CREBB_DROME
ID CREBB_DROME Reviewed; 359 AA.
AC Q9VWW0; A8JUN2; A8JUN4; Q0IGS5; Q0IGV7; Q26329; Q26446; Q7KUW0; Q7KUW1;
AC Q8IQY4;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Cyclic AMP response element-binding protein B;
DE Short=cAMP response element-binding protein B;
DE Short=dCREB-B;
GN Name=CrebB {ECO:0000312|FlyBase:FBgn0265784};
GN Synonyms=CrebB-17A {ECO:0000312|EMBL:AAF48827.1}; ORFNames=CG6103;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB28337.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM F), AND DEVELOPMENTAL STAGE.
RC TISSUE=Head {ECO:0000269|PubMed:8397816};
RX PubMed=8397816; DOI=10.1089/dna.1993.12.589;
RA Usui T., Smolik S.M., Goodman R.H.;
RT "Isolation of Drosophila CREB-B: a novel CRE-binding protein.";
RL DNA Cell Biol. 12:589-595(1993).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAB35092.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D; E; F; G AND J), FUNCTION, SUBUNIT,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP MUTAGENESIS OF LEU-328 AND LEU-335.
RC TISSUE=Head {ECO:0000269|PubMed:7651429};
RX PubMed=7651429; DOI=10.1128/mcb.15.9.5123;
RA Yin J.C.P., Wallach J.S., Wilder E.L., Klingensmith J., Dang D.,
RA Perrimon N., Zhou H., Tully T., Quinn W.G.;
RT "A Drosophila CREB/CREM homolog encodes multiple isoforms, including a
RT cyclic AMP-dependent protein kinase-responsive transcriptional activator
RT and antagonist.";
RL Mol. Cell. Biol. 15:5123-5130(1995).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM G), FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=15219829; DOI=10.1016/j.bbrc.2004.05.165;
RA Poels J., Franssens V., Van Loy T., Martinez A., Suner M.M., Dunbar S.J.,
RA De Loof A., Vanden Broeck J.;
RT "Isoforms of cyclic AMP response element binding proteins in Drosophila S2
RT cells.";
RL Biochem. Biophys. Res. Commun. 320:318-324(2004).
RN [4] {ECO:0000312|EMBL:AAF48827.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAF48827.1}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS D AND F).
RC STRAIN=Berkeley;
RA Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C.,
RA Celniker S.E.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209; SER-212 AND SER-214, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29473541; DOI=10.7554/elife.33007;
RA Lee P.T., Lin G., Lin W.W., Diao F., White B.H., Bellen H.J.;
RT "A kinase-dependent feedforward loop affects CREBB stability and long term
RT memory formation.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Isoform E is a PKA-dependent transcriptional activator.
CC Isoform J is a direct antagonist of activation by isoform E in cell
CC culture. Binds the cAMP response element (CRE) (consensus: 5'-
CC GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular
CC promoters (PubMed:7651429, PubMed:15219829). Has a role in long-term
CC memory (PubMed:29473541). {ECO:0000269|PubMed:15219829,
CC ECO:0000269|PubMed:29473541, ECO:0000269|PubMed:7651429}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:7651429}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00312,
CC ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:7651429}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=E {ECO:0000269|PubMed:7651429}; Synonyms=dCREB2-a
CC {ECO:0000303|PubMed:7651429};
CC IsoId=Q9VWW0-1; Sequence=Displayed;
CC Name=D {ECO:0000269|PubMed:7651429}; Synonyms=dCREB2-d
CC {ECO:0000303|PubMed:7651429};
CC IsoId=Q9VWW0-3; Sequence=VSP_051590;
CC Name=F {ECO:0000269|PubMed:7651429}; Synonyms=dCREB2-c
CC {ECO:0000303|PubMed:7651429}, H;
CC IsoId=Q9VWW0-4; Sequence=VSP_051590, VSP_051592;
CC Name=G; Synonyms=dCREB2-e {ECO:0000269|PubMed:15219829}, I;
CC IsoId=Q9VWW0-2; Sequence=VSP_051590, VSP_051591;
CC Name=J; Synonyms=dCREB2-b {ECO:0000303|PubMed:7651429};
CC IsoId=Q9VWW0-5; Sequence=VSP_051590, VSP_051591, VSP_051592;
CC -!- TISSUE SPECIFICITY: Most cells of the adult brain; cell bodies, but not
CC neuropil. {ECO:0000269|PubMed:7651429}.
