CREB1_BOVIN
ID CREB1_BOVIN Reviewed; 325 AA.
AC P27925; A5PK02; O18957;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 1;
DE Short=CREB-1;
DE Short=cAMP-responsive element-binding protein 1;
DE AltName: Full=Cyclic AMP-responsive DNA-binding protein;
GN Name=CREB1; Synonyms=CREB, CREB2;
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 [MRNA].
RX PubMed=1837490; DOI=10.3109/10425179109020800;
RA Willems L., Kettmann R., Chen G., Portetelle D., Burny A., Derse D.;
RT "Nucleotide sequence of the bovine cyclic-AMP responsive DNA binding
RT protein (CREB2) cDNA.";
RL DNA Seq. 1:415-417(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Adam E., Twizere J.C., Burny A., Kettmann R., Willems L.;
RT "Nucleotide sequence of the CREB protein involved in bovine leukemia virus
RT expression.";
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=1309910; DOI=10.1128/jvi.66.2.766-772.1992;
RA Willems L., Kettmann R., Chen G., Portetelle D., Burny A., Derse D.;
RT "A cyclic AMP-responsive DNA-binding protein (CREB2) is a cellular
RT transactivator of the bovine leukemia virus long terminal repeat.";
RL J. Virol. 66:766-772(1992).
RN [5]
RP FUNCTION.
RX PubMed=8057465; DOI=10.1128/jvi.68.9.5845-5853.1994;
RA Adam E., Kerkhofs P., Mammerickx M., Kettmann R., Burny A., Droogmans L.,
RA Willems L.;
RT "Involvement of the cyclic AMP-responsive element binding protein in bovine
RT leukemia virus expression in vivo.";
RL J. Virol. 68:5845-5853(1994).
RN [6]
RP FUNCTION.
RX PubMed=8627725; DOI=10.1128/jvi.70.3.1990-1999.1996;
RA Adam E., Kerkhofs P., Mammerickx M., Burny A., Kettman R., Willems L.;
RT "The CREB, ATF-1, and ATF-2 transcription factors from bovine leukemia
RT virus-infected B lymphocytes activate viral expression.";
RL J. Virol. 70:1990-1999(1996).
RN [7]
RP PHOSPHORYLATION AT SER-117.
RX PubMed=11752053; DOI=10.1046/j.1471-4159.2001.00666.x;
RA Cammarota M., Bevilaqua L.R., Dunkley P.R., Rostas J.A.;
RT "Angiotensin II promotes the phosphorylation of cyclic AMP-responsive
RT element binding protein (CREB) at Ser133 through an ERK1/2-dependent
RT mechanism.";
RL J. Neurochem. 79:1122-1128(2001).
CC -!- FUNCTION: Phosphorylation-dependent transcription factor that
CC stimulates transcription upon binding to the DNA cAMP response element
CC (CRE), a sequence present in many viral and cellular promoters.
CC Transcription activation is enhanced by the TORC coactivators which act
CC independently of Ser-117 phosphorylation. Involved in different
CC cellular processes including the synchronization of circadian
CC rhythmicity and the differentiation of adipose cells.
CC {ECO:0000269|PubMed:1309910, ECO:0000269|PubMed:8057465,
CC ECO:0000269|PubMed:8627725}.
CC -!- SUBUNIT: Interacts with PPRC1. Binds DNA as a dimer. This dimer is
CC stabilized by magnesium ions. Interacts, through the bZIP domain, with
CC the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. When
CC phosphorylated on Ser-117, binds CREBBP (By similarity). Interacts with
CC CREBL2; regulates CREB1 phosphorylation, stability and transcriptional
CC activity (By similarity). Interacts (phosphorylated form) with TOX3.
CC Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. Interacts
CC with TSSK4; this interaction facilitates phosphorylation on Ser-117.
CC Forms a complex with KMT2A and CREBBP (By similarity). Interacts with
CC TOX4; CREB1 is required for full induction of TOX4-dependent activity
CC and the interaction is increased by cAMP and inhibited by insulin (By
CC similarity). {ECO:0000250|UniProtKB:P16220,
CC ECO:0000250|UniProtKB:Q01147}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation on Lys-288, but not on Lys-269,
CC is required for nuclear localization of this protein. Sumoylation is
CC enhanced under hypoxia, promoting nuclear localization and
CC stabilization (By similarity). {ECO:0000250}.
CC -!- PTM: Stimulated by phosphorylation. Phosphorylation of both Ser-117 and
CC Ser-126 in the SCN regulates the activity of CREB and participates in
CC circadian rhythm generation. Phosphorylation of Ser-117 allows CREBBP
CC binding. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-
CC 117. CaMK4 is much more potent than CaMK2 in activating CREB.
CC Phosphorylated by CaMK2 on Ser-126. Phosphorylation of Ser-126 blocks
CC CREB-mediated transcription even when Ser-117 is phosphorylated.
CC Phosphorylated by CaMK1. Phosphorylation of Ser-255 by HIPK2 in
CC response to genotoxic stress promotes CREB1 activity, facilitating the
CC recruitment of the coactivator CBP. Phosphorylated at Ser-117 by
CC RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress
CC stimuli. CREBL2 positively regulates phosphorylation at Ser-117 thereby
CC stimulating CREB1 transcriptional activity. In liver, phosphorylation
CC is induced by fasting or glucagon in a circadian fashion (By
CC similarity). Phosphorylated by TSSK4 on Ser-117 (By similarity).
CC {ECO:0000250|UniProtKB:P16220}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; X57031; CAA40347.1; -; mRNA.
DR EMBL; AF006042; AAB62381.1; -; mRNA.
DR EMBL; BC142303; AAI42304.1; -; mRNA.
DR PIR; S23007; S23007.
DR RefSeq; NP_776710.1; NM_174285.1.
DR AlphaFoldDB; P27925; -.
DR BMRB; P27925; -.
DR SMR; P27925; -.
DR STRING; 9913.ENSBTAP00000007201; -.
DR iPTMnet; P27925; -.
DR PaxDb; P27925; -.
DR PRIDE; P27925; -.
DR ABCD; P27925; 1 sequenced antibody.
DR GeneID; 281713; -.
DR KEGG; bta:281713; -.
DR CTD; 1385; -.
DR eggNOG; KOG3584; Eukaryota.
DR HOGENOM; CLU_042675_0_1_1; -.
DR InParanoid; P27925; -.
DR OrthoDB; 957343at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0033762; P:response to glucagon; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR003102; Coactivator_CBP_pKID.
DR InterPro; IPR029802; CREB1.
DR InterPro; IPR001630; Leuzip_CREB.
DR PANTHER; PTHR45879; PTHR45879; 1.
DR PANTHER; PTHR45879:SF1; PTHR45879:SF1; 1.
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; Biological rhythms; Differentiation; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..325
FT /note="Cyclic AMP-responsive element-binding protein 1"
FT /id="PRO_0000076600"
FT DOMAIN 85..144
FT /note="KID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312"
FT DOMAIN 267..325
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 124..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..293
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 295..316
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT SITE 298
FT /note="Required for binding TORCs"
FT /evidence="ECO:0000250"
FT MOD_RES 117
FT /note="Phosphoserine; by CaMK1, CaMK2, CaMK4, PKB/AKT1 or
FT PKB/AKT2, RPS6KA3, RPS6KA4, RPS6KA5 and SGK1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00312,
FT ECO:0000269|PubMed:11752053"
FT MOD_RES 126
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:P15337,
FT ECO:0000255|PROSITE-ProRule:PRU00312"
FT MOD_RES 255
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0000250|UniProtKB:P16220,
FT ECO:0000255|PROSITE-ProRule:PRU00312"
FT CROSSLNK 120
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P16220"
FT CROSSLNK 269
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:P16220"
FT CROSSLNK 288
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1)"
FT /evidence="ECO:0000250|UniProtKB:P16220"
FT CONFLICT 60..61
FT /note="QT -> TK (in Ref. 1; CAA40347)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 325 AA; 34877 MW; 61B4B4244FAB474B CRC64;
MESGAENQQS GDAAVTEAES QQMTVQAQPQ IATLAQVSMP AAHATSSAPT VTLVQLPNGQ
TVQVHGVIQA AQPSVIQSPQ VQTVQISTIA ESEDSQESVD SVTDSQKRRE ILSRRPSYRK
ILNDLSSDAP GVPRIEEEKS EEETSAPAIT TVTVPTPIYQ TSSGQYIAIT QGGAIQLANN
GTDGVQGLQT LTMTNAAATQ PGTTILQYAQ TTDGQQILVP SNQVVVQAAS GDVQTYQIRT
APTSTIAPGV VMASSPALPT QPAEEAARKR EVRLMKNREA ARECRRKKKE YVKCLENRVA
VLENQNKTLI EELKALKDLY CHKSD
