Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000686
UniProt IDQ70SY1
Primary gene name(s)CREB3L2
Synonym gene name(s)BBF2H7
Protein nameCyclic AMP-responsive element-binding protein 3-like protein 2
Protein functionTranscription factor involved in unfolded protein response, UPR. In the absence of endoplasmic reticulum, ER stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes, By similarity. In a neuroblastoma cell line, protects cells from ER stress-induced death, PubMed:17178827. In vitro activates transcription of target genes via direct binding to the CRE site, PubMed:17178827. {ECO:0000250|UniProtKB:Q8BH52, ECO:0000269|PubMed:17178827}.
Subcellular locationEndoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q8BH52};
Single-pass type II membrane protein. Note=ER membrane resident protein. Upon ER stress, translocated to the Golgi apparatus where it is cleaved. The cytosolic N-terminal fragment, processed cyclic AMP-responsive element-binding protein 3-like protein 1 is transported into the nucleus. {ECO:0000250|UniProtKB:Q8BH52}.;
SUBCELLULAR LOCATION: Processed cyclic AMP-responsive element-binding protein 3-like protein 2: Nucleus. Note=Upon ER stress, translocated into the nucleus. {ECO:0000250|UniProtKB:Q8BH52}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q70SY1
Gene Ontology
(Biological Process)
Complete annatation
cartilage development [GO:0051216];
chondrocyte differentiation [GO:0002062];
endoplasmic reticulum unfolded protein response [GO:0030968];
ER to Golgi vesicle-mediated transport [GO:0006888];
positive regulation of transcription, DNA-templated [GO:0045893];
response to endoplasmic reticulum stress [GO:0034976]
Gene Ontology
(Molecular Function)
Complete annatation
cAMP response element binding [GO:0035497];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcription regulatory region DNA binding [GO:0044212]
Gene Ontology
(Cellular Component)
Complete annatation
endoplasmic reticulum [GO:0005783];
endoplasmic reticulum membrane [GO:0005789];
integral component of membrane [GO:0016021];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction122277
Phylogenetic treeQ70SY1
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. CD3-0.2618091106232680.4255040802771160.546967803661978
AZA vs. DISU0.2426507658571530.3946580738133680.902586488791209
AZA vs. IL7-0.01108442898911280.9541507981880420.999311006273513
AZA vs. SAHA0.06834293915782810.7798350606079930.94148594101049
DISU vs. CD30.4935577742503520.1747792630158280.287277571769773
DISU vs. IL7-0.2634354521912940.3652951777478240.742469201867009
DISU vs. SAHA-0.1728395969101060.5651963501505650.858852582730593
DMSO vs. AZA-0.04321384129344260.7971400311710821
DMSO vs. CD30.2100397032398370.5120320580900070.6193803561206
DMSO vs. DISU-0.2869212264452630.3380414051892040.837187177683042
DMSO vs. IL70.03906792731626420.8284058474869580.963051812112721
DMSO vs. SAHA0.1048725761085060.6568752691890.891545099104176
HIV vs. Mock in Activation0.2398720852010770.7008513475275340.999983755607037
HIV vs. Mock in Latency0.1489996763395940.3671000773892740.999834320637052
IL7 vs. CD30.2568390776713930.4243932301666410.56034330398579
SAHA vs. CD30.3061918022984210.386410103099960.502915798082702
SAHA vs. IL70.07681756535158890.7525751661919440.888781874607555
(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 2.20080051
(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) TRUE
(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 0.117522 0.509204
(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
unknown unknown unknown unknown unknown
(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

not found

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
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04725 Cholinergic synapse - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04911 Insulin secretion - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04916 Melanogenesis - Homo sapiens (human)
hsa04918 Thyroid hormone synthesis - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04925 Aldosterone synthesis and secretion - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04962 Vasopressin-regulated water reabsorption - Homo sapiens (human)
hsa05016 Huntington's disease - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
hsa05031 Amphetamine addiction - Homo sapiens (human)
hsa05034 Alcoholism - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)