UniProtKB - O43889 (CREB3_HUMAN)
Cyclic AMP-responsive element-binding protein 3
CREB3
Functioni
Caution
GO - Molecular functioni
- cAMP response element binding Source: InterPro
- cAMP response element binding protein binding Source: UniProtKB
- CCR1 chemokine receptor binding Source: UniProtKB
- chromatin binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- protein dimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: ParkinsonsUK-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
GO - Biological processi
- chemotaxis Source: UniProtKB-KW
- cytoplasmic sequestering of transcription factor Source: UniProtKB
- endoplasmic reticulum unfolded protein response Source: Reactome
- establishment of viral latency Source: UniProtKB
- induction of positive chemotaxis Source: UniProtKB
- negative regulation of cell cycle Source: UniProtKB
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
- negative regulation of nuclear receptor transcription coactivator activity Source: UniProtKB
- positive regulation of calcium ion transport Source: UniProtKB
- positive regulation of cell migration Source: UniProtKB
- positive regulation of deacetylase activity Source: UniProtKB
- positive regulation of defense response to virus by host Source: UniProtKB
- positive regulation of monocyte chemotaxis Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: ParkinsonsUK-UCL
- regulation of apoptotic process Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- regulation of cell population proliferation Source: UniProtKB
- release from viral latency Source: UniProtKB
- response to endoplasmic reticulum stress Source: UniProtKB
- transcription, DNA-templated Source: UniProtKB
- viral process Source: UniProtKB-KW
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Chemotaxis, Host-virus interaction, Transcription, Transcription regulation, Unfolded protein response |
Enzyme and pathway databases
PathwayCommonsi | O43889 |
Reactomei | R-HSA-8874211, CREB3 factors activate genes |
SIGNORi | O43889 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclic AMP-responsive element-binding protein 3Short name: CREB-3 Short name: cAMP-responsive element-binding protein 3 Alternative name(s): Leucine zipper protein Luman Transcription factor LZIP-alpha Cleaved into the following chain: Processed cyclic AMP-responsive element-binding protein 3 Short name: N-terminal Luman Short name: Transcriptionally active form |
Gene namesi | Name:CREB3 Synonyms:LZIP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000107175.10 |
HGNCi | HGNC:2347, CREB3 |
MIMi | 606443, gene |
neXtProti | NX_O43889 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 3 Publications; Single-pass type II membrane protein Sequence analysis1 Publication
Golgi apparatus
- Golgi apparatus 1 Publication
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).2 Publications
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).4 Publications
Other locations
Note: (Microbial infection) Sequestered into the cytoplasm by the HCV core protein.1 Publication
Cytosol
- cytosol Source: HPA
Endoplasmic reticulum
- endoplasmic reticulum Source: ParkinsonsUK-UCL
- endoplasmic reticulum membrane Source: UniProtKB
- integral component of endoplasmic reticulum membrane Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- Golgi membrane Source: UniProtKB
Nucleus
- nuclear body Source: UniProtKB
- nuclear chromatin Source: NTNU_SB
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- integral component of membrane Source: UniProtKB
- membrane Source: UniProtKB
- neuronal cell body Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 230 | Cytoplasmic1 PublicationAdd BLAST | 230 | |
Transmembranei | 231 – 247 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 17 | |
Topological domaini | 248 – 371 | Lumenal1 PublicationAdd BLAST | 124 |
Keywords - Cellular componenti
Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 12 – 13 | 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). 1 Publication | 2 | |
Mutagenesisi | 16 – 17 | LL → AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 57-A-A-58 (isoform 2). 2 Publications | 2 | |
Mutagenesisi | 57 – 58 | LL → AA: Does not affect the transcriptional activation of the glucocorticoid receptor NR3C1; when associated with 16-A-A-17 (isoform 2). 1 Publication | 2 | |
Mutagenesisi | 57 – 58 | 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). 1 Publication | 2 | |
Mutagenesisi | 78 – 81 | 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). 2 Publications | 4 | |
Mutagenesisi | 81 | 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. 1 Publication | 1 | |
Mutagenesisi | 160 | 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. 1 Publication | 1 | |
Mutagenesisi | 252 | R → A: Does not inhibit proteolytic cleavage and transcriptional activation. 1 Publication | 1 | |
Mutagenesisi | 264 | R → G: Inhibits proteolytic cleavage and transcriptional activation. 1 Publication | 1 | |
Mutagenesisi | 267 | R → G: Inhibits proteolytic cleavage and transcriptional activation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10488 |
OpenTargetsi | ENSG00000107175 |
PharmGKBi | PA26865 |
Miscellaneous databases
Pharosi | O43889, Tbio |
Polymorphism and mutation databases
BioMutai | CREB3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076602 | 1 – 371 | Cyclic AMP-responsive element-binding protein 3Add BLAST | 371 | |
ChainiPRO_0000296204 | 1 – ? | Processed cyclic AMP-responsive element-binding protein 3 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 307 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 348 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 263 – 264 | Cleavage; by PS11 Publication | 2 | |
Sitei | 266 – 267 | Cleavage; by PS11 Publication | 2 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | O43889 |
MassIVEi | O43889 |
PeptideAtlasi | O43889 |
PRIDEi | O43889 |
ProteomicsDBi | 49217 [O43889-2] 49218 [O43889-3] |
PTM databases
GlyGeni | O43889, 2 sites |
iPTMneti | O43889 |
PhosphoSitePlusi | O43889 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000107175, Expressed in adenohypophysis and 231 other tissues |
Genevisiblei | O43889, HS |
Organism-specific databases
HPAi | ENSG00000107175, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer (PubMed:10675342).
Isoform 1 interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity (PubMed:9271389, PubMed:9389645, PubMed:10629049, PubMed:10984507).
Isoform 1 interacts with CREBZF; the interaction occurs only in combination with HCFC1 (PubMed:15705566). Isoform 1 interacts (via central part and transmembrane region) with DCSTAMP (via C-terminus cytoplasmic domain) (PubMed:20546900).
Isoform 1 interacts with OS9 (PubMed:20546900). Isoform 1 interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation (PubMed:18391022). Isoform 1 interacts (via C-terminal domain) with CCR1 (PubMed:15001559).
9 Publications(Microbial infection) Interacts with the HCV core protein; homodimerization is prevented by the HCV core protein (PubMed:10675342). Isoform 1 interacts (via leucine-zipper and transmembrane domains) with HIV-1 TMgp41 (via cytoplasmic domain); the interaction reduces CREB3 stability (PubMed:17054986). Processed cyclic AMP-responsive element-binding protein 3 interacts with HIV-1 Tat (PubMed:17054986).
2 PublicationsBinary interactionsi
Hide detailsO43889
With | #Exp. | IntAct |
---|---|---|
ALG3 [Q92685] | 4 | EBI-625002,EBI-2848814 |
CREB3L3 [Q68CJ9] | 2 | EBI-625002,EBI-852194 |
HCFC1 [P51610] | 5 | EBI-625002,EBI-396176 |
JUN [P05412] | 4 | EBI-625002,EBI-852823 |
TAF4 [O00268] | 2 | EBI-625002,EBI-1034261 |
Isoform 1 [O43889-2]
GO - Molecular functioni
- cAMP response element binding protein binding Source: UniProtKB
- CCR1 chemokine receptor binding Source: UniProtKB
- protein dimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 115751, 222 interactors |
DIPi | DIP-33935N |
ELMi | O43889 |
IntActi | O43889, 226 interactors |
MINTi | O43889 |
STRINGi | 9606.ENSP00000342136 |
Miscellaneous databases
RNActi | O43889, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 150 – 213 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 92 | Transcription activation (acidic)1 PublicationAdd BLAST | 92 | |
Regioni | 152 – 184 | Basic motifPROSITE-ProRule annotationAdd BLAST | 33 | |
Regioni | 192 – 213 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 22 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 13 – 17 | LXXLL motif 1 | 5 | |
Motifi | 54 – 58 | LXXLL motif 2 | 5 | |
Motifi | 78 – 81 | HCFC1-binding-motif (HBM) | 4 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 316 – 361 | Pro-richAdd BLAST | 46 |
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0709, Eukaryota |
GeneTreei | ENSGT00940000160343 |
HOGENOMi | CLU_047257_0_0_1 |
InParanoidi | O43889 |
OMAi | CLLYHMP |
OrthoDBi | 644485at2759 |
PhylomeDBi | O43889 |
TreeFami | TF316079 |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR029808, Luman |
PANTHERi | PTHR45996:SF4, PTHR45996:SF4, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MELELDAGDQ DLLAFLLEES GDLGTAPDEA VRAPLDWALP LSEVPSDWEV
60 70 80 90 100
DDLLCSLLSP PASLNILSSS NPCLVHHDHT YSLPRETVSM DLESESCRKE
110 120 130 140 150
GTQMTPQHME ELAEQEIARL VLTDEEKSLL EKEGLILPET LPLTKTEEQI
160 170 180 190 200
LKRVRRKIRN KRSAQESRRK KKVYVGGLES RVLKYTAQNM ELQNKVQLLE
210 220 230 240 250
EQNLSLLDQL RKLQAMVIEI SNKTSSSSTC ILVLLVSFCL LLVPAMYSSD
260 270 280 290 300
TRGSLPAEHG VLSRQLRALP SEDPYQLELP ALQSEVPKDS THQWLDGSDC
310 320 330 340 350
VLQAPGNTSC LLHYMPQAPS AEPPLEWPFP DLFSEPLCRG PILPLQANLT
360 370
RKGGWLPTGS PSVILQDRYS G
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 21 | G → E in AAG43527 (Ref. 6) Curated | 1 | |
Sequence conflicti | 230 | C → G in AAD09210 (PubMed:10675342).Curated | 1 | |
Sequence conflicti | 246 | M → I in AAH09402 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 262 | L → C in AAD09210 (PubMed:10675342).Curated | 1 | |
Sequence conflicti | 333 | F → S in AAB69652 (PubMed:9271389).Curated | 1 | |
Sequence conflicti | 338 | C → V in AAD09210 (PubMed:10675342).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_059386 | 229 – 245 | Missing in isoform 2. Add BLAST | 17 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF009368 mRNA Translation: AAB69652.1 AF029674 mRNA Translation: AAB84166.1 U59629 Genomic DNA Translation: AAD09210.1 FJ263669 mRNA Translation: ACN32251.1 U88528 mRNA Translation: AAC04325.1 Sequence problems. AF211847 Genomic DNA Translation: AAG43527.1 AF211848 mRNA Translation: AAG43528.1 AL133410 Genomic DNA No translation available. BC009402 mRNA Translation: AAH09402.1 BC010158 mRNA Translation: AAH10158.1 |
CCDSi | CCDS6588.1 [O43889-2] |
RefSeqi | NP_006359.3, NM_006368.4 [O43889-2] |
Genome annotation databases
Ensembli | ENST00000353704; ENSP00000342136; ENSG00000107175 [O43889-2] |
GeneIDi | 10488 |
KEGGi | hsa:10488 |
UCSCi | uc003zxv.4, human [O43889-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF009368 mRNA Translation: AAB69652.1 AF029674 mRNA Translation: AAB84166.1 U59629 Genomic DNA Translation: AAD09210.1 FJ263669 mRNA Translation: ACN32251.1 U88528 mRNA Translation: AAC04325.1 Sequence problems. AF211847 Genomic DNA Translation: AAG43527.1 AF211848 mRNA Translation: AAG43528.1 AL133410 Genomic DNA No translation available. BC009402 mRNA Translation: AAH09402.1 BC010158 mRNA Translation: AAH10158.1 |
CCDSi | CCDS6588.1 [O43889-2] |
RefSeqi | NP_006359.3, NM_006368.4 [O43889-2] |
3D structure databases
SMRi | O43889 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 115751, 222 interactors |
DIPi | DIP-33935N |
ELMi | O43889 |
IntActi | O43889, 226 interactors |
MINTi | O43889 |
STRINGi | 9606.ENSP00000342136 |
PTM databases
GlyGeni | O43889, 2 sites |
iPTMneti | O43889 |
PhosphoSitePlusi | O43889 |
Polymorphism and mutation databases
BioMutai | CREB3 |
Proteomic databases
jPOSTi | O43889 |
MassIVEi | O43889 |
PeptideAtlasi | O43889 |
PRIDEi | O43889 |
ProteomicsDBi | 49217 [O43889-2] 49218 [O43889-3] |
Protocols and materials databases
Antibodypediai | 26018, 248 antibodies |
DNASUi | 10488 |
Genome annotation databases
Ensembli | ENST00000353704; ENSP00000342136; ENSG00000107175 [O43889-2] |
GeneIDi | 10488 |
KEGGi | hsa:10488 |
UCSCi | uc003zxv.4, human [O43889-2] |
Organism-specific databases
CTDi | 10488 |
DisGeNETi | 10488 |
EuPathDBi | HostDB:ENSG00000107175.10 |
GeneCardsi | CREB3 |
HGNCi | HGNC:2347, CREB3 |
HPAi | ENSG00000107175, Low tissue specificity |
MIMi | 606443, gene |
neXtProti | NX_O43889 |
OpenTargetsi | ENSG00000107175 |
PharmGKBi | PA26865 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0709, Eukaryota |
GeneTreei | ENSGT00940000160343 |
HOGENOMi | CLU_047257_0_0_1 |
InParanoidi | O43889 |
OMAi | CLLYHMP |
OrthoDBi | 644485at2759 |
PhylomeDBi | O43889 |
TreeFami | TF316079 |
Enzyme and pathway databases
PathwayCommonsi | O43889 |
Reactomei | R-HSA-8874211, CREB3 factors activate genes |
SIGNORi | O43889 |
Miscellaneous databases
BioGRID-ORCSi | 10488, 11 hits in 866 CRISPR screens |
ChiTaRSi | CREB3, human |
GeneWikii | CREB3 |
GenomeRNAii | 10488 |
Pharosi | O43889, Tbio |
PROi | PR:O43889 |
RNActi | O43889, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000107175, Expressed in adenohypophysis and 231 other tissues |
Genevisiblei | O43889, HS |
Family and domain databases
InterProi | View protein in InterPro IPR004827, bZIP IPR029808, Luman |
PANTHERi | PTHR45996:SF4, PTHR45996:SF4, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CREB3_HUMAN | |
Accessioni | O43889Primary (citable) accession number: O43889 Secondary accession number(s): D0PTW6 Q9UE77 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 9, 2004 |
Last sequence update: | March 28, 2018 | |
Last modified: | December 2, 2020 | |
This is version 190 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families