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P18850 (ATF6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:ATF6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length670 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor that acts during endoplasmic reticulum stress by activating unfolded protein response target genes. 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. Ref.9

Subunit structure

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. Ref.12

Subcellular location

Endoplasmic reticulum membrane; Single-pass type II membrane protein.

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.

Tissue specificity

Ubiquitous.

Domain

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.

Post-translational modification

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.

N-glycosylated. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR). Ref.11

Phosphorylated in vitro by MAPK14/P38MAPK.

Sequence similarities

Belongs to the bZIP family. ATF subfamily.

Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
Unfolded protein response
   Cellular componentEndoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandDNA-binding
   Molecular functionActivator
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of signaling protein activity involved in unfolded protein response

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

endoplasmic reticulum unfolded protein response

Traceable author statement PubMed 19816510. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response

Traceable author statement Ref.2. Source: ProtInc

protein folding

Traceable author statement Ref.7. Source: ProtInc

regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.7. Source: ProtInc

response to stress

Traceable author statement PubMed 10866666. Source: ProtInc

signal transduction

Traceable author statement Ref.1. Source: ProtInc

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear envelope

Traceable author statement PubMed 10866666. Source: ProtInc

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement Ref.7. Source: ProtInc

   Molecular_functionprotein binding

Inferred from physical interaction Ref.12. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.7Ref.1. Source: ProtInc

transcription coactivator activity

Traceable author statement PubMed 10866666. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CREB3L3Q68CJ92EBI-852157,EBI-852194

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 670670Cyclic AMP-dependent transcription factor ATF-6 alpha
PRO_0000076589
Chain1 – ?Processed cyclic AMP-dependent transcription factor ATF-6 alphaPRO_0000296200

Regions

Topological domain1 – 377377Cytoplasmic Potential
Transmembrane378 – 39821Helical; Signal-anchor for type II membrane protein; Potential
Topological domain399 – 670272Lumenal Potential
Domain306 – 36964bZIP
Region1 – 150150Transcription activation
Region308 – 33932Basic motif
Region348 – 3558Leucine-zipper
Region468 – 589122Interaction with THBS4
Compositional bias124 – 1274Poly-Ser
Compositional bias325 – 3284Poly-Lys
Compositional bias463 – 4664Poly-Pro

Sites

Site419 – 4202Cleavage; by PS1 By similarity

Amino acid modifications

Glycosylation4721N-linked (GlcNAc...) Ref.11
Glycosylation5841N-linked (GlcNAc...) Ref.11
Glycosylation6431N-linked (GlcNAc...) Ref.11

Natural variations

Natural variant671M → L. Ref.1
Corresponds to variant rs1058405 [ dbSNP | Ensembl ].
VAR_022455
Natural variant671M → V. Ref.4
Corresponds to variant rs1058405 [ dbSNP | Ensembl ].
VAR_022456
Natural variant1451A → P. Ref.1 Ref.2
Corresponds to variant rs2070150 [ dbSNP | Ensembl ].
VAR_022457
Natural variant1571P → S. Ref.1 Ref.2
Corresponds to variant rs1135983 [ dbSNP | Ensembl ].
VAR_022458

Experimental info

Mutagenesis3911N → F: Loss of proteolytic cleavage; when associated with L-394. Ref.8
Mutagenesis3941P → L: Loss of proteolytic cleavage; when associated with F-391. Ref.8
Mutagenesis415 – 4162RR → AA: Reduces proteolytic cleavage.
Mutagenesis4191L → V: Reduces proteolytic cleavage. Ref.8
Mutagenesis4741T → I: Loss of glycosylation at Asn-472 and increase of Golgi translocation rate. Ref.11
Mutagenesis5861T → I: Loss of glycosylation at Asn-584 and increase of Golgi translocation rate. Higher increase in Golgi translocation rate; when associated with Ile-645. Ref.11
Mutagenesis6451T → I: Loss of glycosylation at Asn-643 and increase of Golgi translocation rate. Higher increase in Golgi translocation rate; when associated with Ile-586. Ref.11
Sequence conflict1951N → I in AAH14969. Ref.4
Sequence conflict1951N → I in AAH71997. Ref.4
Sequence conflict198 – 2014VPAK → IPPQ in AAH14969. Ref.4
Sequence conflict198 – 2014VPAK → IPPQ in AAH71997. Ref.4
Sequence conflict3071L → I no nucleotide entry Ref.5
Sequence conflict3541T → R no nucleotide entry Ref.5
Sequence conflict366 – 3694NQRL → LRNS no nucleotide entry Ref.5
Sequence conflict4101S → G in AAB64434. Ref.1
Sequence conflict513 – 5142AL → VV in AAB64434. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P18850 [UniParc].

Last modified May 24, 2005. Version 3.
Checksum: 5EBD08CF4121D41A

FASTA67074,585
        10         20         30         40         50         60 
MGEPAGVAGT MESPFSPGLF HRLDEDWDSA LFAELGYFTD TDELQLEAAN ETYENNFDNL 

        70         80         90        100        110        120 
DFDLDLMPWE SDIWDINNQI CTVKDIKAEP QPLSPASSSY SVSSPRSVDS YSSTQHVPEE 

       130        140        150        160        170        180 
LDLSSSSQMS PLSLYGENSN SLSSAEPLKE DKPVTGPRNK TENGLTPKKK IQVNSKPSIQ 

       190        200        210        220        230        240 
PKPLLLPAAP KTQTNSSVPA KTIIIQTVPT LMPLAKQQPI ISLQPAPTKG QTVLLSQPTV 

