Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cyclic AMP-dependent transcription factor ATF-6 alpha

Gene

ATF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.4 Publications

GO - Molecular functioni

  • cAMP response element binding Source: InterPro
  • protein heterodimerization activity Source: ParkinsonsUK-UCL
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: UniProtKB
  • transcription coactivator activity Source: ProtInc
  • transcription factor activity, sequence-specific DNA binding Source: ParkinsonsUK-UCL
  • transcription regulatory region sequence-specific DNA binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • ATF6-mediated unfolded protein response Source: ParkinsonsUK-UCL
  • endoplasmic reticulum unfolded protein response Source: BHF-UCL
  • eye development Source: UniProtKB
  • positive regulation of apoptotic process Source: ParkinsonsUK-UCL
  • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
  • positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Source: ProtInc
  • protein folding Source: ProtInc
  • regulation of transcription from RNA polymerase II promoter Source: ProtInc
  • response to stress Source: ProtInc
  • signal transduction Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
  • visual perception Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118217-MONOMER.
ReactomeiR-HSA-380994. ATF4 activates genes.
R-HSA-381033. ATF6 (ATF6-alpha) activates chaperones.
R-HSA-381183. ATF6 (ATF6-alpha) activates chaperone genes.
SignaLinkiP18850.
SIGNORiP18850.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclic AMP-dependent transcription factor ATF-6 alpha
Short name:
cAMP-dependent transcription factor ATF-6 alpha
Alternative name(s):
Activating transcription factor 6 alpha
Short name:
ATF6-alpha
Cleaved into the following chain:
Gene namesi
Name:ATF6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:791. ATF6.

Subcellular locationi

Processed cyclic AMP-dependent transcription factor ATF-6 alpha :
  • Nucleus

  • Note: Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus. THBS4 promotes its nuclear shuttling.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 377CytoplasmicSequence analysisAdd BLAST377
Transmembranei378 – 398Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini399 – 670LumenalSequence analysisAdd BLAST272

GO - Cellular componenti

  • endoplasmic reticulum Source: ParkinsonsUK-UCL
  • endoplasmic reticulum membrane Source: Reactome
  • Golgi apparatus Source: ParkinsonsUK-UCL
  • Golgi membrane Source: Reactome
  • integral component of endoplasmic reticulum membrane Source: ParkinsonsUK-UCL
  • membrane Source: ParkinsonsUK-UCL
  • nuclear envelope Source: ProtInc
  • nucleoplasm Source: Reactome
  • nucleus Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Achromatopsia 7 (ACHM7)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of achromatopsia, an ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.
See also OMIM:616517
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075681324R → C in ACHM7; reduced ATF6-mediated unfolded protein response. 1 PublicationCorresponds to variant rs761357250dbSNPEnsembl.1
Natural variantiVAR_075682567Y → N in ACHM7. 1 PublicationCorresponds to variant rs796065053dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi391N → F: Loss of proteolytic cleavage; when associated with L-394. 1 Publication1
Mutagenesisi394P → L: Loss of proteolytic cleavage; when associated with F-391. 1 Publication1
Mutagenesisi415 – 416RR → AA: Reduces proteolytic cleavage. 1 Publication2
Mutagenesisi419L → V: Reduces proteolytic cleavage. 1 Publication1
Mutagenesisi474T → I: Loss of glycosylation at Asn-472 and increase of Golgi translocation rate. 1 Publication1
Mutagenesisi586T → I: Loss of glycosylation at Asn-584 and increase of Golgi translocation rate. Higher increase in Golgi translocation rate; when associated with Ile-645. 1 Publication1
Mutagenesisi645T → I: Loss of glycosylation at Asn-643 and increase of Golgi translocation rate. Higher increase in Golgi translocation rate; when associated with Ile-586. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi22926.
MIMi616517. phenotype.
OpenTargetsiENSG00000118217.
PharmGKBiPA25091.

Chemistry databases

DrugBankiDB00852. Pseudoephedrine.

Polymorphism and mutation databases

BioMutaiATF6.
DMDMi66774203.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000765891 – 670Cyclic AMP-dependent transcription factor ATF-6 alphaAdd BLAST670
ChainiPRO_00002962001 – ?Processed cyclic AMP-dependent transcription factor ATF-6 alpha

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi472N-linked (GlcNAc...)1 Publication1
Glycosylationi584N-linked (GlcNAc...)1 Publication1
Glycosylationi643N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

During unfolded protein response an approximative 50 kDa fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases.1 Publication
N-glycosylated. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR).1 Publication
Phosphorylated in vitro by MAPK14/P38MAPK.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei419 – 420Cleavage; by PS1By similarity2

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP18850.
MaxQBiP18850.
PaxDbiP18850.
PeptideAtlasiP18850.
PRIDEiP18850.

PTM databases

iPTMnetiP18850.
PhosphoSitePlusiP18850.

