CREB3L3 cAMP responsive element binding protein 3 like 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CREB3L3provided by HGNC
Official Full Name: cAMP responsive element binding protein 3 like 3provided by HGNC
Primary source: HGNC:HGNC:18855
See related: Ensembl:ENSG00000060566 MIM:611998; AllianceGenome:HGNC:18855
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: CREBH; HYTG2; CREB-H; HYST1481
Summary: 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]
Expression: Biased expression in small intestine (RPKM 71.0), duodenum (RPKM 67.5) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (4153631..4173054)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (4136949..4156361)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (4153628..4173051)

Chromosome 19 - NC_000019.10 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?

A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity.
Title: A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity.
CREBH normalizes dyslipidemia and halts atherosclerosis in diabetes by decreasing circulating remnant lipoproteins.
Title: CREBH normalizes dyslipidemia and halts atherosclerosis in diabetes by decreasing circulating remnant lipoproteins.
Loss-of-Function CREB3L3 Variants in Patients With Severe Hypertriglyceridemia.
Title: Loss-of-Function CREB3L3 Variants in Patients With Severe Hypertriglyceridemia.
CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.
Title: CREBH Regulates Systemic Glucose and Lipid Metabolism.
Beta-TrCP controls ubiquitination and degradation of liver-enriched transcription factor CREB-H.
Title: β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H.
Identify a novel pathogenic mutation in CREB3L3 gene in a family with dominant hypertriglyceridemia with a variable pattern of penetrance.
Title: Novel CREB3L3 Nonsense Mutation in a Family With Dominant Hypertriglyceridemia.
CREBH activated by HBx interacted with HBx protein, leading to a synergistic effect on the expression of AP-1 target genes and the proliferation of hepatocellular carcinoma cells and mouse primary hepatocytes.
Title: HBx induces the proliferation of hepatocellular carcinoma cells via AP1 over-expressed as a result of ER stress.
Taken together, our results demonstrated that human APOA5 is directly regulated by CREBH via CREBHRE and provided a new insight into the role of this liver-specific bZIP transcription factor in lipoprotein metabolism and triglyceride homeostasis
Title: Identification and characterization of cyclic AMP response element-binding protein H response element in the human apolipoprotein A5 gene promoter.
Studies indicate that mutations in CREB3L3 in individuals with extreme hypertriglyceridemia.
Title: The role of CREB-H transcription factor in triglyceride metabolism.
a novel mechanism of action of activated CB1R signaling to induce hepatic gluconeogenesis via direct activation of CREBH
Title: Cannabinoid receptor type 1 (CB1R) signaling regulates hepatic gluconeogenesis via induction of endoplasmic reticulum-bound transcription factor cAMP-responsive element-binding protein H (CREBH) in primary hepatocytes.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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

Associated conditions

Description	Tests
Hypertriglyceridemia 2 MedGen: C5543398 OMIM: 619324 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:481831

NoName (e-PCR)
- UniSTS:483460

SHGC-108116 (e-PCR)
- UniSTS:183190

SHGC-86359 (e-PCR)
- UniSTS:183235

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
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 transcription regulatory region sequence-specific DNA 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 heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in positive regulation of acute inflammatory response	NAS Non-traceable Author Statement 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 transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	IDA Inferred from Direct Assay more info	PubMed
involved_in response to unfolded protein	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
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	IDA Inferred from Direct Assay more info	PubMed

General protein information

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

Names: CREB/ATF family transcription factor; cAMP-responsive element-binding protein, hepatic-specific

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.

mRNA and Protein(s)

NM_001271995.2 → NP_001258924.1 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform b

See identical proteins and their annotated locations for NP_001258924.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (b) is shorter than isoform a.

Source sequence(s)

AB073612, AK313099

Consensus CDS

CCDS62500.1

UniProtKB/Swiss-Prot

Q68CJ9

Related

ENSP00000469355.1, ENST00000595923.5

Conserved Domains (2) summary

cd14689
Location:243 → 303

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

cl19878
Location:168 → 265

DUF2207; Predicted membrane protein (DUF2207)
NM_001271996.2 → NP_001258925.1 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform c

See identical proteins and their annotated locations for NP_001258925.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the coding region, compared to variant 1. The encoded isoform (c) is shorter than isoform a.

Source sequence(s)

AB073612, AK313099, BC143609, DA210258

Consensus CDS

CCDS62499.1

UniProtKB/Swiss-Prot

Q68CJ9

Related

ENSP00000472399.1, ENST00000602257.5

Conserved Domains (1) summary

cd14689
Location:242 → 302

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
NM_001271997.2 → NP_001258926.1 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an exon in the coding region which results in a frameshift, compared to variant 1. The encoded isoform (d) is shorter and has a distinct C-terminus, compared to isoform a.

Source sequence(s)

AB073612, AK313099, BC143610, DA210258

Consensus CDS

CCDS62498.1

UniProtKB/Swiss-Prot

Q68CJ9

Related

ENSP00000470119.1, ENST00000602147.1
NM_032607.3 → NP_115996.1 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform a

See identical proteins and their annotated locations for NP_115996.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AB050902, AB073612, AK313099

Consensus CDS

CCDS12121.1

UniProtKB/Swiss-Prot

B2R7S6, B7ZL69, M0QYW7, Q68CJ9, Q6ZMC5, Q96TB9

Related

ENSP00000078445.1, ENST00000078445.7

Conserved Domains (2) summary

cd14689
Location:244 → 304

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

cl19878
Location:169 → 266

DUF2207; Predicted membrane protein (DUF2207)