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Protein

Cyclic AMP-responsive element-binding protein 3-like protein 1

Gene

Creb3l1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor involved in unfolded protein response (UPR). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By similarity). In the absence of endoplasmic reticulum (ER) stress, inserted into ER membranes, with N-terminal DNA-binding and transcription activation domains oriented toward the cytosolic face of the membrane. In response to ER stress, 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 to effect transcription of specific target genes. 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:15665855). Inhibits cell-cycle progression 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 (By similarity).By similarity3 Publications

GO - Molecular functioni

  • cAMP response element binding Source: UniProtKB
  • chromatin binding Source: MGI
  • DNA binding transcription factor activity Source: MGI
  • SMAD binding Source: MGI
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: MGI
  • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: MGI
  • transcription regulatory region DNA binding Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processTranscription, Transcription regulation, Unfolded protein response

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-responsive element-binding protein 3-like protein 1
Short name:
cAMP-responsive element-binding protein 3-like protein 1
Alternative name(s):
Old astrocyte specifically-induced substance1 Publication
Short name:
OASIS1 Publication
Cleaved into the following chain:
Alternative name(s):
Oasis N-terminal fragment1 Publication
Short name:
OA-N1 Publication
Gene namesi
Name:Creb3l1
Synonyms:Oasis
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1347062 Creb3l1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 376CytoplasmicSequence analysisAdd BLAST376
Transmembranei377 – 397Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini398 – 519LumenalSequence analysisAdd BLAST122

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi392P → L: Loss of proteolytic cleavage; when associated with V-423 and V-426. 1 Publication1
Mutagenesisi423R → A: Loss of proteolytic cleavage; when associated with L-392 and V-426. 1 Publication1
Mutagenesisi426L → V: Loss of proteolytic cleavage; when associated with L-392 and A-423. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002880651 – 519Cyclic AMP-responsive element-binding protein 3-like protein 1Add BLAST519
ChainiPRO_00002962071 – ?Processed cyclic AMP-responsive element-binding protein 3-like protein 1

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki184Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Glycosylationi493N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi498N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi513N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication
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.1 Publication
Upon ER stress, 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). The cleavage is performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). RIP is induced by TGFB1 and ceramide.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei426 – 427Cleavage; by S1PBy similarity2

Keywords - PTMi

Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ9Z125
PRIDEiQ9Z125

PTM databases

PhosphoSitePlusiQ9Z125

Expressioni

Tissue specificityi

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.2 Publications

Developmental stagei

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.2 Publications

Inductioni

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). 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.4 Publications

Gene expression databases

CleanExiMM_CREB3L1

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204979, 1 interactor
STRINGi10090.ENSMUSP00000028663

Structurei

3D structure databases

ProteinModelPortaliQ9Z125
SMRiQ9Z125
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini290 – 353bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 60Required for transcription activationBy similarityAdd BLAST60
Regioni292 – 321Basic motifPROSITE-ProRule annotationAdd BLAST30
Regioni332 – 353Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi392 – 395S2P recognitionBy similarity4
Motifi423 – 426S1P recognitionBy similarity4

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709 Eukaryota
ENOG410ZZQM LUCA
HOGENOMiHOG000060150
HOVERGENiHBG057480
InParanoidiQ9Z125
KOiK09048
PhylomeDBiQ9Z125
TreeFamiTF316079

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR001630 Leuzip_CREB
IPR029805 OASIS
PANTHERiPTHR22952:SF24 PTHR22952:SF24, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
PRINTSiPR00041 LEUZIPPRCREB
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Z125-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDAVLEPFPA DRLFPGSSFL DLGDLNESDF LNNAHFPEHL DHFVENMEDF
60 70 80 90 100
SNDLFSSFFD DPVLDEKSAL LDMELDSPAP GIQAEHSYSL SGDSAPQSPL
110 120 130 140 150
VPVKMEDTTQ DVEHGAWALG NKLCSIMVKQ EQSPELPVDP LAASSAMAAA
160 170 180 190 200
AAMATPPLLG LSPMPRLPIP HQAPGEMTQL PVIKAEPPEM SQFLKVTPED
210 220 230 240 250
LVQMPPTPPS SHGSDSDGSQ SPRSLPPSSP VRPMARSSTA ISTSPLLTAP
260 270 280 290 300
HKLQGTSGPL LLTEEEKRTL IAEGYPIPTK LPLTKAEEKA LKRVRRKIKN
310 320 330 340 350
KISAQESRRK KKEYVECLEK KVETYTSENN ELWKKVETLE TANRTLLQQL
360 370 380 390 400
QKLQTLVTSK ISRPYKMAAT QTGTCLMVAA LCFVLVLGSL VPCLPAFSSG
410 420 430 440 450
SMTVKEDPIA ADSVYAASQM PSRSLLFYDD GAGSWEDGRG ALLPVEPPEG
460 470 480 490 500
WELKPGGPAE QRPQDHLRHD RADSIHETTK YLRETWPEDT DDNGTSPNFS
510
HPEWFHDRDL GPNTTIKLS
Length:519
Mass (Da):56,959
Last modified:May 29, 2007 - v2
Checksum:i9DCB22B9B28DA2E8
GO
Isoform 2 (identifier: Q9Z125-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     503-519: EWFHDRDLGPNTTIKLS → KGVVP

Show »
Length:507
Mass (Da):55,429
Checksum:iAAE2F859DAA1D978
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_025633503 – 519EWFHD…TIKLS → KGVVP in isoform 2. 1 PublicationAdd BLAST17

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017614 mRNA Translation: BAA75670.1
AL732484 Genomic DNA No translation available.
BC016447 mRNA Translation: AAH16447.1
RefSeqiNP_036087.2, NM_011957.2
UniGeneiMm.10353

Genome annotation databases

GeneIDi26427
KEGGimmu:26427
UCSCiuc008kxf.1 mouse [Q9Z125-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCR3L1_MOUSE
AccessioniPrimary (citable) accession number: Q9Z125
Secondary accession number(s): Q91W70
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 29, 2007
Last modified: June 20, 2018
This is version 129 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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