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Protein

Thymidylate kinase

Gene

DTYMK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of dTMP to dTDP.

Catalytic activityi

ATP + dTMP = ADP + dTDP.

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi13 – 208ATPCurated

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. nucleoside phosphate kinase activity Source: Reactome
  3. thymidylate kinase activity Source: MGI
  4. uridylate kinase activity Source: GO_Central

GO - Biological processi

  1. cell cycle Source: ProtInc
  2. cell proliferation Source: ProtInc
  3. cellular response to growth factor stimulus Source: Ensembl
  4. dTDP biosynthetic process Source: GO_Central
  5. dTTP biosynthetic process Source: GO_Central
  6. dUDP biosynthetic process Source: GO_Central
  7. myoblast differentiation Source: Ensembl
  8. nucleobase-containing small molecule interconversion Source: Reactome
  9. nucleobase-containing small molecule metabolic process Source: Reactome
  10. nucleoside monophosphate phosphorylation Source: GOC
  11. nucleotide phosphorylation Source: GOC
  12. response to cadmium ion Source: Ensembl
  13. response to estrogen Source: Ensembl
  14. small molecule metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Nucleotide biosynthesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS11384-MONOMER.
ReactomeiREACT_21330. Synthesis and interconversion of nucleotide di- and triphosphates.
SABIO-RKP23919.
UniPathwayiUPA00575.

Names & Taxonomyi

Protein namesi
Recommended name:
Thymidylate kinase (EC:2.7.4.9)
Alternative name(s):
dTMP kinase
Gene namesi
Name:DTYMK
Synonyms:CDC8, TMPK, TYMK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:3061. DTYMK.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: GO_Central
  2. mitochondrial intermembrane space Source: Ensembl
  3. mitochondrial matrix Source: Ensembl
  4. mitochondrion Source: GO_Central
  5. nucleus Source: GO_Central
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA150.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 212211Thymidylate kinasePRO_0000155210Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine1 Publication
Modified residuei169 – 1691N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP23919.
PaxDbiP23919.
PRIDEiP23919.

PTM databases

PhosphoSiteiP23919.

Expressioni

Gene expression databases

BgeeiP23919.
CleanExiHS_DTYMK.
ExpressionAtlasiP23919. baseline and differential.
GenevestigatoriP23919.

Organism-specific databases

HPAiHPA042593.
HPA042719.

Interactioni

Protein-protein interaction databases

BioGridi108174. 7 interactions.
IntActiP23919. 2 interactions.
MINTiMINT-3010142.
STRINGi9606.ENSP00000304802.

Structurei

Secondary structure

1
212
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi8 – 147Combined sources
Helixi19 – 3214Combined sources
Beta strandi37 – 437Combined sources
Helixi48 – 5710Combined sources
Helixi65 – 7713Combined sources
Helixi80 – 889Combined sources
Beta strandi92 – 976Combined sources
Helixi99 – 1079Combined sources
Helixi114 – 1185Combined sources
Helixi119 – 1213Combined sources
Beta strandi124 – 1263Combined sources
Beta strandi128 – 1347Combined sources
Helixi137 – 1426Combined sources
Helixi149 – 1513Combined sources
Helixi154 – 16714Combined sources
Beta strandi171 – 1733Combined sources
Beta strandi175 – 1795Combined sources
Helixi184 – 20118Combined sources
Helixi202 – 2043Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E2DX-ray1.65A1-212[»]
1E2EX-ray2.00A1-212[»]
1E2FX-ray1.60A1-212[»]
1E2GX-ray1.70A1-212[»]
1E2QX-ray1.70A1-212[»]
1E98X-ray1.90A1-212[»]
1E99X-ray1.80A1-212[»]
1E9AX-ray1.60A1-212[»]
1E9BX-ray1.70A1-212[»]
1E9CX-ray1.60A1-212[»]
1E9DX-ray1.70A1-212[»]
1E9EX-ray1.60A1-212[»]
1E9FX-ray1.90A1-144[»]
A149-212[»]
1NMXX-ray1.70A1-212[»]
1NMYX-ray1.60A4-212[»]
1NMZX-ray1.75A1-212[»]
1NN0X-ray1.60A1-212[»]
1NN1X-ray1.90A1-212[»]
1NN3X-ray1.55A1-212[»]
1NN5X-ray1.50A1-212[»]
2XX3X-ray2.00A1-212[»]
ProteinModelPortaliP23919.
SMRiP23919. Positions 4-212.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23919.

