Reviewed, UniProtKB/Swiss-Prot Q4DA80 (PRCMA_TRYCR)

Names and origin

Protein names

Recommended name:
    Proline racemase A
    EC=5.1.1.4
Alternative name(s):
    TcPRACA
    TcPA45-A
    rTcPA45

Gene names

Name:	PA45-A
ORF Names:	Tc00.1047053506795.80

Organism

Trypanosoma cruzi

Taxonomic identifier

5693 [NCBI]

Taxonomic lineage

Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma › Schizotrypanum

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the interconversion of L- and D-proline. Secreted isoform 1 contributes to parasite immune evasion by acting as a B-cell mitogen. Probably involved in parasite differentiation and infectivity. Ref.1 Ref.4 Ref.5
Catalytic activity	L-proline = D-proline. Ref.1
Enzyme regulation	Inhibited by maleic acid, iodoacetamide, iodoacetate and, most particularly, pyrrole-2-carboxylic acid. Ref.1
Subunit structure	Homodimer. Ref.5 Ref.3
Subcellular location	Isoform 1: Secreted. Membrane. Note: Membrane-bound and secreted upon differentiation of the parasite into non-dividing infective forms, suggesting that isoform 1 appears upon differentiation. Ref.1 Ref.4 Isoform 2: Cytoplasm. Note: Cytoplasmic in replicative non-infective forms. Ref.1 Ref.4
Sequence similarities	Belongs to the proline racemase family.
Biophysicochemical properties	Kinetic parameters: KM=29 mM for L-proline Vmax=0.053 mmol/sec/µg enzyme pH dependence: Optimum pH is 5.5-7.0.
Sequence caution	The sequence EAN89436.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Developmental protein Isomerase
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	proline racemase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q4DA80-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Membrane-bound and secreted upon differentiation of the parasite into non-dividing infective forms, suggesting that isoform 1 appears upon differentiation. Ref.1 Ref.4

Isoform 2 (identifier: Q4DA80-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.

Note: Cytoplasmic in replicative non-infective forms. Ref.1 Ref.4

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Potential

Chain

32 – 423

392

Proline racemase A

PRO_5000057225

Regions

Region

161 – 162

2

Substrate binding

Region

331 – 332

2

Substrate binding

Sites

Active site

160

1

Proton acceptor Probable

Active site

330

1

Proton donor Probable

Binding site

326

1

Substrate

Amino acid modifications

Glycosylation

213

1

N-linked (GlcNAc...) Potential

Glycosylation

266

1

N-linked (GlcNAc...) Potential

Glycosylation

282

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 69

69

Missing in isoform 2.

VSP_025849

Experimental info

Mutagenesis

160

1

C → S: Loss of enzyme activity, without abrogating mitogenic properties. Ref.5

Mutagenesis

330

1

C → S: Loss of enzyme activity, without abrogating mitogenic properties. Ref.5 Ref.3

Sequence conflict

79

1

I → M in AAF97423. Ref.1

Secondary structure

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423

Helix Strand Turn

Details...

Beta strand

74 – 83

10

Beta strand

86 – 93

8

Helix

103 – 113

11

Helix

115 – 122

8

Beta strand

132 – 137

6

Beta strand

145 – 154

10

Helix

161 – 173

13

Beta strand

184 – 192

9

Beta strand

195 – 203

9

Beta strand

211 – 217

7

Beta strand

221 – 231

11

Turn

234 – 236

3

Beta strand

238 – 254

17

Helix

255 – 258

4

Beta strand

262 – 264

3

Helix

267 – 284

18

Beta strand

297 – 305

9

Beta strand

313 – 320

8

Turn

321 – 323

3

Helix

331 – 343

13

Beta strand

353 – 357

5

Beta strand

362 – 374

13

Beta strand

385 – 397

13

Beta strand

399 – 409

11

Turn

414 – 417

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 2. Checksum: 2BF6DFF8F5AB662E	FASTA	423	46,950
	10 20 30 40 50 60 MRKSVCPKQK FFFSAFPFFF FFCVFPLISR TGQEKLLFDQ KYKIIKGEKK EKKKNQRANR 70 80 90 100 110 120 REHQQKREIM RFKKSFTCID MHTEGEAARI VTSGLPHIPG SNMAEKKAYL QENMDYLRRG 130 140 150 160 170 180 IMLEPRGHDD MFGAFLFDPI EEGADLGMVF MDTGGYLNMC GHNSIAAVTA AVETGIVSVP 190 200 210 220 230 240 AKATNVPVVL DTPAGLVRGT AHLQSGTESE VSNASIINVP SFLYQQDVVV VLPKPYGEVR 250 260 270 280 290 300 VDIAFGGNFF AIVPAEQLGI DISVQNLSRL QEAGELLRTE INRSVKVQHP QLPHINTVDC 310 320 330 340 350 360 VEIYGPPTNP EANYKNVVIF GNRQADRSPC GTGTSAKMAT LYAKGQLRIG ETFVYESILG 370 380 390 400 410 420 SLFQGRVLGE ERIPGVKVPV TKDAEEGMLV VTAEITGKAF IMGFNTMLFD PTDPFKNGFT LKQ
	Isoform 2. Checksum: 88801F775E8B9DAA	FASTA	354	38,432
	10 20 30 40 50 60 MRFKKSFTCI DMHTEGEAAR IVTSGLPHIP GSNMAEKKAY LQENMDYLRR GIMLEPRGHD 70 80 90 100 110 120 DMFGAFLFDP IEEGADLGMV FMDTGGYLNM CGHNSIAAVT AAVETGIVSV PAKATNVPVV 130 140 150 160 170 180 LDTPAGLVRG TAHLQSGTES EVSNASIINV PSFLYQQDVV VVLPKPYGEV RVDIAFGGNF 190 200 210 220 230 240 FAIVPAEQLG IDISVQNLSR LQEAGELLRT EINRSVKVQH PQLPHINTVD CVEIYGPPTN 250 260 270 280 290 300 PEANYKNVVI FGNRQADRSP CGTGTSAKMA TLYAKGQLRI GETFVYESIL GSLFQGRVLG 310 320 330 340 350 EERIPGVKVP VTKDAEEGML VVTAEITGKA FIMGFNTMLF DPTDPFKNGF TLKQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase." Reina-San-Martin B., Degrave W., Rougeot C., Cosson A., Chamond N., Cordeiro-da-Silva A., Arala-Chaves M., Coutinho A., Minoprio P. Nat. Med. 6:890-897(2000) [PubMed: 10932226] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION. Strain: CL Brener.
[2]	"Comparative genomics of trypanosomatid parasitic protozoa." El-Sayed N.M.A., Myler P.J., Blandin G., Berriman M., Crabtree J., Aggarwal G., Caler E., Renauld H., Worthey E.A., Hertz-Fowler C., Ghedin E., Peacock C., Bartholomeu D.C., Haas B.J., Tran A.-N., Wortman J.R., Alsmark U.C.M., Angiuoli S. , Anupama A., Badger J., Bringaud F., Cadag E., Carlton J.M., Cerqueira G.C., Creasy T., Delcher A.L., Djikeng A., Embley T.M., Hauser C., Ivens A.C., Kummerfeld S.K., Pereira-Leal J.B., Nilsson D., Peterson J., Salzberg S.L., Shallom J., Silva J.C., Sundaram J., Westenberger S., White O., Melville S.E., Donelson J.E., Andersson B., Stuart K.D., Hall N. Science 309:404-409(2005) [PubMed: 16020724] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CL Brener.
[3]	"Biochemical characterization of proline racemases from the human protozoan parasite Trypanosoma cruzi and definition of putative protein signatures." Chamond N., Gregoire C., Coatnoan N., Rougeot C., Freitas-Junior L.H., da Silveira J.F., Degrave W.M., Minoprio P. J. Biol. Chem. 278:15484-15494(2003) [PubMed: 12735293] [Abstract] Cited for: SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF CYS-330.
[4]	"Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity." Chamond N., Goytia M., Coatnoan N., Barale J.-C., Cosson A., Degrave W.M., Minoprio P. Mol. Microbiol. 58:46-60(2005) [PubMed: 16164548] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION.
[5]	"Crystal structure, catalytic mechanism, and mitogenic properties of Trypanosoma cruzi proline racemase." Buschiazzo A., Goytia M., Schaeffer F., Degrave W., Shepard W., Gregoire C., Chamond N., Cosson A., Berneman A., Coatnoan N., Alzari P.M., Minoprio P. Proc. Natl. Acad. Sci. U.S.A. 103:1705-1710(2006) [PubMed: 16446443] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 32-393 IN COMPLEX WITH SUBSTRATE ANALOG, FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-160 AND CYS-330.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF195522 Genomic DNA. Translation: AAF97423.1.
AAHK01000747 Genomic DNA. Translation: EAN89436.1. Sequence problems.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W61	X-ray	2.10	A/B	32-423	[»]
1W62	X-ray	2.50	A/B	32-423	[»]

SMR

Q4DA80. Positions 3-354.

ModBase

Search...

Enzyme and pathway databases

BRENDA

5.1.1.4. 884.

Family and domain databases

InterPro

IPR008794. Pro_racemase.
[Graphical view]

Pfam

PF05544. Pro_racemase. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PRCMA_TRYCR

Accession

Primary (citable) accession number: Q4DA80
Secondary accession number(s): Q9NCP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 29, 2007
Last sequence update:	May 29, 2007
Last modified:	June 16, 2009
This is version 26 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)