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Protein

Cyclic AMP-dependent transcription factor ATF-6 alpha

Gene

ATF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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-N9-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

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation, Unfolded protein response

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000118217.5
HGNCiHGNC:791 ATF6
MIMi605537 gene
neXtProtiNX_P18850

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 dbSNP:rs761357250EnsemblClinVar.1
Natural variantiVAR_075682567Y → N in ACHM7. 1 PublicationCorresponds to variant dbSNP:rs796065053EnsemblClinVar.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
MalaCardsiATF6
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
Cross-linki87Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Glycosylationi472N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi584N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi643N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

During unfolded protein response, a fragment of approximately 50 kDa 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, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP18850
MaxQBiP18850
PaxDbiP18850
PeptideAtlasiP18850
PRIDEiP18850
ProteomicsDBi53616

PTM databases

GlyConnecti1162
iPTMnetiP18850
PhosphoSitePlusiP18850

Miscellaneous databases

PMAP-CutDBiP18850

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000118217 Expressed in 235 organ(s), highest expression level in corpus epididymis
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116586, 50 interactors
DIPiDIP-29304N
ELMiP18850
IntActiP18850, 29 interactors
MINTiP18850
STRINGi9606.ENSP00000356919

Structurei

3D structure databases

ProteinModelPortaliP18850
SMRiP18850
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

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR029801 ATF6A
IPR004827 bZIP
PANTHERiPTHR22952:SF116 PTHR22952:SF116, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

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 → L1 PublicationCorresponds to variant dbSNP:rs1058405Ensembl.1
Natural variantiVAR_02245667M → V1 PublicationCorresponds to variant dbSNP:rs1058405Ensembl.1
Natural variantiVAR_022457145A → P2 PublicationsCorresponds to variant dbSNP:rs2070150Ensembl.1
Natural variantiVAR_022458157P → S2 PublicationsCorresponds to variant dbSNP:rs1135983Ensembl.1
Natural variantiVAR_075681324R → C in ACHM7; reduced ATF6-mediated unfolded protein response. 1 PublicationCorresponds to variant dbSNP:rs761357250EnsemblClinVar.1
Natural variantiVAR_075682567Y → N in ACHM7. 1 PublicationCorresponds to variant dbSNP:rs796065053EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005887 mRNA Translation: AAB64434.1
AB015856 mRNA Translation: BAA34722.1
AL391825 Genomic DNA No translation available.
AL450995 Genomic DNA No translation available.
AL359541 Genomic DNA No translation available.
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF005887 mRNA Translation: AAB64434.1
AB015856 mRNA Translation: BAA34722.1
AL391825 Genomic DNA No translation available.
AL450995 Genomic DNA No translation available.
AL359541 Genomic DNA No translation available.
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
SMRiP18850
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116586, 50 interactors
DIPiDIP-29304N
ELMiP18850
IntActiP18850, 29 interactors
MINTiP18850
STRINGi9606.ENSP00000356919

Chemistry databases

DrugBankiDB00852 Pseudoephedrine

PTM databases

GlyConnecti1162
iPTMnetiP18850
PhosphoSitePlusiP18850

Polymorphism and mutation databases

BioMutaiATF6
DMDMi66774203

Proteomic databases

EPDiP18850
MaxQBiP18850
PaxDbiP18850
PeptideAtlasiP18850
PRIDEiP18850
ProteomicsDBi53616

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
EuPathDBiHostDB:ENSG00000118217.5
GeneCardsiATF6
H-InvDBiHIX0001253
HGNCiHGNC:791 ATF6
HPAiHPA005935
MalaCardsiATF6
MIMi605537 gene
616517 phenotype
neXtProtiNX_P18850
OpenTargetsiENSG00000118217
PharmGKBiPA25091
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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-CutDBiP18850
PROiPR:P18850
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000118217 Expressed in 235 organ(s), highest expression level in corpus epididymis
CleanExiHS_ATF6
GenevisibleiP18850 HS

Family and domain databases

InterProiView protein in InterPro
IPR029801 ATF6A
IPR004827 bZIP
PANTHERiPTHR22952:SF116 PTHR22952:SF116, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiATF6A_HUMAN
AccessioniPrimary (citable) accession number: P18850
Secondary accession number(s): O15139
, Q5VW62, Q6IPB5, Q9UEC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: May 24, 2005
Last modified: October 10, 2018
This is version 200 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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