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Q61817 (CREB3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:Creb3
Synonyms:Lzip
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 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.

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.

Subunit structure

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.

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein By similarity. Membrane By similarity. Nucleus By similarity. Cytoplasm By similarity. Note: Colocalizes with TM7SF4 in the ER membrane of immature dendritic cell (DC). Colocalizes with CANX, CCR1, HCFC1 in the ER membrane. Colocalizes with HCFC1 in neuronal cell bodies of the trigeminal ganglia By similarity.

Processed cyclic AMP-responsive element-binding protein 3: Nucleus By similarity. 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.

Tissue specificity

Widely expressed. Ref.1

Post-translational modification

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.

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

N-glycosylated By similarity.

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processChemotaxis
Transcription
Transcription regulation
Unfolded protein response
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandDNA-binding
   Molecular functionActivator
Repressor
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchemotaxis

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasmic sequestering of transcription factor

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of viral latency

Inferred from sequence or structural similarity. Source: UniProtKB

induction of positive chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of ligand-dependent nuclear receptor transcription coactivator activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of deacetylase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of defense response to virus by host

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of monocyte chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

release from viral latency

Inferred from sequence or structural similarity. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of endoplasmic reticulum membrane

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear body

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRNA polymerase II regulatory region sequence-specific DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.1. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q61817-1)

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.
Isoform 2 (identifier: Q61817-2)

Also known as: LZIP-2;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 404404Cyclic AMP-responsive element-binding protein 3
PRO_0000076603
Chain1 – ?Processed cyclic AMP-responsive element-binding protein 3PRO_0000296205

Regions

Topological domain1 – 261261Cytoplasmic Potential
Transmembrane262 – 28221Helical; Signal-anchor for type II membrane protein; Potential
Topological domain283 – 404122Lumenal Potential
Domain185 – 24864bZIP
Region187 – 22539Basic motif By similarity
Region227 – 24822Leucine-zipper By similarity
Motif19 – 235LXXLL motif 1
Motif64 – 685LXXLL motif 2
Motif87 – 904HCFC1-binding-motif (HBM)

Sites

Site301 – 3022Cleavage; by PS1 By similarity

Amino acid modifications

Glycosylation3421N-linked (GlcNAc...) Potential
Glycosylation3801N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence102 – 12625Missing in isoform 2.
VSP_011839

Experimental info

Sequence conflict2631S → T in AAC37645. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (LZIP-1) [UniParc].

Last modified November 9, 2004. Version 2.
Checksum: 96E4124256D4BD44

FASTA40445,112
        10         20         30         40         50         60 
MDPGGQDLLA LDPGDQDLLG FLLEESGDLW AATEPDVKAS LDLELSPSEN SVQELSDWEV 

        70         80         90        100        110        120 
EDLLSSLLSP SVSRDVLGSS SSSILHDHNY SLPQEHVSID LGECEMISCR GRRELTGLAG 

       130        140        150        160        170        180 
STFPFADTES FEKEGFHVTP LPGEERAAEQ EMSRLILTEE EKKLLEKEGL TLPSTLPLTK 

       190        200        210        220        230        240 
VEEQVLKRVR RKIRNKRAAQ ESRKKKKVYV VGLESRVLKY TAQNRELQNK VQRLEEQNLS 

       250        260        270        280        290        300 
LLDQLRKLQA MVIEIANKTS SGSTCVLVLV FSFCLLLVPA MYSSDARGSV PAEYVVLHRK 

       310        320        330        340        350        360 
LRALPSEDDH QPKPSALSSE LPMDSTHQSL DSSEHMFLVS SNFSCVLYHA PQAEQPLHWP 

       370        380        390        400 
LWDLSSEMLF SDSNLLLQAN LSESEGWQPN HSPSLVIFQG RYSG 

« Hide

Isoform 2 (LZIP-2) [UniParc].

Checksum: 442BC9840B919997
Show »

FASTA37942,441

References

« Hide 'large scale' references
[1]"LZIP-1 and LZIP-2: two novel members of the bZIP family."
Burbelo P.D., Gabriel G.C., Kibbey M.C., Yamada Y., Kleinman H.K., Weeks B.S.
Gene 139:241-245(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Strain: BALB/c.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: FVB/N.
Tissue: Mammary tumor.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 157-404.
Strain: C57BL/6J.
Tissue: Pancreas.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L22167 Unassigned DNA. Translation: AAC37645.1.
BC002094 mRNA. Translation: AAH02094.1.
AK007665 mRNA. Translation: BAB25173.1.
CCDSCCDS18102.1. [Q61817-2]
UniGeneMm.12407.

3D structure databases

ProteinModelPortalQ61817.
SMRQ61817. Positions 157-242.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ61817. 1 interaction.

PTM databases

PhosphoSiteQ61817.

Proteomic databases

PRIDEQ61817.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:99946. Creb3.

Phylogenomic databases

eggNOGNOG254445.
HOGENOMHOG000133026.
HOVERGENHBG051114.
PhylomeDBQ61817.

Gene expression databases

CleanExMM_CREB3.
GenevestigatorQ61817.

Family and domain databases

InterProIPR004827. bZIP.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROQ61817.
SOURCESearch...

Entry information

Entry nameCREB3_MOUSE
AccessionPrimary (citable) accession number: Q61817
Secondary accession number(s): Q99M21, Q9CVK9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: November 9, 2004
Last modified: July 9, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot