ATF6

Protein identityUniProt · HPA

UniProt accession

P18850

Gene

ATF6

Ensembl

ENSG00000118217

Chromosome

1

Canonical length

670 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Transcription factors

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

670 residues, UniProt reviewed canonical sequence.

>P18850|ATF6
     1  MGEPAGVAGT MESPFSPGLF HRLDEDWDSA LFAELGYFTD TDELQLEAAN ETYENNFDNL
    61  DFDLDLMPWE SDIWDINNQI CTVKDIKAEP QPLSPASSSY SVSSPRSVDS YSSTQHVPEE
   121  LDLSSSSQMS PLSLYGENSN SLSSAEPLKE DKPVTGPRNK TENGLTPKKK IQVNSKPSIQ
   181  PKPLLLPAAP KTQTNSSVPA KTIIIQTVPT LMPLAKQQPI ISLQPAPTKG QTVLLSQPTV
   241  VQLQAPGVLP SAQPVLAVAG GVTQLPNHVV NVVPAPSANS PVNGKLSVTK PVLQSTMRNV
   301  GSDIAVLRRQ QRMIKNRESA CQSRKKKKEY MLGLEARLKA ALSENEQLKK ENGTLKRQLD
   361  EVVSENQRLK VPSPKRRVVC VMIVLAFIIL NYGPMSMLEQ DSRRMNPSVS PANQRRHLLG
   421  FSAKEAQDTS DGIIQKNSYR YDHSVSNDKA LMVLTEEPLL YIPPPPCQPL INTTESLRLN
   481  HELRGWVHRH EVERTKSRRM TNNQQKTRIL QGALEQGSNS QLMAVQYTET TSSISRNSGS
   541  ELQVYYASPR SYQDFFEAIR RRGDTFYVVS FRRDHLLLPA TTHNKTTRPK MSIVLPAINI
   601  NENVINGQDY EVMMQIDCQV MDTRILHIKS SSVPPYLRDQ QRNQTNTFFG SPPAATEATH
   661  VVSTIPESLQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATF6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.65

Highest tissue expression

33 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATF6.

Disease | AllUniProt

Conditions ATF6 is implicated in, by any mechanism.

• Achromatopsia 7 (ACHM7) MIM:616517

Disease | GeneticClinVar

46 pathogenic / likely-pathogenic of 516 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Achromatopsia 7
• Achromatopsia
• Retinal dystrophy
• Bilateral sensorineural hearing impairment
• ATF6-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.7

gnomAD pLI

0

gnomAD missense Z

0.56

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 12% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATF6-mediated unfolded protein response
• endoplasmic reticulum unfolded protein response
• ERAD pathway
• eye development
• positive regulation of apoptotic process
• positive regulation of autophagy
• positive regulation of transcription by RNA polymerase II
• protein folding
• regulation of transcription by RNA polymerase II
• response to endoplasmic reticulum stress
• signal transduction
• visual perception
• positive regulation of ATF6-mediated unfolded protein response

Molecular functions

• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• enzyme binding
• identical protein binding
• protein heterodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II transcription regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding
• transcription cis-regulatory region binding

Cellular components

• chromatin
• cytosol
• endoplasmic reticulum
• endoplasmic reticulum membrane
• Golgi apparatus
• Golgi membrane
• membrane
• nuclear envelope
• nucleoplasm
• nucleus
• RNA polymerase II transcription regulator complex

Protein domainsUniProt · Pfam · InterPro

• Basic-leucine zipper domain
• Basic-leucine zipper domain superfamily
• ATF bZIP Transcription Factors
• bZIP transcription factor

KeywordsUniProt

• Activator
• DNA-binding
• Endoplasmic reticulum
• Glycoprotein
• Golgi apparatus
• Isopeptide bond
• Membrane
• Nucleus
• Signal-anchor
• Transcription
• Transcription regulation
• Transmembrane
• Transmembrane helix
• Ubl conjugation
• Unfolded protein response

InteractionsUniProt · HPA

Protein binding partners of ATF6 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LACC1
• SRF
• THBS4
• YY1
• CREB3L3
• THBS1
• XBP1