KITH_EBVB9
ID KITH_EBVB9 Reviewed; 607 AA.
AC P03177; Q777B9;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 97.
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 B95-8) (HHV-4) (Human herpesvirus 4).
OC Viruses; Duplodnaviria; Heunggongvirae; Peploviricota; Herviviricetes;
OC Herpesvirales; Herpesviridae; Gammaherpesvirinae; Lymphocryptovirus.
OX NCBI_TaxID=10377;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6092825;
RA Bankier A.T., Deininger P.L., Farrell P.J., Barrell B.G.;
RT "Sequence analysis of the 17,166 base-pair EcoRI fragment C of B95-8
RT Epstein-Barr virus.";
RL Mol. Biol. Med. 1:21-45(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=6087149; DOI=10.1038/310207a0;
RA Baer R., Bankier A.T., Biggin M.D., Deininger P.L., Farrell P.J.,
RA Gibson T.J., Hatfull G., Hudson G.S., Satchwell S.C., Seguin C.,
RA Tuffnell P.S., Barrell B.G.;
RT "DNA sequence and expression of the B95-8 Epstein-Barr virus genome.";
RL Nature 310:207-211(1984).
RN [3]
RP IDENTIFICATION OF PROTEIN.
RX PubMed=3019675; DOI=10.1002/j.1460-2075.1986.tb04450.x;
RA Littler E., Zeuthen J., McBride A.A., Soerensen E.T., Powell K.L.,
RA Walsh-Arrand J.E., Arrand J.R.;
RT "Identification of an Epstein-Barr virus-coded thymidine kinase.";
RL EMBO J. 5:1959-1966(1986).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=15534216; DOI=10.1073/pnas.0407320101;
RA Johannsen E., Luftig M., Chase M.R., Weicksel S., Cahir-McFarland E.,
RA Illanes D., Sarracino D., Kieff E.;
RT "Proteins of purified Epstein-Barr virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16286-16291(2004).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=17428875; DOI=10.1128/jvi.00147-07;
RA Gill M.B., Kutok J.L., Fingeroth J.D.;
RT "Epstein-Barr virus thymidine kinase is a centrosomal resident precisely
RT localized to the periphery of centrioles.";
RL J. Virol. 81:6523-6535(2007).
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 -!- SUBCELLULAR LOCATION: Virion tegument. Host nucleus. Note=Localizes to
CC the centrosome and more precisely to the periphery of the centriole,
CC tightly encircling the tubulin-rich centrioles.
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.
CC -!- SIMILARITY: Belongs to the herpesviridae thymidine kinase family.
CC {ECO:0000255|HAMAP-Rule:MF_04029}.
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; V01555; CAA24799.1; -; Genomic_DNA.
DR EMBL; AJ507799; CAD53451.1; -; Genomic_DNA.
DR PIR; A00615; KIBETE.
DR RefSeq; YP_401701.1; NC_007605.1.
DR SMR; P03177; -.
DR IntAct; P03177; 43.
DR MINT; P03177; -.
DR PRIDE; P03177; -.
DR DNASU; 3783741; -.
DR GeneID; 3783741; -.
DR KEGG; vg:3783741; -.
DR SABIO-RK; P03177; -.
DR Proteomes; UP000153037; 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 3: Inferred from homology;
KW ATP-binding; DNA synthesis; Early protein; Host nucleus; Kinase;
KW Nucleotide-binding; Reference proteome; Transferase; Virion;
KW Virion tegument.
FT CHAIN 1..607
FT /note="Thymidine kinase"
FT /id="PRO_0000175059"
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; 67193 MW; 97A4CCDB598A09F1 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 QRKESMRVPI VTHLTNHVPV IKPACSLFLE GAPGVGKTTM
LNHLKAVFGD LTIVVPEPMR YWTHVYENAI KAMHKNVTRA RHGREDTSAE VLACQMKFTT
PFRVLASRKR SLLVTESGAR SVAPLDCWIL HDRHLLSASV VFPLMLLRSQ LLSYSDFIQV
LATFTADPGD TIVWMKLNVE ENMRRLKKRG RKHESGLDAG YLKSVNDAYH AVYCAWLLTQ
YFAPEDIVKV CAGLTTITTV CHQSHTPIIR SGVAEKLYKN SIFSVLKEVI QPFRADAVLL
EVCLAFTRTL AYLQFVLVDL SEFQDDLPGC WTEIYMQALK NPAIRSQFFD WAGLSKVISD
FERGNRD
