CREB3
entrez
10488
canonical
uniprot
O43889
canonical
ensembl
ENSG00000107175
resolver
ensp
ENSP00000342136
resolver
genesymbol
CREB3
resolver
genesymbol_syn
LZIP
resolver
hgnc
HGNC:2347
resolver
uniprot
D0PTW6
resolver
uniprot
O14671
resolver
uniprot
O14919
resolver
uniprot
Q5TCV1
resolver
uniprot
Q96GK8
resolver
uniprot
Q9H2W3
resolver
uniprot
Q9UE77
resolver
uniprot_entry
CREB3_HUMAN
resolver
uniprot_sec
D0PTW6
resolver
uniprot_sec
O14671
resolver
uniprot_sec
O14919
resolver
uniprot_sec
Q5TCV1
resolver
uniprot_sec
Q96GK8
resolver
uniprot_sec
Q9H2W3
resolver
uniprot_sec
Q9UE77
resolver
amino_acid_sequence
MELELDAGDQDLLAFLLEESGDLGTAPDEAVRAPLDWALPLSEVPSDWEVDDLLCSLLSPPASLNILSSSNPCLVHHDHTYSLPRETVSMDLESESCRKEGTQMTPQHMEELAEQEIARLVLTDEEKSLLEKEGLILPETLPLTKTEEQILKRVRRKIRNKRSAQESRRKKKVYVGGLESRVLKYTAQNMELQNKVQLLEEQNLSLLDQLRKLQAMVIEISNKTSSSSTCILVLLVSFCLLLVPAMYSSDTRGSLPAEHGVLSRQLRALPSEDPYQLELPALQSEVPKDSTHQWLDGSDCVLQAPGNTSCLLHYMPQAPSAEPPLEWPFPDLFSEPLCRGPILPLQANLTRKGGWLPTGSPSVILQDRYSG
uniprot
proteins
function
FUNCTION: Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription (PubMed:10984507, PubMed:15845366, PubMed:16940180, PubMed:19779205, PubMed:9271389). 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:15001559, PubMed:17296613, PubMed:19779205). Associates with chromatin to the HERPUD1 promoter (PubMed:16940180). Also induces transcriptional activation of chemokine receptors (PubMed:17296613, PubMed:18587271). {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: (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) 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: [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 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: [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: [Processed cyclic AMP-responsive element-binding protein 3]: (Microbial infection) Activates transcription of genes required for reactivation of the latent HSV-1 virus. Its 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) Its transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator HCV core protein. {ECO:0000269|PubMed:10675342}.
uniprot
proteins
mass_dalton
41379
uniprot
proteins
mutagenesis
MUTAGEN 12..13; /note="LL->AA: Does not inhibit interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 56-A-A-57 and 78-A--A-81 (isoform 1)."; /evidence="ECO:0000269|PubMed:10984507"; MUTAGEN 16..17; /note="LL->AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 57-A-A-58 (isoform 2)."; /evidence="ECO:0000269|PubMed:10984507, ECO:0000269|PubMed:19779205"; MUTAGEN 57..58; /note="LL->AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 16-A-A-17 (isoform 2)."; /evidence="ECO:0000269|PubMed:19779205"; MUTAGEN 57..58; /note="LL->AA: Does not inhibit interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 12-A-A-13 and 78-A--A-81 (isoform 1)."; /evidence="ECO:0000269|PubMed:19779205"; MUTAGEN 78..81; /note="DHTY->AAAA: Inhibits interaction with HCFC1. Reduces transcriptional activation. Inhibits strongly transcriptional activation; when associated with 12-A-A-13 and 56-A-A-57. Colocalizes with HCFC1 in the nucleus (isoform 1)."; /evidence="ECO:0000269|PubMed:10984507, ECO:0000269|PubMed:15705566"; MUTAGEN 81; /note="Y->A: Does not retain HCFC1 in the cytoplasm, does not interact with HCFC1, does not activate promoter and fail to protect cells from a productive infection by HSV-1."; /evidence="ECO:0000269|PubMed:10623756"; MUTAGEN 160; /note="N->G: Does not bind to DNA but retains its ability to interact with HCFC1. Reduces transcriptional activation of unfolded protein response elements (UPRE)-containing promoter. Colocalizes with HCFC1 in the ER membrane."; /evidence="ECO:0000269|PubMed:15705566"; MUTAGEN 252; /note="R->A: Does not inhibit proteolytic cleavage and transcriptional activation."; /evidence="ECO:0000269|PubMed:12138176"; MUTAGEN 264; /note="R->G: Inhibits proteolytic cleavage and transcriptional activation."; /evidence="ECO:0000269|PubMed:12138176"; MUTAGEN 267; /note="R->G: Inhibits proteolytic cleavage and transcriptional activation."; /evidence="ECO:0000269|PubMed:12138176
uniprot
proteins
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}.
uniprot
proteins
protein_family
ATF subfamily
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
pubmed
10623756
uniprot
proteins
pubmed
10629049
uniprot
proteins
pubmed
10675342
uniprot
proteins
pubmed
10984507
uniprot
proteins
pubmed
12138176
uniprot
proteins
pubmed
15001559
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15705566
uniprot
proteins
pubmed
15845366
uniprot
proteins
pubmed
16940180
uniprot
proteins
pubmed
17054986
uniprot
proteins
pubmed
17296613
uniprot
proteins
pubmed
18391022
uniprot
proteins
pubmed
18587271
uniprot
proteins
pubmed
19779205
uniprot
proteins
pubmed
20546900
uniprot
proteins
pubmed
9271389
uniprot
proteins
pubmed
9389645
uniprot
proteins
sequence_length
371
uniprot
proteins
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 1]: Cytoplasm. Note=(Microbial infection) Sequestered into the cytoplasm by the HCV core protein. {ECO:0000269|PubMed:10675342}.; 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}.
uniprot
proteins
transmembrane_region
TRANSMEM 231..247; /note="Helical; Signal-anchor for type II membrane protein"; /evidence="ECO:0000255
uniprot
proteins