Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003198
UniProt IDP04818
Primary gene name(s)TYMS
Synonym gene name(s)TS
Protein nameThymidylate synthase
Protein functionContributes to the de novo mitochondrial thymidylate biosynthesis pathway. {ECO:0000269|PubMed:21876188}.
Subcellular locationNucleus {ECO:0000269|PubMed:21876188}. Cytoplasm {ECO:0000269|PubMed:21876188}. Mitochondrion {ECO:0000269|PubMed:21876188}. Mitochondrion matrix {ECO:0000269|PubMed:21876188}. Mitochondrion inner membrane {ECO:0000269|PubMed:21876188}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P04818
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
cartilage development [GO:0051216];
cell growth [GO:0016049];
cell proliferation [GO:0008283];
circadian rhythm [GO:0007623];
developmental growth [GO:0048589];
DNA biosynthetic process [GO:0071897];
dTMP biosynthetic process [GO:0006231];
dTTP biosynthetic process [GO:0006235];
dUMP metabolic process [GO:0046078];
G1/S transition of mitotic cell cycle [GO:0000082];
immortalization of host cell by virus [GO:0019088];
intestinal epithelial cell maturation [GO:0060574];
liver regeneration [GO:0097421];
pyrimidine nucleoside biosynthetic process [GO:0046134];
regulation of transcription involved in G1/S transition of mitotic cell cycle [GO:0000083];
regulation of translation [GO:0006417];
response to cytokine [GO:0034097];
response to drug [GO:0042493];
response to ethanol [GO:0045471];
response to folic acid [GO:0051593];
response to glucocorticoid [GO:0051384];
response to organophosphorus [GO:0046683];
response to progesterone [GO:0032570];
response to toxic substance [GO:0009636];
response to vitamin A [GO:0033189];
tetrahydrofolate interconversion [GO:0035999];
uracil metabolic process [GO:0019860]
Gene Ontology
(Molecular Function)
Complete annatation
cofactor binding [GO:0048037];
drug binding [GO:0008144];
folic acid binding [GO:0005542];
mRNA binding [GO:0003729];
nucleotide binding [GO:0000166];
thymidylate synthase activity [GO:0004799]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
mitochondrial inner membrane [GO:0005743];
mitochondrial matrix [GO:0005759];
mitochondrion [GO:0005739];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction113149
Phylogenetic treeP04818
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.900646259202860.1243142413211850.209432062185235
AZA vs. DISU-0.5395766037486490.2196912704970580.808881055314084
AZA vs. IL70.5219853518454860.3807946308304350.999311006273513
AZA vs. SAHA-0.9087375835775040.0761237372084630.34301430991515
DISU vs. CD3-2.453133988118580.04720787620093460.103147054044483
DISU vs. IL71.052473079872910.0963114116404120.411185083681453
DISU vs. SAHA-0.3677088070709010.5029625278914560.826933029981256
DMSO vs. AZA-0.1025038840171010.7987357028938291
DMSO vs. CD3-2.015758365707150.1025870830295940.174394241062699
DMSO vs. DISU0.4348409125625050.338734317886720.83759035206982
DMSO vs. IL70.631951527067210.29762148585640.783282803646165
DMSO vs. SAHA-0.812138086729360.1203604946111310.413295286918285
HIV vs. Mock in Activation0.1115073865418070.9588125201834960.999983755607037
HIV vs. Mock in Latency0.09208819301264630.7533275369162810.999834320637052
IL7 vs. CD3-1.371777489994180.2628813370063480.396176490166669
SAHA vs. CD3-2.835293308727430.02363150019907030.0529950458333319
SAHA vs. IL7-1.433948581742330.03561084897084970.145988016694748
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
3 0.000873955 1.8 0.031454664 1.8 0.080999142
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.521509 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
0.137 3.85E-05

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.045 1.007 0.637 0.339 1.316
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
202589_at 2.13 Yes upregulated in CD4+ cells
202589_at 5.76 Yes upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00293 Raltitrexed approved, investigational yes inhibitor
DB00322 Floxuridine approved yes unknown
DB00440 Trimethoprim approved, vet_approved yes inhibitor
DB00544 Fluorouracil approved yes other/unknown
DB00642 Pemetrexed approved, investigational yes inhibitor
DB01101 Capecitabine approved, investigational yes inhibitor
DB00441 Gemcitabine approved unknown inhibitor
DB03800 2&,39;-deoxyuridylic acid experimental unknown unknown
DB04530 S,S-(2-Hydroxyethyl)Thiocysteine experimental unknown unknown
DB01643 Thymidine-5&,39;-Phosphate experimental unknown unknown
DB00432 Trifluridine approved yes inhibitor
DB05308 ANX-510 investigational unknown unknown
DB05116 NB1011 investigational unknown unknown
DB05457 OSI-7904L investigational unknown unknown
DB03541 10-Propargyl-5,8-Dideazafolic Acid experimental unknown unknown
DB07577 6-ETHYL-5-PHENYLPYRIMIDINE-2,4-DIAMINE experimental unknown unknown
DB08478 N-[2-chloro-5-(trifluoromethyl)phenyl]imidodicarbonimidic diamide experimental unknown unknown
DB08479 N-(3,5-dimethoxyphenyl)imidodicarbonimidic diamide experimental unknown unknown
DB08734 6,6-DIMETHYL-1-[3-(2,4,5-TRICHLOROPHENOXY)PROPOXY]-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE experimental unknown unknown
DB00544 Fluorouracil approved unknown substrate
DB00563 Methotrexate approved unknown substrate
DB06813 Pralatrexate approved yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1HVY X-ray 1.9Å A/B/C/D=26-313.
1HW3 X-ray 2.0Å A=1-313.
1HW4 X-ray 2.0Å A=1-313.
1HZW X-ray 2.0Å A/B=1-313.
1I00 X-ray 2.5Å A/B=1-313.
1JU6 X-ray 2.8Å A/B/C/D=1-313.
1JUJ X-ray 3.0Å A/B/C/D=1-313.
1YPV X-ray 1.8Å A=1-313.
2ONB X-ray 2.7Å A=1-313.
2RD8 X-ray 2.5Å A/B=1-313.
2RDA X-ray 2.6Å A/B/C/D/E/F=1-313.
3EAW X-ray 1.8Å X=1-313.
3EBU X-ray 2.0Å A=1-313.
3ED7 X-ray 1.5Å A=26-313.
3EDW X-ray 1.7Å X=1-313.
3EF9 X-ray 3.2Å A=1-313.
3EGY X-ray 2.1Å X=1-313.
3EHI X-ray 2.0Å X=1-313.
3EJL X-ray 3.2Å A/B/C/D=1-313.
3GG5 X-ray 2.7Å A/B/C/D=1-313.
3GH0 X-ray 1.5Å A=1-313.
3GH2 X-ray 1.7Å X=1-313.
3H9K X-ray 2.6Å A/B/C/D/E=1-313.
3HB8 X-ray 2.7Å A/B/C/D/E=1-313.
3N5E X-ray 2.2Å A/B=1-313.
3N5G X-ray 2.2Å A=1-313.
3OB7 X-ray 2.7Å A/B/C/D/E=1-313.
4E28 X-ray 2.3Å A=1-313.
4FGT X-ray 2.0Å A=1-311.
4G2O X-ray 2.2Å X=1-313.
4G6W X-ray 2.3Å X=1-313.
4GD7 X-ray 2.2Å A=1-313.
4GYH X-ray 3.0Å A=1-313.
4H1I X-ray 3.1Å A/B/C/D=1-313.
4JEF X-ray 2.3Å A=26-311.
4KPW X-ray 2.0Å A=1-313.
4O1U X-ray 2.2Å A/B=1-313.
4O1X X-ray 2.3Å A/B/C/D=1-313.
4UP1 X-ray 2.9Å A/B/C/D=1-313.
5HS3 X-ray 3.1Å A/B/C/D/E/F=26-313.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00240 Pyrimidine metabolism - Homo sapiens (human)
hsa00670 One carbon pool by folate - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa01523 Antifolate resistance - Homo sapiens (human)