CREB3 cAMP responsive element binding protein 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CREB3provided by HGNC
Official Full Name: cAMP responsive element binding protein 3provided by HGNC
Primary source: HGNC:HGNC:2347
See related: Ensembl:ENSG00000107175 MIM:606443; AllianceGenome:HGNC:2347
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LZIP; LUMAN; sLZIP
Summary: This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds to the cAMP-response element and regulates cell proliferation. The protein interacts with host cell factor C1, which also associates with the herpes simplex virus (HSV) protein VP16 that induces transcription of HSV immediate-early genes. This protein and VP16 both bind to the same site on host cell factor C1. It is thought that the interaction between this protein and host cell factor C1 plays a role in the establishment of latency during HSV infection. This protein also plays a role in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. Additional transcript variants have been identified, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]
Expression: Ubiquitous expression in prostate (RPKM 27.8), testis (RPKM 25.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p13.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (35732666..35736999)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (35753346..35757679)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (35732663..35736996)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Potentially functional genetic variants in ferroptosis-related CREB3 and GALNT14 genes predict survival of hepatitis B virus-related hepatocellular carcinoma.
Title: Potentially functional genetic variants in ferroptosis-related CREB3 and GALNT14 genes predict survival of hepatitis B virus-related hepatocellular carcinoma.
Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death.
Title: Dysregulated CREB3 cleavage at the nuclear membrane induces karyoptosis-mediated cell death.
CREB3 Plays an Important Role in HPSE-Facilitated HSV-1 Release in Human Corneal Epithelial Cells.
Title: CREB3 Plays an Important Role in HPSE-Facilitated HSV-1 Release in Human Corneal Epithelial Cells.
Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder.
Title: Role of small leucine zipper protein in hepatic gluconeogenesis and metabolic disorder.
Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells.
Title: Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells.
Knockdown of CREB3 activates endoplasmic reticulum stress and induces apoptosis in glioblastoma.
Title: Knockdown of CREB3 activates endoplasmic reticulum stress and induces apoptosis in glioblastoma.
The stability of CREB3/Luman is regulated by protein kinase CK2 phosphorylation.
Title: The stability of CREB3/Luman is regulated by protein kinase CK2 phosphorylation.
Endogenous full-length CREB3 was identified as a novel substrate for ERAD in HEK293 cells.
Title: Regulation of the ER-bound transcription factor Luman/CREB3 in HEK293 cells.
Results show that CREB3 is a direct target of miR-203a and is considered an oncogene in osteosarcoma tumors and cell lines.
Title: Circular RNA circTADA2A promotes osteosarcoma progression and metastasis by sponging miR-203a-3p and regulating CREB3 expression.
CREB3 was identified as a transcriptional regulator of upregulated ER-Golgi trafficking genes ARF4, COPB1, and USO1, and silencing of these genes attenuated the metastatic phenotype in vitro and lung colonization in vivo. Modulation of ER-Golgi trafficking plays an important role in metastatic progression.
Title: A CREB3-regulated ER-Golgi trafficking signature promotes metastatic progression in breast cancer.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of cAMP responsive element binding protein 3 (CREB3; LZIP) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	The central region of luman (residues 100-314) and the residues 751 to 768 of HIV-1 gp41 are required for luman-Env interaction	PubMed
	env	Interaction between the TMgp41 subunit of HIV-1 Env and Luman affects the stability of the full-length Luman protein	PubMed
	env	Overexpression of Luman in cells transfected with HIV-1 provirus decreases the intracellular expression of Gag and Env and leads to a decrease in virion release	PubMed
Pr55(Gag)	gag	Overexpression of Luman in cells transfected with HIV-1 provirus decreases the intracellular expression of Gag and Env and leads to a decrease in virion release	PubMed
Tat	tat	Luman, a transcription factor of the CREB/ATF family, downregulates HIV-1 Tat-mediated transactivation	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-20292 (e-PCR)
- UniSTS:36687

RH11800 (e-PCR)
- UniSTS:80517

RH79942 (e-PCR)
- UniSTS:93092

WI-19282 (e-PCR)
- UniSTS:8931

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CCR1 chemokine receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables cAMP response element binding protein binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	TAS Traceable Author Statement more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coregulator binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in cytoplasmic sequestering of transcription factor	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum unfolded protein response	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment of viral latency	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in induction of positive chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in induction of positive chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in induction of positive chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in integrated stress response signaling	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of cell cycle	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of deacetylase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of defense response to virus by host	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of monocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
involved_in release from viral latency	IDA Inferred from Direct Assay more info	PubMed
involved_in release from viral latency	TAS Traceable Author Statement more info	PubMed
NOT involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IMP Inferred from Mutant Phenotype more info	PubMed
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info
part_of RNA polymerase II transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IMP Inferred from Mutant Phenotype more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
NOT located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: cyclic AMP-responsive element-binding protein 3

Names: basic leucine zipper protein; cyclic AMP response element (CRE)-binding protein/activating transcription factor 1; leucin zipper proitein; small leucine zipper protein; transcription factor LZIP-alpha

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046983.1 RefSeqGene

Range

5347..9680

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_006368.5 → NP_006359.3 cyclic AMP-responsive element-binding protein 3

See identical proteins and their annotated locations for NP_006359.3

Status: REVIEWED

Source sequence(s)

AF211848, BG701230

Consensus CDS

CCDS6588.1

UniProtKB/Swiss-Prot

D0PTW6, O14671, O14919, O43889, Q5TCV1, Q96GK8, Q9H2W3, Q9UE77

UniProtKB/TrEMBL

B2R947

Related

ENSP00000342136.2, ENST00000353704.3

Conserved Domains (2) summary

cd14689
Location:151 → 211

bZIP_CREB3; Basic leucine zipper (bZIP) domain of Cyclic AMP-responsive element-binding protein 3 (CREB3) and similar proteins: a DNA-binding and dimerization domain

cl28204
Location:85 → 222

GlgA; Glycogen synthase [Carbohydrate transport and metabolism]