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This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory respo... See more...
Aliases for CREB3L3 Gene
Aliases for CREB3L3 Gene
External Ids for CREB3L3 Gene
- HGNC: 18855
- Entrez Gene: 84699
- Ensembl: ENSG00000060566
- OMIM: 611998
- UniProtKB: Q68CJ9
Previous GeneCards Identifiers for CREB3L3 Gene
- GC19P004104
- GC19P003917
Summaries for CREB3L3 Gene
-
This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]
GeneCards Summary for CREB3L3 Gene
CREB3L3 (CAMP Responsive Element Binding Protein 3 Like 3) is a Protein Coding gene. Diseases associated with CREB3L3 include Spondyloepimetaphyseal Dysplasia, Strudwick Type and Platyspondylic Lethal Skeletal Dysplasia, Torrance Type. Among its related pathways are Lipoprotein metabolism and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and sequence-specific DNA binding. An important paralog of this gene is CREB3L4.
UniProtKB/Swiss-Prot Summary for CREB3L3 Gene
-
Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression.
Additional gene information for CREB3L3 Gene
- HGNC(18855)
- Entrez Gene(84699)
- Ensembl(ENSG00000060566)
- OMIM(611998)
- UniProtKB(Q68CJ9)
- Open Targets Platform(ENSG00000060566)
- Monarch Initiative
- Search for CREB3L3 at DataMed
- Search for CREB3L3 at HumanCyc
No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CREB3L3 Gene
Genomics for CREB3L3 Gene
GeneHancer (GH) Regulatory Elements Pubs
Promoters and enhancers for CREB3L3 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association
Download GeneHancer data from 2017 publication |
Request up-to-date GeneHancer data (full dataset)
GeneHancers around CREB3L3 on the GeneHancer Hub at the UCSC Golden Path
Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CREB3L3
- Top Transcription factor binding sites by QIAGEN in the CREB3L3 gene promoter:
-
- CREB
- deltaCREB
- Elk-1
- HNF-4alpha1
- STAT3
- TBP
Genomic Locations for CREB3L3 Gene
Genomic Locations for CREB3L3 Gene
- chr19:4,153,631-4,173,054
- (GRCh38/hg38)
- Size:
- 19,424 bases
- Orientation:
- Plus strand
- chr19:4,153,598-4,173,051
- (GRCh37/hg19)
- Size:
- 19,454 bases
- Orientation:
- Plus strand
Genomic View for CREB3L3 Gene
Genes around CREB3L3 on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 19p13.3 by HGNC
- 19p13.3 by Entrez Gene
- 19p13.3 by Ensembl
CREB3L3 Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for CREB3L3 Gene
Proteins for CREB3L3 Gene
-
Protein details for CREB3L3 Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- Q68CJ9-CR3L3_HUMAN
- Recommended name:
- Cyclic AMP-responsive element-binding protein 3-like protein 3
- Protein Accession:
- Q68CJ9
- B2R7S6
- B7ZL69
- M0QYW7
- Q6ZMC5
- Q96TB9
Protein attributes for CREB3L3 Gene
- Size:
- 461 amino acids
- Molecular mass:
- 49077 Da
- Quaternary structure:
-
- Binds DNA as a dimer (By similarity). Probably homodimerizes. Probably forms a heterodimer with ATF6. Interacts with ATF6.
- SequenceCaution:
-
- Sequence=BAD18804.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAD18804.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
Protein Expression for CREB3L3 Gene
Post-translational modifications for CREB3L3 Gene
- Controlled by regulated intramembrane proteolysis (RIP). Following ER stress a fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2).
- N- and O-glycosylated. N-glycosylation is required for optimal proteolytic activation. O-glycosylated with core 1 or possibly core 8 glycans.
-
Glycosylation at Ser379, Asn410, Asn413, Asn420, and Asn427
- NX_Q68CJ9 (NX_Q68CJ9-1)
- Modification sites at PhosphoSitePlus
-
Glycosylation from GlyConnect
- CR3L3_HUMAN (804)
Other Protein References for CREB3L3 Gene
- ENSEMBL proteins:
- REFSEQ proteins:
Antibody Products
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Abcam antibodies for CREB3L3
- Invitrogen Antibodies for CREB3L3 (AFLGC-CREB3L3)
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Protein Products
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No data available for DME Specific Peptides for CREB3L3 Gene
Domains & Families for CREB3L3 Gene
Gene Families for CREB3L3 Gene
- HGNC:
- Human Protein Atlas (HPA):
-
- Predicted intracellular proteins
- Predicted membrane proteins
- Transcription factors
Protein Domains for CREB3L3 Gene
Suggested Antigen Peptide Sequences for CREB3L3 Gene
- GenScript: Design optimal peptide antigens:
-
- CREB3L3 protein (B7ZL69_HUMAN)
- Transcription factor CREB-H (CR3L3_HUMAN)
Graphical View of Domain Structure for InterPro Entry
Q68CJ9- Family:
-
- Belongs to the bZIP family. ATF subfamily.
Function for CREB3L3 Gene
Molecular function for CREB3L3 Gene
- UniProtKB/Swiss-Prot Function:
- Transcription factor that may act during endoplasmic reticulum stress by activating unfolded protein response target genes. Activated in response to cAMP stimulation. In vitro, binds to the cAMP response element (CRE) and box-B element. Activates transcription through box-B element. Activates transcription through CRE (By similarity). Seems to function synergistically with ATF6. In acute inflammatory response, may activate expression of acute phase response (APR) genes. May be involved in growth suppression.
Phenotypes From GWAS Catalog for CREB3L3 Gene
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000976 | transcription regulatory region sequence-specific DNA binding | IDA | 16469704 |
| GO:0000977 | RNA polymerase II regulatory region sequence-specific DNA binding | IDA | 11353085 |
| GO:0000981 | DNA-binding transcription factor activity, RNA polymerase II-specific | ISM | 19274049 |
| GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | IMP | 11353085 |
| GO:0003677 | DNA binding | IEA | -- |
Phenotypes for CREB3L3 Gene
- MGI mutant phenotypes for CREB3L3:
- inferred from 3 alleles
- GenomeRNAi human phenotypes for CREB3L3:
Animal Models for CREB3L3 Gene
Animal Model Products
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CRISPR Products
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Horizon Cell Lines for CREB3L3
No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CREB3L3 Gene
Localization for CREB3L3 Gene
Subcellular locations from UniProtKB/Swiss-Prot for CREB3L3 Gene
- Endoplasmic reticulum membrane. Single-pass type II membrane protein.
- [Processed cyclic AMP-responsive element-binding protein 3-like protein 3]: Nucleus. Note=Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus.
| Compartment | Confidence |
|---|---|
| nucleus | 5 |
| endoplasmic reticulum | 4 |
| cytosol | 4 |
| golgi apparatus | 4 |
| extracellular | 2 |
| mitochondrion | 2 |
| peroxisome | 2 |
| plasma membrane | 1 |
| cytoskeleton | 1 |
| endosome | 1 |
| lysosome | 1 |
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0000139 | Golgi membrane | TAS | -- |
| GO:0000790 | nuclear chromatin | ISA | -- |
| GO:0005634 | nucleus | IDA | 16469704 |
| GO:0005654 | nucleoplasm | TAS | -- |
| GO:0005783 | endoplasmic reticulum | IDA | 16236796 |
No data available for Subcellular locations from the Human Protein Atlas (HPA) for CREB3L3 Gene
Pathways & Interactions for CREB3L3 Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Aldosterone synthesis and secretion |
.41
|
.41
|
| 2 | Relaxin signaling pathway | ||
| 3 | Lipoprotein metabolism | ||
| 4 | cGMP-PKG signaling pathway | ||
| 5 | Amphetamine addiction | ||
Pathways by source for CREB3L3 Gene
3 Sino Biological pathways for CREB3L3 Gene
1 BioSystems pathway for CREB3L3 Gene
5 Reactome pathways for CREB3L3 Gene
33 KEGG pathways for CREB3L3 Gene
Interacting Proteins for CREB3L3 Gene
Selected Interacting proteins:
Q68CJ9-CR3L3_HUMAN
ENSP00000078445
for CREB3L3 Gene via
UniProtKB
STRING
IID
GPS-Prot Interaction Network for CREB3L3
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0002675 | positive regulation of acute inflammatory response | NAS | 16469704 |
| GO:0006355 | regulation of transcription, DNA-templated | IEA | -- |
| GO:0006986 | response to unfolded protein | IEA | -- |
| GO:0030968 | endoplasmic reticulum unfolded protein response | TAS | -- |
| GO:0045944 | positive regulation of transcription by RNA polymerase II | IMP | 11353085 |
No data available for SIGNOR curated interactions for CREB3L3 Gene
Drugs & Compounds for CREB3L3 Gene
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| cyclic amp | Experimental | Pharma | 0 |
Transcripts for CREB3L3 Gene
mRNA/cDNA for CREB3L3 Gene
- 4 REFSEQ mRNAs :
- 9 NCBI additional mRNA sequence :
- 5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :
-
- ENST00000078445 2588 nts (view in UCSC)
- ENST00000595923 1491 nts (view in UCSC)
- ENST00000598894 564 nts (view in UCSC)
- ENST00000602147 1382 nts (view in UCSC)
- ENST00000602257 1475 nts (view in UCSC)
CRISPR Products
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miRNA Products
Inhibitory RNA Products
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Clone Products
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- Sino Biological Human cDNA Clone for CREB3L3
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| ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6a | · | 6b | ^ | 7 | ^ | 8a | · | 8b | ^ | 9 | ^ | 10 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SP1: | |||||||||||||||||||||||||
| SP2: | |||||||||||||||||||||||||
| SP3: | - | - | - |
Relevant External Links for CREB3L3 Gene
- GeneLoc Exon Structure for
- CREB3L3
Expression for CREB3L3 Gene
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
mRNA differential expression in normal tissues according to GTEx for CREB3L3 Gene
This gene is overexpressed in Liver (x47.5) and Small Intestine - Terminal Ileum (x4.0).
