CREB3L2

CREB3L2 (CAMP Responsive Element Binding Protein 3 Like 2) is a Protein Coding gene. Diseases associated with CREB3L2 include Myxofibrosarcoma and Sarcoma. Among its related pathways are Aldosterone synthesis and secretion and Circadian entrainment. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is CREB3L1.

Full Name

CAMP Responsive Element Binding Protein 3 Like 2

Function

Transcription factor involved in unfolded protein response (UPR). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus to effect transcription of specific target genes. Plays a critical role in chondrogenesis by activating the transcription of SEC23A, which promotes the transport and secretion of cartilage matrix proteins, and possibly that of ER biogenesis-related genes (By similarity).

In a neuroblastoma cell line, protects cells from ER stress-induced death (PubMed:17178827).

In vitro activates transcription of target genes via direct binding to the CRE site (PubMed:17178827).

Biological Process

Cartilage development Source: UniProtKB
Chondrocyte differentiation Source: UniProtKB
Endoplasmic reticulum to Golgi vesicle-mediated transport Source: Ensembl
Endoplasmic reticulum unfolded protein response Source: InterPro
Positive regulation of gene expression Source: Ensembl
Positive regulation of neuron projection development Source: Ensembl
Positive regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Response to endoplasmic reticulum stress Source: UniProtKB
Response to wounding Source: Ensembl

Cellular Location

Endoplasmic reticulum membrane. ER membrane resident protein. Upon ER stress, translocated to the Golgi apparatus where it is cleaved. The cytosolic N-terminal fragment (processed cyclic AMP-responsive element-binding protein 3-like protein 1) is transported into the nucleus.
Processed cyclic AMP-responsive element-binding protein 3-like protein 2: Nucleus. Upon ER stress, translocated into the nucleus.

Involvement in disease

A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.

Topology

Cytoplasmic: 1-379
Helical: 380-400
Lumenal: 401-520

PTM

Upon ER stress, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2).
N-glycosylated.
Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L2 is stabilized.