Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P04183 (KITH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thymidine kinase, cytosolic

EC=2.7.1.21
Gene names
Name:TK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length234 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

ATP + thymidine = ADP + thymidine 5'-phosphate.

Subunit structure

Homotetramer. Ref.15 Ref.17

Subcellular location

Cytoplasm.

Post-translational modification

Phosphorylated on Ser-13 in mitosis. Ref.7

Miscellaneous

Two forms have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.

Sequence similarities

Belongs to the thymidine kinase family.

Ontologies

Keywords
   Biological processDNA synthesis
   Cellular componentCytoplasm
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from electronic annotation. Source: UniProtKB-KW

deoxyribonucleoside monophosphate biosynthetic process

Traceable author statement PubMed 3335503. Source: GOC

digestive tract development

Inferred from electronic annotation. Source: Ensembl

fetal process involved in parturition

Inferred from electronic annotation. Source: Ensembl

liver development

Inferred from electronic annotation. Source: Ensembl

nucleobase-containing compound metabolic process

Traceable author statement PubMed 3335503. Source: ProtInc

nucleobase-containing small molecule metabolic process

Traceable author statement. Source: Reactome

nucleotide biosynthetic process

Inferred from experiment. Source: GOC

protein homotetramerization

Inferred from physical interaction Ref.17. Source: UniProtKB

pyrimidine nucleobase metabolic process

Traceable author statement. Source: Reactome

pyrimidine nucleoside salvage

Traceable author statement. Source: Reactome

response to copper ion

Inferred from electronic annotation. Source: Ensembl

response to cortisol

Inferred from electronic annotation. Source: Ensembl

response to nutrient levels

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

skeletal muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

thymidine metabolic process

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 21900206PubMed 22385435. Source: IntAct

nucleoside kinase activity

Inferred from experiment. Source: Reactome

thymidine kinase activity

Traceable author statement PubMed 3335503. Source: ProtInc

zinc ion binding

Inferred from direct assay Ref.17. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-712550,EBI-712550

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.10
Chain2 – 234233Thymidine kinase, cytosolic
PRO_0000174948

Regions

Nucleotide binding26 – 338ATP
Nucleotide binding58 – 603ATP
Nucleotide binding97 – 1004ATP
Region172 – 1765Substrate binding

Sites

Active site981Proton acceptor Potential
Metal binding1531Zinc
Metal binding1561Zinc
Metal binding1851Zinc
Metal binding1881Zinc
Binding site1281Substrate; via amide nitrogen
Binding site1811Substrate

Amino acid modifications

Modified residue21N-acetylserine Ref.10 Ref.11 Ref.13 Ref.14
Modified residue131Phosphoserine Ref.7
Modified residue2311Phosphoserine Ref.8 Ref.11

Experimental info

Sequence conflict1061V → M in AAA61187. Ref.1
Sequence conflict1061V → M in AAA61191. Ref.2

Secondary structure

...................................... 234
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P04183 [UniParc].

Last modified September 19, 2002. Version 2.
Checksum: 76901415C631EF21

FASTA23425,469
        10         20         30         40         50         60 
MSCINLPTVL PGSPSKTRGQ IQVILGPMFS GKSTELMRRV RRFQIAQYKC LVIKYAKDTR 

        70         80         90        100        110        120 
YSSSFCTHDR NTMEALPACL LRDVAQEALG VAVIGIDEGQ FFPDIVEFCE AMANAGKTVI 

       130        140        150        160        170        180 
VAALDGTFQR KPFGAILNLV PLAESVVKLT AVCMECFREA AYTKRLGTEK EVEVIGGADK 

