CREB3_BOVIN
ID CREB3_BOVIN Reviewed; 368 AA.
AC Q8SQ19; Q0V894; Q3T167; Q5EA05; Q5EA30;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 3;
DE Short=CREB-3;
DE Short=cAMP-responsive element-binding protein 3;
DE AltName: Full=Luman;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3;
GN Name=CREB3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-368.
RA Budihal P.C., Misra V.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10623756; DOI=10.1128/jvi.74.2.934-943.2000;
RA Lu R., Misra V.;
RT "Potential role for luman, the cellular homologue of herpes simplex virus
RT VP16 (alpha gene trans-inducing factor), in herpesvirus latency.";
RL J. Virol. 74:934-943(2000).
CC -!- FUNCTION: Endoplasmic reticulum (ER)-bound sequence-specific
CC transcription factor that directly binds DNA and activates
CC transcription. Plays a role in the unfolded protein response (UPR),
CC promoting cell survival versus ER stress-induced apoptotic cell death.
CC Also involved in cell proliferation, migration and differentiation,
CC tumor suppression and inflammatory gene expression. Acts as a positive
CC regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell
CC migration. Associates with chromatin to the HERPUD1 promoter. Also
CC induces transcriptional activation of chemokine receptors. Functions as
CC a negative transcriptional regulator in ligand-induced transcriptional
CC activation of the glucocorticoid receptor NR3C1 by recruiting and
CC activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Also
CC decreases the acetylation level of histone H4. Does not promote the
CC chemotactic activity of leukocyte cells.
CC {ECO:0000250|UniProtKB:O43889}.
CC -!- FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]:
CC This is the transcriptionally active form that translocates to the
CC nucleus and activates unfolded protein response (UPR) target genes
CC during endoplasmic reticulum (ER) stress response. Binds the cAMP
CC response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP
CC sequences present in many promoters to activate transcription of the
CC genes. Binds to the unfolded protein response element (UPRE) consensus
CC sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-
CC ATTGG-N-CCACG-3'). {ECO:0000250|UniProtKB:O43889}.
CC -!- SUBUNIT: Homodimer. Interacts with HCFC1; the interaction is required
CC to stimulate CREB3 transcriptional activity. Interacts with CREBZF; the
CC interaction occurs only in combination with HCFC1. Interacts (via
CC central part and transmembrane region) with DCSTAMP (via C-terminus
CC cytoplasmic domain). Interacts with OS9. Interacts (via leucine-zipper
CC domain) with CREBRF (via leucine-zipper domain); the interaction occurs
CC only after CREB3 activation and promotes CREB3 degradation. Interacts
CC (via C-terminal domain) with CCR1. {ECO:0000250|UniProtKB:O43889}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O43889}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:O43889, ECO:0000255}. Golgi apparatus
CC {ECO:0000250|UniProtKB:O43889}. Nucleus {ECO:0000250|UniProtKB:O43889}.
CC Cytoplasm {ECO:0000250|UniProtKB:O43889}. Note=Colocalizes with HCFC1
CC in neuronal cell bodies of the trigeminal ganglia. Colocalizes with
CC DCSTAMP in the ER membrane of immature dendritic cell (DC). Colocalizes
CC with CANX, CCR1, HCFC1 in the ER membrane.
CC {ECO:0000250|UniProtKB:O43889}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding
CC protein 3]: Nucleus {ECO:0000250|UniProtKB:O43889}. Note=Upon RIP
CC activation the transcriptional active processed cyclic AMP-responsive
CC element-binding protein 3 form translocates into the nucleus. Detected
CC in the nucleus upon dendritic cell maturation and RIP activation.
CC Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in
CC promyelocytic leukemia protein nuclear bodies (PML-NB).
CC {ECO:0000250|UniProtKB:O43889}.
CC -!- TISSUE SPECIFICITY: Expressed in trigeminal ganglia (at protein level).
CC {ECO:0000269|PubMed:10623756}.
CC -!- PTM: First proteolytically cleaved by site-1 protease (S1P) that
CC generates membrane-associated N-terminus and a luminal C-terminus
CC forms. The membrane-associated N-terminus form is further
CC proteolytically processed probably by the site-2 protease (S2P) through
CC a regulated intramembrane proteolysis (RIP), releasing the
CC transcriptional active processed cyclic AMP-responsive element-binding
CC protein 3 form, which is transported to the nucleus. The proteolytic
CC cleavage is strongly induced during dendritic cell (DC) maturation and
CC inhibited by DCSTAMP. That form is rapidly degraded.
