THY1_DICDI
ID THY1_DICDI Reviewed; 303 AA.
AC P15808; Q54VM0;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Flavin-dependent thymidylate synthase {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=FDTS {ECO:0000250|UniProtKB:Q9WYT0};
DE EC=2.1.1.148 {ECO:0000250|UniProtKB:Q9WYT0};
DE AltName: Full=FAD-dependent thymidylate synthase {ECO:0000250|UniProtKB:Q9WYT0};
DE AltName: Full=Thymidylate synthase thy1 {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=TS {ECO:0000250|UniProtKB:Q9WYT0};
DE Short=TSase {ECO:0000250|UniProtKB:Q9WYT0};
GN Name=thyA; Synonyms=thy1; ORFNames=DDB_G0280045;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2813371; DOI=10.1073/pnas.86.20.7966;
RA Dynes J.L., Firtel R.A.;
RT "Molecular complementation of a genetic marker in Dictyostelium using a
RT genomic DNA library.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:7966-7970(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Catalyzes the reductive methylation of 2'-deoxyuridine-5'-
CC monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP) while
CC utilizing 5,10-methylenetetrahydrofolate (mTHF) as the methyl donor,
CC and NADPH and FADH(2) as the reductant. {ECO:0000250|UniProtKB:Q9WYT0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP + H(+) +
CC NADPH = (6S)-5,6,7,8-tetrahydrofolate + dTMP + NADP(+);
CC Xref=Rhea:RHEA:29043, ChEBI:CHEBI:15378, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57453, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:63528, ChEBI:CHEBI:246422; EC=2.1.1.148;
CC Evidence={ECO:0000250|UniProtKB:Q9WYT0};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9WYT0};
CC Note=Binds 4 FAD per tetramer. Each FAD binding site is formed by three
CC monomers. {ECO:0000250|UniProtKB:Q9WYT0};
CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis.
CC {ECO:0000250|UniProtKB:Q9WYT0}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:Q9WYT0}.
CC -!- SIMILARITY: Belongs to the thymidylate synthase ThyX family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA33257.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M27713; AAA33257.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AAFI02000035; EAL67249.1; -; Genomic_DNA.
DR PIR; A33987; YXDOTC.
DR RefSeq; XP_641335.1; XM_636243.1.
DR AlphaFoldDB; P15808; -.
DR SMR; P15808; -.
DR STRING; 44689.DDB0214905; -.
DR PaxDb; P15808; -.
DR EnsemblProtists; EAL67249; EAL67249; DDB_G0280045.
DR GeneID; 8622469; -.
DR KEGG; ddi:DDB_G0280045; -.
DR dictyBase; DDB_G0280045; thyA.
DR eggNOG; ENOG502SRAF; Eukaryota.
DR HOGENOM; CLU_067790_0_0_1; -.
DR InParanoid; P15808; -.
DR OMA; PVACEAF; -.
DR PhylomeDB; P15808; -.
DR UniPathway; UPA00575; -.
DR PRO; PR:P15808; -.
DR Proteomes; UP000002195; Chromosome 3.
DR GO; GO:0045335; C:phagocytic vesicle; HDA:dictyBase.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0070402; F:NADPH binding; IBA:GO_Central.
DR GO; GO:0050797; F:thymidylate synthase (FAD) activity; IGI:dictyBase.
DR GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central.
DR GO; GO:0006231; P:dTMP biosynthetic process; IGI:dictyBase.
DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.30.1360.170; -; 1.
DR HAMAP; MF_01408; ThyX; 1.
DR InterPro; IPR003669; Thymidylate_synthase_ThyX.
DR InterPro; IPR036098; Thymidylate_synthase_ThyX_sf.
DR PANTHER; PTHR34934; PTHR34934; 1.
DR Pfam; PF02511; Thy1; 1.
DR SUPFAM; SSF69796; SSF69796; 1.
DR TIGRFAMs; TIGR02170; thyX; 1.
DR PROSITE; PS51331; THYX; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Methyltransferase; NADP; Nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..303
FT /note="Flavin-dependent thymidylate synthase"
FT /id="PRO_0000175599"
FT DOMAIN 41..258
FT /note="ThyX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT MOTIF 118..128
FT /note="ThyX motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00661"
FT ACT_SITE 224
FT /note="Involved in ionization of N3 of dUMP, leading to its
FT activation"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 95
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 115..118
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 118..120
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 126..130
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 197
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 213..215
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 219
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /ligand_note="ligand shared between neighboring subunits"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
FT BINDING 224
FT /ligand="dUMP"
FT /ligand_id="ChEBI:CHEBI:246422"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q9WYT0"
SQ SEQUENCE 303 AA; 35395 MW; BCBE6901217650F3 CRC64;
MGLDIQTEID KIVIEKVKPE VEYYDVMGGS HRWEVKVHDH GKVALVDTMP RLAPVGQTAD
FSICQAARVS YGAGTKKVTE DKGLIRYLYR HQHTSPFEMV EFKFHCVMPV FIARQWIRHR
TANVNEYSAR YSVLPDKFYH PSIEEVRKQS TSNRQGGEEA LEPKTAQEFL DYLDKVEENY
KTYNELLEKG LSRELGRIGL PVSIYTEWYW KIDLHNLFHF LRLRMDSHSQ KEIRDYANTI
FALIRPIVPV ACEAFIDYAF ESLKLTRLEI EAIRTGSPLN TTNKREIEEF EEKKKLLFPN
TQA
