P04183 (KITH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thymidine kinase, cytosolic
EC=2.7.1.21

Gene names

Name:

TK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	234 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + thymidine = ADP + thymidine 5'-phosphate.
Subunit structure	Homotetramer. Ref.14 Ref.16
Subcellular location	Cytoplasm.
Post-translational modification	Phosphorylated on Ser-13 in mitosis. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
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 process	DNA synthesis
Cellular component	Cytoplasm
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA replication Inferred from electronic annotation. Source: UniProtKB-KW protein homotetramerization Inferred from physical interaction Ref.16. Source: UniProtKB pyrimidine base metabolic process Traceable author statement. Source: Reactome pyrimidine nucleoside salvage Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW thymidine kinase activity Traceable author statement. Source: ProtInc zinc ion binding Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 234

234

Thymidine kinase, cytosolic

PRO_0000174948

Regions

Nucleotide binding

26 – 33

8

ATP

Nucleotide binding

58 – 60

3

ATP

Nucleotide binding

97 – 100

4

ATP

Region

172 – 176

5

Substrate binding

Sites

Active site

98

1

Proton acceptor Potential

Metal binding

153

1

Zinc

Metal binding

156

1

Zinc

Metal binding

185

1

Zinc

Metal binding

188

1

Zinc

Binding site

128

1

Substrate; via amide nitrogen

Binding site

181

1

Substrate

Amino acid modifications

Modified residue

13

1

Phosphoserine Ref.7 Ref.11 Ref.12

Modified residue

15

1

Phosphoserine Ref.11

Modified residue

231

1

Phosphoserine Ref.8 Ref.9 Ref.10

Experimental info

Sequence conflict

106

1

V → M in AAA61187. Ref.1

Sequence conflict

106

1

V → M in AAA61191. Ref.2

Secondary structure

1

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234

Helix Strand Turn

Details...

Beta strand

20 – 26

7

Helix

32 – 45

14

Beta strand

50 – 55

6

Helix

61 – 63

3

Helix

67 – 72

6

Beta strand

73 – 80

8

Helix

81 – 84

4

Helix

85 – 89

5

Beta strand

92 – 98

7

Helix

99 – 101

3

Helix

105 – 114

10

Beta strand

118 – 126

9

Beta strand

130 – 132

3

Helix

136 – 142

7

Beta strand

144 – 148

5

Turn

154 – 156

3

Beta strand

158 – 160

3

Beta strand

162 – 167

6

Turn

178 – 180

3

Beta strand

181 – 184

4

Helix

186 – 189

4

Sequences

	Sequence		Length	Mass (Da)
	P04183 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: 76901415C631EF21	FASTA	234	25,469
	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

References

	« Hide 'large scale' referencesShow '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: 6549046] [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: 3301530] [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. , 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: 14702039] [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: 15489334] [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: 3785218] [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: 9575153] [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: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-231, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13 AND SER-15, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, MASS SPECTROMETRY.
[13]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"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: 15611477] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-193 IN COMPLEX WITH ZINC IONS AND TTP, SUBUNIT.
[15]	"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: 15733844] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 15-194 IN COMPLEX WITH ZINC IONS AND TTP.
[16]	"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: 17407781] [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.

IPI

IPI00299214.

PIR

KIHUT. A27318.

RefSeq

NP_003249.3. NM_003258.4.

UniGene

Hs.515122.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1W4R	X-ray	1.83	A/B/C/D/E/F/G/H	15-194	[»]
1XBT	X-ray	2.40	A/B/C/D/E/F/G/H	1-193	[»]
2ORV	X-ray	2.30	A/B	1-234	[»]
2WVJ	X-ray	2.20	A/B/C/D/E/F/G/H	1-193	[»]

ProteinModelPortal

P04183.

SMR

P04183. Positions 18-191.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04183. 19 interactions.

MINT

MINT-200463.

STRING

P04183.

PTM databases

PhosphoSite

P04183.

Polymorphism databases

DMDM

23503074.

Proteomic databases

PeptideAtlas

P04183.

PRIDE

P04183.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301634; ENSP00000301634; ENSG00000167900.
ENST00000405273; ENSP00000384981; ENSG00000167900.

GeneID

7083.

KEGG

hsa:7083.

UCSC

uc002juw.2. human.

Organism-specific databases

CTD

7083.

GeneCards

GC17M076170.

H-InvDB

HIX0018803.

HGNC

HGNC:11830. TK1.

HPA

CAB004683.

MIM

188300. gene.

neXtProt

NX_P04183.

PharmGKB

PA352.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG14622.

GeneTree

ENSGT00390000011309.

HOGENOM

HBG522108.

HOVERGEN

HBG006215.

InParanoid

P04183.

OMA

STHDRNT.

OrthoDB

EOG4VHK7C.

PhylomeDB

P04183.

Enzyme and pathway databases

BRENDA

2.7.1.21. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P04183.

Bgee

P04183.

CleanEx

HS_TK1.

Genevestigator

P04183.

GermOnline

ENSG00000167900. Homo sapiens.

Family and domain databases

InterPro

IPR001267. Thymidine_kinase.
IPR020633. Thymidine_kinase_CS.
[Graphical view]

KO

K00857.

PANTHER

PTHR11441. TK_cell. 1 hit.

Pfam

PF00265. TK. 1 hit.
[Graphical view]

PIRSF

PIRSF035805. TK_cell. 1 hit.

PROSITE

PS00603. TK_CELLULAR_TYPE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

27705.

SOURCE

Search...

Entry information

Entry name

KITH_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.