CC -!- DEVELOPMENTAL STAGE: Throughout development with lowest levels in first
CC larval instar and late pupae. {ECO:0000269|PubMed:15219829,
CC ECO:0000269|PubMed:7651429, ECO:0000269|PubMed:8397816}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in the mushroom bodies
CC results in a reduction in long-term memory performance, but does not
CC affect anesthesia-resistant memory (ARM) or learning ability.
CC {ECO:0000269|PubMed:29473541}.
CC -!- MISCELLANEOUS: [Isoform G]: Isolated from Schneider 2 cells.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABI34195.3; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=ABI34226.3; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; S65627; AAB28337.1; -; Genomic_DNA.
DR EMBL; S65623; AAB28337.1; JOINED; Genomic_DNA.
DR EMBL; S65626; AAB28337.1; JOINED; Genomic_DNA.
DR EMBL; S79274; AAB35092.1; -; mRNA.
DR EMBL; AE014298; AAF48827.1; -; Genomic_DNA.
DR EMBL; AE014298; AAN09464.2; -; Genomic_DNA.
DR EMBL; AE014298; AAS65402.1; -; Genomic_DNA.
DR EMBL; AE014298; AAS65403.2; -; Genomic_DNA.
DR EMBL; AE014298; ABW09445.2; -; Genomic_DNA.
DR EMBL; AE014298; ABW09446.1; -; Genomic_DNA.
DR EMBL; AE014298; ABW09447.1; -; Genomic_DNA.
DR EMBL; BT028813; ABI34194.2; -; mRNA.
DR EMBL; BT028814; ABI34195.3; ALT_INIT; mRNA.
DR EMBL; BT028845; ABI34226.3; ALT_INIT; mRNA.
DR RefSeq; NP_001097016.2; NM_001103546.3. [Q9VWW0-5]
DR RefSeq; NP_001097017.1; NM_001103547.4. [Q9VWW0-2]
DR RefSeq; NP_001097018.1; NM_001103548.4. [Q9VWW0-5]
DR RefSeq; NP_001259677.1; NM_001272748.2. [Q9VWW0-2]
DR RefSeq; NP_001259678.1; NM_001272749.2. [Q9VWW0-5]
DR RefSeq; NP_996504.1; NM_206781.4. [Q9VWW0-4]
DR RefSeq; NP_996506.2; NM_206783.4. [Q9VWW0-2]
DR AlphaFoldDB; Q9VWW0; -.
DR SMR; Q9VWW0; -.
DR BioGRID; 59134; 31.
DR IntAct; Q9VWW0; 15.
DR STRING; 7227.FBpp0074326; -.
DR iPTMnet; Q9VWW0; -.
DR PaxDb; Q9VWW0; -.
DR DNASU; 32817; -.
DR EnsemblMetazoa; FBtr0074555; FBpp0074327; FBgn0265784. [Q9VWW0-2]
DR EnsemblMetazoa; FBtr0074557; FBpp0074329; FBgn0265784. [Q9VWW0-4]
DR EnsemblMetazoa; FBtr0112878; FBpp0111791; FBgn0265784. [Q9VWW0-2]
DR EnsemblMetazoa; FBtr0112879; FBpp0111792; FBgn0265784. [Q9VWW0-5]
DR EnsemblMetazoa; FBtr0310340; FBpp0302023; FBgn0265784. [Q9VWW0-2]
DR EnsemblMetazoa; FBtr0310341; FBpp0302024; FBgn0265784. [Q9VWW0-5]
DR EnsemblMetazoa; FBtr0346093; FBpp0311927; FBgn0265784. [Q9VWW0-5]
DR EnsemblMetazoa; FBtr0446106; FBpp0402805; FBgn0265784. [Q9VWW0-3]
DR GeneID; 32817; -.
DR KEGG; dme:Dmel_CG6103; -.
DR CTD; 32817; -.
DR FlyBase; FBgn0265784; CrebB.
DR VEuPathDB; VectorBase:FBgn0265784; -.
DR eggNOG; KOG3584; Eukaryota.
DR GeneTree; ENSGT00940000173530; -.
DR InParanoid; Q9VWW0; -.
DR OMA; LHMAPDP; -.
DR PhylomeDB; Q9VWW0; -.
