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Protein

Cyclic AMP-responsive element-binding protein 3

Gene

Creb3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription. Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death. 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. Associates with chromatin to the HERPUD1 promoter. Also induces transcriptional activation of chemokine receptors. 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.By similarity
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').By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processChemotaxis, Transcription, Transcription regulation, Unfolded protein response

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):
Transcription factor LZIP
Cleaved into the following chain:
Gene namesi
Name:Creb3
Synonyms:Lzip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:99946 Creb3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 261CytoplasmicSequence analysisAdd BLAST261
Transmembranei262 – 282Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini283 – 404LumenalSequence analysisAdd BLAST122

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000766031 – 404Cyclic AMP-responsive element-binding protein 3Add BLAST404
ChainiPRO_00002962051 – ?Processed cyclic AMP-responsive element-binding protein 3

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi342N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi380N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

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.By similarity
N-glycosylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei301 – 302Cleavage; by PS1By similarity2

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiQ61817

PTM databases

PhosphoSitePlusiQ61817

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

CleanExiMM_CREB3

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 DCSTAMP (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

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61817, 1 interactor

Structurei

3D structure databases

ProteinModelPortaliQ61817
SMRiQ61817
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini185 – 248bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni187 – 225Basic motifPROSITE-ProRule annotationAdd BLAST39
Regioni227 – 248Leucine-zipperPROSITE-ProRule annotationAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi19 – 23LXXLL motif 15
Motifi64 – 68LXXLL motif 25
Motifi87 – 90HCFC1-binding-motif (HBM)4

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

HOGENOMiHOG000133026
HOVERGENiHBG051114
InParanoidiQ61817
PhylomeDBiQ61817

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR029808 Luman
PANTHERiPTHR22952:SF100 PTHR22952:SF100, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61817-1) [UniParc]FASTAAdd to basket
Also known as: LZIP-1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPGGQDLLA LDPGDQDLLG FLLEESGDLW AATEPDVKAS LDLELSPSEN
60 70 80 90 100
SVQELSDWEV EDLLSSLLSP SVSRDVLGSS SSSILHDHNY SLPQEHVSID
110 120 130 140 150
LGECEMISCR GRRELTGLAG STFPFADTES FEKEGFHVTP LPGEERAAEQ
160 170 180 190 200
EMSRLILTEE EKKLLEKEGL TLPSTLPLTK VEEQVLKRVR RKIRNKRAAQ
210 220 230 240 250
ESRKKKKVYV VGLESRVLKY TAQNRELQNK VQRLEEQNLS LLDQLRKLQA
260 270 280 290 300
MVIEIANKTS SGSTCVLVLV FSFCLLLVPA MYSSDARGSV PAEYVVLHRK
310 320 330 340 350
LRALPSEDDH QPKPSALSSE LPMDSTHQSL DSSEHMFLVS SNFSCVLYHA
360 370 380 390 400
PQAEQPLHWP LWDLSSEMLF SDSNLLLQAN LSESEGWQPN HSPSLVIFQG

RYSG
Length:404
Mass (Da):45,112
Last modified:November 9, 2004 - v2
Checksum:i96E4124256D4BD44
GO
Isoform 2 (identifier: Q61817-2) [UniParc]FASTAAdd to basket
Also known as: LZIP-2

The sequence of this isoform differs from the canonical sequence as follows:
     102-126: Missing.

Show »
Length:379
Mass (Da):42,441
Checksum:i442BC9840B919997
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti263S → T in AAC37645 (PubMed:8112612).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_011839102 – 126Missing in isoform 2. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L22167 Unassigned DNA Translation: AAC37645.1
BC002094 mRNA Translation: AAH02094.1
AK007665 mRNA Translation: BAB25173.1
CCDSiCCDS18102.1 [Q61817-2]
UniGeneiMm.12407

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiCREB3_MOUSE
AccessioniPrimary (citable) accession number: Q61817
Secondary accession number(s): Q99M21, Q9CVK9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: November 9, 2004
Last modified: March 28, 2018
This is version 145 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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