Bifunctional dihydrofolate reductase-thymidylate synthase

Preferred order of sections

Names and origin

Protein names

Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase PIRNR PIRNR000389

Gene names

Name:

DHFR-TS EMBL AAC47230.1

Organism

Cryptosporidium parvum EMBL AAC47230.1

Taxonomic identifier

5807 [NCBI]

Taxonomic lineage

Eukaryota › Alveolata › Apicomplexa › Coccidia › Eucoccidiorida › Eimeriorina › Cryptosporidiidae › Cryptosporidium

Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function

Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism By similarity. PIRNR PIRNR000389

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. PIRNR PIRNR000389

Sequence similarities

In the C-terminal section; belongs to the thymidylate synthase family. PIRNR PIRNR000389

In the N-terminal section; belongs to the dihydrofolate reductase family. PIRNR PIRNR000389

Ontologies

Keywords
Biological process	Nucleotide biosynthesis PIRNR PIRNR000389 One-carbon metabolism PIRNR PIRNR000389
Ligand	NADP PDB 1SEJ PDB 1QZF Nucleotide-binding PDB 1SEJ PDB 1QZF
Molecular function	Methyltransferase PIRNR PIRNR000389 Oxidoreductase PIRNR PIRNR000389 Transferase
Technical term	3D-structure PDB 1SEJ PDB 1QZF
Gene Ontology (GO)
Biological process	dTMP biosynthetic process Inferred from electronic annotation. Source: InterPro glycine biosynthetic process Inferred from electronic annotation. Source: InterPro
Molecular function	dihydrofolate reductase activity Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW thymidylate synthase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Regions

Nucleotide binding

56 – 58

3

NADP PDB 1SEJ PDB 1QZF

Nucleotide binding

76 – 77

2

NADP PDB 1SEJ PDB 1QZF

Nucleotide binding

116 – 117

2

NADP PDB 1SEJ PDB 1QZF

Sites

Binding site

11

1

NADP; via amide nitrogen and carbonyl oxygen PDB 1SEJ PDB 1QZF

Binding site

19

1

NADP; via carbonyl oxygen PDB 1SEJ PDB 1QZF

Binding site

24

1

NADP; via amide nitrogen and carbonyl oxygen PDB 1SEJ

Sequences

Sequence

Length

Mass (Da)

Tools

Q27552 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 4AFFEEA5C2A9B8E0
Show »

FASTA

521

60,192

        10         20         30         40         50         60 
MSEKNVSIVV AASVLSSGIG INGQLPWSIS EDLKFFSKIT NNKCDSNKKN ALIMGRKTWD 

        70         80         90        100        110        120 
SIGRRPLKNR IIVVISSSLP QDEADPNVVV FRNLEDSIEN LMNDDSIENI FVCGGESIYR 

       130        140        150        160        170        180 
DALKDNFVDR IYLTRVALED IEFDTYFPEI PETFLPVYMS QTFCTKNISY DFMIFEKQEK 

       190        200        210        220        230        240 
KTLQNCDPAR GQLKSIDDTV DLLGEIFGIR KMGNRHKFPK EEIYNTPSIR FGREHYEFQY 

       250        260        270        280        290        300 
LDLLSRVLEN GAYRENRTGI STYSIFGQMM RFDMRESFPL LTTKKVAIRS IFEELIWFIK 

       310        320        330        340        350        360 
GDTNGNHLIE KKVYIWSGNG SKEYLERIGL GHREENDLGP IYGFQWRHYN GEYKTMHDDY 

       370        380        390        400        410        420 
TGVGVDQLAK LIETLKNNPK DRRHILTAWN PSALSQMALP PCHVLSQYYV TNDNCLSCNL 

       430        440        450        460        470        480 
YQRSCDLGLG SPFNIASYAI LTMMLAQVCG YEPGELAIFI GDAHIYENHL TQLKEQLSRT 

       490        500        510        520 
PRPFPQLKFK RKVENIEDFK WEDIELIGYY PYPTIKMDMA V

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References

[1]	"Potential antifolate resistance determinants and genotypic variation in the bifunctional dihydrofolate reductase-thymidylate synthase gene from human and bovine isolates of Cryptosporidium parvum." Vasquez J.R., Gooze L., Kim K., Gut J., Petersen C., Nelson R.G. Mol. Biochem. Parasitol. 79:153-165(1996) [PubMed: 8855552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[2]	"Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase." O'Neil R.H., Lilien R.H., Donald B.R., Stroud R.M., Anderson A.C. J. Biol. Chem. 278:52980-52987(2003) [PubMed: 14555647] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH NADP.
[3]	"Two crystal structures of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis reveal protein-ligand interactions including a structural basis for observed antifolate resistance." Anderson A.C. Acta Crystallogr. F 61:258-262(2005) [PubMed: 16511011] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.87 ANGSTROMS) IN COMPLEX WITH NADP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U41366 Genomic DNA. Translation: AAC47230.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QZF	X-ray	2.80	A/B/C/D/E	1-521	[»]
1SEJ	X-ray	2.87	A/B/C/D/E	1-521	[»]

ProteinModelPortal

Q27552.

SMR

Q27552. Positions 3-521.

ModBase

Search...

Protein-protein interaction databases

STRING

Q27552.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

HAMAP

MF_00008. Thymidy_synth_bact.
[Tree]

InterPro

IPR024072. DHFR-like_dom.
IPR012262. DHFR-TS.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
IPR023451. Thymidate_synth/dCMP_Mease.
IPR000398. Thymidylate_synthase.
IPR020940. Thymidylate_synthase_AS.
[Graphical view]

Gene3D

G3DSA:3.40.430.10. G3DSA:3.40.430.10. 1 hit.
G3DSA:3.30.572.10. Thymidylat_synth_C. 2 hits.

PANTHER

PTHR11549:SF2. Thymidylat_synth_C. 1 hit.

Pfam

PF00186. DHFR_1. 1 hit.
PF00303. Thymidylat_synt. 1 hit.
[Graphical view]

PIRSF

PIRSF000389. DHFR-TS. 1 hit.

PRINTS

PR00108. THYMDSNTHASE.

SUPFAM

SSF53597. SSF53597. 1 hit.
SSF55831. Thymidylat_synth_C. 1 hit.

TIGRFAMs

TIGR03284. Thym_sym. 1 hit.

PROSITE

PS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
PS00091. THYMIDYLATE_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

Q27552_CRYPV

Accession

Primary (citable) accession number: Q27552

Entry history

Integrated into UniProtKB/TrEMBL:	November 1, 1996
Last sequence update:	November 1, 1996
Last modified:	December 14, 2011
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)