UniProtKB - Q61817 (CREB3_MOUSE)
Cyclic AMP-responsive element-binding protein 3
Creb3
Functioni
Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Associates with chromatin to the HERPUD1 promoter. Also induces transcriptional activation of chemokine receptors. 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). Also decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells.
By similarityThis is the transcriptionally active form that translocates to the nucleus and activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many promoters to activate transcription of the genes. Binds to the unfolded protein response element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3').
By similarityGO - Molecular functioni
- cAMP response element binding Source: InterPro
- cAMP response element binding protein binding Source: MGI
- CCR1 chemokine receptor binding Source: MGI
- chromatin binding Source: UniProtKB
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGI
- identical protein binding Source: MGI
- protein homodimerization activity Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: UniProtKB
- sequence-specific DNA binding Source: MGI
- sequence-specific double-stranded DNA binding Source: MGI
GO - Biological processi
- chemotaxis Source: UniProtKB-KW
- cytoplasmic sequestering of transcription factor Source: UniProtKB
- establishment of viral latency Source: UniProtKB
- induction of positive chemotaxis Source: UniProtKB
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: MGI
- positive regulation of calcium ion transport Source: MGI
- positive regulation of cell migration Source: MGI
- positive regulation of deacetylase activity Source: UniProtKB
- positive regulation of defense response to virus by host Source: UniProtKB
- positive regulation of monocyte chemotaxis Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: MGI
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: UniProtKB
- regulation of apoptotic process Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- regulation of cell population proliferation Source: MGI
- regulation of transcription by RNA polymerase II Source: GO_Central
- release from viral latency Source: UniProtKB
- response to endoplasmic reticulum stress Source: UniProtKB
- transcription, DNA-templated Source: MGI
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Chemotaxis, Transcription, Transcription regulation, Unfolded protein response |
Enzyme and pathway databases
Reactomei | R-MMU-8874211, CREB3 factors activate genes |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclic AMP-responsive element-binding protein 3Short name: CREB-3 Short name: cAMP-responsive element-binding protein 3 Alternative name(s): Transcription factor LZIP Cleaved into the following chain: |
Gene namesi | Name:Creb3 Synonyms:Lzip |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:99946, Creb3 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Single-pass type II membrane protein Sequence analysisBy similarity
Nucleus
- Nucleus By similarity
Golgi apparatus
- Golgi apparatus By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Note: Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia. Colocalizes with DCSTAMP in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane.By similarity
Nucleus
- 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
Cytosol
- cytosol Source: MGI
Endoplasmic reticulum
- endoplasmic reticulum Source: MGI
- endoplasmic reticulum membrane Source: UniProtKB
- integral component of endoplasmic reticulum membrane Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: MGI
- Golgi membrane Source: UniProtKB
Nucleus
- nuclear body Source: UniProtKB
- nucleus Source: UniProtKB
- RNA polymerase II transcription regulator complex Source: MGI
Other locations
- cytoplasm Source: UniProtKB
- integral component of membrane Source: MGI
- membrane Source: UniProtKB
- neuronal cell body Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 261 | CytoplasmicSequence analysisAdd BLAST | 261 | |
Transmembranei | 262 – 282 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 283 – 404 | LumenalSequence analysisAdd BLAST | 122 |
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076603 | 1 – 404 | Cyclic AMP-responsive element-binding protein 3Add BLAST | 404 | |
ChainiPRO_0000296205 | 1 – ? | Processed cyclic AMP-responsive element-binding protein 3 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 342 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 380 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 301 – 302 | Cleavage; by PS1By similarity | 2 |
