CREB3L2 (cAMP responsive element binding protein 3-like 2)

2004-10-01   Clelia Tiziana Storlazzi , Fredrik Mertens , Ioannis Panagopoulos 

Department of Clinical Genetics, Lund University Hospital, Lund, Sweden (FM, IP)

Identity

HGNC
LOCATION
7q33
LOCUSID
ALIAS
BBF2H7
FUSION GENES

DNA/RNA

Description

122,064 Kb, 12 exons. Exon 1, containing the initiation ATG, is the largest (454 bp) and exon 7 the smallest (59 bp). Exon 12 includes the termination TAA codon. Introns 1 and 9 are the largest (73132 bp) and smallest (281 bp), respectively.

Transcription

The strongest expression was seen in placenta, lung, spleen and intestine, and the weakest in heart, brain, skeletal muscle, thymus, colon and leukocytes. In fetal tissues, the weakest expression was detected in brain and heart. A splice variant, lacking exon 2, was found in placenta, spleen and fetal liver

Proteins

Description

519 amino acids, 57 kDa. The amino acid sequence spanning residues 291-356 of the predicted human CREB3L2 protein contains a consensus B-ZIP domain highly similar to that in the CREB3L1, CREB3L3, CREB3L4, CREB3 and Drosophila Bbf-2 transcription factors with 80, 60, 59, 56 and 71% identity, respectively. It also contains the amino acid sequence RRKKKEY which is exactly conserved among CREB, CREM, ATF1, ATF6 and CREBL1. The leucine zipper motif of CREB3L2 is similar to that in CREB3L3 and CREB3L4 (pattern L-X6-C-X6-L-X6-L-X6-L-X6-L). It contains six repeats and consists of five leucines and one cysteine at the second heptad position (amino acid 328) of the leucine zipper. Downstream of the B-ZIP domain, CREB3L2 also contains a hydrophobic region, which was predicted to be an a-helical transmembrane domain (position 376-397; GTCLMVVVLCFAVAFGSFFQGY) by the prediction program PSORT II. This structural feature is also seen in the other members of the family, i.e. CREB3L1, CREB3L3, CREB3 and CREB3L4.

Function

B-ZIP transcription factor

Homology

CREB3L2 is a member of the old astrocyte specifically induced substance (OASIS) DNA binding and basic leucine zipper dimerization (B-ZIP) family of transcription factors, together with CREB3L1 (also known as OASIS), CREB3L3, CREB3 and CREB3L4.

Implicated in

Disease
Low-grade fibromyxoid sarcoma (LGFMS), variant of fibrosarcoma
Prognosis
Usually cured by surgical excision, but may metastasize in up to 10% of the cases
Cytogenetics
t(7;16)(q33-34;p11) or more complex rearrangements involving 7q and 16p. Some cases show the presence of supernumerary ring chromosomes without any detectable breakpoint in 7q or 16p.
Hybrid gene
The most common transcripts are due to fusion of exon 6 or 7 with exon 5 of FUS and CREB3L2, respectively. The breakpoints in the fusion transcripts so far reported have, however, varied from exon 5-7 of FUS and from intron 4 to exon 6 of CREB3L2.
Fusion protein
FUS/CREB3L2. The chimera is coding for a protein containing the N-terminus of FUS, and the B-ZIP domain and the C-terminus of CREB3L2. In the FUS/CREB3L2 chimera, the bZIP-encoding domain of CREB3L2 comes under the control of the FUS promoter, which, in turn, may cause deregulation of genes normally controlled by CREB3L2.

Bibliography

Pubmed IDLast YearTitleAuthors
109230802000Hyalinizing spindle cell tumor with giant rosettes--a soft tissue tumor with mesenchymal and neuroendocrine features. An immunohistochemical, ultrastructural, and cytogenetic analysis.Bejarano PA et al
151390012004The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma.Panagopoulos I et al
129608072003Low-grade fibromyxoid sarcoma and hyalinizing spindle cell tumor with giant rosettes share a common t(7;16)(q34;p11) translocation.Reid R et al
129154802003Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma.Storlazzi CT et al

Other Information

Locus ID:

NCBI: 64764
MIM: 608834
HGNC: 23720
Ensembl: ENSG00000182158

Variants:

dbSNP: 64764
ClinVar: 64764
TCGA: ENSG00000182158
COSMIC: CREB3L2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000182158ENST00000330387Q70SY1
ENSG00000182158ENST00000420629H7C1W8
ENSG00000182158ENST00000452463Q70SY1
ENSG00000182158ENST00000456390Q70SY1
ENSG00000182158ENST00000458726C9JPH0
ENSG00000182158ENST00000616381A0A087WU77
ENSG00000182158ENST00000620715A0A087WUP1

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
MelanogenesisKEGGko04916
Huntington's diseaseKEGGko05016
Prostate cancerKEGGko05215
MelanogenesisKEGGhsa04916
Huntington's diseaseKEGGhsa05016
Prostate cancerKEGGhsa05215
Vasopressin-regulated water reabsorptionKEGGko04962
Vasopressin-regulated water reabsorptionKEGGhsa04962
Cholinergic synapseKEGGhsa04725
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Cocaine addictionKEGGhsa05030
Cocaine addictionKEGGko05030
Amphetamine addictionKEGGhsa05031
Amphetamine addictionKEGGko05031
AlcoholismKEGGhsa05034
AlcoholismKEGGko05034
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
Insulin secretionKEGGhsa04911
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Thyroid hormone synthesisKEGGhsa04918
Thyroid hormone synthesisKEGGko04918
Adrenergic signaling in cardiomyocytesKEGGhsa04261
Adrenergic signaling in cardiomyocytesKEGGko04261
cGMP-PKG signaling pathwayKEGGhsa04022
cGMP-PKG signaling pathwayKEGGko04022
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Glucagon signaling pathwayKEGGhsa04922
Glucagon signaling pathwayKEGGko04922
Aldosterone synthesis and secretionKEGGhsa04925
Insulin resistanceKEGGhsa04931
Aldosterone synthesis and secretionKEGGko04925
Longevity regulating pathwayKEGGhsa04211

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
171788272007BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer.59
210414432010The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity.50
129154802003Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma.29
177211952007Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group.28
187574312008CREB3L2-PPARgamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis.22
285001822017UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner.13
215365452011FUS-CREB3L2/L1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1.11
239553422013F-box and WD repeat domain-containing-7 (Fbxw7) protein targets endoplasmic reticulum-anchored osteogenic and chondrogenic transcriptional factors for degradation.10
171174152007Characterization of the native CREB3L2 transcription factor and the FUS/CREB3L2 chimera.8

Citation

Clelia Tiziana Storlazzi ; Fredrik Mertens ; Ioannis Panagopoulos

CREB3L2 (cAMP responsive element binding protein 3-like 2)

Atlas Genet Cytogenet Oncol Haematol. 2004-10-01

Online version: http://atlasgeneticsoncology.org/gene/153/creb3l2