CC {ECO:0000250|UniProtKB:O43889}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:O43889}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; BT020739; AAX08756.1; -; mRNA.
DR EMBL; BT020752; AAX08769.1; -; mRNA.
DR EMBL; BT020764; AAX08781.1; -; mRNA.
DR EMBL; BT020801; AAX08818.1; -; mRNA.
DR EMBL; BT021155; AAX31337.1; -; mRNA.
DR EMBL; BT026325; ABG81481.1; -; mRNA.
DR EMBL; BC102092; AAI02093.1; -; mRNA.
DR EMBL; AF387035; AAL84006.1; -; mRNA.
DR RefSeq; NP_776711.1; NM_174286.2.
DR AlphaFoldDB; Q8SQ19; -.
DR SMR; Q8SQ19; -.
DR STRING; 9913.ENSBTAP00000015193; -.
DR PaxDb; Q8SQ19; -.
DR PRIDE; Q8SQ19; -.
DR Ensembl; ENSBTAT00000015193; ENSBTAP00000015193; ENSBTAG00000011429.
DR GeneID; 281715; -.
DR KEGG; bta:281715; -.
DR CTD; 10488; -.
DR VEuPathDB; HostDB:ENSBTAG00000011429; -.
DR VGNC; VGNC:27693; CREB3.
DR eggNOG; KOG0709; Eukaryota.
DR GeneTree; ENSGT00940000160343; -.
DR HOGENOM; CLU_047257_0_0_1; -.
DR InParanoid; Q8SQ19; -.
DR OMA; CLLYHMP; -.
DR OrthoDB; 644485at2759; -.
DR TreeFam; TF316079; -.
DR Reactome; R-BTA-8874211; CREB3 factors activate genes.
DR Proteomes; UP000009136; Chromosome 8.
DR Bgee; ENSBTAG00000011429; Expressed in aorta and 104 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IEA:Ensembl.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; IEA:Ensembl.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; ISS:UniProtKB.
DR GO; GO:0019043; P:establishment of viral latency; ISS:UniProtKB.
DR GO; GO:0050930; P:induction of positive chemotaxis; ISS:UniProtKB.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0090045; P:positive regulation of deacetylase activity; ISS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006990; P:positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0019046; P:release from viral latency; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029808; Luman.
DR PANTHER; PTHR45996:SF4; PTHR45996:SF4; 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; Chemotaxis; Cytoplasm; DNA-binding; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Membrane; Nucleus; Reference proteome;
KW Repressor; Signal-anchor; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix; Unfolded protein response.
FT CHAIN 1..368
FT /note="Cyclic AMP-responsive element-binding protein 3"
FT /id="PRO_0000076601"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3"
FT /id="PRO_0000296203"
FT TOPO_DOM 1..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..368
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 153..216
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..95
FT /note="Transcription activation (acidic)"
FT REGION 155..184
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 186..193
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT MOTIF 16..20
FT /note="LXXLL motif 1"
FT MOTIF 57..61
FT /note="LXXLL motif 2"
FT MOTIF 81..84
FT /note="HCFC1-binding-motif (HBM)"
FT SITE 266..267
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT SITE 269..270
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 46
FT /note="E -> EPVNLNPVQ (in Ref. 1; AAX08756)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 368 AA; 40912 MW; 8DE9D4EAAF636638 CRC64;
MSHMELALDP GDHDLLGFLL EESGGLGAAP DEALTSPPDW ELPLSESLSD WDVEDFLSCL
PSPPAVLNVF SNSDPCLVQH DHTYSLSQEH VSIDLDNESY EKERAQMTPL RVEEPADQEI
ARLILTEEEK RLLEKEGLTL PGMLPLTKME EQVLKRVRRK IRNKKSAQES RRKKKVYVGG
LESRVLKYTA QNLELQNKVQ LLEEQNLSLL DQLRRLQAMV IQTANKASSS STCVLVLLFS
FCLLLVPAMY SSDTRGSLPA EHRVLSRQLR ALPSEDPPQL EPPALQSEVP KDSLNPELQA
ASNSCCLFHL MPQAPRAEPP LQLPLPDGFS GCSCPDSISP LHANLTREEG WLPTPSPTSV
ILQGRYSG