This gene is overexpressed in Peripheral blood mononuclear cells (60.1) and NK cells (8.9).
Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CREB3L3 Gene
Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CREB3L3
SOURCE GeneReport for Unigene cluster for CREB3L3 Gene:
Hs.247744mRNA Expression by UniProt/SwissProt for CREB3L3 Gene:
Q68CJ9-CR3L3_HUMAN
Tissue specificity:
Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues.
Evidence on tissue expression from TISSUES for CREB3L3 Gene
- Liver(4.7)
- Intestine(4.5)
- Nervous system(4.4)
- Blood(2.4)
- Pancreas(2.3)
- Muscle(2.2)
- Spleen(2.2)
- Kidney(2.2)
- Heart(2.1)
Phenotype-based relationships between genes and organs from Gene ORGANizer for CREB3L3 Gene
Germ Layers:
- endoderm
- mesoderm
Systems:
- cardiovascular
- digestive
Regions:
Head and neck:
- ear
Thorax:
- heart
Abdomen:
- duodenum
- intestine
- liver
- pancreas
- small intestine
General:
- blood vessel
Primer Products
-
OriGene qPCR primer pairs for CREB3L3
-
OriGene qPCR primer pairs and template standards for CREB3L3
Gene Expression Assay Products
Orthologs for CREB3L3 Gene
This gene was present in the common ancestor of animals.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| Chimpanzee (Pan troglodytes) |
Mammalia | CREB3L3 30 31 |
|
OneToOne | |
| Dog (Canis familiaris) |
Mammalia | CREB3L3 30 31 |
|
OneToOne | |
| Cow (Bos Taurus) |
Mammalia | CREB3L3 30 31 |
|
OneToOne | |
| Mouse (Mus musculus) |
Mammalia | Creb3l3 30 17 31 |
|
OneToOne | |
| Rat (Rattus norvegicus) |
Mammalia | Creb3l3 30 |
|
||
| Platypus (Ornithorhynchus anatinus) |
Mammalia | CREB3L3 31 |
|
OneToOne | |
| Oppossum (Monodelphis domestica) |
Mammalia | CREB3L3 31 |
|
OneToOne | |
| Chicken (Gallus gallus) |
Aves | CREB3L3 30 31 |
|
OneToOne | |
| Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC101733496 30 |
|
||
| Zebrafish (Danio rerio) |
Actinopterygii | creb3l3a 30 31 |
|
OneToMany | |
| CREB3L3 (2 of 2) 31 |
|
OneToMany | |||
| Worm (Caenorhabditis elegans) |
Secernentea | let-607 31 |
|
OneToMany | |
| Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
- Species where no ortholog for CREB3L3 was found in the sources mined by GeneCards:
-
- A. gosspyii yeast (Eremothecium gossypii)
- Actinobacteria (Mycobacterium tuberculosis)
- African clawed frog (Xenopus laevis)
- African malaria mosquito (Anopheles gambiae)
- Alicante grape (Vitis vinifera)
- Alpha proteobacteria (Wolbachia pipientis)
- Amoeba (Dictyostelium discoideum)
- Archea (Pyrococcus horikoshii)
- Baker's yeast (Saccharomyces cerevisiae)
- Barley (Hordeum vulgare)
- Beta proteobacteria (Neisseria meningitidis)
- Bread mold (Neurospora crassa)
- Chromalveolata (Phytophthora infestans)
- Common water flea (Daphnia pulex)
- Corn (Zea mays)
- E. coli (Escherichia coli)
- Filamentous fungi (Aspergillus nidulans)
- Firmicute Bacteria (Streptococcus pneumoniae)
- Fission Yeast (Schizosaccharomyces pombe)
- Fruit Fly (Drosophila melanogaster)
- Green Algae (Chlamydomonas reinhardtii)
- Honey Bee (Apis mellifera)
- K. Lactis Yeast (Kluyveromyces lactis)
- Lizard (Anolis carolinensis)
- Loblloly Pine (Pinus taeda)
- Malaria Parasite (Plasmodium falciparum)
- Medicago Trunc (Medicago Truncatula)
- Moss (Physcomitrella patens)
- Orangutan (Pongo pygmaeus)
- Pig (Sus scrofa)
- Rainbow Trout (Oncorhynchus mykiss)
- Rice (Oryza sativa)
- Rice Blast Fungus (Magnaporthe grisea)
- Schistosome Parasite (Schistosoma mansoni)
- Sea Anemone (Nematostella vectensis)
- Sea Vase (Ciona intestinalis)
- Sea Urchin (Strongylocentrotus purpuratus)
- Sorghum (Sorghum bicolor)
- Soybean (Glycine max)
