Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001861
UniProt IDP13995
Primary gene name(s)MTHFD2
Synonym gene name(s)NMDMC
Protein nameBifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial [Includes: NAD-dependent methylenetetrahydrofolate dehydrogenase
Protein functionunknown
Subcellular locationMitochondrion.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P13995
Gene Ontology
(Biological Process)
Complete annatation
folic acid-containing compound biosynthetic process [GO:0009396];
folic acid metabolic process [GO:0046655];
one-carbon metabolic process [GO:0006730];
tetrahydrofolate metabolic process [GO:0046653]
Gene Ontology
(Molecular Function)
Complete annatation
magnesium ion binding [GO:0000287];
methenyltetrahydrofolate cyclohydrolase activity [GO:0004477];
methylenetetrahydrofolate dehydrogenase, NAD+ activity [GO:0004487];
methylenetetrahydrofolate dehydrogenase, NADP+ activity [GO:0004488];
phosphate ion binding [GO:0042301]
Gene Ontology
(Cellular Component)
Complete annatation
extracellular space [GO:0005615];
mitochondrial matrix [GO:0005759];
mitochondrion [GO:0005739]
Protein-protein interaction116011
Phylogenetic treeP13995
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. CD33.8729512442826900
AZA vs. DISU0.1457344971959170.565313569393660.951925020821155
AZA vs. IL70.6661988081994150.0005718481475278650.0522667591425722
AZA vs. SAHA-0.442578673272610.0708802722108230.328753607171061
DISU vs. CD3-3.7401368772116600
DISU vs. IL70.5113688279596070.04311675820334770.274139658336342
DISU vs. SAHA-0.5865070469254530.04528480042312440.264549150725233
DMSO vs. AZA-0.07724403398033040.646468721249541
DMSO vs. CD3-3.9587315084264400
DMSO vs. DISU-0.2240818112408670.3598138825021260.847301968151515
DMSO vs. IL70.7503636706941693.42860440335491e-050.00538398035214325
DMSO vs. SAHA-0.3723496937757290.1156207204462840.404298360760737
HIV vs. Mock in Activation0.3183469634507620.6088685631416570.999983755607037
HIV vs. Mock in Latency-0.006067478530323870.970728601878920.999834320637052
IL7 vs. CD3-3.1996253365094200
SAHA vs. CD3-4.3390856974326700
SAHA vs. IL7-1.111204650106916.64129747895981e-060.000220995404410243
(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
1.9 0.001979578 1.3 0.102349874 1.5 0.042671739
(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 0.779735 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
unknown unknown

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
0.958 0.967 0.772 0.578 0.776
(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
201761_at 1.46 Yes upregulated in CD4+ cells
201761_at 1.6 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
DB00116 Tetrahydrofolic acid approved, nutraceutical unknown cofactor
DB00157 NADH nutraceutical unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1ZN4 Model - A/B=37-350.

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

HIV Partner Interaction Type PubMed
Nef interacts with 22190034

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00670 One carbon pool by folate - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)