P18850 (ATF6A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Processed cyclic AMP-dependent transcription factor ATF-6 alpha

Gene names

Name:

ATF6

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	670 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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.
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 process	Transcription Transcription regulation Unfolded protein response
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	DNA-binding
Molecular function	Activator
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome 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 transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear envelope Traceable author statement PubMed 10866666. Source: ProtInc nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	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
CREB3L3	Q68CJ9	2	EBI-852157,EBI-852194

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 670	670	Cyclic AMP-dependent transcription factor ATF-6 alpha		PRO_0000076589
	Chain	1 – ?		Processed cyclic AMP-dependent transcription factor ATF-6 alpha		PRO_0000296200
Regions
	Topological domain	1 – 377	377	Cytoplasmic Potential
	Transmembrane	378 – 398	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	399 – 670	272	Lumenal Potential
	Domain	306 – 369	64	bZIP
	Region	1 – 150	150	Transcription activation
	Region	308 – 339	32	Basic motif By similarity
	Region	348 – 355	8	Leucine-zipper By similarity
	Compositional bias	124 – 127	4	Poly-Ser
	Compositional bias	325 – 328	4	Poly-Lys
	Compositional bias	463 – 466	4	Poly-Pro
Sites
	Site	419 – 420	2	Cleavage; by PS1 By similarity
Amino acid modifications
	Glycosylation	472	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	584	1	N-linked (GlcNAc...) Ref.11
	Glycosylation	643	1	N-linked (GlcNAc...) Ref.11
Natural variations
	Natural variant	67	1	M → L. Ref.1 Corresponds to variant rs1058405 [ dbSNP | Ensembl ].		VAR_022455
	Natural variant	67	1	M → V. Ref.4 Corresponds to variant rs1058405 [ dbSNP | Ensembl ].		VAR_022456
	Natural variant	145	1	A → P. Ref.1 Ref.2 Corresponds to variant rs2070150 [ dbSNP | Ensembl ].		VAR_022457
	Natural variant	157	1	P → S. Ref.1 Ref.2 Corresponds to variant rs1135983 [ dbSNP | Ensembl ].		VAR_022458
Experimental info
	Mutagenesis	391	1	N → F: Loss of proteolytic cleavage; when associated with L-394. Ref.8
	Mutagenesis	394	1	P → L: Loss of proteolytic cleavage; when associated with F-391. Ref.8
	Mutagenesis	415 – 416	2	RR → AA: Reduces proteolytic cleavage.
	Mutagenesis	419	1	L → V: Reduces proteolytic cleavage. Ref.8
	Mutagenesis	474	1	T → I: Loss of glycosylation at Asn-472 and increase of Golgi translocation rate. Ref.11
	Mutagenesis	586	1	T → 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
	Mutagenesis	645	1	T → 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 conflict	195	1	N → I in AAH14969. Ref.4
	Sequence conflict	195	1	N → I in AAH71997. Ref.4
	Sequence conflict	198 – 201	4	VPAK → IPPQ in AAH14969. Ref.4
	Sequence conflict	198 – 201	4	VPAK → IPPQ in AAH71997. Ref.4
	Sequence conflict	307	1	L → I no nucleotide entry Ref.5
	Sequence conflict	354	1	T → R no nucleotide entry Ref.5
	Sequence conflict	366 – 369	4	NQRL → LRNS no nucleotide entry Ref.5
	Sequence conflict	410	1	S → G in AAB64434. Ref.1
	Sequence conflict	513 – 514	2	AL → VV in AAB64434. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P18850 [UniParc]. Last modified May 24, 2005. Version 3. Checksum: 5EBD08CF4121D41A	FASTA	670	74,585
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.
IPI	IPI00002511.
PIR	F34223.
RefSeq	NP_031374.2. NM_007348.3.
UniGene	Hs.492740. Hs.617868.
3D structure databases
ProteinModelPortal	P18850.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29304N.
IntAct	P18850. 12 interactions.
MINT	MINT-268075.
STRING	9606.ENSP00000356919.
PTM databases
PhosphoSite	P18850.
Polymorphism databases
DMDM	66774203.
Proteomic databases
PaxDb	P18850.
PRIDE	P18850.
Protocols and materials databases
DNASU	22926.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367942; ENSP00000356919; ENSG00000118217.
GeneID	22926.
KEGG	hsa:22926.
UCSC	uc001gbq.2. human.
Organism-specific databases
CTD	22926.
GeneCards	GC01P161736.
H-InvDB	HIX0001253.
HGNC	HGNC:791. ATF6.
MIM	605537. gene.
neXtProt	NX_P18850.
PharmGKB	PA25091.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG236121.
HOGENOM	HOG000253938.
HOVERGEN	HBG108357.
InParanoid	P18850.
KO	K09054.
OMA	MDTRILH.
OrthoDB	EOG4DV5MW.
PhylomeDB	P18850.
Enzyme and pathway databases
Pathway_Interaction_DB	p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.
Reactome	REACT_116125. Disease.
Gene expression databases
Bgee	P18850.
CleanEx	HS_ATF6.
Genevestigator	P18850.
GermOnline	ENSG00000118217. Homo sapiens.
Family and domain databases
InterPro	IPR004827. bZIP. [Graphical view]
Pfam	PF00170. bZIP_1. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ATF6. human.
GenomeRNAi	22926.
NextBio	43639.
PMAP-CutDB	P18850.
SOURCE	Search...

Entry information

Entry name

ATF6A_HUMAN

Accession

Primary (citable) accession number: P18850
Secondary accession number(s): O15139 , Q5VW62, Q6IPB5, Q9UEC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	May 24, 2005
Last modified:	May 1, 2013
This is version 143 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.