       250        260        270        280        290        300 
VQLQAPGVLP SAQPVLAVAG GVTQLPNHVV NVVPAPSANS PVNGKLSVTK PVLQSTMRNV 

       310        320        330        340        350        360 
GSDIAVLRRQ QRMIKNRESA CQSRKKKKEY MLGLEARLKA ALSENEQLKK ENGTLKRQLD 

       370        380        390        400        410        420 
EVVSENQRLK VPSPKRRVVC VMIVLAFIIL NYGPMSMLEQ DSRRMNPSVS PANQRRHLLG 

       430        440        450        460        470        480 
FSAKEAQDTS DGIIQKNSYR YDHSVSNDKA LMVLTEEPLL YIPPPPCQPL INTTESLRLN 

       490        500        510        520        530        540 
HELRGWVHRH EVERTKSRRM TNNQQKTRIL QGALEQGSNS QLMAVQYTET TSSISRNSGS 

       550        560        570        580        590        600 
ELQVYYASPR SYQDFFEAIR RRGDTFYVVS FRRDHLLLPA TTHNKTTRPK MSIVLPAINI 

       610        620        630        640        650        660 
NENVINGQDY EVMMQIDCQV MDTRILHIKS SSVPPYLRDQ QRNQTNTFFG SPPAATEATH 

       670 
VVSTIPESLQ 

« Hide

References

« Hide 'large scale' references
[1]"Interaction of ATF6 and serum response factor."
Zhu C., Johansen F.E., Prywes R.
Mol. Cell. Biol. 17:4957-4966(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-67; PRO-145 AND SER-157.
Tissue: Cervix carcinoma.
[2]"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."
Yoshida H., Haze K., Yanagi H., Yura T., Mori K.
J. Biol. Chem. 273:33741-33749(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-145 AND SER-157.
Tissue: Cervix carcinoma.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-202, VARIANT VAL-67.
Tissue: Pancreas.
[5]"Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers."
Hai T., Liu F., Coukos W.J., Green M.R.
Genes Dev. 3:2083-2090(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 302-369.
[6]Erratum
Hai T., Liu F., Coukos W.J., Green M.R.
Genes Dev. 4:682-682(1990)
[7]"Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress."
Haze K., Yoshida H., Yanagi H., Yura T., Mori K.
Mol. Biol. Cell 10:3787-3799(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[8]"ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs."
Ye J., Rawson R.B., Komuro R., Chen X., Dave U.P., Prywes R., Brown M.S., Goldstein J.L.
Mol. Cell 6:1355-1364(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING BY PS1 AND PS2, MUTAGENESIS OF ASN-391; PRO-394; 415-ARG-ARG-416 AND LEU-419.
[9]"Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6alpha and 6beta that activates the mammalian unfolded protein response."
Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., Mori K.
Mol. Cell. Biol. 21:1239-1248(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis."
Hai T., Hartman M.G.
Gene 273:1-11(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Underglycosylation of ATF6 as a novel sensing mechanism for activation of the unfolded protein response."
Hong M., Luo S., Baumeister P., Huang J.M., Gogia R.K., Li M., Lee A.S.
J. Biol. Chem. 279:11354-11363(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-472; ASN-584 AND ASN-643, MUTAGENESIS OF THR-474; THR-586 AND THR-645.
[12]"A thrombospondin-dependent pathway for a protective ER stress response."
Lynch J.M., Maillet M., Vanhoutte D., Schloemer A., Sargent M.A., Blair N.S., Lynch K.A., Okada T., Aronow B.J., Osinska H., Prywes R., Lorenz J.N., Mori K., Lawler J., Robbins J., Molkentin J.D.
Cell 149:1257-1268(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THBS4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS1235.1.
PIRF34223.
RefSeqNP_031374.2. NM_007348.3.
UniGeneHs.492740.
Hs.617868.

3D structure databases

ProteinModelPortalP18850.
SMRP18850. Positions 314-357.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116586. 21 interactions.
DIPDIP-29304N.
IntActP18850. 14 interactions.
MINTMINT-268075.
STRING9606.ENSP00000356919.

PTM databases

PhosphoSiteP18850.

Polymorphism databases

DMDM66774203.

Proteomic databases

MaxQBP18850.
PaxDbP18850.
PRIDEP18850.

Protocols and materials databases

DNASU22926.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367942; ENSP00000356919; ENSG00000118217.
GeneID22926.
KEGGhsa:22926.
UCSCuc001gbq.2. human.

Organism-specific databases

CTD22926.
GeneCardsGC01P161736.
H-InvDBHIX0001253.
HGNCHGNC:791. ATF6.
HPAHPA005935.
MIM605537. gene.
neXtProtNX_P18850.
PharmGKBPA25091.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG236121.
HOGENOMHOG000253938.
HOVERGENHBG108357.
InParanoidP18850.
KOK09054.
OMAMDTRILH.
OrthoDBEOG7GBFWN.
PhylomeDBP18850.
TreeFamTF316079.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
SignaLinkP18850.

Gene expression databases

BgeeP18850.
CleanExHS_ATF6.
GenevestigatorP18850.

Family and domain databases

InterProIPR004827. bZIP.
[Graphical view]
PfamPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSATF6. human.
GeneWikiATF6.
GenomeRNAi22926.
NextBio43639.
PMAP-CutDBP18850.
PROP18850.
SOURCESearch...

Entry information

Entry nameATF6A_HUMAN
AccessionPrimary (citable) accession number: P18850
Secondary accession number(s): O15139 expand/collapse secondary AC list , Q5VW62, Q6IPB5, Q9UEC9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: May 24, 2005
Last modified: July 9, 2014
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM