ID CREB1_HUMAN Reviewed; 341 AA.
AC P16220; P21934; Q6V963; Q9UMA7;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 2.
DT 18-JAN-2017, entry version 206.
DE RecName: Full=Cyclic AMP-responsive element-binding protein 1;
DE Short=CREB-1;
DE Short=cAMP-responsive element-binding protein 1;
GN Name=CREB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
RX PubMed=2142528; DOI=10.1073/pnas.87.14.5258;
RA Berkowitz L.A., Gilman M.Z.;
RT "Two distinct forms of active transcription factor CREB (cAMP response
RT element binding protein).";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5258-5262(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
RX PubMed=2196176;
RA Yoshimura T., Fujisawa J., Yoshida M.;
RT "Multiple cDNA clones encoding nuclear proteins that bind to the tax-
RT dependent enhancer of HTLV-1: all contain a leucine zipper structure
RT and basic amino acid domain.";
RL EMBO J. 9:2537-2542(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-A).
RX PubMed=1966745;
RA Waeber G., Meyer T.E., Hoeffler J.P., Habener J.F.;
RT "Diversification of cyclic AMP-responsive enhancer binding proteins-
RT generated by alternative exon splicing.";
RL Trans. Assoc. Am. Physicians 103:28-37(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
RX PubMed=2974179; DOI=10.1126/science.2974179;
RA Hoeffler J.P., Meyer T.E., Yun Y., Jameson J.L., Habener J.F.;
RT "Cyclic AMP-responsive DNA-binding protein: structure based on a
RT cloned placental cDNA.";
RL Science 242:1430-1433(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM CREB-B).
RX PubMed=1831258; DOI=10.1093/nar/19.15.4290;
RA Short M.L., Manohar C.F., Furtado M.R., Ghadge G.D., Wolinsky S.M.,
RA Thimmapaya B., Jungmann R.A.;
RT "Nucleotide and derived amino-acid sequences of the CRE-binding
RT proteins from rat C6 glioma and HeLa cells.";
RL Nucleic Acids Res. 19:4290-4290(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=15579595; DOI=10.1530/rep.1.00036;
RA Huang X., Zhang J., Lu L., Yin L., Xu M., Wang Y., Zhou Z., Sha J.;
RT "Cloning and expression of a novel CREB mRNA splice variant in human
RT testis.";
RL Reproduction 128:775-782(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM CREB-A).
RC TISSUE=Eye;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8.
RX PubMed=8381074; DOI=10.1210/endo.132.2.8381074;
RA Meyer T.E., Waeber G., Lin J., Beckmann W., Habener J.F.;
RT "The promoter of the gene encoding 3',5'-cyclic adenosine
RT monophosphate (cAMP) response element binding protein contains cAMP
RT response elements: evidence for positive autoregulation of gene
RT transcription.";
RL Endocrinology 132:770-780(1993).
RN [9]
RP INTERACTION WITH HBV PROTEIN X.
RX PubMed=1827531; DOI=10.1126/science.1827531;
RA Maguire H.F., Hoeffler J.P., Siddiqui A.;
RT "HBV X protein alters the DNA binding specificity of CREB and ATF-2 by
RT protein-protein interactions.";
RL Science 252:842-844(1991).
RN [10]
RP INTERACTION WITH HTLV-1 TAX-1.
RX PubMed=1386673; DOI=10.1073/pnas.89.15.7070;
RA Zhao L.J., Giam C.-Z.;
RT "Human T-cell lymphotropic virus type I (HTLV-I) transcriptional
RT activator, Tax, enhances CREB binding to HTLV-I 21-base-pair repeats
RT by protein-protein interaction.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7070-7074(1992).
RN [11]
RP PHOSPHORYLATION AT SER-133, AND MUTAGENESIS OF SER-133.
RX PubMed=8065343; DOI=10.1128/MCB.14.9.6107;
RA Matthews R.P., Guthrie C.R., Wailes L.M., Zhao X., Means A.R.,
RA McKnight G.S.;
RT "Calcium/calmodulin-dependent protein kinase types II and IV
RT differentially regulate CREB-dependent gene expression.";
RL Mol. Cell. Biol. 14:6107-6116(1994).
RN [12]
RP PHOSPHORYLATION AT SER-133.
RX PubMed=7608156; DOI=10.1074/jbc.270.27.16378;
RA Lee H.-J.J., Mignacca R.C., Sakamoto K.M.;
RT "Transcriptional activation of egr-1 by granulocyte-macrophage colony-
RT stimulating factor but not interleukin 3 requires phosphorylation of
RT cAMP response element-binding protein (CREB) on serine 133.";
RL J. Biol. Chem. 270:15979-15983(1995).
RN [13]
RP PHOSPHORYLATION AT SER-133.
RX PubMed=9829964; DOI=10.1074/jbc.273.49.32377;
RA Du K., Montminy M.;
RT "CREB is a regulatory target for the protein kinase Akt/PKB.";
RL J. Biol. Chem. 273:32377-32379(1998).
RN [14]
RP PHOSPHORYLATION AT SER-133.
RX PubMed=9770464; DOI=10.1073/pnas.95.21.12202;
RA De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P.;
RT "Rsk-2 activity is necessary for epidermal growth factor-induced
RT phosphorylation of CREB protein and transcription of c-fos gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12202-12207(1998).
RN [15]
RP INTERACTION WITH CRTC1.
RX PubMed=14536081; DOI=10.1016/j.molcel.2003.08.013;
RA Conkright M.D., Canettieri G., Screaton R., Guzman E., Miraglia L.,
RA Hogenesch J.B., Montminy M.;
RT "TORCs: transducers of regulated CREB activity.";
RL Mol. Cell 12:413-423(2003).
RN [16]
RP SUMOYLATION AT LYS-285 AND LYS-304, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF LYS-155; LYS-285 AND LYS-304.
RX PubMed=12552083; DOI=10.1073/pnas.0337412100;
RA Comerford K.M., Leonard M.O., Karhausen J., Carey R., Colgan S.P.,
RA Taylor C.T.;
RT "Small ubiquitin-related modifier-1 modification mediates resolution
RT of CREB-dependent responses to hypoxia.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:986-991(2003).
RN [17]
RP INTERACTION WITH CRTC3.
RX PubMed=14506290; DOI=10.1073/pnas.1932773100;
RA Iourgenko V., Zhang W., Mickanin C., Daly I., Jiang C., Hexham J.M.,
RA Orth A.P., Miraglia L., Meltzer J., Garza D., Chirn G.-W.,
RA McWhinnie E., Cohen D., Skelton J., Terry R., Yu Y., Bodian D.,
RA Buxton F.P., Zhu J., Song C., Labow M.A.;
RT "Identification of a family of cAMP response element-binding protein
RT coactivators by genome-scale functional analysis in mammalian cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12147-12152(2003).
RN [18]
RP INTERACTION WITH CRTC2.
RX PubMed=15454081; DOI=10.1016/j.cell.2004.09.015;
RA Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G.,
RA Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H.,
RA Okamoto M., Montminy M.;
RT "The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive
RT coincidence detector.";
RL Cell 119:61-74(2004).
RN [19]
RP INTERACTION WITH ARRB1.
RX PubMed=16325578; DOI=10.1016/j.cell.2005.09.011;
RA Kang J., Shi Y., Xiang B., Qu B., Su W., Zhu M., Zhang M., Bao G.,
RA Wang F., Zhang X., Yang R., Fan F., Chen X., Pei G., Ma L.;
RT "A nuclear function of beta-arrestin1 in GPCR signaling: regulation of
RT histone acetylation and gene transcription.";
RL Cell 123:833-847(2005).
RN [20]
RP PHOSPHORYLATION AT SER-133 BY SGK1, AND INTERACTION WITH SGK1.
RX PubMed=15733869; DOI=10.1016/j.febslet.2005.01.040;
RA David S., Kalb R.G.;
RT "Serum/glucocorticoid-inducible kinase can phosphorylate the cyclic
RT AMP response element binding protein, CREB.";
RL FEBS Lett. 579:1534-1538(2005).
RN [21]
RP INTERACTION WITH PPRC1.
