Q9Z125 · CR3L1_MOUSE
- ProteinCyclic AMP-responsive element-binding protein 3-like protein 1
- GeneCreb3l1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids519 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cyclic AMP-responsive element-binding protein 3-like protein 1
Precursor of the transcription factor form (Processed cyclic AMP-responsive element-binding protein 3-like protein 1), which is embedded in the endoplasmic reticulum membrane with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress or DNA damage, transported to the Golgi, where it is cleaved in a site-specific manner by resident proteases S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is translocated to the nucleus where it activates transcription of specific target genes involved in the cell-cycle progression inhibition.
Processed cyclic AMP-responsive element-binding protein 3-like protein 1
Transcription factor involved in cell type specific DNA damage and unfolded protein response (UPR) (PubMed:19767743, PubMed:37178686).
Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By similarity).
Plays a critical role in bone formation through the transcription of COL1A1, and possibly COL1A2, and the secretion of bone matrix proteins. Directly binds to the UPR element (UPRE)-like sequence in an osteoblast-specific COL1A1 promoter region and induces its transcription. Does not regulate COL1A1 in other tissues, such as skin (PubMed:19767743).
Required to protect astrocytes from ER stress-induced cell death. In astrocytes, binds to the cAMP response element (CRE) of the BiP/HSPA5 promoter and participate in its transcriptional activation (PubMed:12480185, PubMed:15665855).
In astrocytes and osteoblasts, upon DNA damage, inhibits cell-cycle progression after G2/M phase by binding to promoters and activating transcription of genes encoding cell-cycle inhibitors, such as p21/CDKN1A (PubMed:37178686).
Required for TGFB1 to activate genes involved in the assembly of collagen extracellular matrix (By similarity).
Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By similarity).
Plays a critical role in bone formation through the transcription of COL1A1, and possibly COL1A2, and the secretion of bone matrix proteins. Directly binds to the UPR element (UPRE)-like sequence in an osteoblast-specific COL1A1 promoter region and induces its transcription. Does not regulate COL1A1 in other tissues, such as skin (PubMed:19767743).
Required to protect astrocytes from ER stress-induced cell death. In astrocytes, binds to the cAMP response element (CRE) of the BiP/HSPA5 promoter and participate in its transcriptional activation (PubMed:12480185, PubMed:15665855).
In astrocytes and osteoblasts, upon DNA damage, inhibits cell-cycle progression after G2/M phase by binding to promoters and activating transcription of genes encoding cell-cycle inhibitors, such as p21/CDKN1A (PubMed:37178686).
Required for TGFB1 to activate genes involved in the assembly of collagen extracellular matrix (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 426-427 | Cleavage; by MBTPS1 | ||||
Sequence: LF |
GO annotations
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameCyclic AMP-responsive element-binding protein 3-like protein 1
- Short namescAMP-responsive element-binding protein 3-like protein 1
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9Z125
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Single-pass type II membrane protein
Note: ER membrane resident protein. Upon ER stress, translocated to the Golgi apparatus where it is cleaved. The cytosolic N-terminal fragment (processed cyclic AMP-responsive element-binding protein 3-like protein 1) is transported into the nucleus.
