CR3L1_MOUSE
ID CR3L1_MOUSE Reviewed; 519 AA.
AC Q9Z125; Q91W70;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 25-MAY-2022, entry version 146.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 3-like protein 1;
DE Short=cAMP-responsive element-binding protein 3-like protein 1;
DE AltName: Full=Old astrocyte specifically-induced substance {ECO:0000303|PubMed:10350641};
DE Short=OASIS {ECO:0000303|PubMed:10350641};
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3-like protein 1;
DE AltName: Full=Oasis N-terminal fragment {ECO:0000303|PubMed:19767743};
DE Short=OA-N {ECO:0000303|PubMed:19767743};
GN Name=Creb3l1; Synonyms=Oasis;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RC STRAIN=ICR;
RX PubMed=10350641; DOI=10.1016/s0169-328x(99)00102-3;
RA Honma Y., Kanazawa K., Mori T., Tanno Y., Tojo M., Kiyosawa H., Takeda J.,
RA Nikaido T., Tsukamoto T., Yokoya S., Wanaka A.;
RT "Identification of a novel gene, OASIS, which encodes for a putative
RT CREB/ATF family transcription factor in the long-term cultured astrocytes
RT and gliotic tissue.";
RL Brain Res. Mol. Brain Res. 69:93-103(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION AS TRANSCRIPTION ACTIVATOR, BINDING TO CRE CONSENSUS SEQUENCE,
RP INDUCTION, AND IDENTIFICATION OF THE TRANSACTIVATION DOMAIN.
RX PubMed=12480185; DOI=10.1016/s0169-328x(02)00521-1;
RA Nikaido T., Iseki K., Mori T., Takaki H., Yokoya S., Hagino S., Takeda J.,
RA Zhang Y., Takeuchi M., Kikuchi S., Wanaka A.;
RT "Expression of OASIS, a CREB/ATF family transcription factor, in CNS lesion
RT and its transcriptional activity.";
RL Brain Res. Mol. Brain Res. 108:129-138(2002).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=12684764; DOI=10.1007/s00429-003-0311-z;
RA Hikake T., Mori T., Iseki K., Hagino S., Zhang Y., Takagi H., Yokoya S.,
RA Wanaka A.;
RT "Comparison of expression patterns between CREB family transcription factor
RT OASIS and proteoglycan core protein genes during murine tooth
RT development.";
RL Anat. Embryol. (Berl.) 206:373-380(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY ER STRESS, GLYCOSYLATION, AND
RP MUTAGENESIS OF PRO-392; ARG-423 AND LEU-426.
RX PubMed=15665855; DOI=10.1038/ncb1213;
RA Kondo S., Murakami T., Tatsumi K., Ogata M., Kanemoto S., Otori K.,
RA Iseki K., Wanaka A., Imaizumi K.;
RT "OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes.";
RL Nat. Cell Biol. 7:186-194(2005).
RN [7]
RP FUNCTION IN OSTEOGENESIS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP INDUCTION BY BMP2 AND RUNX2, CLEAVAGE UPON ER STRESS, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19767743; DOI=10.1038/ncb1963;
RA Murakami T., Saito A., Hino S., Kondo S., Kanemoto S., Chihara K.,
RA Sekiya H., Tsumagari K., Ochiai K., Yoshinaga K., Saitoh M., Nishimura R.,
RA Yoneda T., Kou I., Furuichi T., Ikegawa S., Ikawa M., Okabe M., Wanaka A.,
RA Imaizumi K.;
RT "Signalling mediated by the endoplasmic reticulum stress transducer OASIS
RT is involved in bone formation.";
RL Nat. Cell Biol. 11:1205-1211(2009).
RN [8]
RP UBIQUITINATION.
RX PubMed=22705851; DOI=10.1038/cdd.2012.77;
RA Kondo S., Hino S.I., Saito A., Kanemoto S., Kawasaki N., Asada R.,
RA Izumi S., Iwamoto H., Oki M., Miyagi H., Kaneko M., Nomura Y., Urano F.,
RA Imaizumi K.;
RT "Activation of OASIS family, ER stress transducers, is dependent on its
RT stabilization.";
RL Cell Death Differ. 19:1939-1949(2012).
CC -!- FUNCTION: Transcription factor involved in unfolded protein response
CC (UPR). Binds the DNA consensus sequence 5'-GTGXGCXGC-3' (By
CC similarity). In the absence of endoplasmic reticulum (ER) stress,
CC inserted into ER membranes, with N-terminal DNA-binding and
CC transcription activation domains oriented toward the cytosolic face of
CC the membrane. In response to ER stress, transported to the Golgi, where
CC it is cleaved in a site-specific manner by resident proteases
CC S1P/MBTPS1 and S2P/MBTPS2. The released N-terminal cytosolic domain is
CC translocated to the nucleus to effect transcription of specific target
CC genes. Plays a critical role in bone formation through the
CC transcription of COL1A1, and possibly COL1A2, and the secretion of bone
CC matrix proteins. Directly binds to the UPR element (UPRE)-like sequence
CC in an osteoblast-specific COL1A1 promoter region and induces its
CC transcription. Does not regulate COL1A1 in other tissues, such as skin
CC (PubMed:19767743). Required to protect astrocytes from ER stress-
CC induced cell death. In astrocytes, binds to the cAMP response element
CC (CRE) of the BiP/HSPA5 promoter and participate in its transcriptional
CC activation (PubMed:15665855). Inhibits cell-cycle progression by
CC binding to promoters and activating transcription of genes encoding
CC cell-cycle inhibitors, such as p21/CDKN1A (By similarity). Required for
CC TGFB1 to activate genes involved in the assembly of collagen
CC extracellular matrix (By similarity). {ECO:0000250|UniProtKB:Q96BA8,
CC ECO:0000269|PubMed:12480185, ECO:0000269|PubMed:15665855,
CC ECO:0000269|PubMed:19767743}.
CC -!- SUBUNIT: Interacts with SMAD4, the interaction takes place upon TGFB1
CC induction and SMAD4 acts as CREB3L1 coactivator to induce the
CC expression of genes involved in assembly of collagen extracellular
CC matrix. {ECO:0000250|UniProtKB:Q96BA8}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15665855, ECO:0000269|PubMed:19767743}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:15665855}. Note=ER
CC membrane resident protein. Upon ER stress, translocated to the Golgi
CC apparatus where it is cleaved. The cytosolic N-terminal fragment
CC (processed cyclic AMP-responsive element-binding protein 3-like protein
CC 1) is transported into the nucleus. {ECO:0000269|PubMed:15665855,
CC ECO:0000269|PubMed:19767743}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3-like protein 1]: Nucleus {ECO:0000269|PubMed:15665855,
CC ECO:0000269|PubMed:19767743}. Note=Upon ER stress, transported into the
CC nucleus. {ECO:0000269|PubMed:15665855, ECO:0000269|PubMed:19767743}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Z125-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z125-2; Sequence=VSP_025633;
CC -!- TISSUE SPECIFICITY: Expressed in cortical and trabecular bones. Highly
CC expressed in osteoblasts, but not detected in osteoclasts, nor in
CC macrophages (PubMed:19767743). Expressed at relatively low levels in
CC lung and kidney. Weakly expressed in brain and spleen.
CC {ECO:0000269|PubMed:10350641, ECO:0000269|PubMed:19767743}.
CC -!- DEVELOPMENTAL STAGE: In the embryo, primarily expressed in the
CC cartilage, tooth germs and salivary gland. Expressed in the inner
CC enamel epithelium during the cap and bell stages (14.5 dpc - 18.5 dpc),
CC in the preodontoblasts during differentiation stage (18.5 dpc - P0) and
CC in the differentiating odontoblasts during the early secretory stage
CC (P2.5-P4.5). After birth, at P14, detected at low levels in the
CC cerebral cortex, hippocampus and thalamus. In the adult brain,
CC expression becomes weaker. {ECO:0000269|PubMed:10350641,
CC ECO:0000269|PubMed:12684764}.
CC -!- INDUCTION: Up-regulated in astrocytes residing in or close to CNS
CC lesions, such as cryo-injured cerebral cortex and stab-injured spinal
CC cord (PubMed:12480185, PubMed:15665855). Up-regulated by ER stress in
CC astrocytes (at protein level). This induction is accompanied by
CC increased proteolytic cleavage that releases the N-terminal
CC transcription factor domain (PubMed:15665855). Up-regulated by BMP2 and
CC RUNX2 in calvaria osteoblasts. This induction at the transcript and
CC protein levels is accompanied by increased proteolytic cleavage that
CC releases the N-terminal transcription factor domain, possibly through
CC mild ER stress (PubMed:19767743). Also induced by BMP2 in bone marrow
CC stromal cells. {ECO:0000269|PubMed:10350641,
CC ECO:0000269|PubMed:12480185, ECO:0000269|PubMed:15665855,
CC ECO:0000269|PubMed:19767743}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15665855}.
CC -!- PTM: Ubiquitinated by HRD1/SYVN1; undergoes 'Lys-48'-linked
CC ubiquitination, followed by rapid proteasomal degradation under normal
CC conditions. Upon ER stress, SYVN1 E3 ubiquitin-protein ligase
CC dissociates from its substrate, ubiquitination does not occur and
CC CREB3L1 is stabilized. {ECO:0000269|PubMed:22705851}.
CC -!- PTM: Upon ER stress, translocated to the Golgi apparatus, where it is
CC processed by regulated intramembrane proteolysis (RIP) to release the
CC cytosol-facing N-terminal transcription factor domain
CC (PubMed:19767743). The cleavage is performed sequentially by site-1 and
CC site-2 proteases (S1P/MBTPS1 and S2P/MBTPS2). RIP is induced by TGFB1
CC and ceramide. {ECO:0000250|UniProtKB:Q96BA8,
CC ECO:0000269|PubMed:19767743}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate, but show growth retardation. They exhibit severe osteopenia,
CC involving a decrease in type I collagen in the bone matrix and a
CC decline in the activity of osteoblasts. Osteoblasts show abnormally
CC expanded rough endoplasmic reticulum, containing of a large amount of
CC bone matrix proteins, including COL1A1 and osteocalcin/BGLAP.
CC {ECO:0000269|PubMed:19767743}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; AB017614; BAA75670.1; -; mRNA.
DR EMBL; AL732484; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016447; AAH16447.1; -; mRNA.
DR RefSeq; NP_036087.2; NM_011957.2.
DR AlphaFoldDB; Q9Z125; -.
DR SMR; Q9Z125; -.
DR BioGRID; 204979; 5.
DR IntAct; Q9Z125; 1.
DR STRING; 10090.ENSMUSP00000028663; -.
DR GlyGen; Q9Z125; 3 sites.
DR PhosphoSitePlus; Q9Z125; -.
DR PaxDb; Q9Z125; -.
DR PRIDE; Q9Z125; -.
DR ProteomicsDB; 278029; -. [Q9Z125-1]
DR ProteomicsDB; 278030; -. [Q9Z125-2]
DR DNASU; 26427; -.
DR GeneID; 26427; -.
DR KEGG; mmu:26427; -.
DR UCSC; uc008kxf.1; mouse. [Q9Z125-2]
DR CTD; 90993; -.
DR MGI; MGI:1347062; Creb3l1.
DR eggNOG; KOG0709; Eukaryota.
DR InParanoid; Q9Z125; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; Q9Z125; -.
DR TreeFam; TF316079; -.
DR BioGRID-ORCS; 26427; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Creb3l1; mouse.
DR PRO; PR:Q9Z125; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9Z125; protein.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0035497; F:cAMP response element binding; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:0070278; P:extracellular matrix constituent secretion; IDA:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:UniProtKB.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030278; P:regulation of ossification; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029805; OASIS.
DR PANTHER; PTHR46004:SF1; PTHR46004:SF1; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Developmental protein; DNA-binding;
KW Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Membrane; Nucleus;
KW Reference proteome; Signal-anchor; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix; Ubl conjugation;
KW Unfolded protein response.
FT CHAIN 1..519
FT /note="Cyclic AMP-responsive element-binding protein 3-like
FT protein 1"
FT /id="PRO_0000288065"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3-like protein 1"
FT /id="PRO_0000296207"
FT TOPO_DOM 1..376
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 377..397
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..519
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 290..353
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..60
FT /note="Required for transcription activation"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT REGION 200..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 292..321
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 332..353
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 449..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 392..395
FT /note="S2P recognition"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT MOTIF 423..426
FT /note="S1P recognition"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT COMPBIAS 207..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..490
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 426..427
FT /note="Cleavage; by S1P"
FT /evidence="ECO:0000250"
FT CARBOHYD 493
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 184
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT VAR_SEQ 503..519
FT /note="EWFHDRDLGPNTTIKLS -> KGVVP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10350641"
FT /id="VSP_025633"
FT MUTAGEN 392
FT /note="P->L: Loss of proteolytic cleavage; when associated
FT with V-423 and V-426."
FT /evidence="ECO:0000269|PubMed:15665855"
FT MUTAGEN 423
FT /note="R->A: Loss of proteolytic cleavage; when associated
FT with L-392 and V-426."
FT /evidence="ECO:0000269|PubMed:15665855"
FT MUTAGEN 426
FT /note="L->V: Loss of proteolytic cleavage; when associated
FT with L-392 and A-423."
FT /evidence="ECO:0000269|PubMed:15665855"
SQ SEQUENCE 519 AA; 56959 MW; 9DCB22B9B28DA2E8 CRC64;
MDAVLEPFPA DRLFPGSSFL DLGDLNESDF LNNAHFPEHL DHFVENMEDF SNDLFSSFFD
DPVLDEKSAL LDMELDSPAP GIQAEHSYSL SGDSAPQSPL VPVKMEDTTQ DVEHGAWALG
NKLCSIMVKQ EQSPELPVDP LAASSAMAAA AAMATPPLLG LSPMPRLPIP HQAPGEMTQL
PVIKAEPPEM SQFLKVTPED LVQMPPTPPS SHGSDSDGSQ SPRSLPPSSP VRPMARSSTA
ISTSPLLTAP HKLQGTSGPL LLTEEEKRTL IAEGYPIPTK LPLTKAEEKA LKRVRRKIKN
KISAQESRRK KKEYVECLEK KVETYTSENN ELWKKVETLE TANRTLLQQL QKLQTLVTSK
ISRPYKMAAT QTGTCLMVAA LCFVLVLGSL VPCLPAFSSG SMTVKEDPIA ADSVYAASQM
PSRSLLFYDD GAGSWEDGRG ALLPVEPPEG WELKPGGPAE QRPQDHLRHD RADSIHETTK
YLRETWPEDT DDNGTSPNFS HPEWFHDRDL GPNTTIKLS
