Gene Report

Basic Information

Approved Symbol	CREB3
Approved Name	cAMP responsive element binding protein 3
Previous Name	"cAMP responsive element binding protein 3 (luman)"
Symbol Alias	LZIP, Luman
Location	9p13.3
Position	chr9:35736724-35737005 (+)
External Links	Entrez Gene: 10488 Ensembl: ENSG00000107175 UCSC: uc003zxv.3 HGNC ID: 2347
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between CREB3 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
cAMP responsive element binding protein 1	Tochigi, 2008	patients and normal controls		Genes differentially expressed in major depression Genes differentially expressed in major depression

Positive relationships between CREB3 and other components at different levels (count: 0)

Positive relationship network of CREB3 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between CREB3 and MDD (count: 0)

Negative relationships between CREB3 and other components at different levels (count: 0)

CREB3 related SNPs in MK4MDD (count: 0)

CREB3 related proteins in MK4MDD (count: 0)

CREB3 related GO terms (count: 47)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0090045	positive regulation of deacetylase activity	biological process	IDA[19779205]
GO:0005794	Golgi apparatus	cellular component	IMP[10623756]
GO:0016604	nuclear body	cellular component	IDA[18391022]
GO:0005515	protein binding	molecular function	IPI[9271389\|10629049\|10675342\|10871379\|15001559\|15705566\|18391022\|20102225\|20195357\|20546900]
GO:0030335	positive regulation of cell migration	biological process	IMP[15001559]
GO:0008140	cAMP response element binding protein binding	molecular function	IDA[9271389]
GO:2000326	negative regulation of ligand-dependent nuclear receptor transcription coactivator activity	biological process	IDA[19779205]; IDA[19779205]
GO:0005789	endoplasmic reticulum membrane	cellular component	IDA[20091349]; IEA
GO:0030176	integral component of endoplasmic reticulum membrane	cellular component	IDA[20546900]
GO:1902236	negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	biological process	IDA[16940180]
GO:0016020	membrane	cellular component	IDA[19779205]; IDA[19779205]
GO:0042803	protein homodimerization activity	molecular function	IDA[10675342\|20141198]
GO:0006990	positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response	biological process	IDA[16940180\|18391022]
GO:0050930	induction of positive chemotaxis	biological process	IDA[19779205]; IDA[19779205]; IMP[15001559]
GO:0043025	neuronal cell body	cellular component	IDA[20091349]
GO:0000139	Golgi membrane	cellular component	IDA[20091349]
GO:0019046	release from viral latency	biological process	IDA[20091349]; TAS[10623756]
GO:0006351	transcription, DNA-templated	biological process	IDA[9271389]
GO:0051928	positive regulation of calcium ion transport	biological process	IMP[15001559]
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	IDA[15845366\|16940180\|17296613\|20091349\|20141198]; IMP[16940180]
GO:0031726	CCR1 chemokine receptor binding	molecular function	IDA[15001559]
GO:0005634	nucleus	cellular component	IC[16940180]; IDA[10675342\|19779205\|20141198\|20546900]
GO:0003677	DNA binding	molecular function	IDA[9271389\|10675342]
GO:0042127	regulation of cell proliferation	biological process	IMP[10675342]
GO:0046983	protein dimerization activity	molecular function	TAS[10623756]
GO:0006935	chemotaxis	biological process	IEA
GO:0019043	establishment of viral latency	biological process	IDA[20091349]
GO:0003682	chromatin binding	molecular function	IDA[16940180]
GO:0045893	positive regulation of transcription, DNA-templated	biological process	IDA[9271389]
GO:0016032	viral process	biological process	IEA
GO:0035497	cAMP response element binding	molecular function	IEA
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding	molecular function	IDA[15845366\|16940180]
GO:0001558	regulation of cell growth	biological process	IDA[20141198]
GO:0003700	transcription factor activity, sequence-specific DNA binding	molecular function	IDA[10675342\|20091349\|20141198]
GO:0005829	cytosol	cellular component	IMP[15001559]
GO:0000982	transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding	molecular function	IDA[16940180]
GO:0045786	negative regulation of cell cycle	biological process	NAS[10623756]
GO:0002230	positive regulation of defense response to virus by host	biological process	IDA[20091349]
GO:0006366	transcription from RNA polymerase II promoter	biological process	IMP[16940180]
GO:0001077	transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding	molecular function	IMP[16940180]
GO:0016021	integral component of membrane	cellular component	IDA[10623756]; IEA
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	molecular function	IDA[16940180]
GO:0005737	cytoplasm	cellular component	IDA[18391022\|19779205\|20091349]; IMP[10623756\|10675342]
GO:0005783	endoplasmic reticulum	cellular component	IDA[16236796]; IMP[10623756]
GO:0090026	positive regulation of monocyte chemotaxis	biological process	IDA[17296613]
GO:0034976	response to endoplasmic reticulum stress	biological process	IDA[16940180\|18391022]; IDA[15845366]
GO:0042994	cytoplasmic sequestering of transcription factor	biological process	IDA[20091349]

CREB3 related KEGG pathways (count: 4)

ID	Name	Brief Description	Full Description
Literature-origin KEGG pathway
hsa05215	prostate cancer	Prostate cancer	The identification of key molecular alterations in prostate-...... The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes that catalyze conjunction of glutathione with harmful, electrophilic molecules, thereby protecting cells from carcinogenic factors. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by such carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. After therapeutic reduction in the levels of testosterone and dihydrotestosterone, the emergence of androgen-independent prostate cancer has been associated with mutations in the androgen receptor (AR) that permit receptor activation by other ligands, increased expression of androgen receptors accompanying AR amplification, and ligand-independent androgen-receptor activation. More...

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04916	melanogenesis	Melanogenesis	Cutaneous melanin pigment plays a critical role in camouflag...... Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism. More...
hsa04962	vasopressin regulated_water_reabsorption	Vasopressin-regulated water reabsorption	In the kidney, the antidiuretic hormone vasopressin (AVP) is...... In the kidney, the antidiuretic hormone vasopressin (AVP) is a critical regulator of water homeostasis by controlling the water movement from lumen to the interstitium for water reabsorption and adjusting the urinary water excretion. In normal physiology, AVP is secreted into the circulation by the posterior pituitary gland, in response to an increase in serum osmolality or a decrease in effective circulating volume. When reaching the kidney, AVP binds to V2 receptors on the basolateral surface of the collecting duct epithelium, triggering a G-protein-linked signaling cascade, which leads to water channel aquaporin-2 (AQP2) vesicle insertion into the apical plasma membrane. This results in higher water permeability in the collecting duct and, driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels, which are constitutively expressed on the basolateral side of these cells. When isotonicity is restored, reduced blood AVP levels results in AQP2 internalization, leaving the apical membrane watertight again. More...
hsa05016	huntingtons disease	Huntington's disease	Huntington disease (HD) is an autosomal-dominant neurodegene...... Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NR2B/NR1 NMDAR activity, and destabilizing mitochondrial Ca2+ handling. As a result, stimulation of glutamate receptors leads to supranormal Ca2+ responses in HD MSN and mitochondrial Ca2+ overload. The mHtt translocates to the nucleus, where it forms intranuclear inclusions, though they are not primarily responsible for toxicity. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction. More...

CREB3 related BioCarta pathways (count: 0)

CREB3 related Reactome pathways (count: 0)

CREB3 related interactors from protein-protein interaction data in HPRD (count: 8)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
CREB3	CCR1	No	in vivo;yeast 2-hybrid	15001559
CREB3	BNIP2	No	yeast 2-hybrid	16189514
CREB3	NFIL3	Yes	in vitro	12805554
CREB3	STX8	No	yeast 2-hybrid	16189514
CREB3	APPBP2	No	yeast 2-hybrid	16189514
CREB3	EMD	No	yeast 2-hybrid	16189514
CREB3	MALL	No	yeast 2-hybrid	16189514
CREB3	HCFC1	No	in vitro;in vivo	9658067 , 9389645 , 12235138 , 12271126 , 15705566

Gene Report

Gene mapped GO terms

Literature-origin KEGG pathway

Gene mapped KEGG pathways