Description: Homo sapiens cAMP responsive element binding protein 1 (CREB1), transcript variant B, mRNA. RefSeq Summary (NM_134442): This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Alternate splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]. Transcript (Including UTRs) Position: hg19 chr2:208,394,616-208,470,284 Size: 75,669 Total Exon Count: 9 Strand: + Coding Region Position: hg19 chr2:208,420,360-208,461,782 Size: 41,423 Coding Exon Count: 8
ID:CREB1_HUMAN DESCRIPTION: RecName: Full=Cyclic AMP-responsive element-binding protein 1; Short=CREB-1; Short=cAMP-responsive element-binding protein 1; FUNCTION: Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells. SUBUNIT: Interacts with PPRC1. Binds DNA as a dimer. This dimer is stabilized by magnesium ions. Interacts, through the bZIP domain, with the coactivators TORC1/CRTC1, TORC2/CRTC2 and TORC3/CRTC3. When phosphorylated on Ser-133, binds CREBBP (By similarity). Interacts with CREBL2; regulates CREB1 phosphorylation, stability and transcriptional activity (By similarity). Interacts (phosphorylated form) with TOX3. Interacts with ARRB1. Binds to HIPK2. Interacts with SGK1. INTERACTION: O00470:MEIS1; NbExp=9; IntAct=EBI-711855, EBI-1210694; Q6SA08:TSSK4; NbExp=5; IntAct=EBI-711855, EBI-1202583; SUBCELLULAR LOCATION: Nucleus. PTM: Stimulated by phosphorylation. Phosphorylation of both Ser- 133 and Ser-142 in the SCN regulates the activity of CREB and participates in circadian rhythm generation. Phosphorylation of Ser-133 allows CREBBP binding (By similarity). CREBL2 positively regulates phosphorylation at Ser-133 thereby stimulating CREB1 transcriptional activity (By similarity). Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-133. CaMK4 is much more potent than CaMK2 in activating CREB. Phosphorylated by CaMK2 on Ser-142. Phosphorylation of Ser-142 blocks CREB-mediated transcription even when Ser-133 is phosphorylated. Phosphorylated by CaMK1 (By similarity). Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP. Phosphorylated at Ser-133 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli. PTM: Sumoylated with SUMO1. Sumoylation on Lys-304, but not on Lys-285, is required for nuclear localization of this protein. Sumoylation is enhanced under hypoxia, promoting nuclear localization and stabilization. DISEASE: Defects in CREB1 may be a cause of angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. Note=A chromosomal aberration involving CREB1 is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type. DISEASE: Note=A CREB1 mutation has been found in a patient with multiple congenital anomalies consisting of agenesis of the corpus callosum, cerebellar hypoplasia, severe neonatal respiratory distress refractory to surfactant, thymus hypoplasia, and thyroid follicular hypoplasia (PubMed:22267179). SIMILARITY: Belongs to the bZIP family. SIMILARITY: Contains 1 bZIP (basic-leucine zipper) domain. SIMILARITY: Contains 1 KID (kinase-inducible) domain.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): CREB1 CDC HuGE Published Literature: CREB1 Positive Disease Associations: suicide Related Studies:
suicide Perlis, R. H. et al. 2007, Association Between Treatment-Emergent Suicidal Ideation With Citalopram and Polymorphisms Near Cyclic Adenosine Monophosphate Response Element Binding Protein in the STAR*D Study, Arch Gen Psychiatry 2007 64(6) 689-97.
