ID TYSY_HHV8P Reviewed; 337 AA. AC P90463; D0UZM0; Q2HRC4; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 24-JAN-2024, entry version 111. DE RecName: Full=Thymidylate synthase; DE Short=TS; DE Short=TSase; DE EC=2.1.1.45; GN Name=70; OS Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's OS sarcoma-associated herpesvirus). OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes; OC Herpesvirales; Orthoherpesviridae; Gammaherpesvirinae; Rhadinovirus; OC Rhadinovirus humangamma8; Human herpesvirus 8. OX NCBI_TaxID=868565; OH NCBI_TaxID=9606; Homo sapiens (Human). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8962146; DOI=10.1073/pnas.93.25.14862; RA Russo J.J., Bohenzky R.A., Chien M.-C., Chen J., Yan M., Maddalena D., RA Parry J.P., Peruzzi D., Edelman I.S., Chang Y., Moore P.S.; RT "Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8)."; RL Proc. Natl. Acad. Sci. U.S.A. 93:14862-14867(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9151804; DOI=10.1128/jvi.71.6.4187-4192.1997; RA Neipel F., Albrecht J.-C., Fleckenstein B.; RT "Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus RT human herpesvirus 8: determinants of its pathogenicity?"; RL J. Virol. 71:4187-4192(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16760382; DOI=10.1099/vir.0.81919-0; RA Rezaee S.A.R., Cunningham C., Davison A.J., Blackbourn D.J.; RT "Kaposi's sarcoma-associated herpesvirus immune modulation: an overview."; RL J. Gen. Virol. 87:1781-1804(2006). 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; CC -!- PATHWAY: Pyrimidine metabolism; dTTP biosynthesis. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the thymidylate synthase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U75698; AAC57092.1; -; Genomic_DNA. DR EMBL; U83348; AAC56948.1; -; Genomic_DNA. DR EMBL; U93872; AAB62673.1; -; Genomic_DNA. DR EMBL; U71365; AAC34940.1; -; Genomic_DNA. DR EMBL; AF148805; ABD28859.1; -; Genomic_DNA. DR RefSeq; YP_001129361.1; NC_009333.1. DR PDB; 5H38; X-ray; 1.70 A; A/B=51-334. DR PDB; 5H39; X-ray; 2.00 A; A/B=51-335. DR PDB; 5H3A; X-ray; 2.40 A; A/B=51-333. DR PDBsum; 5H38; -. DR PDBsum; 5H39; -. DR PDBsum; 5H3A; -. DR SMR; P90463; -. DR BioGRID; 1776984; 10. DR DNASU; 4961481; -. DR GeneID; 4961481; -. DR KEGG; vg:4961481; -. DR UniPathway; UPA00575; -. DR Proteomes; UP000000942; Segment. DR GO; GO:0004799; F:thymidylate synthase activity; IEA:UniProtKB-EC. DR GO; GO:0006231; P:dTMP biosynthetic process; IEA:InterPro. DR GO; GO:0006235; P:dTTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR CDD; cd00351; TS_Pyrimidine_HMase; 1. DR Gene3D; 3.30.572.10; Thymidylate synthase/dCMP hydroxymethylase domain; 1. DR HAMAP; MF_00008; Thymidy_synth_bact; 1. 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; PF00303; Thymidylat_synt; 1. DR PRINTS; PR00108; THYMDSNTHASE. DR SUPFAM; SSF55831; Thymidylate synthase/dCMP hydroxymethylase; 1. DR PROSITE; PS00091; THYMIDYLATE_SYNTHASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Methyltransferase; Nucleotide biosynthesis; KW Reference proteome; Transferase. FT CHAIN 1..337 FT /note="Thymidylate synthase" FT /id="PRO_0000141065" FT ACT_SITE 219 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 74 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:P0A884" FT BINDING 199..200 FT /ligand="dUMP" FT /ligand_id="ChEBI:CHEBI:246422" FT /ligand_note="ligand shared between dimeric partners" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 239..242 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:P0A884" FT BINDING 242 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT BINDING 250 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:P0A884" FT BINDING 280..282 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:P0A884" FT BINDING 336 FT /ligand="(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate" FT /ligand_id="ChEBI:CHEBI:15636" FT /evidence="ECO:0000250|UniProtKB:P0A884" FT HELIX 54..67 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 78..90 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:5H3A" FT HELIX 105..116 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 122..126 FT /evidence="ECO:0007829|PDB:5H38" FT TURN 127..129 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 134..137 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 139..145 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 159..165 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 173..175 FT /evidence="ECO:0007829|PDB:5H3A" FT HELIX 184..194 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 208..213 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 214..216 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 219..228 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 231..242 FT /evidence="ECO:0007829|PDB:5H38" FT TURN 243..246 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 247..265 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 268..282 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 283..285 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 286..292 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 302..305 FT /evidence="ECO:0007829|PDB:5H38" FT HELIX 312..314 FT /evidence="ECO:0007829|PDB:5H39" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:5H38" FT STRAND 320..323 FT /evidence="ECO:0007829|PDB:5H38" SQ SEQUENCE 337 AA; 38555 MW; D0EB0CE60A3384EC CRC64; MFPFVPLSLY VAKKLFRARG FRFCQKPGVL ALAPEVDPCS IQHEVTGAET PHEELQYLRQ LREILCRGSD RLDRTGIGTL SLFGMQARYS LRDHFPLLTT KRVFWRGVVQ ELLWFLKGST DSRELSRTGV KIWDKNGSRE FLAGRGLAHR REGDLGPVYG FQWRHFGAAY VDADADYTGQ GFDQLSYIVD LIKNNPHDRR IIMCAWNPAD LSLMALPPCH LLCQFYVADG ELSCQLYQRS GDMGLGVPFN IASYSLLTYM LAHVTGLRPG EFIHTLGDAH IYKTHIEPLR LQLTRTPRPF PRLEILRSVS SMEEFTPDDF RLVDYCPHPT IRMEMAV //