- Stem Rust Fungus (Puccinia graminis)
- Sugarcane (Saccharum officinarum)
- Thale Cress (Arabidopsis thaliana)
- Tomato (Lycopersicon esculentum)
- Toxoplasmosis (Toxoplasma gondii)
- Trichoplax (Trichoplax adhaerens)
- Wheat (Triticum aestivum)
Evolution for CREB3L3 Gene
- ENSEMBL:
- Gene Tree for CREB3L3 (if available)
- TreeFam:
- Gene Tree for CREB3L3 (if available)
- Aminode:
- Evolutionary constrained regions (ECRs) for CREB3L3: view image
Paralogs for CREB3L3 Gene
Variants for CREB3L3 Gene
Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CREB3L3 Gene
| SNP ID | Clinical significance and condition | Chr 19 pos | Variation | AA Info | Type |
|---|---|---|---|---|---|
| 714753 | Benign: not provided | 4,171,828(+) | G/A | SYNONYMOUS_VARIANT,THREE_PRIME_UTR_VARIANT | |
| 731136 | Benign: not provided | 4,171,930(+) | A/G | SYNONYMOUS_VARIANT,THREE_PRIME_UTR_VARIANT | |
| 845893 | Uncertain Significance: not provided | 4,157,190(+) | C/T | MISSENSE_VARIANT | |
| 852932 | Likely Pathogenic: not provided | 4,164,502(+) | G/A | SPLICE_ACCEPTOR_VARIANT,INTRON_VARIANT |
| Variant ID | Type | Subtype | PubMed ID |
|---|---|---|---|
| esv2717979 | CNV | deletion | 23290073 |
| esv3643488 | CNV | gain | 21293372 |
| esv3643489 | CNV | loss | 21293372 |
| nsv1109160 | CNV | deletion | 24896259 |
| nsv833716 | CNV | loss | 17160897 |
| nsv962993 | CNV | duplication | 23825009 |
Residual Variation Intolerance Score:
83.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score:
1.64;
31.39% of all genes are more intolerant (likely to be disease-causing)
Additional Variant Information for CREB3L3 Gene
SNP Genotyping and Copy Number Assay Products
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CREB3L3 Gene
Disorders for CREB3L3 Gene
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| spondyloepimetaphyseal dysplasia, strudwick type |
|
|
| platyspondylic lethal skeletal dysplasia, torrance type |
|
|
| hepatocellular carcinoma |
|
|
| otospondylomegaepiphyseal dysplasia, autosomal recessive |
|
|
Search CREB3L3 in MalaCards
View complete list of genes associated with diseases
Additional Disease Information for CREB3L3
- Genetic Association Database
- (GAD)
- ATLAS of Genetics and Cytogenetics in Oncology and Haematology
- Open Targets Platform
No data available for UniProtKB/Swiss-Prot and Genatlas for CREB3L3 Gene
Publications for CREB3L3 Gene
- CREB-H: a novel mammalian transcription factor belonging to the CREB/ATF family and functioning via the box-B element with a liver-specific expression. (PMID: 11353085) Omori Y … Sugano S (Nucleic acids research 2001) 2 3 4
- Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. (PMID: 16469704) Zhang K … Kaufman RJ (Cell 2006) 3 4
- Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas. (PMID: 15221005) Yamada S … Nakagawara A (Oncogene 2004) 3 4
- A reference map of the human binary protein interactome. (PMID: 32296183) Luck K … Calderwood MA (Nature 2020) 3
- CREBH Regulates Systemic Glucose and Lipid Metabolism. (PMID: 29738435) Nakagawa Y … Shimano H (International journal of molecular sciences 2018) 3
ExternalLinks
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- Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for CREB3L3
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for CREB3L3
- Search GeneCopoeia for miRNA 3'UTR Target clone products for CREB3L3
- Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CREB3L3
- Boster Bio Antibodies for CREB3L3
- Browse Boster Bio ELISA Kits
- Biorbyt antibodies for CREB3L3
Sources for CREB3L3 Gene
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