Processed cyclic AMP-responsive element-binding protein 3-like protein 1
Note: Upon ER stress or DNA damage, transported into the nucleus.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-376 | Cytoplasmic | ||||
Sequence: MDAVLEPFPADRLFPGSSFLDLGDLNESDFLNNAHFPEHLDHFVENMEDFSNDLFSSFFDDPVLDEKSALLDMELDSPAPGIQAEHSYSLSGDSAPQSPLVPVKMEDTTQDVEHGAWALGNKLCSIMVKQEQSPELPVDPLAASSAMAAAAAMATPPLLGLSPMPRLPIPHQAPGEMTQLPVIKAEPPEMSQFLKVTPEDLVQMPPTPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPHKLQGTSGPLLLTEEEKRTLIAEGYPIPTKLPLTKAEEKALKRVRRKIKNKISAQESRRKKKEYVECLEKKVETYTSENNELWKKVETLETANRTLLQQLQKLQTLVTSKISRPYKMAATQTGTCL | ||||||
Transmembrane | 377-397 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: MVAALCFVLVLGSLVPCLPAF | ||||||
Topological domain | 398-519 | Lumenal | ||||
Sequence: SSGSMTVKEDPIAADSVYAASQMPSRSLLFYDDGAGSWEDGRGALLPVEPPEGWELKPGGPAEQRPQDHLRHDRADSIHETTKYLRETWPEDTDDNGTSPNFSHPEWFHDRDLGPNTTIKLS |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mutant mice are born at the expected Mendelian rate, but show growth retardation. They exhibit severe osteopenia, involving a decrease in type I collagen in the bone matrix and a decline in the activity of osteoblasts. Osteoblasts show abnormally expanded rough endoplasmic reticulum, containing of a large amount of bone matrix proteins, including COL1A1 and osteocalcin/BGLAP.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 392 | Loss of proteolytic cleavage; when associated with V-423 and V-426. | ||||
Sequence: P → L | ||||||
Mutagenesis | 423 | Loss of proteolytic cleavage; when associated with L-392 and V-426. | ||||
Sequence: R → A | ||||||
Mutagenesis | 426 | Loss of proteolytic cleavage; when associated with L-392 and A-423. | ||||
Sequence: L → V |
PTM/Processing
Features
Showing features for chain, cross-link, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000296207 | 1-? | Processed cyclic AMP-responsive element-binding protein 3-like protein 1 | |||
Chain | PRO_0000288065 | 1-519 | Cyclic AMP-responsive element-binding protein 3-like protein 1 | |||
Sequence: MDAVLEPFPADRLFPGSSFLDLGDLNESDFLNNAHFPEHLDHFVENMEDFSNDLFSSFFDDPVLDEKSALLDMELDSPAPGIQAEHSYSLSGDSAPQSPLVPVKMEDTTQDVEHGAWALGNKLCSIMVKQEQSPELPVDPLAASSAMAAAAAMATPPLLGLSPMPRLPIPHQAPGEMTQLPVIKAEPPEMSQFLKVTPEDLVQMPPTPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPHKLQGTSGPLLLTEEEKRTLIAEGYPIPTKLPLTKAEEKALKRVRRKIKNKISAQESRRKKKEYVECLEKKVETYTSENNELWKKVETLETANRTLLQQLQKLQTLVTSKISRPYKMAATQTGTCLMVAALCFVLVLGSLVPCLPAFSSGSMTVKEDPIAADSVYAASQMPSRSLLFYDDGAGSWEDGRGALLPVEPPEGWELKPGGPAEQRPQDHLRHDRADSIHETTKYLRETWPEDTDDNGTSPNFSHPEWFHDRDLGPNTTIKLS | ||||||
Cross-link | 184 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Glycosylation | 493 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 498 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 513 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated.
Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked ubiquitination, followed by rapid proteasomal degradation under normal conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase dissociates from its substrate, ubiquitination does not occur and CREB3L1 is stabilized.
Upon ER stress or DNA damage, translocated to the Golgi apparatus, where it is processed by regulated intramembrane proteolysis (RIP) to release the cytosol-facing N-terminal transcription factor domain (PubMed:19767743, PubMed:37178686).
The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). RIP is induced by TGFB1 and ceramide
The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). RIP is induced by TGFB1 and ceramide
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in cortical and trabecular bones. Highly expressed in osteoblasts, but not detected in osteoclasts, nor in macrophages (PubMed:19767743).
Expressed at relatively low levels in lung and kidney. Weakly expressed in brain and spleen. Expressed in astrocytes (PubMed:37178686).
Expressed at relatively low levels in lung and kidney. Weakly expressed in brain and spleen. Expressed in astrocytes (PubMed:37178686).
Induction
Up-regulated in astrocytes residing in or close to CNS lesions, such as cryo-injured cerebral cortex and stab-injured spinal cord (PubMed:12480185, PubMed:15665855).
Up-regulated by ER stress in astrocytes (at protein level). This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain (PubMed:15665855).
Induced in astrocytes upon DNA damage (PubMed:37178686).
Up-regulated by BMP2 and RUNX2 in calvaria osteoblasts. This induction at the transcript and protein levels is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain, possibly through mild ER stress (PubMed:19767743).
Also induced by BMP2 in bone marrow stromal cells
Up-regulated by ER stress in astrocytes (at protein level). This induction is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain (PubMed:15665855).
Induced in astrocytes upon DNA damage (PubMed:37178686).
Up-regulated by BMP2 and RUNX2 in calvaria osteoblasts. This induction at the transcript and protein levels is accompanied by increased proteolytic cleavage that releases the N-terminal transcription factor domain, possibly through mild ER stress (PubMed:19767743).
Also induced by BMP2 in bone marrow stromal cells
Developmental stage
In the embryo, primarily expressed in the cartilage, tooth germs and salivary gland. Expressed in the inner enamel epithelium during the cap and bell stages (14.5 dpc - 18.5 dpc), in the preodontoblasts during differentiation stage (18.5 dpc - P0) and in the differentiating odontoblasts during the early secretory stage (P2.5-P4.5). After birth, at P14, detected at low levels in the cerebral cortex, hippocampus and thalamus. In the adult brain, expression becomes weaker.
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-60 | Required for transcription activation | ||||
Sequence: MDAVLEPFPADRLFPGSSFLDLGDLNESDFLNNAHFPEHLDHFVENMEDFSNDLFSSFFD | ||||||
Region | 200-259 | Disordered | ||||
Sequence: DLVQMPPTPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPHKLQGTSGP | ||||||
Compositional bias | 207-251 | Polar residues | ||||
Sequence: TPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPH | ||||||
Domain | 290-353 | bZIP | ||||
Sequence: ALKRVRRKIKNKISAQESRRKKKEYVECLEKKVETYTSENNELWKKVETLETANRTLLQQLQKL | ||||||
Region | 292-321 | Basic motif | ||||
Sequence: KRVRRKIKNKISAQESRRKKKEYVECLEKK | ||||||
Region | 332-353 | Leucine-zipper | ||||
Sequence: LWKKVETLETANRTLLQQLQKL | ||||||
Motif | 392-395 | S2P recognition | ||||
Sequence: PCLP | ||||||
Motif | 423-426 | S1P recognition | ||||
Sequence: RSLL | ||||||
Region | 449-519 | Disordered | ||||
Sequence: EGWELKPGGPAEQRPQDHLRHDRADSIHETTKYLRETWPEDTDDNGTSPNFSHPEWFHDRDLGPNTTIKLS | ||||||
Compositional bias | 459-490 | Basic and acidic residues | ||||
Sequence: AEQRPQDHLRHDRADSIHETTKYLRETWPEDT |
Sequence similarities
Belongs to the bZIP family. ATF subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9Z125-1
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.
- Name1
- Length519
- Mass (Da)56,959
- Last updated2007-05-29 v2
- Checksum9DCB22B9B28DA2E8
Q9Z125-2
- Name2
- Differences from canonical
- 503-519: EWFHDRDLGPNTTIKLS → KGVVP
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0R4J082 | A0A0R4J082_MOUSE | Creb3l1 | 520 |
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 207-251 | Polar residues | ||||
Sequence: TPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPH | ||||||
Compositional bias | 459-490 | Basic and acidic residues | ||||
Sequence: AEQRPQDHLRHDRADSIHETTKYLRETWPEDT | ||||||
Alternative sequence | VSP_025633 | 503-519 | in isoform 2 | |||
Sequence: EWFHDRDLGPNTTIKLS → KGVVP |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB017614 EMBL· GenBank· DDBJ | BAA75670.1 EMBL· GenBank· DDBJ | mRNA | ||
AL732484 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC016447 EMBL· GenBank· DDBJ | AAH16447.1 EMBL· GenBank· DDBJ | mRNA |