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   02-SEP-2026, entry version 90.
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   AlphaFoldDB; Q4DA80; -.
DR   SMR; Q4DA80; -.
DR   DIP; DIP-61100N; -.
DR   STRING; 353153.Q4DA80; -.
DR   GlyCosmos; Q4DA80; 3 sites, No reported glycans.
DR   PaxDb; 353153-Q4DA80; -.
DR   EnsemblProtists; EAN89436; EAN89436; Tc00.1047053506795.80.
DR   GeneID; 3542225; -.
DR   KEGG; tcr:506795.80; -.
DR   eggNOG; ENOG502QRPF; Eukaryota.
DR   InParanoid; Q4DA80; -.
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; EXP:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; EXP:UniProtKB.
DR   GO; GO:0016020; C:membrane; EXP:UniProtKB.
DR   GO; GO:0047580; F:4-hydroxyproline epimerase activity; IEA:TreeGrafter.
DR   GO; GO:0018112; F:proline racemase activity; EXP:UniProtKB.
DR   FunFam; 3.10.310.10:FF:000005; Proline racemase; 1.
DR   Gene3D; 3.10.310.10; Diaminopimelate Epimerase, Chain A, domain 1; 2.
DR   InterPro; IPR008794; Pro_racemase_fam.
DR   PANTHER; PTHR33442:SF5; BIFUNCTIONAL TRANS-3-HYDROXY-L-PROLINE DEHYDRATASE_2-EPIMERASE; 1.
DR   PANTHER; PTHR33442; TRANS-3-HYDROXY-L-PROLINE DEHYDRATASE; 1.
DR   Pfam; PF05544; Pro_racemase; 1.
DR   SFLD; SFLDS00028; Proline_Racemase; 1.
DR   SUPFAM; SSF54506; Diaminopimelate epimerase-like; 1.
DR   PDBsum; 1W61; -.
DR   PDBsum; 1W62; -.
DR   PDBsum; 6HJE; -.
DR   PDBsum; 6HJF; -.
DR   PDBsum; 6HJG; -.
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   HELIX           178..180
FT                   /evidence="ECO:0007829|PDB:6HJE"
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
//