Q5CGA3 (Q5CGA3_CRYHO) Unreviewed, UniProtKB/TrEMBL

Names and origin

Protein names

Recommended name:
Bifunctional dihydrofolate reductase-thymidylate synthase PIRNR PIRNR000389

Gene names

ORF Names:

Chro.40506 EMBL EAL35637.1

Organism

Cryptosporidium hominis

Taxonomic identifier

237895 [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 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3 Nucleotide-binding PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
Molecular function	Methyltransferase PIRNR PIRNR000389 Oxidoreductase PIRNR PIRNR000389 Transferase
Technical term	3D-structure PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3 Complete proteome Reference proteome
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 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
	Nucleotide binding	75 – 78	4	NADP PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
	Nucleotide binding	114 – 119	6	NADP PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
	Region	9 – 10	2	Methotrexate binding PDB 2OIP PDB 3HJ3
	Region	32 – 33	2	Methotrexate binding PDB 2OIP PDB 3HJ3
Sites
	Binding site	11	1	NADP; via amide nitrogen and carbonyl oxygen PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
	Binding site	19	1	NADP; via carbonyl oxygen PDB 2OIP PDB 3DL5 PDB 3HJ3
	Binding site	24	1	NADP; via carbonyl oxygen PDB 2OIP PDB 3DL6 PDB 3HJ3
	Binding site	37	1	Methotrexate PDB 2OIP
	Binding site	70	1	Methotrexate PDB 2OIP PDB 3HJ3
	Binding site	92	1	NADP; via carbonyl oxygen PDB 2OIP PDB 3DL5 PDB 3DL6 PDB 3HJ3
	Binding site	113	1	Methotrexate; via carbonyl oxygen PDB 2OIP PDB 3HJ3

Sequences

	Sequence		Length	Mass (Da)
	Q5CGA3 [UniParc]. Last modified April 12, 2005. Version 1. Checksum: 4AFFEEA5C2A9B8E0	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The genome of Cryptosporidium hominis." Xu P., Widmer G., Wang Y., Ozaki L.S., Alves J.M., Serrano M.G., Puiu D., Manque P., Akiyoshi D., Mackey A.J., Pearson W.R., Dear P.H., Bankier A.T., Peterson D.L., Abrahamsen M.S., Kapur V., Tzipori S., Buck G.A. Nature 431:1107-1112(2004) [PubMed: 15510150] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: TU502.
[2]	"Explaining an unusually fast parasitic enzyme: folate tail-binding residues dictate substrate positioning and catalysis in Cryptosporidium hominis thymidylate synthase." Martucci W.E., Vargo M.A., Anderson K.S. Biochemistry 47:8902-8911(2008) [PubMed: 18672899] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) IN COMPLEX WITH NADP.
[3]	"Exploring Novel Strategies for AIDS Protozoal Pathogens: a-Helix Mimetics Targeting A Key Allosteric Protein-Protein Interaction in C. hominis TS-DHFR." Martucci W.E., Rodriguez J.L., Vargo M.A., Marr M., Hamilton A.D., Anderson K.S. Submitted (MAY-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH METHOTREXATE AND NADP.
[4]	"Nonconserved residues Ala287 and Ser290 of the Cryptosporidium hominis thymidylate synthase domain facilitate its rapid rate of catalysis." Doan L.T., Martucci W.E., Vargo M.A., Atreya C.E., Anderson K.S. Biochemistry 46:8379-8391(2007) [PubMed: 17580969] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 3-521 IN COMPLEX WITH METHOTREXATE AND NADP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AAEL01000355 Genomic DNA. Translation: EAL35637.1.

RefSeq

XP_665866.1. XM_660774.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OIP	X-ray	2.80	A/B/C/D/E	3-521	[»]
3DL5	X-ray	2.74	A/B/C/D/E	1-521	[»]
3DL6	X-ray	3.25	A/B/C/D/E	1-521	[»]
3HJ3	X-ray	2.70	A/B/C/D	1-521	[»]

ProteinModelPortal

Q5CGA3.

SMR

Q5CGA3. Positions 3-521.

ModBase

Search...

Protein-protein interaction databases

STRING

Q5CGA3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

3413852.

KEGG

cho:Chro.40506.

Organism-specific databases

EuPathDB

EupathDB:Chro.40506.

Phylogenomic databases

ProtClustDB

PTZ00164.

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.

KO

K13998.

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

Q5CGA3_CRYHO

Accession

Primary (citable) accession number: Q5CGA3

Entry history

Integrated into UniProtKB/TrEMBL:	April 12, 2005
Last sequence update:	April 12, 2005
Last modified:	December 14, 2011
This is version 50 of the entry and version 1 of the sequence. [Complete history]

Entry status

Unreviewed (UniProtKB/TrEMBL)