Q61817 (CREB3_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 122. History...
Names and origin
|Protein names||Recommended name:|
Cyclic AMP-responsive element-binding protein 3
Short name=cAMP-responsive element-binding protein 3
Transcription factor LZIP
Cleaved into the following chain:
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||404 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays a role in the unfolded protein response (UPR). Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells By similarity.
Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter By similarity.
Homodimer. Interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Interacts with CREBZF; the interaction occurs only in combination with HCFC1. Interacts (via central part and transmembrane region) with TM7SF4 (via C-terminus cytoplasmic domain). Interacts with OS9. Interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Interacts (via C-terminal domain) with CCR1 By similarity.
Endoplasmic reticulum membrane; Single-pass type II membrane protein By similarity. Membrane By similarity. Nucleus By similarity. Cytoplasm By similarity. Note: Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia By similarity.
Processed cyclic AMP-responsive element-binding protein 3: Nucleus By similarity. Note: Upon RIP activation the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB) By similarity.
Widely expressed. Ref.1
The ER membrane embedded cyclic AMP-responsive element-binding protein 3 form is first proteolytically cleaved by site-1 protease (S1P) that generates membrane-associated N-terminus and a luminal C-terminus forms. The membrane-associated N-terminus form is further proteolytically processed probably by the site-2 protease (S2P) through a regulated intramembrane proteolysis (RIP), releasing the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form, which is transported to the nucleus. The proteolytic cleavage is strongly induced during dendritic cell (DC) maturation and inhibited by TM7SF4 By similarity.
The processed cyclic AMP-responsive element-binding protein 3 is rapidly degraded By similarity.
N-glycosylated By similarity.
Contains 1 bZIP (basic-leucine zipper) domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: Q61817-1) |
Also known as: LZIP-1;
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: Q61817-2) |
Also known as: LZIP-2;
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 404||404||Cyclic AMP-responsive element-binding protein 3||PRO_0000076603|
|Chain||1 – ?||Processed cyclic AMP-responsive element-binding protein 3||PRO_0000296205|
|Topological domain||1 – 261||261||Cytoplasmic Potential|
|Transmembrane||262 – 282||21||Helical; Signal-anchor for type II membrane protein; Potential|
|Topological domain||283 – 404||122||Lumenal Potential|
|Domain||185 – 248||64||bZIP|
|Region||187 – 225||39||Basic motif By similarity|
|Region||227 – 248||22||Leucine-zipper By similarity|
|Motif||19 – 23||5||LXXLL motif 1|
|Motif||64 – 68||5||LXXLL motif 2|
|Motif||87 – 90||4||HCFC1-binding-motif (HBM)|
|Site||301 – 302||2||Cleavage; by PS1 By similarity|
Amino acid modifications
|Glycosylation||342||1||N-linked (GlcNAc...) Potential|
|Glycosylation||380||1||N-linked (GlcNAc...) Potential|
|Alternative sequence||102 – 126||25||Missing in isoform 2.||VSP_011839|
|Sequence conflict||263||1||S → T in AAC37645. Ref.1|
|||"LZIP-1 and LZIP-2: two novel members of the bZIP family."|
Burbelo P.D., Gabriel G.C., Kibbey M.C., Yamada Y., Kleinman H.K., Weeks B.S.
Gene 139:241-245(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Mammary tumor.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 157-404.
|+||Additional computationally mapped references.|
|L22167 Unassigned DNA. Translation: AAC37645.1.|
BC002094 mRNA. Translation: AAH02094.1.
AK007665 mRNA. Translation: BAB25173.1.
3D structure databases
|SMR||Q61817. Positions 157-242. |
Protein-protein interaction databases
|IntAct||Q61817. 1 interaction.|
Protocols and materials databases
|MGI||MGI:99946. Creb3. |
Gene expression databases
Family and domain databases
|InterPro||IPR004827. bZIP. |
|Pfam||PF00170. bZIP_1. 1 hit. |
|SMART||SM00338. BRLZ. 1 hit. |
|PROSITE||PS50217. BZIP. 1 hit. |
PS00036. BZIP_BASIC. 1 hit.
|Accession||Primary (citable) accession number: Q61817|
Secondary accession number(s): Q99M21, Q9CVK9
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|