Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003624
UniProt IDP27144
Primary gene name(s)AK4
Synonym gene name(s)AK3, AK3L1
Protein nameAdenylate kinase 4, mitochondrial
Protein functionInvolved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity. {ECO:0000255|HAMAP-Rule:MF_03170, ECO:0000269|PubMed:19073142, ECO:0000269|PubMed:19766732, ECO:0000269|PubMed:23416111}.
Subcellular locationMitochondrion matrix {ECO:0000255|HAMAP-Rule:MF_03170, ECO:0000269|PubMed:11485571, ECO:0000269|PubMed:19766732}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P27144
Gene Ontology
(Biological Process)
Complete annatation
ADP biosynthetic process [GO:0006172];
AMP metabolic process [GO:0046033];
ATP metabolic process [GO:0046034];
brain development [GO:0007420];
GTP metabolic process [GO:0046039];
liver development [GO:0001889];
nucleobase-containing small molecule interconversion [GO:0015949];
nucleoside diphosphate phosphorylation [GO:0006165];
nucleoside triphosphate biosynthetic process [GO:0009142];
response to drug [GO:0042493]
Gene Ontology
(Molecular Function)
Complete annatation
adenylate kinase activity [GO:0004017];
ATP binding [GO:0005524];
GTP binding [GO:0005525];
nucleoside diphosphate kinase activity [GO:0004550];
nucleoside phosphate kinase activity [GO:0050145];
nucleoside triphosphate adenylate kinase activity [GO:0046899]
Gene Ontology
(Cellular Component)
Complete annatation
extracellular exosome [GO:0070062];
mitochondrial matrix [GO:0005759];
mitochondrion [GO:0005739]
Protein-protein interaction106708
Phylogenetic treeP27144
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. CD33.1233970700255600
AZA vs. DISU-0.1129338026838430.6593383718189180.960561603296512
AZA vs. IL70.7809775112257477.1885805680183e-050.0120392749890822
AZA vs. SAHA0.7778122836126330.001783409274957350.0307939420512108
DISU vs. CD3-3.247802476726212.22044604925031e-161.40634469522686e-14
DISU vs. IL70.8844208259462570.0005451154165325710.0181404302521601
DISU vs. SAHA0.8931442009903910.002543140307351370.0403156548919054
DMSO vs. AZA-0.0904292971320410.6548706994782141
DMSO vs. CD3-3.2189809469641200
DMSO vs. DISU0.0222995255080790.9280883723041920.990853289109825
DMSO vs. IL70.8781126891607321.90945624056749e-060.000556652243370514
DMSO vs. SAHA0.8608579685944050.0003484942022374820.00861909196677523
HIV vs. Mock in Activation0.173520387814440.7816591975899450.999983755607037
HIV vs. Mock in Latency0.2446737692904680.589825982274770.999834320637052
IL7 vs. CD3-2.336365957352534.58177940032556e-121.20736295281656e-10
SAHA vs. CD3-2.369073029563841.73532965774825e-103.52444985744827e-09
SAHA vs. IL7-0.005170248758136730.9831866898544130.993710617125574
(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
unknown unknown unknown unknown unknown unknown
(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) unknown
(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 -0.215401 0.16531
(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
1.049 0.891 1.036 0.958 0.849
(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
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00300 Tenofovir approved, investigational unknown substrate
DB00718 Adefovir Dipivoxil approved, investigational unknown substrate

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2AR7 X-ray 2.1Å A/B=1-223.
2BBW X-ray 2.0Å A/B=1-223.
3NDP X-ray 2.3Å A/B=1-223.

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
hsa00230 Purine metabolism - Homo sapiens (human)
hsa00730 Thiamine metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)