Keywords - PTMi
GlycoproteinProteomic databases
PRIDEi | Q61817 |
ProteomicsDBi | 284121 [Q61817-1] 284122 [Q61817-2] |
PTM databases
GlyGeni | Q61817, 2 sites |
PhosphoSitePlusi | Q61817 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
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 DCSTAMP (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 similarityGO - Molecular functioni
- cAMP response element binding protein binding Source: MGI
- CCR1 chemokine receptor binding Source: MGI
- identical protein binding Source: MGI
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
IntActi | Q61817, 1 interactor |
STRINGi | 10090.ENSMUSP00000100008 |
Miscellaneous databases
RNActi | Q61817, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 185 – 248 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 187 – 225 | Basic motifPROSITE-ProRule annotationAdd BLAST | 39 | |
Regioni | 227 – 248 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 22 | |
Regioni | 305 – 327 | DisorderedSequence analysisAdd BLAST | 23 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 19 – 23 | LXXLL motif 1 | 5 | |
Motifi | 64 – 68 | LXXLL motif 2 | 5 | |
Motifi | 87 – 90 | HCFC1-binding-motif (HBM) | 4 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0709, Eukaryota |
InParanoidi | Q61817 |
PhylomeDBi | Q61817 |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR046347, bZIP_sf IPR029808, Luman |
PANTHERi | PTHR45996:SF4, PTHR45996:SF4, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57959, SSF57959, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDPGGQDLLA LDPGDQDLLG FLLEESGDLW AATEPDVKAS LDLELSPSEN
60 70 80 90 100
SVQELSDWEV EDLLSSLLSP SVSRDVLGSS SSSILHDHNY SLPQEHVSID
110 120 130 140 150
LGECEMISCR GRRELTGLAG STFPFADTES FEKEGFHVTP LPGEERAAEQ
160 170 180 190 200
EMSRLILTEE EKKLLEKEGL TLPSTLPLTK VEEQVLKRVR RKIRNKRAAQ
210 220 230 240 250
ESRKKKKVYV VGLESRVLKY TAQNRELQNK VQRLEEQNLS LLDQLRKLQA
260 270 280 290 300
MVIEIANKTS SGSTCVLVLV FSFCLLLVPA MYSSDARGSV PAEYVVLHRK
310 320 330 340 350
LRALPSEDDH QPKPSALSSE LPMDSTHQSL DSSEHMFLVS SNFSCVLYHA
360 370 380 390 400
PQAEQPLHWP LWDLSSEMLF SDSNLLLQAN LSESEGWQPN HSPSLVIFQG
RYSG
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PW77 | E9PW77_MOUSE | Cyclic AMP-responsive element-bindi... | Creb3 | 403 | Annotation score: | ||
Q3UNH6 | Q3UNH6_MOUSE | Cyclic AMP-responsive element-bindi... | Creb3 | 379 | Annotation score: | ||
E0CYW8 | E0CYW8_MOUSE | Cyclic AMP-responsive element-bindi... | Creb3 | 47 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 263 | S → T in AAC37645 (PubMed:8112612).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_011839 | 102 – 126 | Missing in isoform 2. 1 PublicationAdd BLAST | 25 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L22167 Unassigned DNA Translation: AAC37645.1 BC002094 mRNA Translation: AAH02094.1 AK007665 mRNA Translation: BAB25173.1 |
CCDSi | CCDS18102.1 [Q61817-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L22167 Unassigned DNA Translation: AAC37645.1 BC002094 mRNA Translation: AAH02094.1 AK007665 mRNA Translation: BAB25173.1 |
CCDSi | CCDS18102.1 [Q61817-2] |
3D structure databases
AlphaFoldDBi | Q61817 |
SMRi | Q61817 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q61817, 1 interactor |
STRINGi | 10090.ENSMUSP00000100008 |
PTM databases
GlyGeni | Q61817, 2 sites |
PhosphoSitePlusi | Q61817 |
Proteomic databases
PRIDEi | Q61817 |
ProteomicsDBi | 284121 [Q61817-1] 284122 [Q61817-2] |
Organism-specific databases
MGIi | MGI:99946, Creb3 |
Phylogenomic databases
eggNOGi | KOG0709, Eukaryota |
InParanoidi | Q61817 |
PhylomeDBi | Q61817 |
Enzyme and pathway databases
Reactomei | R-MMU-8874211, CREB3 factors activate genes |
Miscellaneous databases
ChiTaRSi | Creb3, mouse |
PROi | PR:Q61817 |
RNActi | Q61817, protein |
SOURCEi | Search... |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR046347, bZIP_sf IPR029808, Luman |
PANTHERi | PTHR45996:SF4, PTHR45996:SF4, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
SUPFAMi | SSF57959, SSF57959, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CREB3_MOUSE | |
Accessioni | Q61817Primary (citable) accession number: Q61817 Secondary accession number(s): Q99M21, Q9CVK9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 9, 2004 |
Last sequence update: | November 9, 2004 | |
Last modified: | May 25, 2022 | |
This is version 160 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families