ATF6 (ATF6-alpha) activates chaperone genes (Homo sapiens)

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1, 3, 6-97465, 62cytosolendoplasmic reticulum lumennucleoplasmHSPA5XBP1 geneNFYB XBP1-2ATF6(1-380)DDIT3 geneHSPA5 geneNFYC NFYA HSP90B1CALR geneATF4CALRDDIT3HSP90B1 geneNF-Y


The N-terminal fragment of ATF6-alpha contains a bZIP domain and binds the sequence CCACG in ER Stress Response Elements (ERSEs). ATF6-alpha binds ERSEs together with the heterotrimeric transcription factor NF-Y, which binds the sequence CCAAT in the ERSEs, and together the two factors activate transcription of ER stress-responsive genes. Evidence from overexpression and knockdowns indicates that ATF6-alpha is a potent activator but its homolog ATF6-beta is not and ATF6-beta may actually reduce expression of ER stress proteins. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 381183
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce

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  1. Wang Y, Shen J, Arenzana N, Tirasophon W, Kaufman RJ, Prywes R.; ''Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response.''; PubMed Europe PMC Scholia
  2. Maki RG, Old LJ, Srivastava PK.; ''Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins.''; PubMed Europe PMC Scholia
  3. Fox RM, Andrew DJ.; ''Transcriptional regulation of secretory capacity by bZip transcription factors.''; PubMed Europe PMC Scholia
  4. Yoshida H, Haze K, Yanagi H, Yura T, Mori K.; ''Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors.''; PubMed Europe PMC Scholia
  5. Averous J, Bruhat A, Jousse C, Carraro V, Thiel G, Fafournoux P.; ''Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation.''; PubMed Europe PMC Scholia
  6. Yoshida H, Okada T, Haze K, Yanagi H, Yura T, Negishi M, Mori K.; ''ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response.''; PubMed Europe PMC Scholia
  7. Thuerauf DJ, Morrison L, Glembotski CC.; ''Opposing roles for ATF6alpha and ATF6beta in endoplasmic reticulum stress response gene induction.''; PubMed Europe PMC Scholia
  8. Okada T, Yoshida H, Akazawa R, Negishi M, Mori K.; ''Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response.''; PubMed Europe PMC Scholia
  9. Li M, Baumeister P, Roy B, Phan T, Foti D, Luo S, Lee AS.; ''ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1.''; PubMed Europe PMC Scholia


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101570view11:43, 1 November 2018ReactomeTeamreactome version 66
101106view21:27, 31 October 2018ReactomeTeamreactome version 65
100635view20:01, 31 October 2018ReactomeTeamreactome version 64
100185view16:46, 31 October 2018ReactomeTeamreactome version 63
99735view15:12, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99303view12:46, 31 October 2018ReactomeTeamreactome version 62
94489view08:51, 14 September 2017MkutmonReactome pathway rename
87089view14:26, 18 July 2016MkutmonOntology Term : 'transcription pathway' added !
86603view09:22, 11 July 2016ReactomeTeamreactome version 56
83392view11:06, 18 November 2015ReactomeTeamVersion54
81745view08:15, 26 August 2015ReactomeTeamVersion53
78848view16:52, 5 February 2015JmeliusConnecte line
76828view08:05, 17 July 2014ReactomeTeamFixed remaining interactions
76532view11:50, 16 July 2014ReactomeTeamFixed remaining interactions
75865view09:51, 11 June 2014ReactomeTeamRe-fixing comment source
75565view10:36, 10 June 2014ReactomeTeamReactome 48 Update
74920view13:44, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74564view08:36, 30 April 2014ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
ATF4ProteinP18848 (Uniprot-TrEMBL)
ATF6(1-380)ProteinP18850 (Uniprot-TrEMBL)
CALR geneGeneProductENSG00000179218 (Ensembl)
CALRProteinP27797 (Uniprot-TrEMBL)
DDIT3 geneGeneProductENSG00000175197 (Ensembl)
DDIT3ProteinP35638 (Uniprot-TrEMBL)
HSP90B1 geneGeneProductENSG00000166598 (Ensembl)
HSP90B1ProteinP14625 (Uniprot-TrEMBL)
HSPA5 geneGeneProductENSG00000044574 (Ensembl)
HSPA5ProteinP11021 (Uniprot-TrEMBL)
NF-YComplexR-HSA-381204 (Reactome) NF-Y is a ubiquitous heterotrimeric transcription factor comprising subunits NF-Y A, NF-Y B, and NF-Y C. It binds the sequence CCAAT.
NFYA ProteinP23511 (Uniprot-TrEMBL)
NFYB ProteinP25208 (Uniprot-TrEMBL)
NFYC ProteinQ13952 (Uniprot-TrEMBL)
XBP1 geneGeneProductENSG00000100219 (Ensembl)
XBP1-2ProteinP17861-2 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
ATF4ArrowR-HSA-1791107 (Reactome)
ATF4ArrowR-HSA-1791150 (Reactome)
ATF6(1-380)ArrowR-HSA-1791082 (Reactome)
ATF6(1-380)ArrowR-HSA-1791107 (Reactome)
ATF6(1-380)ArrowR-HSA-1791121 (Reactome)
ATF6(1-380)ArrowR-HSA-1791150 (Reactome)
ATF6(1-380)ArrowR-HSA-1791163 (Reactome)
CALR geneR-HSA-1791082 (Reactome)
CALRArrowR-HSA-1791082 (Reactome)
DDIT3 geneR-HSA-1791107 (Reactome)
DDIT3ArrowR-HSA-1791107 (Reactome)
HSP90B1 geneR-HSA-1791163 (Reactome)
HSP90B1ArrowR-HSA-1791163 (Reactome)
HSPA5 geneR-HSA-1791150 (Reactome)
HSPA5ArrowR-HSA-1791150 (Reactome)
NF-YArrowR-HSA-1791107 (Reactome)
NF-YArrowR-HSA-1791121 (Reactome)
NF-YArrowR-HSA-1791150 (Reactome)
R-HSA-1791082 (Reactome) The Calreticulin gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791107 (Reactome) The CHOP (DDIT3) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791121 (Reactome) The XBP1 gene is transcribed to yield mRNA, the mRNA is spliced to yield Xbp(s) mRNA, and the mRNA is translated to yield protein.
R-HSA-1791150 (Reactome) The BIP (HSPA5) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
R-HSA-1791163 (Reactome) The Endoplasmin (HSP90B1) gene is transcribed to yield mRNA and the mRNA is translated to yield protein.
XBP1 geneR-HSA-1791121 (Reactome)
XBP1-2ArrowR-HSA-1791121 (Reactome)
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