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

  • CAMP Responsive Element Binding Protein 3 Like 3 2 3 5
  • Cyclic AMP-Responsive Element-Binding Protein 3-Like Protein 3 3 4
  • CAMP-Responsive Element-Binding Protein, Hepatic-Specific 2 3
  • CREBH 3 4
  • CAMP-Responsive Element-Binding Protein 3-Like Protein 3 4
  • CREB/ATF Family Transcription Factor 3
  • Transcription Factor CREB-H 4
  • HYST1481 3
  • CREB-H 3

External Ids for CREB3L3 Gene

Previous GeneCards Identifiers for CREB3L3 Gene

  • GC19P004104
  • GC19P003917

Summaries for CREB3L3 Gene

Entrez Gene Summary 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 Hepatocellular Carcinoma. Among its related pathways are Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 and Circadian entrainment. 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

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 for CREB3L3 Gene

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 UCSC Golden Path with GeneCards custom track

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
chr19:4,153,601-4,173,054
(GRCh38/hg38)
Size:
19,454 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:
CREB3L3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CREB3L3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene 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
    Secondary Accessions:
    • 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; Positions=445; Evidence={ECO:0000305}; Sequence=BAD18804.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};

    Alternative splice isoforms for CREB3L3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry 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
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • CR3L3_HUMAN (804)

Other Protein References for CREB3L3 Gene

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

Blocks:
InterPro:
ProtoNet:

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

UniProtKB/Swiss-Prot:

CR3L3_HUMAN :
  • Belongs to the bZIP family. ATF subfamily.
Family:
  • Belongs to the bZIP family. ATF subfamily.
genes like me logo Genes that share domains with CREB3L3: view

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

Gene Ontology (GO) - Molecular Function 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 --
genes like me logo Genes that share ontologies with CREB3L3: view
genes like me logo Genes that share phenotypes with CREB3L3: view

Animal Models for CREB3L3 Gene

MGI Knock Outs for CREB3L3:

Animal Model Products

CRISPR Products

Clone Products

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.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CREB3L3 gene
Compartment Confidence
nucleus 5
endoplasmic reticulum 4
cytosol 4
golgi apparatus 4
extracellular 1

Gene Ontology (GO) - Cellular Components for CREB3L3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005634 nucleus IDA 16469704
GO:0005654 nucleoplasm TAS --
GO:0005783 endoplasmic reticulum IDA 16236796
GO:0005789 endoplasmic reticulum membrane TAS --
genes like me logo Genes that share ontologies with CREB3L3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CREB3L3 Gene

Pathways & Interactions for CREB3L3 Gene

genes like me logo Genes that share pathways with CREB3L3: view

Gene Ontology (GO) - Biological Process for CREB3L3 Gene

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
genes like me logo Genes that share ontologies with CREB3L3: view

No data available for SIGNOR curated interactions for CREB3L3 Gene

Drugs & Compounds for CREB3L3 Gene

(1) Drugs for CREB3L3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
genes like me logo Genes that share compounds with CREB3L3: view

Transcripts for CREB3L3 Gene

mRNA/cDNA for CREB3L3 Gene

(4) REFSEQ mRNAs :
(9) Additional mRNA sequences :
(7) Selected AceView cDNA sequences:
(5) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CREB3L3 Gene

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
ECgene alternative splicing isoforms for
CREB3L3

Expression for CREB3L3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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).

Protein differential expression in normal tissues from HIPED for CREB3L3 Gene

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



Protein tissue co-expression partners for CREB3L3 Gene

NURSA nuclear receptor signaling pathways regulating expression of CREB3L3 Gene:

CREB3L3

SOURCE GeneReport for Unigene cluster for CREB3L3 Gene:

Hs.247744

mRNA 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(4.3)
  • Nervous system(4.2)

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
genes like me logo Genes that share expression patterns with CREB3L3: view

Orthologs for CREB3L3 Gene

This gene was present in the common ancestor of animals.

Orthologs for CREB3L3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CREB3L3 33 32
  • 98.92 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CREB3L3 33 32
  • 79.18 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CREB3L3 33 32
  • 79.09 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Creb3l3 17 33 32
  • 75 (n)
rat
(Rattus norvegicus)
Mammalia Creb3l3 32
  • 73.26 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CREB3L3 33
  • 70 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CREB3L3 33
  • 56 (a)
OneToOne
chicken
(Gallus gallus)
Aves CREB3L3 33 32
  • 65.75 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC101733496 32
  • 54.67 (n)
zebrafish
(Danio rerio)
Actinopterygii creb3l3a 33 32
  • 61.34 (n)
OneToMany
CREB3L3 (2 of 2) 33
  • 41 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea let-607 33
  • 17 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 33
  • 23 (a)
OneToMany
Species where no ortholog for CREB3L3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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 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

Paralogs for CREB3L3 Gene

(1) SIMAP similar genes for CREB3L3 Gene using alignment to 4 proteins:

  • CR3L3_HUMAN
  • B7ZL69_HUMAN
  • M0QYW7_HUMAN
  • Q9Y4A3_HUMAN
genes like me logo Genes that share paralogs with CREB3L3: view

Variants for CREB3L3 Gene

Sequence variations from dbSNP and Humsavar for CREB3L3 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs1000061108 -- 4,172,722(+) C/T 3_prime_UTR_variant
rs1000233955 -- 4,153,637(+) G/A 5_prime_UTR_variant
rs1000310191 -- 4,156,802(+) C/G intron_variant
rs1000394031 -- 4,170,978(+) C/G intron_variant
rs1000468498 -- 4,161,826(+) T/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for CREB3L3 Gene

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

Variation tolerance for CREB3L3 Gene

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

Human Gene Mutation Database (HGMD)
CREB3L3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CREB3L3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CREB3L3 Gene

Disorders for CREB3L3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for CREB3L3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hepatocellular carcinoma
  • hcc
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for CREB3L3

genes like me logo Genes that share disorders with CREB3L3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CREB3L3 Gene

Publications for CREB3L3 Gene

  1. 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 56
  2. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. (PMID: 16469704) Zhang K … Kaufman RJ (Cell 2006) 3 4 56
  3. 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 56
  4. CREBH Regulates Systemic Glucose and Lipid Metabolism. (PMID: 29738435) Nakagawa Y … Shimano H (International journal of molecular sciences 2018) 3 56
  5. β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H. (PMID: 27029215) Cheng Y … Jin DY (Scientific reports 2016) 3 56

Products for CREB3L3 Gene

Sources for CREB3L3 Gene