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NameCyclic AMP-responsive element-binding protein 3
Synonyms
  • CREB-3
  • Leucine zipper protein
  • Luman
  • LZIP
  • Transcription factor LZIP-alpha
Gene NameCREB3
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009196|Cyclic AMP-responsive element-binding protein 3
MELELDAGDQDLLAFLLEESGDLGTAPDEAVRAPLDWALPLSEVPSDWEVDDLLCSLLSP
PASLNILSSSNPCLVHHDHTYSLPRETVSMDLGECEISLTGRTGFMGLAIHTFPFAESES
CRKEGTQMTPQHMEELAEQEIARLVLTDEEKSLLEKEGLILPETLPLTKTEEQILKRVRR
KIRNKRSAQESRRKKKVYVGGLESRVLKYTAQNMELQNKVQLLEEQNLSLLDQLRKLQAM
VIEISNKTSSSSTCILVLLVSFCLLLVPAMYSSDTRGSLPAEHGVLSRQLRALPSEDPYQ
LELPALQSEVPKDSTHQWLDGSDCVLQAPGNTSCLLHYMPQAPSAEPPLEWPFPDLFSEP
LCRGPILPLQANLTRKGGWLPTGSPSVILQDRYSG
Number of residues395
Molecular Weight43916.65
Theoretical pINot Available
GO Classification
Functions
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • DNA binding
  • cAMP response element binding protein binding
  • protein dimerization activity
  • transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
  • chromatin binding
  • cAMP response element binding
  • CCR1 chemokine receptor binding
  • transcription factor activity, sequence-specific DNA binding
  • RNA polymerase II regulatory region sequence-specific DNA binding
  • protein homodimerization activity
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding
Processes
  • regulation of cell proliferation
  • positive regulation of cell migration
  • positive regulation of calcium ion transport
  • positive regulation of transcription, DNA-templated
  • induction of positive chemotaxis
  • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
  • positive regulation of transcription from RNA polymerase II promoter
  • positive regulation of deacetylase activity
  • cytoplasmic sequestering of transcription factor
  • positive regulation of monocyte chemotaxis
  • transcription, DNA-templated
  • regulation of cell growth
  • response to endoplasmic reticulum stress
  • chemotaxis
  • transcription from RNA polymerase II promoter
  • establishment of viral latency
  • positive regulation of defense response to virus by host
  • negative regulation of ligand-dependent nuclear receptor transcription coactivator activity
  • viral process
  • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response
  • release from viral latency
  • negative regulation of cell cycle
Components
  • cytoplasm
  • membrane
  • integral component of endoplasmic reticulum membrane
  • nucleus
  • Golgi membrane
  • endoplasmic reticulum
  • neuronal cell body
  • nuclear body
  • endoplasmic reticulum membrane
  • Golgi apparatus
  • integral component of membrane
  • cytosol
General FunctionTranscriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific FunctionEndoplasmic 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 also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring 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 3 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). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells.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. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down-regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral and 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.
Pfam Domain Function
Transmembrane Regions255-271
GenBank Protein IDNot Available
UniProtKB IDO43889
UniProtKB Entry NameCREB3_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0013664|Cyclic AMP-responsive element-binding protein 3 (CREB3)
ATGGAGCTGGAATTGGATGCTGGTGACCAAGACCTGCTGGCCTTCCTGCTAGAGGAAAGT
GGAGATTTGGGGACGGCACCCGATGAGGCCGTGAGGGCCCCACTGGACTGGGCGCTGCCG
CTTTCTGAGGTACCGAGCGACTGGGAAGTAGATGATTTGCTGTGCTCCCTGCTGAGTCCC
CCAGCGTCGTTGAACATTCTCAGCTCCTCCAACCCCTGCCTTGTCCACCATGACCACACC
TACTCCCTCCCACGGGAAACTGTCTCTATGGATCTAGAGAGTGAGAGCTGTAGAAAAGAG
GGGACCCAGATGACTCCACAGCATATGGAGGAGCTGGCAGAGCAGGAGATTGCTAGGCTA
GTACTGACAGATGAGGAGAAGAGTCTATTGGAGAAGGAGGGGCTTATTCTGCCTGAGACA
CTTCCTCTCACTAAGACAGAGGAACAAATTCTGAAACGTGTGCGGAGGAAGATTCGAAAT
AAAAGATCTGCTCAAGAGAGCCGCAGGAAAAAGAAGGTGTATGTTGGGGGTTTAGAGAGC
AGGGTCTTGAAATACACAGCCCAGAATATGGAGCTTCAGAACAAAGTACAGCTTCTGGAG
GAACAGAATTTGTCCCTTCTAGATCAACTGAGGAAACTCCAGGCCATGGTGATTGAGATA
TCAAACAAAACCAGCAGCAGCAGCACCTGCATCTTGGTCCTACTAGTCTCCTTCTGCCTC
CTCCTTGTACCTGCTATGTACTCCTCTGACACAAGGGGGAGCCTGCCAGCTGAGCATGGA
GTGTTGTCCCGCCAGCTTCGTGCCCTCCCCAGTGAGGACCCTTACCAGCTGGAGCTGCCT
GCCCTGCAGTCAGAAGTGCCGAAAGACAGCACACACCAGTGGTTGGACGGCTCAGACTGT
GTACTCCAGGCCCCTGGCAACACTTCCTGCCTGCTGCATTACATGCCTCAGGCTCCCAGT
GCAGAGCCTCCCCTGGAGTGGCCATTCCCTGACCTCTTCTCAGAGCCTCTCTGCCGAGGT
CCCATCCTCCCCCTGCAGGCAAATCTCACAAGGAAGGGAGGATGGCTTCCTACTGGTAGC
CCCTCTGTCATTTTGCAGGACAGATACTCAGGCTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:2347
Chromosome Location9
LocusNot Available
References
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  2. Freiman RN, Herr W: Viral mimicry: common mode of association with HCF by VP16 and the cellular protein LZIP. Genes Dev. 1997 Dec 1;11(23):3122-7. 9389645
  3. Jin DY, Wang HL, Zhou Y, Chun AC, Kibler KV, Hou YD, Kung H, Jeang KT: Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation. EMBO J. 2000 Feb 15;19(4):729-40. 10675342
  4. Kang H, Kim YS, Ko J: A novel isoform of human LZIP negatively regulates the transactivation of the glucocorticoid receptor. Mol Endocrinol. 2009 Nov;23(11):1746-57. doi: 10.1210/me.2009-0009. Epub 2009 Sep 24. 19779205
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  9. Luciano RL, Wilson AC: N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the host cell factor-1 binding motif. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10757-62. 10984507
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