RX PubMed=16908542; DOI=10.1128/MCB.00585-06;
RA Vercauteren K., Pasko R.A., Gleyzer N., Marino V.M., Scarpulla R.C.;
RT "PGC-1-related coactivator: immediate early expression and
RT characterization of a CREB/NRF-1 binding domain associated with
RT cytochrome c promoter occupancy and respiratory growth.";
RL Mol. Cell. Biol. 26:7409-7419(2006).
RN [22]
RP CHROMOSOMAL TRANSLOCATION WITH EWSR1, AND ASSOCIATION WITH ANGIOMATOID
RP FIBROUS HISTIOCYTOMA.
RX PubMed=17724745; DOI=10.1002/gcc.20491;
RA Antonescu C.R., Dal Cin P., Nafa K., Teot L.A., Surti U.,
RA Fletcher C.D., Ladanyi M.;
RT "EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous
RT histiocytoma.";
RL Genes Chromosomes Cancer 46:1051-1060(2007).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP PHOSPHORYLATION AT SER-271 BY HIPK2, MUTAGENESIS OF SER-271, AND
RP INTERACTION WITH HIPK2.
RX PubMed=20573984; DOI=10.1091/mbc.E10-01-0015;
RA Sakamoto K., Huang B.-W., Iwasaki K., Hailemariam K.,
RA Ninomiya-Tsuji J., Tsuji Y.;
RT "Regulation of genotoxic stress response by homeodomain-interacting
RT protein kinase 2 through phosphorylation of cyclic AMP response
RT element-binding protein at serine 271.";
RL Mol. Biol. Cell 21:2966-2974(2010).
RN [27]
RP INTERACTION WITH TOX3, AND MUTAGENESIS OF SER-133.
RX PubMed=21172805; DOI=10.1242/jcs.068759;
RA Dittmer S., Kovacs Z., Yuan S.H., Siszler G., Kogl M., Summer H.,
RA Geerts A., Golz S., Shioda T., Methner A.;
RT "TOX3 is a neuronal survival factor that induces transcription
RT depending on the presence of CITED1 or phosphorylated CREB in the
RT transcriptionally active complex.";
RL J. Cell Sci. 124:252-260(2011).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP POSSIBLE INVOLVEMENT IN MULTIPLE CONGENITAL ANOMALIES, VARIANT
RP GLY-116, AND CHARACTERIZATION OF VARIANT GLY-116.
RX PubMed=22267179; DOI=10.1002/humu.22027;
RA Kitazawa S., Kondo T., Mori K., Yokoyama N., Matsuo M., Kitazawa R.;
RT "A p.D116G mutation in CREB1 leads to novel multiple malformation
RT syndrome resembling CrebA knockout mouse.";
RL Hum. Mutat. 33:651-654(2012).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA Wang L., Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT liver phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Phosphorylation-dependent transcription factor that
CC stimulates transcription upon binding to the DNA cAMP response
CC element (CRE), a sequence present in many viral and cellular
CC promoters. Transcription activation is enhanced by the TORC
CC coactivators which act independently of Ser-133 phosphorylation.
CC Involved in different cellular processes including the
CC synchronization of circadian rhythmicity and the differentiation
CC of adipose cells.
CC -!- SUBUNIT: Interacts with PPRC1. Binds DNA as a dimer. This dimer is
CC stabilized by magnesium ions. Interacts, through the bZIP domain,
CC with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3.
CC When phosphorylated on Ser-133, binds CREBBP (By similarity).
CC Interacts with CREBL2; regulates CREB1 phosphorylation, stability
CC and transcriptional activity (By similarity). Interacts
CC (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to
CC HIPK2. Interacts with SGK1. {ECO:0000250,
CC ECO:0000269|PubMed:1386673, ECO:0000269|PubMed:14506290,
CC ECO:0000269|PubMed:14536081, ECO:0000269|PubMed:15454081,
CC ECO:0000269|PubMed:15733869, ECO:0000269|PubMed:16325578,
CC ECO:0000269|PubMed:16908542, ECO:0000269|PubMed:1827531,
CC ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:21172805}.
