CREB3_MOUSE
ID CREB3_MOUSE Reviewed; 404 AA.
AC Q61817; Q99M21; Q9CVK9;
DT 09-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 09-NOV-2004, sequence version 2.
DT 03-AUG-2022, entry version 161.
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=Transcription factor LZIP;
DE Contains:
DE RecName: Full=Processed cyclic AMP-responsive element-binding protein 3;
GN Name=Creb3; Synonyms=Lzip;
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 (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=8112612; DOI=10.1016/0378-1119(94)90763-3;
RA Burbelo P.D., Gabriel G.C., Kibbey M.C., Yamada Y., Kleinman H.K.,
RA Weeks B.S.;
RT "LZIP-1 and LZIP-2: two novel members of the bZIP family.";
RL Gene 139:241-245(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 157-404.
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LZIP-1;
CC IsoId=Q61817-1; Sequence=Displayed;
CC Name=2; Synonyms=LZIP-2;
CC IsoId=Q61817-2; Sequence=VSP_011839;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8112612}.
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; L22167; AAC37645.1; -; Unassigned_DNA.
DR EMBL; BC002094; AAH02094.1; -; mRNA.
DR EMBL; AK007665; BAB25173.1; -; mRNA.
DR CCDS; CCDS18102.1; -. [Q61817-2]
DR AlphaFoldDB; Q61817; -.
DR SMR; Q61817; -.
DR IntAct; Q61817; 1.
DR STRING; 10090.ENSMUSP00000100008; -.
DR GlyGen; Q61817; 2 sites.
DR PhosphoSitePlus; Q61817; -.
DR PRIDE; Q61817; -.
DR ProteomicsDB; 284121; -. [Q61817-1]
DR ProteomicsDB; 284122; -. [Q61817-2]
DR MGI; MGI:99946; Creb3.
DR eggNOG; KOG0709; Eukaryota.
DR InParanoid; Q61817; -.
DR PhylomeDB; Q61817; -.
DR Reactome; R-MMU-8874211; CREB3 factors activate genes.
DR ChiTaRS; Creb3; mouse.
DR PRO; PR:Q61817; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61817; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
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:0016021; C:integral component of membrane; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0008140; F:cAMP response element binding protein binding; ISO:MGI.
DR GO; GO:0031726; F:CCR1 chemokine receptor binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
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:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
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:0042127; P:regulation of cell population proliferation; ISO:MGI.
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 GO; GO:0006351; P:transcription, DNA-templated; ISO:MGI.
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 2: Evidence at transcript level;
KW Activator; Alternative splicing; Chemotaxis; Cytoplasm; DNA-binding;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Membrane; Nucleus;
KW Reference proteome; Repressor; Signal-anchor; Transcription;
KW Transcription regulation; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT CHAIN 1..404
FT /note="Cyclic AMP-responsive element-binding protein 3"
FT /id="PRO_0000076603"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-responsive element-binding
FT protein 3"
FT /id="PRO_0000296205"
FT TOPO_DOM 1..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..404
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 185..248
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 187..225
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 227..248
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 305..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 19..23
FT /note="LXXLL motif 1"
FT MOTIF 64..68
FT /note="LXXLL motif 2"
FT MOTIF 87..90
FT /note="HCFC1-binding-motif (HBM)"
FT SITE 301..302
FT /note="Cleavage; by PS1"
FT /evidence="ECO:0000250"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 102..126
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011839"
FT CONFLICT 263
FT /note="S -> T (in Ref. 1; AAC37645)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 404 AA; 45112 MW; 96E4124256D4BD44 CRC64;
MDPGGQDLLA LDPGDQDLLG FLLEESGDLW AATEPDVKAS LDLELSPSEN SVQELSDWEV
EDLLSSLLSP SVSRDVLGSS SSSILHDHNY SLPQEHVSID LGECEMISCR GRRELTGLAG
STFPFADTES FEKEGFHVTP LPGEERAAEQ EMSRLILTEE EKKLLEKEGL TLPSTLPLTK
VEEQVLKRVR RKIRNKRAAQ ESRKKKKVYV VGLESRVLKY TAQNRELQNK VQRLEEQNLS
LLDQLRKLQA MVIEIANKTS SGSTCVLVLV FSFCLLLVPA MYSSDARGSV PAEYVVLHRK
LRALPSEDDH QPKPSALSSE LPMDSTHQSL DSSEHMFLVS SNFSCVLYHA PQAEQPLHWP
LWDLSSEMLF SDSNLLLQAN LSESEGWQPN HSPSLVIFQG RYSG
