InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CREB3

Summary

InnateDB Protein

IDBP-63799.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CREB3

Protein Name

cAMP responsive element binding protein 3

Synonyms

LUMAN; LZIP;

Species

Homo sapiens

Ensembl Protein

ENSP00000342136

InnateDB Gene

IDBG-63795 (CREB3)

Protein Structure

UniProt Annotation

Function

Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. Isoform 3 functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells.Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down- regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]- 3') and C/EBP sequences present in many viral and cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter.

Subcellular Localization

Isoform 2: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Membrane. Note=Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia (By similarity). Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Sequestred into the cytoplasm by the HCV core protein. {ECO:0000250}.Isoform 3: Nucleus. Cytoplasm. Note=Predominantly in the nucleus.Processed cyclic AMP-responsive element- binding protein 3: Nucleus. Note=Upon RIP activation the transcriptional active processed cyclic AMP-responsive element- binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB).

Disease Associations

Tissue Specificity

Expressed in dendritic cells (DC). Weakly expressed in monocytes (at protein level). Ubiquitous. {ECO:0000269PubMed:10675342, ECO:0000269PubMed:19779205, ECO:0000269PubMed:20546900, ECO:0000269PubMed:9271389, ECO:0000269PubMed:9389645}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 141 experimentally validated interaction(s) in this database.

Experimentally validated
Total	141 [view]
Protein-Protein	140 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000982	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0008140	cAMP response element binding protein binding
GO:0031726	CCR1 chemokine receptor binding
GO:0042803	protein homodimerization activity
GO:0043565	sequence-specific DNA binding
GO:0046983	protein dimerization activity

Biological Process

GO:0001558	regulation of cell growth
GO:0002230	positive regulation of defense response to virus by host
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006366	transcription from RNA polymerase II promoter
GO:0006935	chemotaxis
GO:0006986	response to unfolded protein
GO:0006990	positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response
GO:0016032	viral process
GO:0019043	establishment of viral latency
GO:0019046	release from viral latency
GO:0030335	positive regulation of cell migration
GO:0034976	response to endoplasmic reticulum stress
GO:0042127	regulation of cell proliferation
GO:0042994	cytoplasmic sequestering of transcription factor
GO:0045786	negative regulation of cell cycle
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0050930	induction of positive chemotaxis
GO:0051928	positive regulation of calcium ion transport
GO:0090026	positive regulation of monocyte chemotaxis
GO:0090045	positive regulation of deacetylase activity
GO:2000326	negative regulation of ligand-dependent nuclear receptor transcription coactivator activity

Cellular Component

GO:0000139	Golgi membrane
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005794	Golgi apparatus
GO:0005829	cytosol
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0016604	nuclear body
GO:0030176	integral component of endoplasmic reticulum membrane
GO:0043025	neuronal cell body