CC -!- INTERACTION:
CC Self; NbExp=3; IntAct=EBI-711855, EBI-711855;
CC P03259-2:- (xeno); NbExp=2; IntAct=EBI-711855, EBI-7225021;
CC P18846:ATF1; NbExp=6; IntAct=EBI-711855, EBI-852794;
CC Q92793:CREBBP; NbExp=2; IntAct=EBI-711855, EBI-81215;
CC Q6UUV9:CRTC1; NbExp=3; IntAct=EBI-711855, EBI-1644259;
CC Q09472:EP300; NbExp=2; IntAct=EBI-711855, EBI-447295;
CC P0C746:HBZ (xeno); NbExp=2; IntAct=EBI-711855, EBI-10890294;
CC Q9DGW5:MDV005 (xeno); NbExp=2; IntAct=EBI-711855, EBI-10889526;
CC O00470:MEIS1; NbExp=9; IntAct=EBI-711855, EBI-1210694;
CC O95644:NFATC1; NbExp=3; IntAct=EBI-711855, EBI-6907210;
CC Q13469:NFATC2; NbExp=2; IntAct=EBI-711855, EBI-716258;
CC Q16649:NFIL3; NbExp=3; IntAct=EBI-711855, EBI-3951858;
CC Q96RG2:PASK; NbExp=2; IntAct=EBI-711855, EBI-1042651;
CC Q6SA08:TSSK4; NbExp=5; IntAct=EBI-711855, EBI-1202583;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
CC ProRule:PRU00312, ECO:0000255|PROSITE-ProRule:PRU00978,
CC ECO:0000269|PubMed:12552083}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=CREB-A;
CC IsoId=P16220-1; Sequence=Displayed;
CC Name=CREB-B;
CC IsoId=P16220-2; Sequence=VSP_000596;
CC Name=3; Synonyms=htCREB;
CC IsoId=P16220-3; Sequence=VSP_043914;
CC Note=Highly expressed in adult testis and sperm.;
CC -!- PTM: Stimulated by phosphorylation. Phosphorylation of both Ser-
CC 133 and Ser-142 in the SCN regulates the activity of CREB and
CC participates in circadian rhythm generation. Phosphorylation of
CC Ser-133 allows CREBBP binding. In liver, phosphorylation is
CC induced by fasting or glucagon in a circadian fashion (By
CC similarity). CREBL2 positively regulates phosphorylation at Ser-
CC 133 thereby stimulating CREB1 transcriptional activity (By
CC similarity). Phosphorylated upon calcium influx by CaMK4 and CaMK2
CC on Ser-133. CaMK4 is much more potent than CaMK2 in activating
CC CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser-
CC 142 blocks CREB-mediated transcription even when Ser-133 is
CC phosphorylated. Phosphorylated by CaMK1 (By similarity).
CC Phosphorylation of Ser-271 by HIPK2 in response to genotoxic
CC stress promotes CREB1 activity, facilitating the recruitment of
CC the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4
CC and RPS6KA5 in response to mitogenic or stress stimuli.
CC {ECO:0000250, ECO:0000269|PubMed:15733869,
CC ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:7608156,
CC ECO:0000269|PubMed:8065343, ECO:0000269|PubMed:9770464,
CC ECO:0000269|PubMed:9829964}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation on Lys-304, but not on
CC Lys-285, is required for nuclear localization of this protein.
CC Sumoylation is enhanced under hypoxia, promoting nuclear
CC localization and stabilization. {ECO:0000269|PubMed:12552083}.
CC -!- DISEASE: Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A
CC distinct variant of malignant fibrous histiocytoma that typically
CC occurs in children and adolescents and is manifest by nodular
CC subcutaneous growth. Characteristic microscopic features include
CC lobulated sheets of histiocyte-like cells intimately associated
CC with areas of hemorrhage and cystic pseudovascular spaces, as well
CC as a striking cuffing of inflammatory cells, mimicking a lymph
CC node metastasis. Note=The gene represented in this entry may be
CC involved in disease pathogenesis. A chromosomal aberration
CC involving CREB1 is found in a patient with angiomatoid fibrous
CC histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates
CC a EWSR1/CREB1 fusion gene that is most common genetic abnormality
CC in this tumor type.
CC -!- DISEASE: Note=A CREB1 mutation has been found in a patient with
CC multiple congenital anomalies consisting of agenesis of the corpus
CC callosum, cerebellar hypoplasia, severe neonatal respiratory
CC distress refractory to surfactant, thymus hypoplasia, and thyroid
CC follicular hypoplasia. {ECO:0000269|PubMed:22267179}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00978}.
CC -!- SIMILARITY: Contains 1 KID (kinase-inducible) domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00312}.
DR EMBL; S72459; AAB20597.1; -; Genomic_DNA.
DR EMBL; X55545; CAA39151.1; -; mRNA.
DR EMBL; M34356; AAA35717.1; -; mRNA.
DR EMBL; M34356; AAA35716.1; -; mRNA.
DR EMBL; M27691; AAA35715.1; -; mRNA.
DR EMBL; X60003; CAA42620.1; -; mRNA.
DR EMBL; AY347527; AAQ24858.1; -; mRNA.
DR EMBL; BC010636; AAH10636.1; -; mRNA.
DR EMBL; S53724; AAD13869.1; -; Genomic_DNA.
DR CCDS; CCDS2374.1; -. [P16220-2]
DR CCDS; CCDS2375.1; -. [P16220-1]
DR PIR; A37340; A35769.
DR PIR; B37340; B35769.
DR PIR; S22298; S22298.
DR RefSeq; NP_004370.1; NM_004379.4. [P16220-2]
DR RefSeq; NP_604391.1; NM_134442.4. [P16220-1]
DR RefSeq; XP_011508947.1; XM_011510645.1. [P16220-1]
DR RefSeq; XP_011508949.1; XM_011510647.2. [P16220-2]
DR UniGene; Hs.516646; -.
DR UniGene; Hs.717136; -.
DR PDB; 2LXT; NMR; -; C=116-149.
DR PDBsum; 2LXT; -.
DR ProteinModelPortal; P16220; -.
DR SMR; P16220; -.
DR BioGrid; 107775; 143.
DR DIP; DIP-765N; -.
DR IntAct; P16220; 78.
DR MINT; MINT-1338714; -.
DR STRING; 9606.ENSP00000387699; -.
DR ChEMBL; CHEMBL5587; -.
DR DrugBank; DB00131; Adenosine monophosphate.
DR DrugBank; DB01183; Naloxone.
DR iPTMnet; P16220; -.
DR PhosphoSitePlus; P16220; -.
DR BioMuta; CREB1; -.
DR DMDM; 117434; -.
DR EPD; P16220; -.
DR PaxDb; P16220; -.
DR PeptideAtlas; P16220; -.
DR PRIDE; P16220; -.
DR DNASU; 1385; -.
DR Ensembl; ENST00000353267; ENSP00000236995; ENSG00000118260. [P16220-2]
DR Ensembl; ENST00000430624; ENSP00000405539; ENSG00000118260. [P16220-2]
DR Ensembl; ENST00000432329; ENSP00000387699; ENSG00000118260. [P16220-1]
DR GeneID; 1385; -.
DR KEGG; hsa:1385; -.
DR CTD; 1385; -.
DR DisGeNET; 1385; -.
DR GeneCards; CREB1; -.
DR HGNC; HGNC:2345; CREB1.
DR HPA; CAB003803; -.
DR HPA; HPA019150; -.
DR MalaCards; CREB1; -.
DR MIM; 123810; gene.
DR MIM; 612160; phenotype.
DR neXtProt; NX_P16220; -.
DR OpenTargets; ENSG00000118260; -.
DR Orphanet; 97338; Melanoma of soft parts.
DR PharmGKB; PA26864; -.
DR eggNOG; KOG3584; Eukaryota.
DR eggNOG; ENOG410ZZJZ; LUCA.
DR GeneTree; ENSGT00390000008655; -.
DR HOGENOM; HOG000007365; -.
DR HOVERGEN; HBG011077; -.
DR InParanoid; P16220; -.
DR KO; K05870; -.
DR OMA; QXISTIA; -.
DR OrthoDB; EOG091G0FTJ; -.
DR PhylomeDB; P16220; -.
DR TreeFam; TF106464; -.
DR BioCyc; ZFISH:ENSG00000118260-MONOMER; -.
DR Reactome; R-HSA-111931; PKA-mediated phosphorylation of CREB.
DR Reactome; R-HSA-111932; CaMK IV-mediated phosphorylation of CREB.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR Reactome; R-HSA-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-HSA-199920; CREB phosphorylation.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-2197563; NOTCH2 intracellular domain regulates transcription.
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-442717; CREB phosphorylation through the activation of CaMKK.
DR Reactome; R-HSA-442720; CREB phosphorylation through the activation of Adenylate Cyclase.
DR Reactome; R-HSA-442729; CREB phosphorylation through the activation of CaMKII.
DR Reactome; R-HSA-442742; CREB phosphorylation through the activation of Ras.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR SignaLink; P16220; -.
DR SIGNOR; P16220; -.
DR ChiTaRS; CREB1; human.
DR GeneWiki; CREB1; -.
DR GenomeRNAi; 1385; -.
DR PMAP-CutDB; P16220; -.
DR PRO; PR:P16220; -.
DR Proteomes; UP000005640; Chromosome 2.
DR Bgee; ENSG00000118260; -.
DR CleanEx; HS_CREB1; -.
DR ExpressionAtlas; P16220; baseline and differential.
DR Genevisible; P16220; HS.
DR GO; GO:1990589; C:ATF4-CREB1 transcription factor complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0005719; C:nuclear euchromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0035497; F:cAMP response element binding; IDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0001102; F:RNA polymerase II activating transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0003712; F:transcription cofactor activity; TAS:ProtInc.
DR GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:BHF-UCL.
DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IC:NTNU_SB.
DR GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; IDA:BHF-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0071398; P:cellular response to fatty acid; IEA:Ensembl.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IEA:Ensembl.
DR GO; GO:1990314; P:cellular response to insulin-like growth factor stimulus; IEA:Ensembl.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEA:Ensembl.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
DR GO; GO:0071294; P:cellular response to zinc ion; IEA:Ensembl.
DR GO; GO:0034670; P:chemotaxis to arachidonic acid; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0007595; P:lactation; IEA:Ensembl.
DR GO; GO:0060430; P:lung saccule development; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0055025; P:positive regulation of cardiac muscle tissue development; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0046887; P:positive regulation of hormone secretion; IEA:Ensembl.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcriptional preinitiation complex assembly; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032916; P:positive regulation of transforming growth factor beta3 production; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0008361; P:regulation of cell size; IEA:Ensembl.
DR GO; GO:0042752; P:regulation of circadian rhythm; IEA:Ensembl.
DR GO; GO:0048145; P:regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0060251; P:regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0033762; P:response to glucagon; ISS:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; IDA:MGI.
DR GO; GO:0033363; P:secretory granule organization; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060509; P:Type I pneumocyte differentiation; IEA:Ensembl.
DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR003102; Coactivator_CBP_pKID.
DR InterPro; IPR001630; Leuzip_CREB.
DR Pfam; PF00170; bZIP_1; 1.
DR Pfam; PF02173; pKID; 1.
DR PRINTS; PR00041; LEUZIPPRCREB.
DR SMART; SM00338; BRLZ; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
DR PROSITE; PS50953; KID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Biological rhythms;
KW Chromosomal rearrangement; Complete proteome; Differentiation;
KW DNA-binding; Host-virus interaction; Isopeptide bond; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 341 Cyclic AMP-responsive element-binding
FT protein 1.
FT /FTId=PRO_0000076597.
FT DOMAIN 101 160 KID. {ECO:0000255|PROSITE-
FT ProRule:PRU00312}.
FT DOMAIN 283 341 bZIP. {ECO:0000255|PROSITE-
FT ProRule:PRU00978}.
FT REGION 284 309 Basic motif. {ECO:0000255|PROSITE-
FT ProRule:PRU00978}.
FT REGION 311 332 Leucine-zipper. {ECO:0000255|PROSITE-
FT ProRule:PRU00978}.
FT SITE 314 314 Required for binding TORCs.
FT MOD_RES 133 133 Phosphoserine; by CaMK1, CaMK2, CaMK4,
FT PKB/AKT1 or PKB/AKT2, RPS6KA3, RPS6KA4,
FT RPS6KA5 and SGK1. {ECO:0000255|PROSITE-
FT ProRule:PRU00312,
FT ECO:0000269|PubMed:15733869,
FT ECO:0000269|PubMed:7608156,
FT ECO:0000269|PubMed:8065343,
FT ECO:0000269|PubMed:9770464,
FT ECO:0000269|PubMed:9829964}.
FT MOD_RES 142 142 Phosphoserine.
FT {ECO:0000244|PubMed:23186163}.
FT MOD_RES 271 271 Phosphoserine; by HIPK2.
FT {ECO:0000255|PROSITE-ProRule:PRU00312,
FT ECO:0000269|PubMed:20573984}.
FT CROSSLNK 285 285 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO1).
FT {ECO:0000269|PubMed:12552083}.
FT CROSSLNK 304 304 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO1).
FT {ECO:0000269|PubMed:12552083}.
FT VAR_SEQ 88 101 Missing (in isoform CREB-B).
FT {ECO:0000303|PubMed:1831258,
FT ECO:0000303|PubMed:2974179}.
FT /FTId=VSP_000596.
FT VAR_SEQ 162 272 Missing (in isoform 3).
FT {ECO:0000303|PubMed:15579595}.
FT /FTId=VSP_043914.
FT VARIANT 116 116 D -> G (found in a patient with multiple
FT congenital anomalies; does not affect
FT CREB1 phosphorylation at S-133; fails to
FT interact with CREBBP; dbSNP:rs387906617).
FT {ECO:0000269|PubMed:22267179}.
FT /FTId=VAR_068077.
FT MUTAGEN 133 133 S->A: Does not interact with TOX3 and
FT inhibits induction of transcription by
FT TOX3. Loss of phosphorylation by CaMK4.
FT {ECO:0000269|PubMed:21172805,
FT ECO:0000269|PubMed:8065343}.
FT MUTAGEN 155 155 K->R: No effect on sumoylation.
FT {ECO:0000269|PubMed:12552083}.
FT MUTAGEN 271 271 S->A: Impaired phosphorylation by HIPK2
FT and subsequent transactivation.
FT {ECO:0000269|PubMed:20573984}.
FT MUTAGEN 271 271 S->E: Potentiated transactivation.
FT {ECO:0000269|PubMed:20573984}.
FT MUTAGEN 285 285 K->R: Decreased sumoylation, in vivo and
FT in vitro. {ECO:0000269|PubMed:12552083}.
FT MUTAGEN 304 304 K->R: Decreased sumoylation, in vivo and
FT in vitro. Loss of nuclear localization.
FT {ECO:0000269|PubMed:12552083}.
FT CONFLICT 4 4 E -> D (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 8 8 E -> D (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 160 160 T -> A (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 167 167 T -> A (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 169 169 T -> A (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 176 176 Q -> R (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 184 184 A -> T (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 188 188 G -> R (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 195 195 N -> S (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 210 210 T -> A (in Ref. 5; CAA42620).
FT {ECO:0000305}.
FT CONFLICT 292 292 K -> E (in Ref. 6; AAQ24858).
FT {ECO:0000305}.
FT HELIX 120 128 {ECO:0000244|PDB:2LXT}.
FT HELIX 132 142 {ECO:0000244|PDB:2LXT}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 289 303 ipat:BZIP_BASIC [T]
FT MYHIT 283 334 iprf:BZIP [T]
FT MYHIT 281 339 ismart:BRLZ [T]
FT MYHIT 101 160 iprf:KID [T]
FT MYHIT 281 336 ipfam:bZIP_1 [T]
FT MYHIT 113 153 ipfam:pKID [T]
SQ SEQUENCE 341 AA; 36688 MW; D5E989AE40BF69AF CRC64;
MTMESGAENQ QSGDAAVTEA ENQQMTVQAQ PQIATLAQVS MPAAHATSSA PTVTLVQLPN
GQTVQVHGVI QAAQPSVIQS PQVQTVQSSC KDLKRLFSGT QISTIAESED SQESVDSVTD
SQKRREILSR RPSYRKILND LSSDAPGVPR IEEEKSEEET SAPAITTVTV PTPIYQTSSG
QYIAITQGGA IQLANNGTDG VQGLQTLTMT NAAATQPGTT ILQYAQTTDG QQILVPSNQV
VVQAASGDVQ TYQIRTAPTS TIAPGVVMAS SPALPTQPAE EAARKREVRL MKNREAAREC
RRKKKEYVKC LENRVAVLEN QNKTLIEELK ALKDLYCHKS D
//
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