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Protein

Cyclic AMP-responsive element-binding protein 3

Gene

Creb3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei301 – 3022Cleavage; by PS1By similarity

GO - Molecular functioni

  1. cAMP response element binding protein binding Source: MGI
  2. CCR1 chemokine receptor binding Source: MGI
  3. chromatin binding Source: UniProtKB
  4. DNA binding Source: MGI
  5. protein homodimerization activity Source: UniProtKB
  6. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  7. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Source: MGI
  8. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
  9. RNA polymerase II regulatory region sequence-specific DNA binding Source: UniProtKB
  10. sequence-specific DNA binding Source: MGI
  11. sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  1. chemotaxis Source: UniProtKB-KW
  2. cytoplasmic sequestering of transcription factor Source: UniProtKB
  3. establishment of viral latency Source: UniProtKB
  4. induction of positive chemotaxis Source: UniProtKB
  5. negative regulation of ligand-dependent nuclear receptor transcription coactivator activity Source: UniProtKB
  6. positive regulation of calcium ion transport Source: MGI
  7. positive regulation of cell migration Source: MGI
  8. positive regulation of deacetylase activity Source: UniProtKB
  9. positive regulation of defense response to virus by host Source: UniProtKB
  10. positive regulation of monocyte chemotaxis Source: UniProtKB
  11. positive regulation of transcription, DNA-templated Source: MGI
  12. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  13. positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: UniProtKB
  14. regulation of cell growth Source: UniProtKB
  15. regulation of cell proliferation Source: MGI
  16. release from viral latency Source: UniProtKB
  17. response to endoplasmic reticulum stress Source: UniProtKB
  18. transcription, DNA-templated Source: MGI
  19. transcription from RNA polymerase II promoter Source: MGI
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):
Transcription factor LZIP
Cleaved into the following chain:
Gene namesi
Name:Creb3
Synonyms:Lzip
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:99946. Creb3.

Subcellular locationi

Endoplasmic reticulum membrane By similarity; Single-pass type II membrane protein By similarity. Membrane By similarity. Nucleus PROSITE-ProRule annotation. 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).By similarity
Chain 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 – 261261CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei262 – 28221Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini283 – 404122LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: MGI
  3. endoplasmic reticulum Source: MGI
  4. endoplasmic reticulum membrane Source: UniProtKB
  5. Golgi apparatus Source: MGI
  6. Golgi membrane Source: UniProtKB
  7. integral component of endoplasmic reticulum membrane Source: UniProtKB
  8. integral component of membrane Source: MGI
  9. membrane Source: UniProtKB
  10. neuronal cell body Source: UniProtKB
  11. nuclear body Source: UniProtKB
  12. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 404404Cyclic AMP-responsive element-binding protein 3PRO_0000076603Add
BLAST
Chaini1 – ?Processed cyclic AMP-responsive element-binding protein 3PRO_0000296205

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
Glycosylationi380 – 3801N-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

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiQ61817.

PTM databases

PhosphoSiteiQ61817.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

CleanExiMM_CREB3.
GenevestigatoriQ61817.

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

Protein-protein interaction databases

IntActiQ61817. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ61817.
SMRiQ61817. Positions 157-242.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini185 – 24864bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni187 – 22539Basic motifPROSITE-ProRule annotationAdd
BLAST
Regioni227 – 24822Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi19 – 235LXXLL motif 1
Motifi64 – 685LXXLL motif 2
Motifi87 – 904HCFC1-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

eggNOGiNOG254445.
HOGENOMiHOG000133026.
HOVERGENiHBG051114.
InParanoidiQ61817.
PhylomeDBiQ61817.

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]

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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti263 – 2631S → T in AAC37645. (PubMed:8112612)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei102 – 12625Missing in isoform 2. 1 PublicationVSP_011839Add
BLAST

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ61817.
SMRiQ61817. Positions 157-242.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61817. 1 interaction.

PTM databases

PhosphoSiteiQ61817.

Proteomic databases

PRIDEiQ61817.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:99946. Creb3.

Phylogenomic databases

eggNOGiNOG254445.
HOGENOMiHOG000133026.
HOVERGENiHBG051114.
InParanoidiQ61817.
PhylomeDBiQ61817.

Miscellaneous databases

PROiQ61817.
SOURCEiSearch...

Gene expression databases

CleanExiMM_CREB3.
GenevestigatoriQ61817.

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. "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.
    , 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.

Entry informationi

Entry nameiCREB3_MOUSE
AccessioniPrimary (citable) accession number: Q61817
Secondary accession number(s): Q99M21, Q9CVK9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 9, 2004
Last sequence update: November 9, 2004
Last modified: February 4, 2015
This is version 127 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.