CR3L1_RAT
ID CR3L1_RAT Reviewed; 520 AA.
AC Q66HA2;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 128.
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;
DE Short=OASIS;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3-like protein 1;
GN Name=Creb3l1; Synonyms=Oasis;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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).
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 (By similarity). Required to protect astrocytes from ER stress-induced
CC cell death. In astrocytes, binds to the cAMP response element (CRE) of
CC the BiP/HSPA5 promoter and participate in its transcriptional
CC activation (By similarity). Required for TGFB1 to activate genes
CC involved in the assembly of collagen extracellular matrix (By
CC similarity). {ECO:0000250|UniProtKB:Q96BA8,
CC ECO:0000250|UniProtKB:Q9Z125}.
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; Single-pass type
CC II membrane protein. Note=ER membrane resident protein. Upon ER stress,
CC translocated to the Golgi apparatus where it is cleaved. The cytosolic
CC N-terminal fragment (processed cyclic AMP-responsive element-binding
CC protein 3-like protein 1) is transported into the nucleus.
CC {ECO:0000250|UniProtKB:Q9Z125}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3-like protein 1]: Nucleus. Note=Upon ER stress, translocated
CC into the nucleus. {ECO:0000250|UniProtKB:Q9Z125}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Z125}.
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:0000250|UniProtKB:Q9Z125}.
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. The cleavage is
CC performed sequentially by site-1 and site-2 proteases (S1P/MBTPS1 and
CC S2P/MBTPS2). RIP is induced by TGFB1 and ceramide.
CC {ECO:0000250|UniProtKB:Q96BA8, ECO:0000250|UniProtKB:Q9Z125}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; BC081951; AAH81951.1; -; mRNA.
DR RefSeq; NP_001005562.1; NM_001005562.1.
DR AlphaFoldDB; Q66HA2; -.
DR SMR; Q66HA2; -.
DR BioGRID; 263234; 2.
DR STRING; 10116.ENSRNOP00000007771; -.
DR GlyGen; Q66HA2; 2 sites.
DR PaxDb; Q66HA2; -.
DR PRIDE; Q66HA2; -.
DR GeneID; 362165; -.
DR KEGG; rno:362165; -.
DR UCSC; RGD:1359613; rat.
DR CTD; 90993; -.
DR RGD; 1359613; Creb3l1.
DR VEuPathDB; HostDB:ENSRNOG00000005413; -.
DR eggNOG; KOG0709; Eukaryota.
DR HOGENOM; CLU_037638_1_0_1; -.
DR InParanoid; Q66HA2; -.
DR OMA; TENNELW; -.
DR OrthoDB; 644485at2759; -.
DR PhylomeDB; Q66HA2; -.
DR TreeFam; TF316079; -.
DR PRO; PR:Q66HA2; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000005413; Expressed in colon and 18 other tissues.
DR Genevisible; Q66HA2; RN.
DR GO; GO:0000785; C:chromatin; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035497; F:cAMP response element binding; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
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:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0070278; P:extracellular matrix constituent secretion; ISS:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0040037; P:negative regulation of fibroblast growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISS: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; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030278; P:regulation of ossification; ISO:RGD.
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 2: Evidence at transcript level;
KW Activator; Developmental protein; DNA-binding; Endoplasmic reticulum;
KW Glycoprotein; Isopeptide bond; Membrane; Nucleus; Reference proteome;
KW Signal-anchor; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..520
FT /note="Cyclic AMP-responsive element-binding protein 3-like
FT protein 1"
FT /id="PRO_0000288066"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3-like protein 1"
FT /id="PRO_0000296208"
FT TOPO_DOM 1..375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 376..396
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 397..520
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 289..352
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 72..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..258
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 291..320
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 331..352
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 446..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 391..394
FT /note="S2P recognition"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT MOTIF 422..425
FT /note="S1P recognition"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
FT COMPBIAS 202..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 425..426
FT /note="Cleavage; by S1P"
FT /evidence="ECO:0000250"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 183
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q96BA8"
SQ SEQUENCE 520 AA; 57134 MW; E23974CC13932863 CRC64;
MDAVLEPFPA DRLFPGSSFL DLGDLNESDF LNNAHFPEHL DHFVENMEDF SNDLFSSFFD
DPVLDEKSPL LDMELDSPAP GIQAEHSYSL SGDSAPQSPL VPVKMEDTTQ DMEHGAWALG
NKLCSIMVKQ EQSPELPVDP LAASSAMAAA TMATPPLLGL SPISRLPIPH QAPGEMTQLP
VIKAEPPEMS QFLKVTQEDL VQMPPTPPSS HGSDSDGSQS PRSLPPSSPV RPMARSSTAI
STSPLLTAPH KLQGTSGPLL LTEEEKRTLI AEGYPIPTKL PLTKAEEKAL KRVRRKIKNK
ISAQESRRKK KEYVECLEKK VETYTSENNE LWKKVETLET ANRTLLQQLQ KLQTLVTSKI
SRPYKMAATQ TGTCLMVAAL CFVLVLGSLA PCLPAFSSGS KTVKEDPVAA DSVYAASQMP
SRSLLFYDDG AGSWEDGHRG ALLPVEPPEG WELKPGGPAE PRPQDHLRHD HADSIHETTK
YLRETWPEDT EDNGASPNFS HPKEWFHDRD LGPNTTIKLS
