P16220 · CREB1_HUMAN
- 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
Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (PubMed:14536081).
Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity).
Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (By similarity).
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
The subsequence IAPGVVMASSPALPTQPAEEAARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD, which contains the bZIP_1 domain, shows transcriptional repressor activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended nameCyclic AMP-responsive element-binding protein 1
- Short namesCREB-1; cAMP-responsive element-binding protein 1
Gene names
- Community suggested namesCREB1
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP16220
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Angiomatoid fibrous histiocytoma (AFH)
- Note
- DescriptionA distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.
- See alsoMIM:612160
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_068077 | 102 | found in a patient with multiple congenital anomalies; does not affect CREB1 phosphorylation at S-119; fails to interact with CREBBP; dbSNP:rs387906617 | |||
Sequence: D → G | ||||||
Mutagenesis | 119 | Does not interact with TOX3 and inhibits induction of transcription by TOX3. Loss of phosphorylation by CaMK4. Loss of phosphorylation by TSSK4. | ||||
Sequence: S → A | ||||||
Mutagenesis | 141 | No effect on sumoylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 257 | Impaired phosphorylation by HIPK2 and subsequent transactivation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 257 | Potentiated transactivation. | ||||
Sequence: S → E | ||||||
Mutagenesis | 271 | Decreased sumoylation, in vivo and in vitro. | ||||
Sequence: K → R | ||||||
Mutagenesis | 290 | Decreased sumoylation, in vivo and in vitro. Loss of nuclear localization. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 222 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000076597 | 1-327 | UniProt | Cyclic AMP-responsive element-binding protein 1 | |||
Sequence: MTMESGAENQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAAHATSSAPTVTLVQLPNGQTVQVHGVIQAAQPSVIQSPQVQTVQISTIAESEDSQESVDSVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPIYQTSSGQYIAITQGGAIQLANNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQILVPSNQVVVQAASGDVQTYQIRTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD | |||||||
Modified residue | 119 | UniProt | Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5, SGK1 and TSSK4 | ||||
Sequence: S | |||||||
Cross-link | 122 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 128 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 128 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 129 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 256 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 257 | UniProt | Phosphoserine; by HIPK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 257 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 271 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | |||||||
Cross-link | 290 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 326 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity (By similarity).
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 (By similarity).
Phosphorylation of Ser-257 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. Phosphorylated by TSSK4 on Ser-119 (PubMed:15964553).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity (By similarity).
Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. Interacts with TSSK4; this interaction facilitates phosphorylation on Ser-119 (PubMed:15964553).
Forms a complex with KMT2A and CREBBP (By similarity) (PubMed:14506290, PubMed:14536081, PubMed:15454081, PubMed:15733869, PubMed:15964553, PubMed:16325578, PubMed:16908542, PubMed:20573984, PubMed:21172805, PubMed:23651431).
Interacts with TOX4; CREB1 is required for full induction of TOX4-dependent activity and the interaction is increased by cAMP and inhibited by insulin (By similarity).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-26 | Disordered | ||||
Sequence: MTMESGAENQQSGDAAVTEAENQQMT | ||||||
Domain | 87-146 | KID | ||||
Sequence: QISTIAESEDSQESVDSVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEET | ||||||
Region | 94-113 | Disordered | ||||
Sequence: SEDSQESVDSVTDSQKRREI | ||||||
Region | 125-148 | Disordered | ||||
Sequence: NDLSSDAPGVPRIEEEKSEEETSA | ||||||
Domain | 269-327 | bZIP | ||||
Sequence: ARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD | ||||||
Region | 270-295 | Basic motif | ||||
Sequence: RKREVRLMKNREAARECRRKKKEYVK | ||||||
Region | 297-318 | Leucine-zipper | ||||
Sequence: LENRVAVLENQNKTLIEELKAL |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
P16220-2
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
- SynonymsCREB-B
- Length327
- Mass (Da)35,136
- Last updated2020-10-07 v3
- ChecksumF5BA8200EE5184B7
P16220-1
- Name2
- SynonymsCREB-A
- Differences from canonical
- 86-86: V → VQSSCKDLKRLFSGT
P16220-3
- Name3
- SynonymshtCREB
- NoteHighly expressed in adult testis and sperm.
Computationally mapped potential isoform sequences
There are 8 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 4 | in Ref. 5; CAA42620 | ||||
Sequence: E → D | ||||||
Sequence conflict | 8 | in Ref. 5; CAA42620 | ||||
Sequence: E → D | ||||||
Alternative sequence | VSP_060702 | 86 | in isoform 2 and isoform 3 | |||
Sequence: V → VQSSCKDLKRLFSGT | ||||||
Sequence conflict | 146 | in Ref. 5; CAA42620 | ||||
Sequence: T → A | ||||||
Alternative sequence | VSP_060703 | 148-258 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 153 | in Ref. 5; CAA42620 | ||||
Sequence: T → A | ||||||
Sequence conflict | 155 | in Ref. 5; CAA42620 | ||||
Sequence: T → A | ||||||
Sequence conflict | 162 | in Ref. 5; CAA42620 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 170 | in Ref. 5; CAA42620 | ||||
Sequence: A → T | ||||||
Sequence conflict | 174 | in Ref. 5; CAA42620 | ||||
Sequence: G → R | ||||||
Sequence conflict | 181 | in Ref. 5; CAA42620 | ||||
Sequence: N → S | ||||||
Sequence conflict | 196 | in Ref. 5; CAA42620 | ||||
Sequence: T → A | ||||||
Sequence conflict | 278 | in Ref. 6; AAQ24858 | ||||
Sequence: K → E |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
S72459 EMBL· GenBank· DDBJ | AAB20597.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X55545 EMBL· GenBank· DDBJ | CAA39151.1 EMBL· GenBank· DDBJ | mRNA | ||
M34356 EMBL· GenBank· DDBJ | AAA35717.1 EMBL· GenBank· DDBJ | mRNA | ||
M34356 EMBL· GenBank· DDBJ | AAA35716.1 EMBL· GenBank· DDBJ | mRNA | ||
M27691 EMBL· GenBank· DDBJ | AAA35715.1 EMBL· GenBank· DDBJ | mRNA | ||
X60003 EMBL· GenBank· DDBJ | CAA42620.1 EMBL· GenBank· DDBJ | mRNA | ||
AY347527 EMBL· GenBank· DDBJ | AAQ24858.1 EMBL· GenBank· DDBJ | mRNA | ||
BC010636 EMBL· GenBank· DDBJ | AAH10636.1 EMBL· GenBank· DDBJ | mRNA | ||
S53724 EMBL· GenBank· DDBJ | AAD13869.1 EMBL· GenBank· DDBJ | Genomic DNA |