| IED ID | IndEnz0002016257 |
| Enzyme Type ID | protease016257 |
| Protein Name |
Cyclic AMP-responsive element-binding protein 3 CREB-3 cAMP-responsive element-binding protein 3 Leucine zipper protein Luman Transcription factor LZIP-alpha Cleaved into: Processed cyclic AMP-responsive element-binding protein 3 N-terminal Luman Transcriptionally active form |
| Gene Name | CREB3 LZIP |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MELELDAGDQDLLAFLLEESGDLGTAPDEAVRAPLDWALPLSEVPSDWEVDDLLCSLLSPPASLNILSSSNPCLVHHDHTYSLPRETVSMDLESESCRKEGTQMTPQHMEELAEQEIARLVLTDEEKSLLEKEGLILPETLPLTKTEEQILKRVRRKIRNKRSAQESRRKKKVYVGGLESRVLKYTAQNMELQNKVQLLEEQNLSLLDQLRKLQAMVIEISNKTSSSSTCILVLLVSFCLLLVPAMYSSDTRGSLPAEHGVLSRQLRALPSEDPYQLELPALQSEVPKDSTHQWLDGSDCVLQAPGNTSCLLHYMPQAPSAEPPLEWPFPDLFSEPLCRGPILPLQANLTRKGGWLPTGSPSVILQDRYSG |
| Enzyme Length | 371 |
| Uniprot Accession Number | O43889 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription (PubMed:9271389, PubMed:19779205, PubMed:10984507, PubMed:15845366, PubMed:16940180). Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death (PubMed:15845366, PubMed:16940180). Also involved in cell proliferation, migration and differentiation, tumor suppression and inflammatory gene expression. Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration (PubMed:19779205, PubMed:15001559, PubMed:17296613). Associates with chromatin to the HERPUD1 promoter (PubMed:16940180). Also induces transcriptional activation of chemokine receptors (PubMed:18587271, PubMed:17296613). {ECO:0000269|PubMed:10984507, ECO:0000269|PubMed:15001559, ECO:0000269|PubMed:15845366, ECO:0000269|PubMed:16940180, ECO:0000269|PubMed:17296613, ECO:0000269|PubMed:18587271, ECO:0000269|PubMed:19779205, ECO:0000269|PubMed:9271389}.; FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]: This is the transcriptionally active form that translocates to the nucleus and activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many promoters to activate transcription of the genes. Binds to the unfolded protein response element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). {ECO:0000269|PubMed:16940180}.; FUNCTION: [Isoform 2]: Functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Also decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells. {ECO:0000269|PubMed:19779205}.; FUNCTION: (Microbial infection) Plays a role in human immunodeficiency virus type 1 (HIV-1) virus protein expression. {ECO:0000269|PubMed:17054986}.; FUNCTION: [Isoform 1]: (Microbial infection) Plays a role in herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestering host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:15705566}.; FUNCTION: [Isoform 1]: (Microbial infection) May play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HCV) core protein. {ECO:0000269|PubMed:10675342}.; FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]: (Microbial infection) Activates transcription of genes required for reactivation of the latent HSV-1 virus. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral promoters. {ECO:0000269|PubMed:10623756}.; FUNCTION: [Processed cyclic AMP-responsive element-binding protein 3]: (Microbial infection) It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator HCV core protein. {ECO:0000269|PubMed:10675342}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (1); Chain (2); Domain (1); Glycosylation (2); Motif (3); Mutagenesis (10); Region (3); Sequence caution (1); Sequence conflict (6); Site (2); Topological domain (2); Transmembrane (1) |
| Keywords | Activator;Alternative splicing;Chemotaxis;Cytoplasm;DNA-binding;Endoplasmic reticulum;Glycoprotein;Golgi apparatus;Host-virus interaction;Membrane;Nucleus;Reference proteome;Repeat;Repressor;Signal-anchor;Transcription;Transcription regulation;Transmembrane;Transmembrane helix;Unfolded protein response |
| Interact With | Q92685; Itself; Q68CJ9; Q9NS37; P35638; P51610; P05412; O00268; Q15109; Q92685; Q9BVK2; P05090; P29972; P41181; P55087; P09871; P06681; P32246; Q9UJ71; Q9BXR6; Q8N6F1-2; Q8IUR6; P78329; Q9H295; Q15125; P50402; P37268; Q01740; P31513; P17302; A0A0C4DFT7; P51610; P24593; Q8TAF8; Q6FG55; Q99735; Q99519; P26678; P60201-2; Q01453; P05155; P11686; Q9BZD2; P11166; P14672; Q9BRI3; P82251; O43759-2; Q8TAA9; Q9Y397; P29846 |
| Induction | INDUCTION: Up-regulated upon differentiation of monocytes towards immature dendritic cells (DC). Down-regulated upon DC maturation. Up-regulated by endoplasmic reticulum stress triggered by thapsigargin (Tg) or tunicamycin (Tm). Up-regulated by CCR1-dependent chemokines in an immediate early response and biphasic manner and by NF-kappa-B. {ECO:0000269|PubMed:15845366, ECO:0000269|PubMed:16940180, ECO:0000269|PubMed:17296613, ECO:0000269|PubMed:18391022, ECO:0000269|PubMed:20546900}. |
| Subcellular Location | SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:12138176, ECO:0000269|PubMed:18391022}; Single-pass type II membrane protein {ECO:0000255, ECO:0000269|PubMed:12138176}. Golgi apparatus {ECO:0000269|PubMed:10623756}. Note=Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia (PubMed:10623756). Colocalizes with DCSTAMP in the ER membrane of immature dendritic cell (DC) (PubMed:20546900). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane (PubMed:10623756). {ECO:0000269|PubMed:10623756, ECO:0000269|PubMed:20546900}.; SUBCELLULAR LOCATION: [Isoform 2]: Nucleus {ECO:0000269|PubMed:19779205}. Cytoplasm {ECO:0000269|PubMed:19779205}. Note=Predominantly in the nucleus (PubMed:19779205). Not associated with membranes (PubMed:19779205). {ECO:0000269|PubMed:19779205}.; SUBCELLULAR LOCATION: [Processed cyclic AMP-responsive element-binding protein 3]: Nucleus. Note=Upon RIP activation the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form translocates into the nucleus. Detected in the nucleus upon dendritic cell maturation and RIP activation. Colocalizes with CREBRF in nuclear foci. Colocalizes with CREBZF in promyelocytic leukemia protein nuclear bodies (PML-NB). {ECO:0000269|PubMed:10675342, ECO:0000269|PubMed:15705566, ECO:0000269|PubMed:18391022, ECO:0000269|PubMed:20546900}.; SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Note=(Microbial infection) Sequestered into the cytoplasm by the HCV core protein. {ECO:0000269|PubMed:10675342}. |
| Modified Residue | |
| Post Translational Modification | PTM: First proteolytically cleaved by site-1 protease (S1P) that generates membrane-associated N-terminus and a luminal C-terminus forms. The membrane-associated N-terminus form is further proteolytically processed probably by the site-2 protease (S2P) through a regulated intramembrane proteolysis (RIP), releasing the transcriptional active processed cyclic AMP-responsive element-binding protein 3 form, which is transported to the nucleus. The proteolytic cleavage is strongly induced during dendritic cell (DC) maturation and inhibited by DCSTAMP. That form is rapidly degraded. {ECO:0000269|PubMed:12138176, ECO:0000269|PubMed:16940180, ECO:0000269|PubMed:17054986, ECO:0000269|PubMed:18391022, ECO:0000269|PubMed:20546900}.; PTM: N-glycosylated. {ECO:0000269|PubMed:12138176, ECO:0000269|PubMed:16940180}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10564271; 10856300; 10871379; 11163209; 11821395; 12110171; 12271126; 15299016; 15657421; 16189514; 16236796; 17192849; 18189280; 18985028; 20064372; 20102225; 20195357; 20473547; 21516116; 21988832; 22004728; 22009750; 23023215; 23583719; 24185178; 24441043; 24481121; 25077563; 25241761; 25358080; 27405867; 28179603; 28246167; 28662179; 28840565; 29249802; 30940151; 31291699; 31612863; 31941600; 33803345; |
| Motif | MOTIF 13..17; /note=LXXLL motif 1; MOTIF 54..58; /note=LXXLL motif 2; MOTIF 78..81; /note=HCFC1-binding-motif (HBM) |
| Gene Encoded By | |
| Mass | 41,379 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |