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FLASH GENE

Symbol

CREB3L1

contributors: mct - updated : 23-12-2013

HGNC name	cAMP responsive element binding protein 3-like 1
HGNC id	18856

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a putative C-terminal hydrophobic transmembrane domain, a typical structural feature for the transcription factors activated by regulated intramembrane proteolysis
	a bZip domain
	a predicted transmembrane domain
	an adjacent cleavage site for the Golgi protease S1P, with conserved features which indicate that it represents a specific subclass of S1P sites

HOMOLOGY

interspecies	homolog to rattus Creb3l1 (91.9pc)
	homolog to murine Creb3l1 (92.3pc)

intraspecies

homolog to CREB3L2

Homologene

FAMILY

CREB/ATF family of transcription factors

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus
text	truncation of transmembrane domain resulted in a significant increase in transcriptional activity and altered its subcellular localization from the endoplasmic reticulum to the nucleus

basic FUNCTION	involved in regulation of transcription, DNA-dependent (transcriptional activator)
	activating the transcription of COL1A1 through an UPRE-like sequence in the osteoblast-specific COL1A1 promoter region, and thus is critical for bone formation (Murakami 2009)
	CREB3L1 and CREB3L2, have the ability to up-regulate the secretory pathway in nonsecretory cell types
	may play a role in bone formation through the expression of type I collagen and the secretion of bone matrix proteins in fracture healing
	basic leucine zipper transmembrane transcription factor localized in the endoplasmic reticulum (ER) that is cleaved in its transmembrane region in response to ER stress
	plays crucial roles in promoting the differentiation of early goblet cells to mature goblet cells in the large intestine
	may play roles not only in the differentiation of goblet cells but also in protecting these cells from ER stress
	CREB3L2 and CREB3L1 are ER stress transducers with roles in chondrogenesis and osteogenesis
	modulates cell- or tissue-specific unfolded protein response signalling
	plays an important role in suppressing tumorigenesis and its loss of expression is required for the development of a metastatic phenotype

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

CREB3L4 and CREB3L1 may form a heterodimer that promotes the expression of target genes required for the differentiation of goblet cells

INTERACTION

DNA

RNA

small molecule

protein	transcription factor GCM1, which is necessary for astrocyte differentiation in Drosophila, is revealed to be a target of CREB3L1
	CREB3L1 and CREB3L2 are substrates of FBXW7 controling osteogenesis and chondrogenesis by targeting CREB3L1 and CREB3L2, respectively, for degradation

cell & other

REGULATION

induced by	gliosis
		by bone morphogenetic protein-2 (BMP2)

Other

regulation of transcriptional activation by the transmembrane domain, processed by regulated intramembrane proteolysis in response to ER stress

ASSOCIATED DISORDERS

corresponding disease(s)

OIXVI

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion       with FUS, rarely in low-grade fibromyxoid sarcoma (LGFMS) tumoral fusion       with EWSR1, in small cell osteosarcoma

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Creb3l1(-/-) mice showed severe osteopenia (Murakami 2009)
	in the large intestine of Oasis -/- mice, the number of mature goblet cells that contain abundant secretory granules was reduced dramatically