CREB3L1
entrez
90993
canonical
uniprot
Q96BA8
canonical
ensembl
ENSG00000157613
resolver
ensp
ENSP00000481956
resolver
ensp
ENSP00000533045
resolver
ensp
ENSP00000786561
resolver
genesymbol
CREB3L1
resolver
genesymbol_syn
OASIS
resolver
hgnc
HGNC:18856
resolver
uniprot
B2RA75
resolver
uniprot
Q8N2D5
resolver
uniprot
Q96CP0
resolver
uniprot_entry
B2RA75_HUMAN
resolver
uniprot_entry
CR3L1_HUMAN
resolver
uniprot_sec
Q8N2D5
resolver
uniprot_sec
Q96CP0
resolver
amino_acid_sequence
MDAVLEPFPADRLFPGSSFLDLGDLNESDFLNNAHFPEHLDHFTENMEDFSNDLFSSFFDDPVLDEKSPLLDMELDSPTPGIQAEHSYSLSGDSAPQSPLVPIKMEDTTQDAEHGAWALGHKLCSIMVKQEQSPELPVDPLAAPSAMAAAAAMATTPLLGLSPLSRLPIPHQAPGEMTQLPVIKAEPLEVNQFLKVTPEDLVQMPPTPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPHKLQGTSGPLLLTEEEKRTLIAEGYPIPTKLPLTKAEEKALKRVRRKIKNKISAQESRRKKKEYVECLEKKVETFTSENNELWKKVETLENANRTLLQQLQKLQTLVTNKISRPYKMAATQTGTCLMVAALCFVLVLGSLVPCLPEFSSGSQTVKEDPLAADGVYTASQMPSRSLLFYDDGAGLWEDGRSTLLPMEPPDGWEINPGGPAEQRPRDHLQHDHLDSTHETTKYLSEAWPKDGGNGTSPDFSHSKEWFHDRDLGPNTTIKLS
uniprot
proteins
disease_involvement
DISEASE: Osteogenesis imperfecta 16 (OI16) [MIM:616229]: An autosomal recessive form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI16 is a severe form. {ECO:0000269|PubMed:24079343}. Note=The disease may be caused by variants affecting the gene represented in this entry. OI16 affected patients show a genomic deletion encompassing CREB3L1 and the first exon of DGKZ. The absence of this exon does not affect all DGKZ isoforms, some are still produced at normal level. It cannot be ruled out that DGKZ could contribute to the phenotype, but in view of its role in bone formation, CREB3L1 is a strong OI16-causing candidate (PubMed:24079343). This hypothesis is corroborated by the observation of CREB3L1 knockout mice which exhibit features reminiscent of severe human osteogenesis imperfecta. {ECO:0000269|PubMed:24079343}.
uniprot
proteins
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 (PubMed:12054625, PubMed:16417584, PubMed:25310401). 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 (PubMed:12054625, PubMed:21767813, PubMed:25310401). {ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:16417584, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:25310401}.; FUNCTION: [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). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (PubMed:21767813). 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 (By similarity). 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 (By similarity). 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 (By similarity). Required for TGFB1 to activate genes involved in the assembly of collagen extracellular matrix (PubMed:25310401). {ECO:0000250|UniProtKB:Q9Z125, ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:25310401}.; FUNCTION: (Microbial infection) May play a role in limiting virus spread by inhibiting proliferation of virus-infected cells. Upon infection with diverse DNA and RNA viruses, inhibits cell-cycle progression by binding to promoters and activating transcription of genes encoding cell-cycle inhibitors, such as p21/CDKN1A (PubMed:21767813). {ECO:0000269|PubMed:21767813}.
uniprot
proteins
mass_dalton
57005
uniprot
proteins
mutagenesis
MUTAGEN 392; /note="P->A: Abolishes proteolytic cleavage by MBTPS2; when associated with A-395."; /evidence="ECO:0000269|PubMed:21767813"; MUTAGEN 392; /note="P->L: Abolishes proteolytic cleavage by MBTPS2."; /evidence="ECO:0000269|PubMed:16417584"; MUTAGEN 395; /note="P->A: Abolishes proteolytic cleavage by MBTPS2; when associated with A-392."; /evidence="ECO:0000269|PubMed:21767813"; MUTAGEN 423; /note="R->A: Abolishes proteolytic cleavage by MBTPS1."; /evidence="ECO:0000269|PubMed:16417584, ECO:0000269|PubMed:21767813"; MUTAGEN 426; /note="L->V: Abolishes proteolytic cleavage by MBTPS1."; /evidence="ECO:0000269|PubMed:16417584
uniprot
proteins
post_translational_modification
PTM: 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. The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2) (PubMed:16417584, PubMed:21767813, PubMed:25310401, PubMed:27499293). RIP is induced by TGFB1 and ceramide (PubMed:25310401, PubMed:27499293). {ECO:0000269|PubMed:16417584, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:25310401, ECO:0000269|PubMed:27499293}.; PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Z125}.; PTM: 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. {ECO:0000269|PubMed:22705851}.
uniprot
proteins
protein_family
ATF subfamily
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
pubmed
12054625
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16417584
uniprot
proteins
pubmed
21767813
uniprot
proteins
pubmed
22705851
uniprot
proteins
pubmed
24079343
uniprot
proteins
pubmed
25310401
uniprot
proteins
pubmed
27499293
uniprot
proteins
pubmed
28112733
uniprot
proteins
sequence_length
519
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Cyclic AMP-responsive element-binding protein 3-like protein 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:16417584, ECO:0000269|PubMed:25310401}; 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. {ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:16417584, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:25310401}.; SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding protein 3-like protein 1]: Nucleus {ECO:0000269|PubMed:24079343, ECO:0000269|PubMed:25310401}. Note=Upon ER stress or DNA damage, transported into the nucleus. {ECO:0000269|PubMed:12054625, ECO:0000269|PubMed:21767813, ECO:0000269|PubMed:24079343, ECO:0000269|PubMed:25310401}.
uniprot
proteins
transmembrane_region
TRANSMEM 375..395; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins