CREB3L3 (cAMP responsive element binding protein 3 like 3)

Gene

• Entrez ID: 84699
• Gene name: CAMP responsive element binding protein 3 like 3
• Gene symbol: CREB3L3
• Synonyms (NCBI Gene): CREB-H, CREBH, HYST1481, HYTG2
• Chromosome: 19
• Chromosome location: 19p13.3
• 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 enco

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1969371	hsa-miR-3120-5p	CLIP-seq
MIRT2205501	hsa-miR-2467-3p	CLIP-seq
MIRT2205502	hsa-miR-2861	CLIP-seq
MIRT2205503	hsa-miR-3184	CLIP-seq
MIRT2205504	hsa-miR-3192	CLIP-seq
MIRT2205505	hsa-miR-423-5p	CLIP-seq
MIRT2205506	hsa-miR-4300	CLIP-seq
MIRT2205507	hsa-miR-4540	CLIP-seq
MIRT2205508	hsa-miR-661	CLIP-seq
MIRT2205509	hsa-miR-920	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	16469704
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	11353085
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	11353085
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	11353085
GO:0002675	Process	Positive regulation of acute inflammatory response	NAS	16469704
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	16469704, 20102225, 23661758, 32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	16469704
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005783	Component	Endoplasmic reticulum	IDA	16236796, 16469704
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005829	Component	Cytosol	TAS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006986	Process	Response to unfolded protein	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	ISS
GO:0034976	Process	Response to endoplasmic reticulum stress	IDA	16469704
GO:0034976	Process	Response to endoplasmic reticulum stress	IEA
GO:0042802	Function	Identical protein binding	IPI	20102225, 23661758
GO:0042803	Function	Protein homodimerization activity	IPI	16469704
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	16469704
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	11353085
GO:0046982	Function	Protein heterodimerization activity	IPI	16469704

Other IDs

• MIM: 611998
• HGNC: 18855
• e!Ensembl: ENSG00000060566

Protein

• UniProt ID: Q68CJ9
• Protein name: Cyclic AMP-responsive element-binding protein 3-like protein 3 (cAMP-responsive element-binding protein 3-like protein 3) (Transcription factor CREB-H) [Cleaved into: Processed cyclic AMP-responsive element-binding protein 3-like protein 3]
• Protein 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. Activate
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00170	bZIP_1	241 → 304	bZIP transcription factor	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Exclusively expressed in liver. Underexpressed in hepatocellular carcinoma tissues. {ECO:0000269|PubMed:11353085, ECO:0000269|PubMed:15800215}.
• Sequence:

  MNTDLAAGKMASAACSMDPIDSFELLDLLFDRQDGILRHVELGEGWGHVKDQQVLPNPDS
  DDFLSSILGSGDSLPSSPLWSPEGSDSGISEDLPSDPQDTPPRSGPATSPAGCHPAQPGK
  GPCLSYHPGNSCSTTTPGPVIQVPEASVTIDLEMWSPGGRICAEKPADPVDLSPRCNLTV
  KDLLLSGSSGDLQQHHLGASYLLRPGAGHCQELVLTEDEKKLLAKEGITLPTQLPLTKYE
  ERVLKKIRRKIRNKQSAQESRKKKKEYIDGLETRMSACTAQNQELQRKVLHLEKQNLSLL
  EQLKKLQAIVVQSTSKSAQTGTCVAVLLLSFALIILPSISPFGPNKTESPGDFAPVRVFS
  RTLHNDAASRVAADAVPGSEAPGPRPEADTTREESPGSPGADWGFQDTANLTNSTEELDN
  ATLVLRNATEGLGQVALLDWVAPGPSTGSGRAGLEAAGDEL

• Sequence length: 461

Pathways

KEGG:

cGMP-PKG signaling pathway
cAMP signaling pathway
PI3K-Akt signaling pathway
AMPK signaling pathway
Longevity regulating pathway
Adrenergic signaling in cardiomyocytes
TNF signaling pathway
Thermogenesis
Cholinergic synapse
Dopaminergic synapse
Insulin secretion
Estrogen signaling pathway
Melanogenesis
Thyroid hormone synthesis
Glucagon signaling pathway
Aldosterone synthesis and secretion
Relaxin signaling pathway
Cortisol synthesis and secretion
Parathyroid hormone synthesis, secretion and action
Insulin resistance
Cushing syndrome
Growth hormone synthesis, secretion and action
Vasopressin-regulated water reabsorption
Huntington disease
Prion disease
Cocaine addiction
Amphetamine addiction
Alcoholism
Hepatitis B
Human cytomegalovirus infection
Human papillomavirus infection
Human T-cell leukemia virus 1 infection
Viral carcinogenesis
Chemical carcinogenesis - receptor activation
Prostate cancer

Reactome:

CREB3 factors activate genes

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypertriglyceridemia 2	Likely pathogenic; Pathogenic	rs912378886, rs2145120326	RCV001450096 RCV001450097	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CREB3L3-related disorder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Episodic kinesigenic dyskinesia 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTRIGLYCERIDEMIA	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertriglyceridemia 1	Conflicting classifications of pathogenicity	ClinVar Disgenet, GenCC Disgenet, GenCC	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TRANSIENT INFANTILE HYPERTRIGLYCERIDEMIA AND HEPATOSTEATOSIS	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Relationship Type	References	Evidence Score
Complex Regional Pain Syndromes	Associate	31217010	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Associate	37880674	★☆☆☆☆ Found in Text Mining only
Hypertriglyceridemia	Associate	22135386, 32580631, 39562229	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatitis	Associate	39562229	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Associate	34930465	★☆☆☆☆ Found in Text Mining only