Q9Z125 · CR3L1_MOUSE

  • Protein
    Cyclic AMP-responsive element-binding protein 3-like protein 1
  • Gene
    Creb3l1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Features

Showing features for site.

TypeIDPosition(s)Description
Site426-427Cleavage; by MBTPS1

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentendoplasmic reticulum
Cellular Componentendoplasmic reticulum membrane
Cellular ComponentGolgi membrane
Cellular Componentmembrane
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular FunctioncAMP response element binding
Molecular Functionchromatin binding
Molecular FunctionDNA-binding transcription activator activity, RNA polymerase II-specific
Molecular FunctionDNA-binding transcription factor activity
Molecular Functiontranscription cis-regulatory region binding
Biological Processendoplasmic reticulum unfolded protein response
Biological Processextracellular matrix constituent secretion
Biological Processmitotic G2 DNA damage checkpoint signaling
Biological Processnegative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
Biological Processosteoblast differentiation
Biological Processpositive regulation of collagen biosynthetic process
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of ossification

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Cyclic AMP-responsive element-binding protein 3-like protein 1
  • Short names
    cAMP-responsive element-binding protein 3-like protein 1
  • Alternative names
    • Old astrocyte specifically-induced substance
      (OASIS
      )
  • Cleaved into 1 chains

Gene names

    • Name
      Creb3l1
    • Synonyms
      Oasis

Organism names

  • Taxonomic identifier
  • Strains
    • ICR
    • C57BL/6J
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9Z125
  • Secondary accessions
    • Q91W70

Proteomes

Organism-specific databases

Subcellular Location

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

Nucleus
Note: Upon ER stress or DNA damage, transported into the nucleus.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-376Cytoplasmic
Transmembrane377-397Helical; Signal-anchor for type II membrane protein
Topological domain398-519Lumenal

Keywords

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.

TypeIDPosition(s)Description
Mutagenesis392Loss of proteolytic cleavage; when associated with V-423 and V-426.
Mutagenesis423Loss of proteolytic cleavage; when associated with L-392 and V-426.
Mutagenesis426Loss of proteolytic cleavage; when associated with L-392 and A-423.

PTM/Processing

Features

Showing features for chain, cross-link, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002962071-?Processed cyclic AMP-responsive element-binding protein 3-like protein 1
ChainPRO_00002880651-519Cyclic AMP-responsive element-binding protein 3-like protein 1
Cross-link184Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Glycosylation493N-linked (GlcNAc...) asparagine
Glycosylation498N-linked (GlcNAc...) asparagine
Glycosylation513N-linked (GlcNAc...) asparagine

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

Keywords

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).

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

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.

Interaction

Subunit

Interacts with SMAD4, the interaction takes place upon TGFB1 induction and SMAD4 acts as a CREB3L1 coactivator to induce the expression of genes involved in assembly of collagen extracellular matrix.

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias, domain, motif.

TypeIDPosition(s)Description
Region1-60Required for transcription activation
Region200-259Disordered
Compositional bias207-251Polar residues
Domain290-353bZIP
Region292-321Basic motif
Region332-353Leucine-zipper
Motif392-395S2P recognition
Motif423-426S1P recognition
Region449-519Disordered
Compositional bias459-490Basic and acidic residues

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Length
    519
  • Mass (Da)
    56,959
  • Last updated
    2007-05-29 v2
  • Checksum
    9DCB22B9B28DA2E8
MDAVLEPFPADRLFPGSSFLDLGDLNESDFLNNAHFPEHLDHFVENMEDFSNDLFSSFFDDPVLDEKSALLDMELDSPAPGIQAEHSYSLSGDSAPQSPLVPVKMEDTTQDVEHGAWALGNKLCSIMVKQEQSPELPVDPLAASSAMAAAAAMATPPLLGLSPMPRLPIPHQAPGEMTQLPVIKAEPPEMSQFLKVTPEDLVQMPPTPPSSHGSDSDGSQSPRSLPPSSPVRPMARSSTAISTSPLLTAPHKLQGTSGPLLLTEEEKRTLIAEGYPIPTKLPLTKAEEKALKRVRRKIKNKISAQESRRKKKEYVECLEKKVETYTSENNELWKKVETLETANRTLLQQLQKLQTLVTSKISRPYKMAATQTGTCLMVAALCFVLVLGSLVPCLPAFSSGSMTVKEDPIAADSVYAASQMPSRSLLFYDDGAGSWEDGRGALLPVEPPEGWELKPGGPAEQRPQDHLRHDRADSIHETTKYLRETWPEDTDDNGTSPNFSHPEWFHDRDLGPNTTIKLS

Q9Z125-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 503-519: EWFHDRDLGPNTTIKLS → KGVVP

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0R4J082A0A0R4J082_MOUSECreb3l1520

Features

Showing features for compositional bias, alternative sequence.

TypeIDPosition(s)Description
Compositional bias207-251Polar residues
Compositional bias459-490Basic and acidic residues
Alternative sequenceVSP_025633503-519in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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