Family & Domainsi

Sequence similaritiesi

Belongs to the thymidylate kinase family.Curated

Phylogenomic databases

eggNOGiCOG0125.
HOGENOMiHOG000229079.
HOVERGENiHBG051418.
InParanoidiP23919.
KOiK00943.
OMAiMIDSYLR.
OrthoDBiEOG7WQ7T8.
PhylomeDBiP23919.
TreeFamiTF324638.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00165. Thymidylate_kinase.
InterProiIPR027417. P-loop_NTPase.
IPR018095. Thymidylate_kin_CS.
IPR018094. Thymidylate_kinase.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00041. DTMP_kinase. 1 hit.
PROSITEiPS01331. THYMIDYLATE_KINASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P23919-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAARRGALIV LEGVDRAGKS TQSRKLVEAL CAAGHRAELL RFPERSTEIG
60 70 80 90 100
KLLSSYLQKK SDVEDHSVHL LFSANRWEQV PLIKEKLSQG VTLVVDRYAF
110 120 130 140 150
SGVAFTGAKE NFSLDWCKQP DVGLPKPDLV LFLQLQLADA AKRGAFGHER
160 170 180 190 200
YENGAFQERA LRCFHQLMKD TTLNWKMVDA SKSIEAVHED IRVLSEDAIR
210
TATEKPLGEL WK
Length:212
Mass (Da):23,819
Last modified:December 7, 2004 - v4
Checksum:iA52876625B3621B1
GO
Isoform 2 (identifier: P23919-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     111-134: Missing.

Note: No experimental confirmation available.

Show »
Length:188
Mass (Da):21,064
Checksum:i38FE4F99F6DDA886
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31A → P in CAG46783 (Ref. 3) Curated
Sequence conflicti31 – 377CAAGHRA → SRGPPP in CAA38528 (PubMed:2017365).Curated
Sequence conflicti58 – 581Q → K in AAA21719 (PubMed:8024690).Curated
Sequence conflicti68 – 681V → A in CAG46783 (Ref. 3) Curated
Sequence conflicti183 – 1842SI → RL in CAA38528 (PubMed:2017365).Curated
Sequence conflicti190 – 1912DI → EL (PubMed:2017365).Curated
Sequence conflicti190 – 1912DI → EL (PubMed:8024690).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei111 – 13424Missing in isoform 2. 1 PublicationVSP_054164Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54729 mRNA. Translation: CAA38528.1.
L16991 mRNA. Translation: AAA21719.1.
CR541986 mRNA. Translation: CAG46783.1.
BC001827 mRNA. Translation: AAH01827.1.
BC171902 mRNA. Translation: AAI71902.1.
CCDSiCCDS2552.1. [P23919-1]
PIRiS26845.
RefSeqiNP_001158503.1. NM_001165031.1. [P23919-2]
NP_036277.2. NM_012145.3. [P23919-1]
UniGeneiHs.471873.

Genome annotation databases

EnsembliENST00000305784; ENSP00000304802; ENSG00000168393. [P23919-1]
GeneIDi1841.
KEGGihsa:1841.
UCSCiuc002wbz.2. human. [P23919-1]

Polymorphism databases

DMDMi56405325.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X54729 mRNA. Translation: CAA38528.1.
L16991 mRNA. Translation: AAA21719.1.
CR541986 mRNA. Translation: CAG46783.1.
BC001827 mRNA. Translation: AAH01827.1.
BC171902 mRNA. Translation: AAI71902.1.
CCDSiCCDS2552.1. [P23919-1]
PIRiS26845.
RefSeqiNP_001158503.1. NM_001165031.1. [P23919-2]
NP_036277.2. NM_012145.3. [P23919-1]
UniGeneiHs.471873.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1E2DX-ray1.65A1-212[»]
1E2EX-ray2.00A1-212[»]
1E2FX-ray1.60A1-212[»]
1E2GX-ray1.70A1-212[»]
1E2QX-ray1.70A1-212[»]
1E98X-ray1.90A1-212[»]
1E99X-ray1.80A1-212[»]
1E9AX-ray1.60A1-212[»]
1E9BX-ray1.70A1-212[»]
1E9CX-ray1.60A1-212[»]
1E9DX-ray1.70A1-212[»]
1E9EX-ray1.60A1-212[»]
1E9FX-ray1.90A1-144[»]
A149-212[»]
1NMXX-ray1.70A1-212[»]
1NMYX-ray1.60A4-212[»]
1NMZX-ray1.75A1-212[»]
1NN0X-ray1.60A1-212[»]
1NN1X-ray1.90A1-212[»]
1NN3X-ray1.55A1-212[»]
1NN5X-ray1.50A1-212[»]
2XX3X-ray2.00A1-212[»]
ProteinModelPortaliP23919.
SMRiP23919. Positions 4-212.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108174. 7 interactions.
IntActiP23919. 2 interactions.
MINTiMINT-3010142.
STRINGi9606.ENSP00000304802.

Chemistry

BindingDBiP23919.
ChEMBLiCHEMBL4388.

PTM databases

PhosphoSiteiP23919.

Polymorphism databases

DMDMi56405325.

Proteomic databases

MaxQBiP23919.
PaxDbiP23919.
PRIDEiP23919.

Protocols and materials databases

DNASUi1841.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305784; ENSP00000304802; ENSG00000168393. [P23919-1]
GeneIDi1841.
KEGGihsa:1841.
UCSCiuc002wbz.2. human. [P23919-1]

Organism-specific databases

CTDi1841.
GeneCardsiGC02M242615.
H-InvDBHIX0161852.
HGNCiHGNC:3061. DTYMK.
HPAiHPA042593.
HPA042719.
MIMi188345. gene.
neXtProtiNX_P23919.
PharmGKBiPA150.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0125.
HOGENOMiHOG000229079.
HOVERGENiHBG051418.
InParanoidiP23919.
KOiK00943.
OMAiMIDSYLR.
OrthoDBiEOG7WQ7T8.
PhylomeDBiP23919.
TreeFamiTF324638.

Enzyme and pathway databases

UniPathwayiUPA00575.
BioCyciMetaCyc:HS11384-MONOMER.
ReactomeiREACT_21330. Synthesis and interconversion of nucleotide di- and triphosphates.
SABIO-RKP23919.

Miscellaneous databases

EvolutionaryTraceiP23919.
GeneWikiiDTYMK.
GenomeRNAii1841.
NextBioi7537.
PROiP23919.
SOURCEiSearch...

Gene expression databases

BgeeiP23919.
CleanExiHS_DTYMK.
ExpressionAtlasiP23919. baseline and differential.
GenevestigatoriP23919.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
HAMAPiMF_00165. Thymidylate_kinase.
InterProiIPR027417. P-loop_NTPase.
IPR018095. Thymidylate_kin_CS.
IPR018094. Thymidylate_kinase.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00041. DTMP_kinase. 1 hit.
PROSITEiPS01331. THYMIDYLATE_KINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of the human deoxythymidylate kinase gene in yeast."
    Su J.Y., Sclafani R.A.
    Nucleic Acids Res. 19:823-827(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth."
    Huang S.H., Tang A., Drisco B., Zhang S.Q., Seeger R., Li C., Jong A.
    DNA Cell Biol. 13:461-471(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. "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] (ISOFORMS 1 AND 2).
    Tissue: Brain and Muscle.
  5. "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] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
  6. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-169, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  9. "Structures of human thymidylate kinase in complex with prodrugs: implications for the structure-based design of novel compounds."
    Ostermann N., Segura-Pena D., Meier C., Veit T., Monnerjahn C., Konrad M., Lavie A.
    Biochemistry 42:2568-2577(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).

Entry informationi

Entry nameiKTHY_HUMAN
AccessioniPrimary (citable) accession number: P23919
Secondary accession number(s): B7ZW70, Q6FGX1, Q9BUX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: December 7, 2004
Last modified: March 4, 2015
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.