       190        200        210        220        230 
YHSVCRLCYF KKASGQPAGP DNKENCPVPG KPGEAVAARK LFAPQQILQC SPAN 

« Hide

References

« Hide 'large scale' references
[1]"Human thymidine kinase gene: molecular cloning and nucleotide sequence of a cDNA expressible in mammalian cells."
Bradshaw H.D. Jr., Deininger P.L.
Mol. Cell. Biol. 4:2316-2320(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Sequence, structure and promoter characterization of the human thymidine kinase gene."
Flemington E., Bradshaw H.D. Jr., Traina-Dorge V., Slagel V., Deininger P.L.
Gene 52:267-277(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph, Skin and Uterus.
[6]"Genetic analysis of the human thymidine kinase gene promoter."
Kreidberg J.A., Kelly T.J.
Mol. Cell. Biol. 6:2903-2909(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-22.
[7]"Serine 13 is the site of mitotic phosphorylation of human thymidine kinase."
Chang Z.F., Huang D.Y., Chi L.M.
J. Biol. Chem. 273:12095-12100(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-13.
[8]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Structures of thymidine kinase 1 of human and mycoplasmic origin."
Welin M., Kosinska U., Mikkelsen N.E., Carnrot C., Zhu C., Wang L., Eriksson S., Munch-Petersen B., Eklund H.
Proc. Natl. Acad. Sci. U.S.A. 101:17970-17975(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-193 IN COMPLEX WITH ZINC IONS AND TTP, SUBUNIT.
[16]"Structure of a type II thymidine kinase with bound dTTP."
Birringer M.S., Claus M.T., Folkers G., Kloer D.P., Schulz G.E., Scapozza L.
FEBS Lett. 579:1376-1382(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 15-194 IN COMPLEX WITH ZINC IONS AND TTP.
[17]"Binding of ATP to TK1-like enzymes is associated with a conformational change in the quaternary structure."
Segura-Pena D., Lutz S., Monnerjahn C., Konrad M., Lavie A.
J. Mol. Biol. 369:129-141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH ZINC IONS; SUBSTRATE AND ATP ANALOG, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K02581 mRNA. Translation: AAA61187.1.
M15205 Genomic DNA. Translation: AAA61191.1.
AK314950 mRNA. Translation: BAG37455.1.
BT006941 mRNA. Translation: AAP35587.1.
BC006484 mRNA. Translation: AAH06484.1.
BC007872 mRNA. Translation: AAH07872.1.
BC007986 mRNA. Translation: AAH07986.1.
M13643 Genomic DNA. Translation: AAA61189.1.
PIRKIHUT. A27318.
RefSeqNP_003249.3. NM_003258.4.
UniGeneHs.515122.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1W4RX-ray1.83A/B/C/D/E/F/G/H15-194[»]
1XBTX-ray2.40A/B/C/D/E/F/G/H1-193[»]
2ORVX-ray2.30A/B1-234[»]
2WVJX-ray2.20A/B/C/D/E/F/G/H1-193[»]
ProteinModelPortalP04183.
SMRP04183. Positions 18-191.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112938. 160 interactions.
IntActP04183. 157 interactions.
MINTMINT-200463.
STRING9606.ENSP00000301634.

Chemistry

BindingDBP04183.
ChEMBLCHEMBL2883.

PTM databases

PhosphoSiteP04183.

Polymorphism databases

DMDM23503074.

Proteomic databases

PaxDbP04183.
PeptideAtlasP04183.
PRIDEP04183.

Protocols and materials databases

DNASU7083.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301634; ENSP00000301634; ENSG00000167900.
ENST00000405273; ENSP00000384981; ENSG00000167900.
GeneID7083.
KEGGhsa:7083.
UCSCuc002juw.2. human.

Organism-specific databases

CTD7083.
GeneCardsGC17M076170.
HGNCHGNC:11830. TK1.
HPACAB004683.
MIM188300. gene.
neXtProtNX_P04183.
PharmGKBPA352.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1435.
HOGENOMHOG000076390.
HOVERGENHBG006215.
InParanoidP04183.
KOK00857.
OrthoDBEOG7MSMPX.
PhylomeDBP04183.
TreeFamTF314839.

Enzyme and pathway databases

BioCycMetaCyc:HS09657-MONOMER.
BRENDA2.7.1.21. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP04183.

Gene expression databases

ArrayExpressP04183.
BgeeP04183.
CleanExHS_TK1.
GenevestigatorP04183.

Family and domain databases

InterProIPR027417. P-loop_NTPase.
IPR001267. Thymidine_kinase.
IPR020633. Thymidine_kinase_CS.
[Graphical view]
PANTHERPTHR11441. PTHR11441. 1 hit.
PfamPF00265. TK. 1 hit.
[Graphical view]
PIRSFPIRSF035805. TK_cell. 1 hit.
SUPFAMSSF52540. SSF52540. 1 hit.
PROSITEPS00603. TK_CELLULAR_TYPE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTK1. human.
EvolutionaryTraceP04183.
GeneWikiThymidine_kinase_1.
GenomeRNAi7083.
NextBio27705.
PROP04183.
SOURCESearch...

Entry information

Entry nameKITH_HUMAN
AccessionPrimary (citable) accession number: P04183
Secondary accession number(s): B2RC58, Q969V0, Q9UMG9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 1987
Last sequence update: September 19, 2002
Last modified: April 16, 2014
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM