ID A0A1U8MEM0_GOSHI Unreviewed; 529 AA.
AC A0A1U8MEM0;
DT 10-MAY-2017, integrated into UniProtKB/TrEMBL.
DT 10-MAY-2017, sequence version 1.
DT 27-MAR-2024, entry version 29.
DE RecName: Full=Bifunctional dihydrofolate reductase-thymidylate synthase {ECO:0000256|PIRNR:PIRNR000389};
GN Name=LOC107937003 {ECO:0000313|RefSeq:XP_016725302.1};
OS Gossypium hirsutum (Upland cotton) (Gossypium mexicanum).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Malvales; Malvaceae; Malvoideae; Gossypium.
OX NCBI_TaxID=3635 {ECO:0000313|Proteomes:UP000189702, ECO:0000313|RefSeq:XP_016725302.1};
RN [1] {ECO:0000313|Proteomes:UP000189702}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. TM-1 {ECO:0000313|Proteomes:UP000189702};
RX PubMed=25893780; DOI=10.1038/nbt.3208;
RA Li F., Fan G., Lu C., Xiao G., Zou C., Kohel R.J., Ma Z., Shang H., Ma X.,
RA Wu J., Liang X., Huang G., Percy R.G., Liu K., Yang W., Chen W., Du X.,
RA Shi C., Yuan Y., Ye W., Liu X., Zhang X., Liu W., Wei H., Wei S., Huang G.,
RA Zhang X., Zhu S., Zhang H., Sun F., Wang X., Liang J., Wang J., He Q.,
RA Huang L., Wang J., Cui J., Song G., Wang K., Xu X., Yu J.Z., Zhu Y., Yu S.;
RT "Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1)
RT provides insights into genome evolution.";
RL Nat. Biotechnol. 33:524-530(2015).
RN [2] {ECO:0000313|RefSeq:XP_016725302.1}
RP IDENTIFICATION.
RC TISSUE=Leaf {ECO:0000313|RefSeq:XP_016725302.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Bifunctional enzyme. Involved in de novo dTMP biosynthesis.
CC Key enzyme in folate metabolism. Can play two different roles depending
CC on the source of dihydrofolate: de novo synthesis of tetrahydrofolate
CC or recycling of the dihydrofolate released as one of the end products
CC of the TS catalyzed reaction. Catalyzes an essential reaction for de
CC novo glycine and purine synthesis, DNA precursor synthesis, and for the
CC conversion of dUMP to dTMP. {ECO:0000256|ARBA:ARBA00024992}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP = 7,8-
CC dihydrofolate + dTMP; Xref=Rhea:RHEA:12104, ChEBI:CHEBI:15636,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:63528, ChEBI:CHEBI:246422;
CC EC=2.1.1.45; Evidence={ECO:0000256|ARBA:ARBA00001707};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate +
CC H(+) + NADPH; Xref=Rhea:RHEA:15009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57451, ChEBI:CHEBI:57453, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.5.1.3;
CC Evidence={ECO:0000256|ARBA:ARBA00001315};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-
CC tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
CC {ECO:0000256|ARBA:ARBA00004903, ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thymidylate
CC synthase family. {ECO:0000256|ARBA:ARBA00006900,
CC ECO:0000256|PIRNR:PIRNR000389}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the dihydrofolate
CC reductase family. {ECO:0000256|ARBA:ARBA00010176,
CC ECO:0000256|PIRNR:PIRNR000389}.
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DR RefSeq; XP_016725302.1; XM_016869813.1.
DR AlphaFoldDB; A0A1U8MEM0; -.
DR STRING; 3635.A0A1U8MEM0; -.
DR PaxDb; 3635-A0A1U8MEM0; -.
DR GeneID; 107937003; -.
DR KEGG; ghi:107937003; -.
DR OrthoDB; 1118873at2759; -.
DR UniPathway; UPA00077; UER00158.
DR Proteomes; UP000189702; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0004146; F:dihydrofolate reductase activity; IBA:GO_Central.
DR GO; GO:0004799; F:thymidylate synthase activity; IBA:GO_Central.
DR GO; GO:0006231; P:dTMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00209; DHFR; 1.
DR CDD; cd00351; TS_Pyrimidine_HMase; 1.
DR Gene3D; 3.40.430.10; Dihydrofolate Reductase, subunit A; 1.
DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1.
DR HAMAP; MF_00008; Thymidy_synth_bact; 1.
DR InterPro; IPR024072; DHFR-like_dom_sf.
DR InterPro; IPR012262; DHFR-TS.
DR InterPro; IPR001796; DHFR_dom.
DR InterPro; IPR045097; Thymidate_synth/dCMP_Mease.
DR InterPro; IPR023451; Thymidate_synth/dCMP_Mease_dom.
DR InterPro; IPR036926; Thymidate_synth/dCMP_Mease_sf.
DR InterPro; IPR000398; Thymidylate_synthase.
DR InterPro; IPR020940; Thymidylate_synthase_AS.
DR NCBIfam; TIGR03284; thym_sym; 1.
DR PANTHER; PTHR11548:SF2; THYMIDYLATE SYNTHASE; 1.
DR PANTHER; PTHR11548; THYMIDYLATE SYNTHASE 1; 1.
DR Pfam; PF00186; DHFR_1; 1.
DR Pfam; PF00303; Thymidylat_synt; 1.
DR PIRSF; PIRSF000389; DHFR-TS; 1.
DR PRINTS; PR00108; THYMDSNTHASE.
DR SUPFAM; SSF53597; Dihydrofolate reductase-like; 1.
DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1.
DR PROSITE; PS51330; DHFR_2; 1.
DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1.
PE 3: Inferred from homology;
KW Methyltransferase {ECO:0000256|ARBA:ARBA00022603,
KW ECO:0000256|PIRNR:PIRNR000389};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW Nucleotide biosynthesis {ECO:0000256|ARBA:ARBA00022727,
KW ECO:0000256|PIRNR:PIRNR000389};
KW One-carbon metabolism {ECO:0000256|PIRNR:PIRNR000389};
KW Oxidoreductase {ECO:0000256|PIRNR:PIRNR000389};
KW Reference proteome {ECO:0000313|Proteomes:UP000189702};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|PIRNR:PIRNR000389}.
FT DOMAIN 25..202
FT /note="DHFR"
FT /evidence="ECO:0000259|PROSITE:PS51330"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 411
FT /evidence="ECO:0000256|PIRSR:PIRSR000389-1,
FT ECO:0000256|PROSITE-ProRule:PRU10016"
SQ SEQUENCE 529 AA; 59402 MW; 86D6E7A7CF17BB18 CRC64;
MSADTMMNVP NGNGNGNAQP DPQRTYQVVV AATKDMGVGK DGKLPWKLPS DLKFFKDITL
TTSDSGKKNA VIMGRKTWES IPLKNRPLPG CLNVVLTRSG SFDIATAENV VICGSMTSAL
ELLAASPYCL SIEKVFVIGG GQIFRESLNA AGCDAIHITE IETNIECDTF MPAIDTAVFQ
PWYSSFPMVE NDIRYCFTTY VRVRTSTVEH LCQNCDLVVD KKSDTGKFEV KKFSFLPKMI
FHKHEEYLYL NMIQDIISGG NLKDDRTGTG TLSKFGCQMR FNLRKTFPLL TTKKVFWRGV
VEELLWFISG STNAKVLQEK GIHIWDGNAS RDFLDSIGLT SREEGDLGPV YGFQWRHFGA
RYTDMHADYT GQGFDQLLDA IDKIKNNPND RRIILSAWNP SDLKLMALPP CHMFAQFYVA
NEELSCQMYQ RSADMGLGVP FNIASYALLT CMIAHVCDLI PGDFIHVLGD THVYSTHVRP
LQEQLQKLPK PFPILKINPE KKNIDSFVAS GFKRIGYDPH EKIEMKMAV
//
