Q4DA80; -.
DR EnsemblProtists; EAN89436; EAN89436; Tc00.1047053506795.80.
DR GeneID; 3542225; -.
DR KEGG; tcr:506795.80; -.
DR eggNOG; ENOG502QRPF; Eukaryota.
DR OrthoDB; 894373at2759; -.
DR BRENDA; 5.1.1.4; 6524.
DR SABIO-RK; Q4DA80; -.
DR EvolutionaryTrace; Q4DA80; -.
DR Proteomes; UP000002296; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0018112; F:proline racemase activity; IEA:UniProtKB-EC.
DR InterPro; IPR008794; Pro_racemase_fam.
DR PANTHER; PTHR33442; PTHR33442; 1.
DR Pfam; PF05544; Pro_racemase; 1.
DR SFLD; SFLDS00028; Proline_Racemase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Developmental protein;
KW Glycoprotein; Isomerase; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..423
FT /note="Proline racemase A"
FT /id="PRO_5000057225"
FT ACT_SITE 160
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT ACT_SITE 330
FT /note="Proton donor"
FT /evidence="ECO:0000305"
FT BINDING 161..162
FT /ligand="substrate"
FT BINDING 326
FT /ligand="substrate"
FT BINDING 331..332
FT /ligand="substrate"
FT CARBOHYD 213
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_025849"
FT MUTAGEN 160
FT /note="C->S: Loss of enzyme activity, without abrogating
FT mitogenic properties."
FT /evidence="ECO:0000269|PubMed:16446443"
FT MUTAGEN 330
FT /note="C->S: Loss of enzyme activity, without abrogating
FT mitogenic properties."
FT /evidence="ECO:0000269|PubMed:12735293,
FT ECO:0000269|PubMed:16446443"
FT CONFLICT 79
FT /note="I -> M (in Ref. 1; AAF97423)"
FT /evidence="ECO:0000305"
FT HELIX 52..67
FT /evidence="ECO:0007829|PDB:6HJG"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 76..83
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 115..122
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 145..154
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 161..173
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 184..192
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 195..203
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 221..231
FT /evidence="ECO:0007829|PDB:6HJF"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 238..254
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 267..284
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 297..305
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 313..320
FT /evidence="ECO:0007829|PDB:6HJF"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:6HJF"
FT HELIX 331..343
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 352..357
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 362..373
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 385..397
FT /evidence="ECO:0007829|PDB:6HJF"
FT STRAND 399..407
FT /evidence="ECO:0007829|PDB:6HJF"
FT TURN 414..417
FT /evidence="ECO:0007829|PDB:6HJF"
SQ SEQUENCE 423 AA; 46950 MW; 2BF6DFF8F5AB662E CRC64;
MRKSVCPKQK FFFSAFPFFF FFCVFPLISR TGQEKLLFDQ KYKIIKGEKK EKKKNQRANR
REHQQKREIM RFKKSFTCID MHTEGEAARI VTSGLPHIPG SNMAEKKAYL QENMDYLRRG
IMLEPRGHDD MFGAFLFDPI EEGADLGMVF MDTGGYLNMC GHNSIAAVTA AVETGIVSVP
AKATNVPVVL DTPAGLVRGT AHLQSGTESE VSNASIINVP SFLYQQDVVV VLPKPYGEVR
VDIAFGGNFF AIVPAEQLGI DISVQNLSRL QEAGELLRTE INRSVKVQHP QLPHINTVDC
VEIYGPPTNP EANYKNVVIF GNRQADRSPC GTGTSAKMAT LYAKGQLRIG ETFVYESILG
SLFQGRVLGE ERIPGVKVPV TKDAEEGMLV VTAEITGKAF IMGFNTMLFD PTDPFKNGFT
LKQ
