KITH_EBVG
ID KITH_EBVG Reviewed; 607 AA.
AC Q3KSQ2;
DT 26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Thymidine kinase {ECO:0000255|HAMAP-Rule:MF_04029};
DE EC=2.7.1.21 {ECO:0000255|HAMAP-Rule:MF_04029};
GN Name=TK {ECO:0000255|HAMAP-Rule:MF_04029}; ORFNames=BXLF1;
OS Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=10376;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16306603; DOI=10.1128/jvi.79.24.15323-15330.2005;
RA Zeng M.-S., Li D.-J., Liu Q.-L., Song L.-B., Li M.-Z., Zhang R.-H.,
RA Yu X.-J., Wang H.-M., Ernberg I., Zeng Y.-X.;
RT "Genomic sequence analysis of Epstein-Barr virus strain GD1 from a
RT nasopharyngeal carcinoma patient.";
RL J. Virol. 79:15323-15330(2005).
CC -!- FUNCTION: Catalyzes the transfer of the gamma-phospho group of ATP to
CC thymidine to generate dTMP in the salvage pathway of pyrimidine
CC synthesis. The dTMP serves as a substrate for DNA polymerase during
CC viral DNA replication. Allows the virus to be reactivated and to grow
CC in non-proliferative cells lacking a high concentration of
CC phosphorylated nucleic acid precursors. {ECO:0000255|HAMAP-
CC Rule:MF_04029}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + thymidine = ADP + dTMP + H(+); Xref=Rhea:RHEA:19129,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17748, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:63528, ChEBI:CHEBI:456216; EC=2.7.1.21;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04029};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04029}.
CC -!- INTERACTION:
CC Q3KSQ2; P0C731: BGLF4; NbExp=2; IntAct=EBI-2621028, EBI-2621032;
CC -!- SUBCELLULAR LOCATION: Virion tegument. Host nucleus {ECO:0000250}.
CC Note=Localizes to the centrosome and more precisely to the periphery of
CC the centriole, tightly encircling the tubulin-rich centrioles.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Phosphorylates and thereby activates certain drugs like
CC acyclovir (ACV), valacyclovir, and famciclovir to a toxic form, that
CC leads to successful suppression of the infection, while the uninfected
CC cell does not have this ability because it lacks TK. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
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DR EMBL; AY961628; AAY41147.1; -; Genomic_DNA.
DR IntAct; Q3KSQ2; 8.
DR PRIDE; Q3KSQ2; -.
DR Proteomes; UP000007641; Genome.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0019033; C:viral tegument; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004797; F:thymidine kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0071897; P:DNA biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0006230; P:TMP biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_04029; HSV_KITH; 1.
DR InterPro; IPR001889; Herpes_TK.
DR InterPro; IPR013672; Herpes_TK_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF00693; Herpes_TK; 1.
DR Pfam; PF08465; Herpes_TK_C; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 1: Evidence at protein level;
KW ATP-binding; DNA synthesis; Early protein; Host nucleus; Kinase;
KW Nucleotide-binding; Transferase; Virion; Virion tegument.
FT CHAIN 1..607
FT /note="Thymidine kinase"
FT /id="PRO_0000375958"
FT REGION 1..160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 180..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..35
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..125
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 144..160
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..196
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 317
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 291..298
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 355
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 445
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
FT BINDING 451
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04029"
SQ SEQUENCE 607 AA; 67207 MW; 163836CEDA39C52C CRC64;
MAGFPGKEAG PPGGWRKCQE DESPENERHE NFYAEIDDFA PSVLTPTGSD SGAGEEDDDG
LYQVPTHWPP LMAPTGLSGE RVPCRTQAAV TSNTGNSPGS RHTSCPFTLP RGAQPPAPAH
QKPTAPTPKP RSRECGPSKT PDPFSWFRKT SCTEGGADST SRSFMYQKGF EEGLAGLGLD
DKSDCESEDE SNFRRPSSHS ALKQKNGGKG KPSGLFEHLA AHGREFSKLS KHAAQLKRLS
GSVMNVLNLD DAQDTRQAKA QRKESTRVPI VIHLTNHVPV IKPACSLFLE GAPGVGKTTM
LNHLKAVFGD LTIVVPEPMR YWTHVYENAI KAMHKNVTRA RHGREDTSAE VLACQMKFTT
PFRVLASRKR SLLVTESGAR SVAPLDCWIL HDRHLLSASV VFPLMLLRSQ LLSYSDFIQV
LATFTADPGD TIVWMKLNVE ENMRRLKKRG RKHESGLDAG YLKSVNDAYH AVYCAWLLTQ
YFAPEDIVKV CAGLTTITTV CHQSHTPIIR SGVAEKLYKN SIYSVLKEVI QPYRADAVLL
EVCLAFTRTL AYLQFVLVDL SEFQDDLPGC WTEIYMQALK NPAIRSQFFD WAGLSKVISD
FERGNRD
