Q01147 · CREB1_MOUSE
- ProteinCyclic AMP-responsive element-binding protein 1
- GeneCreb1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids327 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity).
Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (By similarity).
Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (PubMed:11970866, PubMed:21728997).
Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (PubMed:30566056).
Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (By similarity).
Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (PubMed:11970866, PubMed:21728997).
Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (PubMed:30566056).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 300 | Required for binding TORCs | ||||
Sequence: R |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCyclic AMP-responsive element-binding protein 1
- Short namesCREB-1; cAMP-responsive element-binding protein 1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ01147
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 119 | Loss of phosphorylation by RPS6KA4 and RPS6KA5. | ||||
Sequence: S → A | ||||||
Mutagenesis | 123-124 | Abolishes CREBBP binding. | ||||
Sequence: IL → AA | ||||||
Mutagenesis | 128 | Attenuates light-induced phase shifts of locomotion and expression of c-Fos and mPer1 in the SCN. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 10 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000076598 | 1-327 | Cyclic AMP-responsive element-binding protein 1 | |||
Sequence: MTMESGADNQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAAHATSSAPTVTLVQLPNGQTVQVHGVIQAAQPSVIQSPQVQTVQISTIAESEDSQESVDSVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPIYQTSSGQYIAITQGGAIQLANNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQILVPSNQVVVQAASGDVQTYQIRTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD | ||||||
Modified residue | 119 | Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1 | ||||
Sequence: S | ||||||
Cross-link | 122 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 128 | Phosphoserine; by CaMK2 | ||||
Sequence: S | ||||||
Modified residue | 257 | Phosphoserine; by HIPK2 | ||||
Sequence: S | ||||||
Cross-link | 271 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | ||||||
Cross-link | 290 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K |
Post-translational modification
Phosphorylation of Ser-119 allows CREBBP binding. Stimulated by phosphorylation. Phosphorylated Ser-128 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum. In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations. In the retina, only phosphorylation of Ser-119 can be detected upon light exposure. Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119. CaMK4 is much more potent than CAMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-128. Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated. Phosphorylated by CaMK1. Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP (By similarity).
Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Phosphorylated by TSSK4 on Ser-119 (By similarity).
Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity. In liver, phosphorylation is induced by fasting or glucagon in a circadian fashion. Phosphorylated by TSSK4 on Ser-119 (By similarity).
Sumoylated with SUMO1. Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the heart (at protein level).
Gene expression databases
Interaction
Subunit
Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3. Interacts (phosphorylated form) with TOX3 (By similarity).
When phosphorylated on Ser-119, binds CREBBP. Interacts with ARRB1. Binds to HIPK2 (By similarity).
Interacts with SGK1 (By similarity).
Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (By similarity).
Forms a complex with KMT2A and CREBBP (By similarity).
Interacts with TOX4; CREB1 is required for full induction of TOX4-dependent activity and the interaction is increased by cAMP and inhibited by insulin (PubMed:34914893).
When phosphorylated on Ser-119, binds CREBBP. Interacts with ARRB1. Binds to HIPK2 (By similarity).
Interacts with SGK1 (By similarity).
Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (By similarity).
Forms a complex with KMT2A and CREBBP (By similarity).
Interacts with TOX4; CREB1 is required for full induction of TOX4-dependent activity and the interaction is increased by cAMP and inhibited by insulin (PubMed:34914893).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q01147 | Crebl2 Q32M00 | 4 | EBI-2291098, EBI-5314489 | |
BINARY | Q01147 | Ncor1 Q60974 | 4 | EBI-2291098, EBI-349004 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-27 | Disordered | ||||
Sequence: MTMESGADNQQSGDAAVTEAENQQMTV | ||||||
Domain | 87-146 | KID | ||||
Sequence: QISTIAESEDSQESVDSVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEET | ||||||
Region | 94-113 | Disordered | ||||
Sequence: SEDSQESVDSVTDSQKRREI | ||||||
Region | 126-151 | Disordered | ||||
Sequence: DLSSDAPGVPRIEEEKSEEETSAPAI | ||||||
Domain | 269-327 | bZIP | ||||
Sequence: ARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD | ||||||
Region | 270-295 | Basic motif | ||||
Sequence: RKREVRLMKNREAARECRRKKKEYVK | ||||||
Region | 297-318 | Leucine-zipper | ||||
Sequence: LENRVAVLENQNKTLIEELKAL |
Sequence similarities
Belongs to the bZIP family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing. At least 6 isoforms may be produced.
Q01147-2
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.
- Name1
- SynonymsDelta
- Length327
- Mass (Da)35,122
- Last updated2020-10-07 v2
- Checksum00D1F26B00D48442
Q01147-1
- Name2
- SynonymsAlpha
- Differences from canonical
- 86-86: V → VQSSCKDLKRLFSGT
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q61441 | Q61441_MOUSE | Creb1 | 90 | ||
Q62347 | Q62347_MOUSE | Creb1 | 287 | ||
A0A087WRI6 | A0A087WRI6_MOUSE | Creb1 | 317 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_060704 | 86 | in isoform 2 | |||
Sequence: V → VQSSCKDLKRLFSGT |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X67719 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67721 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67724 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67725 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67726 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67727 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67728 EMBL· GenBank· DDBJ | CAA47953.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67719 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67721 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67722 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67724 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67725 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67726 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67727 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X67728 EMBL· GenBank· DDBJ | CAA47954.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M95106 EMBL· GenBank· DDBJ | AAA37456.1 EMBL· GenBank· DDBJ | mRNA |