Linked Life Data

O43889

Source:http://identifiers.org/uniprot/O43889

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
FUNCTION: Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. Isoform 3 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). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells. FUNCTION: Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down- regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]- 3') and C/EBP sequences present in many viral and cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter. SUBUNIT: Homodimer; homodimerization is prevented by the HCV core protein. Interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Isoform 2 interacts with CREBZF; the interaction occurs only in combination with HCFC1. Isoform 2 interacts (via central part and transmembrane region) with TM7SF4 (via C-terminus cytoplasmic domain). Isoform 2 interacts with OS9. Isoform 2 interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Isoform 2 interacts (via C-terminal domain) with CCR1. Isoform 2 interacts (via leucine-zipper and transmembrane domains) with HIV- 1 ENV (via cytoplasmic domain). Isoform 2 interacts (via leucine- zipper and transmembrane domains) with HIV-1 TMgp41 (via cytoplasmic domain); the interaction reduces CREB3 stability. Interacts with the HCV core protein. Processed cyclic AMP- responsive element-binding protein 3 interacts with HIV-1 Tat. SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum membrane; Single-pass type II membrane protein. Membrane. Note=Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia (By similarity). Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Sequestred into the cytoplasm by the HCV core protein. SUBCELLULAR LOCATION: Isoform 3: Nucleus. Cytoplasm. Note=Predominantly in the nucleus. 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). ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=O43889-1; Sequence=Displayed; Name=2; Synonyms=LZIP; IsoId=O43889-2; Sequence=VSP_011838; Name=3; Synonyms=smal LZIP, sLZIP; IsoId=O43889-3; Sequence=VSP_011838, VSP_043805; Note=Does not contain a helical transmembrane domain; TISSUE SPECIFICITY: Expressed in dendritic cells (DC). Weakly expressed in monocytes (at protein level). Ubiquitous. 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. PTM: The ER membrane embedded cyclic AMP-responsive element- binding protein 3 form is 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 TM7SF4. PTM: The processed cyclic AMP-responsive element-binding protein 3 is rapidly degraded. PTM: N-glycosylated. SIMILARITY: Belongs to the bZIP family. ATF subfamily. SIMILARITY: Contains 1 bZIP domain. CAUTION: All experiments concerning the proteolytic cleavage are done with isoform 2. GENE SYNONYMS:CREB3 LZIP. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 395 AA; 43917 MW; 1C412AA0D51CB7B2 CRC64;
biopax3:xref
biopax3:displayName
CREB3_HUMAN
biopax3:name
CREB-3, CREB3, Leucin zipper proitein, Luman, N-terminal Luman, Processed cyclic AMP-responsive element-binding protein 3, Transcription factor LZIP-alpha, Transcriptionally active form, cAMP-responsive element-binding protein 3
biopax3:organism
biopax3:sequence
MELELDAGDQDLLAFLLEESGDLGTAPDEAVRAPLDWALPLSEVPSDWEVDDLLCSLLSPPASLNILSSSNPCLVHHDHTYSLPRETVSMDLGECEISLTGRTGFMGLAIHTFPFAESESCRKEGTQMTPQHMEELAEQEIARLVLTDEEKSLLEKEGLILPETLPLTKTEEQILKRVRRKIRNKRSAQESRRKKKVYVGGLESRVLKYTAQNMELQNKVQLLEEQNLSLLDQLRKLQAMVIEISNKTSSSSTCILVLLVSFCLLLVPAMYSSDTRGSLPAEHGVLSRQLRALPSEDPYQLELPALQSEVPKDSTHQWLDGSDCVLQAPGNTSCLLHYMPQAPSAEPPLEWPFPDLFSEPLCRGPILPLQANLTRKGGWLPTGSPSVILQDRYSG
biopax3:standardName
Cyclic AMP-responsive element-binding protein 3