Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003616
UniProt IDO43865
Primary gene name(s)AHCYL1
Synonym gene name(s)DCAL, IRBIT, XPVKONA
Protein nameAdenosylhomocysteinase 2
Protein functionMultifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3(- and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1, PubMed:16793548. When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates of ITPR1 to interact with CFTR and SLC26A6 mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid, By similarity. Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(- secretion, PubMed:16769890. Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation, By similarity. Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2, PubMed:20584908. Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition, PubMed:18829453. May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state, PubMed:19224921. Acts as a, dATP-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression, PubMed:25237103. {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:25237103}.
Subcellular locationEndoplasmic reticulum {ECO:0000250|UniProtKB:Q80SW1}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q80SW1}. Microsome {ECO:0000250|UniProtKB:Q80SW1}. Apical cell membrane {ECO:0000250|UniProtKB:B5DFN2}. Note=Associates with membranes when phosphorylated, probably through interaction with ITPR1. {ECO:0000250|UniProtKB:Q80SW1}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O43865
Gene Ontology
(Biological Process)
Complete annatation
angiotensin-activated signaling pathway [GO:0038166];
epithelial fluid transport [GO:0042045];
mRNA polyadenylation [GO:0006378];
one-carbon metabolic process [GO:0006730];
positive regulation of sodium ion transport [GO:0010765];
protein export from nucleus [GO:0006611];
regulation of anion transport [GO:0044070];
regulation of cardiac conduction [GO:1903779];
regulation of ion transmembrane transporter activity [GO:0032412];
regulation of mRNA 3'-end processing [GO:0031440];
response to calcium ion [GO:0051592];
S-adenosylhomocysteine catabolic process [GO:0019510];
S-adenosylmethionine cycle [GO:0033353]
Gene Ontology
(Molecular Function)
Complete annatation
hydrolase activity [GO:0016787];
RNA binding [GO:0003723]
Gene Ontology
(Cellular Component)
Complete annatation
apical plasma membrane [GO:0016324];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum membrane [GO:0005789];
extracellular exosome [GO:0070062]
Protein-protein interaction115987
Phylogenetic treeO43865
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. CD30.9496364293363160.004047135703350580.0121583474827387
AZA vs. DISU0.1386705358657540.5834002321381210.955158276076142
AZA vs. IL70.03595619802988960.8517377698595440.999311006273513
AZA vs. SAHA0.2258295767129070.3551795123944820.724581811856781
DISU vs. CD3-0.8239825845857360.02394798765963680.0596779576758745
DISU vs. IL7-0.1117349443644040.6572662565591870.902065624329001
DISU vs. SAHA0.08854869034533220.7612866084494370.933020287545049
DMSO vs. AZA-0.02192960039963150.8959615020040921
DMSO vs. CD3-0.9840638062709150.002311353312206890.00706872465456694
DMSO vs. DISU-0.1628052371060620.5044610150940740.910379656216314
DMSO vs. IL70.0653232081058330.7165496821133170.942417244622078
DMSO vs. SAHA0.2413086761426730.306825805003770.659089467960635
HIV vs. Mock in Activation0.05876861551570090.9246580732302410.999983755607037
HIV vs. Mock in Latency-0.0490358783001310.7663802302509580.999834320637052
IL7 vs. CD3-0.9060720241026410.005232955907488180.0174158411114086
SAHA vs. CD3-0.748927330233340.03472664276259580.0734246361676132
SAHA vs. IL70.1863376512293640.4453685046658160.684931753066772
(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 -0.0818857 0.615005
(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
1.008 1.377 1.373 1.26 1.872
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3MTG X-ray 2.6Å A/B=89-530.

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

HIV Partner Interaction Type PubMed
Tat modulates 21956116

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00270 Cysteine and methionine metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)