DR Reactome; R-DME-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-DME-199920; CREB phosphorylation.
DR Reactome; R-DME-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-DME-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; Q9VWW0; -.
DR BioGRID-ORCS; 32817; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 32817; -.
DR PRO; PR:Q9VWW0; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0265784; Expressed in saliva-secreting gland and 21 other tissues.
DR ExpressionAtlas; Q9VWW0; baseline and differential.
DR Genevisible; Q9VWW0; DM.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0007623; P:circadian rhythm; TAS:FlyBase.
DR GO; GO:0007611; P:learning or memory; NAS:FlyBase.
DR GO; GO:0045475; P:locomotor rhythm; NAS:FlyBase.
DR GO; GO:0007616; P:long-term memory; IDA:FlyBase.
DR GO; GO:0072375; P:medium-term memory; IMP:FlyBase.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:FlyBase.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IGI:FlyBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0045187; P:regulation of circadian sleep/wake cycle, sleep; TAS:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0007622; P:rhythmic behavior; TAS:FlyBase.
DR GO; GO:0030431; P:sleep; IMP:FlyBase.
DR GO; GO:0040040; P:thermosensory behavior; IMP:FlyBase.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR003102; Coactivator_CBP_pKID.
DR InterPro; IPR001630; Leuzip_CREB.
DR PANTHER; PTHR45879; PTHR45879; 2.
DR Pfam; PF00170; bZIP_1; 1.
DR Pfam; PF02173; pKID; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
DR PROSITE; PS50953; KID; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..359
FT /note="Cyclic AMP response element-binding protein B"
FT /id="PRO_0000076636"
FT DOMAIN 198..257
FT /note="KID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312"
FT DOMAIN 300..359
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..238
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 301..326
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 328..349
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..73
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312,
FT ECO:0000269|PubMed:18327897"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312,
FT ECO:0000269|PubMed:18327897"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312,
FT ECO:0000269|PubMed:18327897"
FT VAR_SEQ 101..128
FT /note="Missing (in isoform D, isoform F, isoform G and
FT isoform J)"
FT /evidence="ECO:0000303|PubMed:15219829,
FT ECO:0000303|PubMed:7651429, ECO:0000303|Ref.6"
FT /id="VSP_051590"
FT VAR_SEQ 185..188
FT /note="Missing (in isoform G and isoform J)"
FT /evidence="ECO:0000303|PubMed:15219829,
FT ECO:0000303|PubMed:7651429"
FT /id="VSP_051591"
FT VAR_SEQ 245..291
FT /note="GASLPMSDGVLNSQLAGTGAGGNAANSSLMQLDPTYYLSNRMSYNTN -> D
FT (in isoform F and isoform J)"
FT /evidence="ECO:0000303|PubMed:7651429, ECO:0000303|Ref.6"
FT /id="VSP_051592"
FT MUTAGEN 328
FT /note="L->V: Fails to block PKA-dependent activation by
FT isoform E; in isoform G."
FT /evidence="ECO:0000269|PubMed:7651429"
FT MUTAGEN 335
FT /note="L->V: Fails to block PKA-dependent activation by
FT isoform E; in isoform G."
FT /evidence="ECO:0000269|PubMed:7651429"
FT CONFLICT 46
FT /note="G -> GG (in Ref. 2; AAB35092)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="A -> V (in Ref. 2; AAB35092)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="T -> A (in Ref. 6; ABI34195/ABI34226)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 37939 MW; 382CDE11C43BFB45 CRC64;
MDNSIVEENG NSSAASGSND VVDVVAQQAA AAVGGGGGGG GGGGGGNPQQ QQQNPQSTTA
GGPTGATNNA QGGGVSSVLT TTANCNIQYP IQTLAQHGLQ VSIWGPGAWC QLSSVRCYGS
QPEVATKDVQ SVIQANPSGV IQTAAGTQQQ QQALAAATAM QKVVYVAKPP NSTVIHTTPG
NAVQVRNKIP PTFPCKIKPE PNTQHPEDSD ESLSDDDSQH HRSELTRRPS YNKIFTEISG
PDMSGASLPM SDGVLNSQLA GTGAGGNAAN SSLMQLDPTY YLSNRMSYNT NNSGIAEDQT
RKREIRLQKN REAARECRRK KKEYIKCLEN RVAVLENQNK ALIEELKSLK ELYCQTKND