[PubMed 17548750]
Polymorphisms that span CREB1 were associated with treatment-emergent suicidality among men with depression, extending an observation of association with male anger expression in a prior independent cohort. If replicated, this finding would suggest that pharmacogenetic testing could facilitate the identification of the small subset of individuals at greater risk during short-term antidepressant treatment.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P16220
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
AK312747 - Homo sapiens cDNA, FLJ93156, Homo sapiens cAMP responsive element binding protein 1 (CREB1),transcript variant B, mRNA. LF205222 - JP 2014500723-A/12725: Polycomb-Associated Non-Coding RNAs. LF213835 - JP 2014500723-A/21338: Polycomb-Associated Non-Coding RNAs. BC095407 - Homo sapiens cAMP responsive element binding protein 1, mRNA (cDNA clone MGC:110900 IMAGE:30344522), complete cds. X55545 - Homo sapiens mRNA for CREB protein. M27691 - Human transactivator protein (CREB) mRNA, complete cds. BC010636 - Homo sapiens cAMP responsive element binding protein 1, mRNA (cDNA clone MGC:9284 IMAGE:3872792), complete cds. AK298740 - Homo sapiens cDNA FLJ56700 complete cds, highly similar to cAMP response element-binding protein. AY347527 - Homo sapiens CREB mRNA, complete cds. AK315226 - Homo sapiens cDNA, FLJ96224, Homo sapiens cAMP responsive element binding protein 1 (CREB1),transcript variant A, mRNA. MA440799 - JP 2018138019-A/12725: Polycomb-Associated Non-Coding RNAs. MA449412 - JP 2018138019-A/21338: Polycomb-Associated Non-Coding RNAs. JD136829 - Sequence 117853 from Patent EP1572962. JD180853 - Sequence 161877 from Patent EP1572962. LF212826 - JP 2014500723-A/20329: Polycomb-Associated Non-Coding RNAs. JD240487 - Sequence 221511 from Patent EP1572962. LF318185 - JP 2014500723-A/125688: Polycomb-Associated Non-Coding RNAs. MA448403 - JP 2018138019-A/20329: Polycomb-Associated Non-Coding RNAs. MA553762 - JP 2018138019-A/125688: Polycomb-Associated Non-Coding RNAs. CU679771 - Synthetic construct Homo sapiens gateway clone IMAGE:100019015 5' read CREB1 mRNA. AB385549 - Synthetic construct DNA, clone: pF1KB5414, Homo sapiens CREB1 gene for cAMP response element-binding protein, complete cds, without stop codon, in Flexi system. CR407617 - Homo sapiens full open reading frame cDNA clone RZPDo834B062D for gene CREB1, cAMP responsive element binding protein 1 complete cds, without stopcodon. DQ894336 - Synthetic construct Homo sapiens clone IMAGE:100008796; FLH169826.01L; RZPDo839G0895D cAMP responsive element binding protein 1 (CREB1) gene, encodes complete protein. BT019509 - Homo sapiens cAMP responsive element binding protein 1 mRNA, complete cds. DQ891157 - Synthetic construct clone IMAGE:100003787; FLH169830.01X; RZPDo839G0896D cAMP responsive element binding protein 1 (CREB1) gene, encodes complete protein. KJ890966 - Synthetic construct Homo sapiens clone ccsbBroadEn_00360 CREB1 gene, encodes complete protein. M34356 - Human active transcription factor CREB mRNA, complete cds. X60003 - Human delta CREB mRNA for cAMP-responsive element (CRE) binding protein. LF318199 - JP 2014500723-A/125702: Polycomb-Associated Non-Coding RNAs. AK302333 - Homo sapiens cDNA FLJ57667 complete cds, highly similar to cAMP response element-binding protein. LF318200 - JP 2014500723-A/125703: Polycomb-Associated Non-Coding RNAs. S78693 - alpha CREB-1=cyclic AMP response element-binding protein-1 alpha isoform {alternatively spliced, internal fragment} [human, placenta, mRNA Partial, 64 nt]. S78695 - alpha beta CREB-1=cyclic AMP response element-binding protein-1 alpha beta isoform {alternatively spliced, internal fragment} [human, placenta, mRNA Partial, 81 nt]. JD286222 - Sequence 267246 from Patent EP1572962. JD297313 - Sequence 278337 from Patent EP1572962. LF318204 - JP 2014500723-A/125707: Polycomb-Associated Non-Coding RNAs. JD429537 - Sequence 410561 from Patent EP1572962. LF318205 - JP 2014500723-A/125708: Polycomb-Associated Non-Coding RNAs. JD183919 - Sequence 164943 from Patent EP1572962. JD334025 - Sequence 315049 from Patent EP1572962. JD528338 - Sequence 509362 from Patent EP1572962. JD562697 - Sequence 543721 from Patent EP1572962. JD093428 - Sequence 74452 from Patent EP1572962. LF318206 - JP 2014500723-A/125709: Polycomb-Associated Non-Coding RNAs. JD235366 - Sequence 216390 from Patent EP1572962. JD160403 - Sequence 141427 from Patent EP1572962. JD561872 - Sequence 542896 from Patent EP1572962. JD148622 - Sequence 129646 from Patent EP1572962. JD179378 - Sequence 160402 from Patent EP1572962. JD381259 - Sequence 362283 from Patent EP1572962. JD044023 - Sequence 25047 from Patent EP1572962. JD482036 - Sequence 463060 from Patent EP1572962. JD499659 - Sequence 480683 from Patent EP1572962. JD286713 - Sequence 267737 from Patent EP1572962. JD511545 - Sequence 492569 from Patent EP1572962. JD319539 - Sequence 300563 from Patent EP1572962. JD319540 - Sequence 300564 from Patent EP1572962. JD105752 - Sequence 86776 from Patent EP1572962. JD071050 - Sequence 52074 from Patent EP1572962. JD119120 - Sequence 100144 from Patent EP1572962. JD278366 - Sequence 259390 from Patent EP1572962. JD144694 - Sequence 125718 from Patent EP1572962. JD085874 - Sequence 66898 from Patent EP1572962. JD337206 - Sequence 318230 from Patent EP1572962. JD205971 - Sequence 186995 from Patent EP1572962. JD344625 - Sequence 325649 from Patent EP1572962. JD443377 - Sequence 424401 from Patent EP1572962. AK126342 - Homo sapiens cDNA FLJ44370 fis, clone TRACH3008902. LF318207 - JP 2014500723-A/125710: Polycomb-Associated Non-Coding RNAs. AK123952 - Homo sapiens cDNA FLJ41958 fis, clone PUAEN2001345. LF318208 - JP 2014500723-A/125711: Polycomb-Associated Non-Coding RNAs. LF318210 - JP 2014500723-A/125713: Polycomb-Associated Non-Coding RNAs. LF318211 - JP 2014500723-A/125714: Polycomb-Associated Non-Coding RNAs. AK091534 - Homo sapiens cDNA FLJ34215 fis, clone FCBBF3021985. LF318212 - JP 2014500723-A/125715: Polycomb-Associated Non-Coding RNAs. AK095116 - Homo sapiens cDNA FLJ37797 fis, clone BRSSN1000153. MA553776 - JP 2018138019-A/125702: Polycomb-Associated Non-Coding RNAs. MA553777 - JP 2018138019-A/125703: Polycomb-Associated Non-Coding RNAs. MA553781 - JP 2018138019-A/125707: Polycomb-Associated Non-Coding RNAs. MA553782 - JP 2018138019-A/125708: Polycomb-Associated Non-Coding RNAs. MA553783 - JP 2018138019-A/125709: Polycomb-Associated Non-Coding RNAs. MA553784 - JP 2018138019-A/125710: Polycomb-Associated Non-Coding RNAs. MA553785 - JP 2018138019-A/125711: Polycomb-Associated Non-Coding RNAs. MA553787 - JP 2018138019-A/125713: Polycomb-Associated Non-Coding RNAs. MA553788 - JP 2018138019-A/125714: Polycomb-Associated Non-Coding RNAs. MA553789 - JP 2018138019-A/125715: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04612 - Antigen processing and presentation hsa04916 - Melanogenesis hsa04962 - Vasopressin-regulated water reabsorption hsa05016 - Huntington's disease hsa05215 - Prostate cancer
BioCarta from NCI Cancer Genome Anatomy Project h_carm1Pathway - Transcription Regulation by Methyltransferase of CARM1 h_hifPathway - Hypoxia-Inducible Factor in the Cardiovascular System h_melanocytepathway - Melanocyte Development and Pigmentation Pathway h_crebPathway - Transcription factor CREB and its extracellular signals h_CaCaMPathway - Ca++/ Calmodulin-dependent Protein Kinase Activation h_HuntingtonPathway - Inhibition of Huntington's disease neurodegeneration by histone deacetylase inhibitors h_dreampathway - Repression of Pain Sensation by the Transcriptional Regulator DREAM h_HBxPathway - Calcium Signaling by HBx of Hepatitis B virus h_hcmvPathway - Human Cytomegalovirus and Map Kinase Pathways h_mapkPathway - MAPKinase Signaling Pathway h_erk5Pathway - Role of Erk5 in Neuronal Survival h_gpcrPathway - Signaling Pathway from G-Protein Families h_p38mapkPathway - p38 MAPK Signaling Pathway h_arenrf2Pathway - Oxidative Stress Induced Gene Expression Via Nrf2
Reactome (by CSHL, EBI, and GO)
Protein P16220 (Reactome details) participates in the following event(s):