Miscellaneous databases

PMAP-CutDBP18850.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000118217.
CleanExiHS_ATF6.
GenevisibleiP18850. HS.

Organism-specific databases

HPAiHPA005935.

Interactioni

Subunit structurei

Homodimer and heterodimer with ATF6-beta. The dimer interacts with the nuclear transcription factor Y (NF-Y) trimer through direct binding to NF-Y subunit C (NF-YC). Interacts also with the transcription factors GTF2I, YY1 and SRF. Interacts (via lumenal domain) with THBS1 (By similarity). Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation (PubMed:22682248). Interacts with XBP1 isoform 2; the interaction occurs in a ER stress-dependent manner (PubMed:17765680).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself4EBI-852157,EBI-852157
CREB3L3Q68CJ92EBI-852157,EBI-852194
HSPA5P110212EBI-852157,EBI-354921
XBP1P178612EBI-852157,EBI-6942961

GO - Molecular functioni

  • protein heterodimerization activity Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi116586. 41 interactors.
DIPiDIP-29304N.
IntActiP18850. 23 interactors.
MINTiMINT-268075.
STRINGi9606.ENSP00000356919.

Structurei

3D structure databases

ProteinModelPortaliP18850.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini306 – 369bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 150Transcription activationAdd BLAST150
Regioni308 – 339Basic motifAdd BLAST32
Regioni348 – 355Leucine-zipper8
Regioni468 – 589Interaction with THBS41 PublicationAdd BLAST122

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi124 – 127Poly-Ser4
Compositional biasi325 – 328Poly-Lys4
Compositional biasi463 – 466Poly-Pro4

Domaini

The basic domain functions as a nuclear localization signal.
The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE.

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

eggNOGiKOG4343. Eukaryota.
ENOG410ZAAP. LUCA.
GeneTreeiENSGT00530000063762.
HOGENOMiHOG000253938.
HOVERGENiHBG108357.
InParanoidiP18850.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
PhylomeDBiP18850.
TreeFamiTF316079.

Family and domain databases

InterProiIPR029801. ATF6A.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF116. PTHR22952:SF116. 2 hits.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P18850-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGEPAGVAGT MESPFSPGLF HRLDEDWDSA LFAELGYFTD TDELQLEAAN
60 70 80 90 100
ETYENNFDNL DFDLDLMPWE SDIWDINNQI CTVKDIKAEP QPLSPASSSY
110 120 130 140 150
SVSSPRSVDS YSSTQHVPEE LDLSSSSQMS PLSLYGENSN SLSSAEPLKE
160 170 180 190 200
DKPVTGPRNK TENGLTPKKK IQVNSKPSIQ PKPLLLPAAP KTQTNSSVPA
210 220 230 240 250
KTIIIQTVPT LMPLAKQQPI ISLQPAPTKG QTVLLSQPTV VQLQAPGVLP
260 270 280 290 300
SAQPVLAVAG GVTQLPNHVV NVVPAPSANS PVNGKLSVTK PVLQSTMRNV
310 320 330 340 350
GSDIAVLRRQ QRMIKNRESA CQSRKKKKEY MLGLEARLKA ALSENEQLKK
360 370 380 390 400
ENGTLKRQLD EVVSENQRLK VPSPKRRVVC VMIVLAFIIL NYGPMSMLEQ
410 420 430 440 450
DSRRMNPSVS PANQRRHLLG FSAKEAQDTS DGIIQKNSYR YDHSVSNDKA
460 470 480 490 500
LMVLTEEPLL YIPPPPCQPL INTTESLRLN HELRGWVHRH EVERTKSRRM
510 520 530 540 550
TNNQQKTRIL QGALEQGSNS QLMAVQYTET TSSISRNSGS ELQVYYASPR
560 570 580 590 600
SYQDFFEAIR RRGDTFYVVS FRRDHLLLPA TTHNKTTRPK MSIVLPAINI
610 620 630 640 650
NENVINGQDY EVMMQIDCQV MDTRILHIKS SSVPPYLRDQ QRNQTNTFFG
660 670
SPPAATEATH VVSTIPESLQ
Length:670
Mass (Da):74,585
Last modified:May 24, 2005 - v3
Checksum:i5EBD08CF4121D41A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti195N → I in AAH14969 (PubMed:15489334).Curated1
Sequence conflicti195N → I in AAH71997 (PubMed:15489334).Curated1
Sequence conflicti198 – 201VPAK → IPPQ in AAH14969 (PubMed:15489334).Curated4
Sequence conflicti198 – 201VPAK → IPPQ in AAH71997 (PubMed:15489334).Curated4
Sequence conflicti307L → I no nucleotide entry (PubMed:2516827).Curated1
Sequence conflicti354T → R no nucleotide entry (PubMed:2516827).Curated1
Sequence conflicti366 – 369NQRL → LRNS no nucleotide entry (PubMed:2516827).Curated4
Sequence conflicti410S → G in AAB64434 (PubMed:9271374).Curated1
Sequence conflicti513 – 514AL → VV in AAB64434 (PubMed:9271374).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02245567M → L.1 PublicationCorresponds to variant rs1058405dbSNPEnsembl.1
Natural variantiVAR_02245667M → V.1 PublicationCorresponds to variant rs1058405dbSNPEnsembl.1
Natural variantiVAR_022457145A → P.2 PublicationsCorresponds to variant rs2070150dbSNPEnsembl.1
Natural variantiVAR_022458157P → S.2 PublicationsCorresponds to variant rs1135983dbSNPEnsembl.1
Natural variantiVAR_075681324R → C in ACHM7; reduced ATF6-mediated unfolded protein response. 1 PublicationCorresponds to variant rs761357250dbSNPEnsembl.1
Natural variantiVAR_075682567Y → N in ACHM7. 1 PublicationCorresponds to variant rs796065053dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005887 mRNA. Translation: AAB64434.1.
AB015856 mRNA. Translation: BAA34722.1.
AL391825, AL359541, AL450995 Genomic DNA. Translation: CAH73985.1.
AL450995, AL359541, AL391825 Genomic DNA. Translation: CAH71144.1.
AL359541, AL391825, AL450995 Genomic DNA. Translation: CAH74152.1.
BC014969 mRNA. Translation: AAH14969.1.
BC071997 mRNA. Translation: AAH71997.1.
CCDSiCCDS1235.1.
PIRiF34223.
RefSeqiNP_031374.2. NM_007348.3.
UniGeneiHs.492740.
Hs.617868.

Genome annotation databases

EnsembliENST00000367942; ENSP00000356919; ENSG00000118217.
GeneIDi22926.
KEGGihsa:22926.
UCSCiuc001gbs.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005887 mRNA. Translation: AAB64434.1.
AB015856 mRNA. Translation: BAA34722.1.
AL391825, AL359541, AL450995 Genomic DNA. Translation: CAH73985.1.
AL450995, AL359541, AL391825 Genomic DNA. Translation: CAH71144.1.
AL359541, AL391825, AL450995 Genomic DNA. Translation: CAH74152.1.
BC014969 mRNA. Translation: AAH14969.1.
BC071997 mRNA. Translation: AAH71997.1.
CCDSiCCDS1235.1.
PIRiF34223.
RefSeqiNP_031374.2. NM_007348.3.
UniGeneiHs.492740.
Hs.617868.

3D structure databases

ProteinModelPortaliP18850.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116586. 41 interactors.
DIPiDIP-29304N.
IntActiP18850. 23 interactors.
MINTiMINT-268075.
STRINGi9606.ENSP00000356919.

Chemistry databases

DrugBankiDB00852. Pseudoephedrine.

PTM databases

iPTMnetiP18850.
PhosphoSitePlusiP18850.

Polymorphism and mutation databases

BioMutaiATF6.
DMDMi66774203.

Proteomic databases

EPDiP18850.
MaxQBiP18850.
PaxDbiP18850.
PeptideAtlasiP18850.
PRIDEiP18850.

Protocols and materials databases

DNASUi22926.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367942; ENSP00000356919; ENSG00000118217.
GeneIDi22926.
KEGGihsa:22926.
UCSCiuc001gbs.4. human.

Organism-specific databases

CTDi22926.
DisGeNETi22926.
GeneCardsiATF6.
H-InvDBHIX0001253.
HGNCiHGNC:791. ATF6.
HPAiHPA005935.
MIMi605537. gene.
616517. phenotype.
neXtProtiNX_P18850.
OpenTargetsiENSG00000118217.
PharmGKBiPA25091.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4343. Eukaryota.
ENOG410ZAAP. LUCA.
GeneTreeiENSGT00530000063762.
HOGENOMiHOG000253938.
HOVERGENiHBG108357.
InParanoidiP18850.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
PhylomeDBiP18850.
TreeFamiTF316079.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000118217-MONOMER.
ReactomeiR-HSA-380994. ATF4 activates genes.
R-HSA-381033. ATF6 (ATF6-alpha) activates chaperones.
R-HSA-381183. ATF6 (ATF6-alpha) activates chaperone genes.
SignaLinkiP18850.
SIGNORiP18850.

Miscellaneous databases

ChiTaRSiATF6. human.
GeneWikiiATF6.
GenomeRNAii22926.
PMAP-CutDBP18850.
PROiP18850.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118217.
CleanExiHS_ATF6.
GenevisibleiP18850. HS.

Family and domain databases

InterProiIPR029801. ATF6A.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF116. PTHR22952:SF116. 2 hits.
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...

Entry informationi

Entry nameiATF6A_HUMAN
AccessioniPrimary (citable) accession number: P18850
Secondary accession number(s): O15139
, Q5VW62, Q6IPB5, Q9UEC9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: May 24, 2005
Last modified: November 30, 2016
This is version 180 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.