CREB3 (cAMP responsive element binding protein 3)

Gene

• Entrez ID: 10488
• Gene name: CAMP responsive element binding protein 3
• Gene symbol: CREB3
• Synonyms: LUMAN, LZIP, sLZIP
• Chromosome: 9
• Chromosome location: 9p13.3
• Summary: This gene encodes a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds to the cAMP-response element and regulates cell proliferation. The protein interacts with host cell factor C1, which also associates with the herpes simplex virus (HSV) protein VP16 that induces transcription of HSV immediate-early genes. This protein and VP16 both bind to the same site on host cell factor C1. It is thought that the interaction between this protein and host cell factor C1 plays a role in the establishment of latency during HSV infection. This protein also plays a role in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. Additional transcript variants have been identified, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT019911	hsa-miR-375	Microarray	20215506

Transcription factors

Transcription factor	Regulation	Reference
NFKB1	Unknown	17296613
RELA	Unknown	17296613

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA	16940180
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	16940180
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IDA	16940180
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	16940180
GO:0005515	Function	Protein binding	IPI	10629049, 10871379, 15705566, 17483474, 18391022, 20102225, 20195357, 21516116, 29547901, 31515488
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IC	16940180
GO:0005634	Component	Nucleus	IDA	20546900
GO:0005654	Component	Nucleoplasm	TAS
GO:0005783	Component	Endoplasmic reticulum	IDA	16236796
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	IDA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006935	Process	Chemotaxis	IEA
GO:0006990	Process	Positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response	IDA	16940180
GO:0016021	Component	Integral component of membrane	IEA
GO:0016032	Process	Viral process	IEA
GO:0030968	Process	Endoplasmic reticulum unfolded protein response	TAS
GO:0035497	Function	CAMP response element binding	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	16940180, 17296613
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	16940180
GO:0090026	Process	Positive regulation of monocyte chemotaxis	IDA	17296613
GO:1902236	Process	Negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	IDA	16940180
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 606443
• HGNC: 2347
• e!Ensembl: ENSG00000107175

Protein

• UniProt ID: O43889
• Protein name: Cyclic AMP-responsive element-binding protein 3 (CREB-3) (cAMP-responsive element-binding protein 3) (Leucine zipper protein) (Luman) (Transcription factor LZIP-alpha) [Cleaved into: Processed cyclic AMP-responsive element-binding protein 3 (N-terminal Luman) (Transcriptionally active form)]
• Protein function: Endoplasmic reticulum (ER)-bound sequence-specific transcription factor that directly binds DNA and activates transcription (PubMed:9271389, PubMed:19779205, PubMed:10984507, PubMed:15845366, PubMed:16940180). Plays a role in the unfolded protein response (UPR), promoting cell survival versus ER stress-induced apoptotic cell death (PubMed:15845366, PubMed:16940180). 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 (PubMed:19779205, PubMed:15001559, PubMed:17296613). Associates with chromatin to the HERPUD1 promoter (PubMed:16940180). Also induces transcriptional activation of chemokine receptors (PubMed:18587271, PubMed:17296613). ; [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'). ; [Isoform 2]: 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. ; (Microbial infection) Plays a role in human immunodeficiency virus type 1 (HIV-1) virus protein expression. ; [Isoform 1]: (Microbial infection) Plays a role in herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestering host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. ; [Isoform 1]: (Microbial infection) May play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HCV) core protein. ; [Processed cyclic AMP-responsive element-binding protein 3]: (Microbial infection) Activates transcription of genes required for reactivation of the latent HSV-1 virus. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral promoters. ; [Processed cyclic AMP-responsive element-binding protein 3]: (Microbial infection) It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator HCV core protein.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00170	bZIP_1	148 → 211	bZIP transcription factor	Coiled-coil

• Sequence:

  MELELDAGDQDLLAFLLEESGDLGTAPDEAVRAPLDWALPLSEVPSDWEVDDLLCSLLSP
  PASLNILSSSNPCLVHHDHTYSLPRETVSMDLESESCRKEGTQMTPQHMEELAEQEIARL
  VLTDEEKSLLEKEGLILPETLPLTKTEEQILKRVRRKIRNKRSAQESRRKKKVYVGGLES
  RVLKYTAQNMELQNKVQLLEEQNLSLLDQLRKLQAMVIEISNKTSSSSTCILVLLVSFCL
  LLVPAMYSSDTRGSLPAEHGVLSRQLRALPSEDPYQLELPALQSEVPKDSTHQWLDGSDC
  VLQAPGNTSCLLHYMPQAPSAEPPLEWPFPDLFSEPLCRGPILPLQANLTRKGGWLPTGS
  PSVILQDRYSG

• Sequence length: 371