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Protein

Cyclic AMP-responsive element-binding protein 3

Gene

CREB3

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 a role in the unfolded protein response (UPR). Acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. 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). Decreases the acetylation level of histone H4. Does not promote the chemotactic activity of leukocyte cells (By similarity).By similarity
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. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Chemotaxis, Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-responsive element-binding protein 3
Short name:
CREB-3
Short name:
cAMP-responsive element-binding protein 3
Alternative name(s):
Luman
Cleaved into the following chain:
Gene namesi
Name:CREB3
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 8

Subcellular locationi

  • Endoplasmic reticulum membrane By similarity; Single-pass type II membrane protein By similarity
  • Membrane By similarity
  • Nucleus PROSITE-ProRule annotation
  • Cytoplasm 1 Publication

  • Note: Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane (By similarity). Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia.By similarity
Processed cyclic AMP-responsive element-binding protein 3 :
  • Nucleus PROSITE-ProRule annotation

  • 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) (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 229229CytoplasmicSequence analysisAdd
BLAST
Transmembranei230 – 25021Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini251 – 368118LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 368368Cyclic AMP-responsive element-binding protein 3PRO_0000076601Add
BLAST
Chaini1 – ?Processed cyclic AMP-responsive element-binding protein 3PRO_0000296203

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi344 – 3441N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

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 (By similarity).By similarity
The processed cyclic AMP-responsive element-binding protein 3 is rapidly degraded.By similarity
N-glycosylated.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei266 – 2672Cleavage; by PS1By similarity
Sitei269 – 2702Cleavage; by PS1By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8SQ19.

Expressioni

Tissue specificityi

Expressed in trigeminal ganglia (at protein level).1 Publication

Interactioni

Subunit structurei

Homodimer. Interacts with HCFC1; the interaction is required to stimulate CREB3 transcriptional activity. Interacts with CREBZF; the interaction occurs only in combination with HCFC1. Interacts (via central part and transmembrane region) with TM7SF4 (via C-terminus cytoplasmic domain). Interacts with OS9. Interacts (via leucine-zipper domain) with CREBRF (via leucine-zipper domain); the interaction occurs only after CREB3 activation and promotes CREB3 degradation. Interacts (via C-terminal domain) with CCR1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015193.

Structurei

3D structure databases

ProteinModelPortaliQ8SQ19.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini153 – 21664bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 9595Transcription activation (acidic)Add
BLAST
Regioni155 – 18430Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni186 – 1938Leucine-zipperPROSITE-ProRule annotation

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 205LXXLL motif 1
Motifi57 – 615LXXLL motif 2
Motifi81 – 844HCFC1-binding-motif (HBM)

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000133026.
HOVERGENiHBG051114.
InParanoidiQ8SQ19.
KOiK09048.
OMAiPSDWEVD.
OrthoDBiEOG7KM5SZ.
TreeFamiTF316079.

Family and domain databases

InterProiIPR004827. bZIP.
IPR029808. Luman.
[Graphical view]
PANTHERiPTHR22952:SF100. PTHR22952:SF100. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q8SQ19-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSHMELALDP GDHDLLGFLL EESGGLGAAP DEALTSPPDW ELPLSESLSD
60 70 80 90 100
WDVEDFLSCL PSPPAVLNVF SNSDPCLVQH DHTYSLSQEH VSIDLDNESY
110 120 130 140 150
EKERAQMTPL RVEEPADQEI ARLILTEEEK RLLEKEGLTL PGMLPLTKME
160 170 180 190 200
EQVLKRVRRK IRNKKSAQES RRKKKVYVGG LESRVLKYTA QNLELQNKVQ
210 220 230 240 250
LLEEQNLSLL DQLRRLQAMV IQTANKASSS STCVLVLLFS FCLLLVPAMY
260 270 280 290 300
SSDTRGSLPA EHRVLSRQLR ALPSEDPPQL EPPALQSEVP KDSLNPELQA
310 320 330 340 350
ASNSCCLFHL MPQAPRAEPP LQLPLPDGFS GCSCPDSISP LHANLTREEG
360
WLPTPSPTSV ILQGRYSG
Length:368
Mass (Da):40,912
Last modified:April 26, 2005 - v2
Checksum:i8DE9D4EAAF636638
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti46 – 461E → EPVNLNPVQ in AAX08756 (PubMed:16305752).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT020739 mRNA. Translation: AAX08756.1.
BT020752 mRNA. Translation: AAX08769.1.
BT020764 mRNA. Translation: AAX08781.1.
BT020801 mRNA. Translation: AAX08818.1.
BT021155 mRNA. Translation: AAX31337.1.
BT026325 mRNA. Translation: ABG81481.1.
BC102092 mRNA. Translation: AAI02093.1.
AF387035 mRNA. Translation: AAL84006.1.
RefSeqiNP_776711.1. NM_174286.2.
UniGeneiBt.7492.

Genome annotation databases

EnsembliENSBTAT00000015193; ENSBTAP00000015193; ENSBTAG00000011429.
GeneIDi281715.
KEGGibta:281715.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT020739 mRNA. Translation: AAX08756.1.
BT020752 mRNA. Translation: AAX08769.1.
BT020764 mRNA. Translation: AAX08781.1.
BT020801 mRNA. Translation: AAX08818.1.
BT021155 mRNA. Translation: AAX31337.1.
BT026325 mRNA. Translation: ABG81481.1.
BC102092 mRNA. Translation: AAI02093.1.
AF387035 mRNA. Translation: AAL84006.1.
RefSeqiNP_776711.1. NM_174286.2.
UniGeneiBt.7492.

3D structure databases

ProteinModelPortaliQ8SQ19.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015193.

Proteomic databases

PaxDbiQ8SQ19.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000015193; ENSBTAP00000015193; ENSBTAG00000011429.
GeneIDi281715.
KEGGibta:281715.

Organism-specific databases

CTDi10488.

Phylogenomic databases

eggNOGiKOG0709. Eukaryota.
ENOG410ZZQM. LUCA.
GeneTreeiENSGT00520000055538.
HOGENOMiHOG000133026.
HOVERGENiHBG051114.
InParanoidiQ8SQ19.
KOiK09048.
OMAiPSDWEVD.
OrthoDBiEOG7KM5SZ.
TreeFamiTF316079.

Family and domain databases

InterProiIPR004827. bZIP.
IPR029808. Luman.
[Graphical view]
PANTHERiPTHR22952:SF100. PTHR22952:SF100. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Crossbred X Angus.
    Tissue: Ileum.
  3. Budihal P.C., Misra V.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-368.
  4. "Potential role for luman, the cellular homologue of herpes simplex virus VP16 (alpha gene trans-inducing factor), in herpesvirus latency."
    Lu R., Misra V.
    J. Virol. 74:934-943(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiCREB3_BOVIN
AccessioniPrimary (citable) accession number: Q8SQ19
Secondary accession number(s): Q0V894
, Q3T167, Q5EA05, Q5EA30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: April 26, 2005
Last modified: June 8, 2016
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.