ATF6A_HUMAN
ID ATF6A_HUMAN Reviewed; 670 AA.
AC P18850; O15139; Q5VW62; Q6IPB5; Q9UEC9;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Cyclic AMP-dependent transcription factor ATF-6 alpha;
DE Short=cAMP-dependent transcription factor ATF-6 alpha;
DE AltName: Full=Activating transcription factor 6 alpha;
DE Short=ATF6-alpha;
DE Contains:
DE RecName: Full=Processed cyclic AMP-dependent transcription factor ATF-6 alpha;
GN Name=ATF6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS LEU-67;
RP PRO-145 AND SER-157.
RC TISSUE=Cervix carcinoma;
RX PubMed=9271374; DOI=10.1128/mcb.17.9.4957;
RA Zhu C., Johansen F.E., Prywes R.;
RT "Interaction of ATF6 and serum response factor.";
RL Mol. Cell. Biol. 17:4957-4966(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS PRO-145 AND SER-157.
RC TISSUE=Cervix carcinoma;
RX PubMed=9837962; DOI=10.1074/jbc.273.50.33741;
RA Yoshida H., Haze K., Yanagi H., Yura T., Mori K.;
RT "Identification of the cis-acting endoplasmic reticulum stress response
RT element responsible for transcriptional induction of mammalian glucose-
RT regulated proteins; involvement of basic-leucine zipper transcription
RT factors.";
RL J. Biol. Chem. 273:33741-33749(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-202, AND VARIANT VAL-67.
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 302-369, AND SUBUNIT.
RX PubMed=2516827; DOI=10.1101/gad.3.12b.2083;
RA Hai T., Liu F., Coukos W.J., Green M.R.;
RT "Transcription factor ATF cDNA clones: an extensive family of leucine
RT zipper proteins able to selectively form DNA-binding heterodimers.";
RL Genes Dev. 3:2083-2090(1989).
RN [6]
RP ERRATUM OF PUBMED:2516827.
RA Hai T., Liu F., Coukos W.J., Green M.R.;
RL Genes Dev. 4:682-682(1990).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10564271; DOI=10.1091/mbc.10.11.3787;
RA Haze K., Yoshida H., Yanagi H., Yura T., Mori K.;
RT "Mammalian transcription factor ATF6 is synthesized as a transmembrane
RT protein and activated by proteolysis in response to endoplasmic reticulum
RT stress.";
RL Mol. Biol. Cell 10:3787-3799(1999).
RN [8]
RP FUNCTION, PROTEOLYTIC PROCESSING BY MBTPS1 AND MBTPS2, AND MUTAGENESIS OF
RP ASN-391; PRO-394; 415-ARG-ARG-416 AND LEU-419.
RX PubMed=11163209; DOI=10.1016/s1097-2765(00)00133-7;
RA Ye J., Rawson R.B., Komuro R., Chen X., Dave U.P., Prywes R., Brown M.S.,
RA Goldstein J.L.;
RT "ER stress induces cleavage of membrane-bound ATF6 by the same proteases
RT that process SREBPs.";
RL Mol. Cell 6:1355-1364(2000).
RN [9]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=11779464; DOI=10.1016/s0092-8674(01)00611-0;
RA Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K.;
RT "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress
RT to produce a highly active transcription factor.";
RL Cell 107:881-891(2001).
RN [10]
RP FUNCTION.
RX PubMed=11158310; DOI=10.1128/mcb.21.4.1239-1248.2001;
RA Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., Mori K.;
RT "Endoplasmic reticulum stress-induced formation of transcription factor
RT complex ERSF including NF-Y (CBF) and activating transcription factors
RT 6alpha and 6beta that activates the mammalian unfolded protein response.";
RL Mol. Cell. Biol. 21:1239-1248(2001).
RN [11]
RP REVIEW.
RX PubMed=11483355; DOI=10.1016/s0378-1119(01)00551-0;
RA Hai T., Hartman M.G.;
RT "The molecular biology and nomenclature of the activating transcription
RT factor/cAMP responsive element binding family of transcription factors:
RT activating transcription factor proteins and homeostasis.";
RL Gene 273:1-11(2001).
RN [12]
RP PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION.
RX PubMed=12782636; DOI=10.1074/jbc.m300923200;
RA Okada T., Haze K., Nadanaka S., Yoshida H., Seidah N.G., Hirano Y.,
RA Sato R., Negishi M., Mori K.;
RT "A serine protease inhibitor prevents endoplasmic reticulum stress-induced
RT cleavage but not transport of the membrane-bound transcription factor
RT ATF6.";
RL J. Biol. Chem. 278:31024-31032(2003).
RN [13]
RP GLYCOSYLATION AT ASN-472; ASN-584 AND ASN-643, AND MUTAGENESIS OF THR-474;
RP THR-586 AND THR-645.
RX PubMed=14699159; DOI=10.1074/jbc.m309804200;
RA Hong M., Luo S., Baumeister P., Huang J.M., Gogia R.K., Li M., Lee A.S.;
RT "Underglycosylation of ATF6 as a novel sensing mechanism for activation of
RT the unfolded protein response.";
RL J. Biol. Chem. 279:11354-11363(2004).
RN [14]
RP INTERACTION WITH XBP1.
RX PubMed=17765680; DOI=10.1016/j.devcel.2007.07.018;
RA Yamamoto K., Sato T., Matsui T., Sato M., Okada T., Yoshida H., Harada A.,
RA Mori K.;
RT "Transcriptional induction of mammalian ER quality control proteins is
RT mediated by single or combined action of ATF6alpha and XBP1.";
RL Dev. Cell 13:365-376(2007).
RN [15]
RP INTERACTION WITH THBS4.
RX PubMed=22682248; DOI=10.1016/j.cell.2012.03.050;
RA Lynch J.M., Maillet M., Vanhoutte D., Schloemer A., Sargent M.A.,
RA Blair N.S., Lynch K.A., Okada T., Aronow B.J., Osinska H., Prywes R.,
RA Lorenz J.N., Mori K., Lawler J., Robbins J., Molkentin J.D.;
RT "A thrombospondin-dependent pathway for a protective ER stress response.";
RL Cell 149:1257-1268(2012).
RN [16]
RP INVOLVEMENT IN ACHM7.
RX PubMed=26063662; DOI=10.1007/s00439-015-1571-4;
RG University of Washington Center for Mendelian Genomics;
RA Ansar M., Santos-Cortez R.L., Saqib M.A., Zulfiqar F., Lee K., Ashraf N.M.,
RA Ullah E., Wang X., Sajid S., Khan F.S., Amin-ud-Din M., Smith J.D.,
RA Shendure J., Bamshad M.J., Nickerson D.A., Hameed A., Riazuddin S.,
RA Ahmed Z.M., Ahmad W., Leal S.M.;
RT "Mutation of ATF6 causes autosomal recessive achromatopsia.";
RL Hum. Genet. 134:941-950(2015).
RN [17]
RP FUNCTION, INVOLVEMENT IN ACHM7, VARIANTS ACHM7 CYS-324 AND ASN-567, AND
RP CHARACTERIZATION OF VARIANT ACHM7 CYS-324.
RX PubMed=26029869; DOI=10.1038/ng.3319;
RA Kohl S., Zobor D., Chiang W.C., Weisschuh N., Staller J.,
RA Gonzalez Menendez I., Chang S., Beck S.C., Garcia Garrido M.,
RA Sothilingam V., Seeliger M.W., Stanzial F., Benedicenti F., Inzana F.,
RA Heon E., Vincent A., Beis J., Strom T.M., Rudolph G., Roosing S.,
RA Hollander A.I., Cremers F.P., Lopez I., Ren H., Moore A.T., Webster A.R.,
RA Michaelides M., Koenekoop R.K., Zrenner E., Kaufman R.J., Tsang S.H.,
RA Wissinger B., Lin J.H.;
RT "Mutations in the unfolded protein response regulator ATF6 cause the cone
RT dysfunction disorder achromatopsia.";
RL Nat. Genet. 47:757-765(2015).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-87, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [19]
RP INTERACTION WITH LACC1.
RX PubMed=31875558; DOI=10.1016/j.celrep.2019.11.105;
RA Huang C., Hedl M., Ranjan K., Abraham C.;
RT "LACC1 required for NOD2-induced, ER stress-mediated innate immune outcomes
RT in human macrophages and LACC1 risk variants modulate these outcomes.";
RL Cell Rep. 29:4525-4539(2019).
RN [20]
RP UBIQUITINATION BY RNF186, AND MUTAGENESIS OF LYS-152.
RX PubMed=34623328; DOI=10.1172/jci145472;
RA Ranjan K., Hedl M., Sinha S., Zhang X., Abraham C.;
RT "Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate
RT receptor-induced unfolded protein response.";
RL J. Clin. Invest. 131:0-0(2021).
CC -!- FUNCTION: [Cyclic AMP-dependent transcription factor ATF-6 alpha]:
CC Precursor of the transcription factor form (Processed cyclic AMP-
CC dependent transcription factor ATF-6 alpha), which is embedded in the
CC endoplasmic reticulum membrane (PubMed:10564271, PubMed:11158310,
CC PubMed:11779464). Endoplasmic reticulum stress promotes processing of
CC this form, releasing the transcription factor form that translocates
CC into the nucleus, where it activates transcription of genes involved in
CC the unfolded protein response (UPR) (PubMed:10564271, PubMed:11158310,
CC PubMed:11779464). {ECO:0000269|PubMed:10564271,
CC ECO:0000269|PubMed:11158310, ECO:0000269|PubMed:11779464}.
CC -!- FUNCTION: [Processed cyclic AMP-dependent transcription factor ATF-6
CC alpha]: Transcription factor that initiates the unfolded protein
CC response (UPR) during endoplasmic reticulum stress by activating
CC transcription of genes involved in the UPR (PubMed:10564271,
CC PubMed:11163209, PubMed:11158310, PubMed:11779464). Binds DNA on the
CC 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-
CC N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3')
CC (PubMed:10564271, PubMed:11158310, PubMed:11779464). Binding to ERSE
CC requires binding of NF-Y to ERSE. Could also be involved in activation
CC of transcription by the serum response factor (PubMed:10564271,
CC PubMed:11158310, PubMed:11779464). May play a role in foveal
CC development and cone function in the retina (PubMed:26029869).
CC {ECO:0000269|PubMed:10564271, ECO:0000269|PubMed:11158310,
CC ECO:0000269|PubMed:11163209, ECO:0000269|PubMed:11779464,
CC ECO:0000269|PubMed:26029869}.
CC -!- SUBUNIT: Interacts with XBP1 isoform 2; the interaction occurs in a ER
CC stress-dependent manner (PubMed:17765680). Interacts with LACC1
CC (PubMed:31875558). {ECO:0000269|PubMed:17765680,
CC ECO:0000269|PubMed:31875558}.
CC -!- SUBUNIT: [Cyclic AMP-dependent transcription factor ATF-6 alpha]:
CC Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which
CC facilitates its processing, activation and nuclear translocation
CC (PubMed:22682248). Interacts (via lumenal domain) with THBS1 (By
CC similarity). {ECO:0000250|UniProtKB:F6VAN0,
CC ECO:0000269|PubMed:22682248}.
CC -!- SUBUNIT: [Processed cyclic AMP-dependent transcription factor ATF-6
CC alpha]: Homodimer and heterodimer with ATF6-beta. The dimer interacts
CC with the nuclear transcription factor Y (NF-Y) trimer through direct
CC binding to NF-Y subunit C (NF-YC). Interacts also with the
CC transcription factors GTF2I, YY1 and SRF. {ECO:0000269|PubMed:2516827}.
CC -!- INTERACTION:
CC P18850; P18850: ATF6; NbExp=5; IntAct=EBI-852157, EBI-852157;
CC P18850; Q99941: ATF6B; NbExp=2; IntAct=EBI-852157, EBI-2841031;
CC P18850; Q68CJ9: CREB3L3; NbExp=2; IntAct=EBI-852157, EBI-852194;
CC P18850; Q53ET0: CRTC2; NbExp=3; IntAct=EBI-852157, EBI-1181987;
CC P18850; P11021: HSPA5; NbExp=2; IntAct=EBI-852157, EBI-354921;
CC P18850; P17861: XBP1; NbExp=4; IntAct=EBI-852157, EBI-6942961;
CC P18850; Q3U182: Crtc2; Xeno; NbExp=2; IntAct=EBI-852157, EBI-8018890;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10564271, ECO:0000269|PubMed:12782636}; Single-pass
CC type II membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:12782636}; Single-pass type II membrane protein
CC {ECO:0000255}. Note=Translocates from the endoplasmic reticulum to the
CC Golgi, where it is processed. {ECO:0000269|PubMed:12782636}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-dependent transcription
CC factor ATF-6 alpha]: Nucleus {ECO:0000269|PubMed:10564271,
CC ECO:0000269|PubMed:12782636}. Note=Under ER stress the cleaved N-
CC terminal cytoplasmic domain translocates into the nucleus
CC (PubMed:10564271, PubMed:12782636). THBS4 promotes its nuclear
CC shuttling (By similarity). {ECO:0000250|UniProtKB:F6VAN0,
CC ECO:0000269|PubMed:10564271, ECO:0000269|PubMed:12782636}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9271374}.
CC -!- DOMAIN: The basic domain functions as a nuclear localization signal.
CC {ECO:0000269|PubMed:10564271}.
CC -!- DOMAIN: The basic leucine-zipper domain is sufficient for association
CC with the NF-Y trimer and binding to ERSE.
CC {ECO:0000269|PubMed:10564271}.
CC -!- PTM: During unfolded protein response, a fragment of approximately 50
CC kDa containing the cytoplasmic transcription factor domain is released
CC by proteolysis. The cleavage seems to be performed sequentially by
CC site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases.
CC {ECO:0000269|PubMed:11163209, ECO:0000269|PubMed:12782636}.
CC -!- PTM: N-glycosylated. The glycosylation status may serve as a sensor for
CC ER homeostasis, resulting in ATF6 activation to trigger the unfolded
CC protein response (UPR). {ECO:0000269|PubMed:14699159}.
CC -!- PTM: Ubiquitinated by RNF186 at Lys-152, which is required for pattern
CC recognition receptor-induced unfolded protein response-associated
CC outcomes. {ECO:0000269|PubMed:34623328}.
CC -!- DISEASE: Achromatopsia 7 (ACHM7) [MIM:616517]: A form of achromatopsia,
CC an ocular stationary disorder due to the absence of functioning cone
CC photoreceptors in the retina. It is characterized by total
CC colorblindness, low visual acuity, photophobia and nystagmus.
CC {ECO:0000269|PubMed:26029869, ECO:0000269|PubMed:26063662}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; AF005887; AAB64434.1; -; mRNA.
DR EMBL; AB015856; BAA34722.1; -; mRNA.
DR EMBL; AL391825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014969; AAH14969.1; -; mRNA.
DR EMBL; BC071997; AAH71997.1; -; mRNA.
DR CCDS; CCDS1235.1; -.
DR PIR; F34223; F34223.
DR RefSeq; NP_031374.2; NM_007348.3.
DR AlphaFoldDB; P18850; -.
DR SMR; P18850; -.
DR BioGRID; 116586; 135.
DR ComplexPortal; CPX-6593; bZIP transcription factor complex, ATF6-ATF6.
DR ComplexPortal; CPX-6595; bZIP transcription factor complex, ATF6-ATF6B.
DR ComplexPortal; CPX-6597; bZIP transcription factor complex, ATF6-XBP1.
DR DIP; DIP-29304N; -.
DR ELM; P18850; -.
DR IntAct; P18850; 47.
DR MINT; P18850; -.
DR STRING; 9606.ENSP00000356919; -.
DR DrugBank; DB00852; Pseudoephedrine.
DR GlyConnect; 1162; 1 N-Linked glycan (1 site).
DR GlyGen; P18850; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; P18850; -.
DR PhosphoSitePlus; P18850; -.
DR BioMuta; ATF6; -.
DR DMDM; 66774203; -.
DR EPD; P18850; -.
DR jPOST; P18850; -.
DR MassIVE; P18850; -.
DR MaxQB; P18850; -.
DR PaxDb; P18850; -.
DR PeptideAtlas; P18850; -.
DR PRIDE; P18850; -.
DR ProteomicsDB; 53616; -.
DR Antibodypedia; 20515; 652 antibodies from 46 providers.
DR DNASU; 22926; -.
DR Ensembl; ENST00000367942.4; ENSP00000356919.3; ENSG00000118217.7.
DR Ensembl; ENST00000681738.1; ENSP00000505025.1; ENSG00000118217.7.
DR Ensembl; ENST00000681801.1; ENSP00000505998.1; ENSG00000118217.7.
DR GeneID; 22926; -.
DR KEGG; hsa:22926; -.
DR MANE-Select; ENST00000367942.4; ENSP00000356919.3; NM_007348.4; NP_031374.2.
DR UCSC; uc001gbs.4; human.
DR CTD; 22926; -.
DR DisGeNET; 22926; -.
DR GeneCards; ATF6; -.
DR GeneReviews; ATF6; -.
DR HGNC; HGNC:791; ATF6.
DR HPA; ENSG00000118217; Low tissue specificity.
DR MalaCards; ATF6; -.
DR MIM; 605537; gene.
DR MIM; 616517; phenotype.
DR neXtProt; NX_P18850; -.
DR OpenTargets; ENSG00000118217; -.
DR Orphanet; 49382; Achromatopsia.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA25091; -.
DR VEuPathDB; HostDB:ENSG00000118217; -.
DR eggNOG; KOG4343; Eukaryota.
DR GeneTree; ENSGT00940000159221; -.
DR HOGENOM; CLU_026136_1_0_1; -.
DR InParanoid; P18850; -.
DR OMA; LCHRPDE; -.
DR OrthoDB; 696548at2759; -.
DR PhylomeDB; P18850; -.
DR TreeFam; TF316079; -.
DR PathwayCommons; P18850; -.
DR Reactome; R-HSA-380994; ATF4 activates genes in response to endoplasmic reticulum stress.
DR Reactome; R-HSA-381033; ATF6 (ATF6-alpha) activates chaperones.
DR Reactome; R-HSA-381183; ATF6 (ATF6-alpha) activates chaperone genes.
DR SignaLink; P18850; -.
DR SIGNOR; P18850; -.
DR BioGRID-ORCS; 22926; 15 hits in 1098 CRISPR screens.
DR ChiTaRS; ATF6; human.
DR GeneWiki; ATF6; -.
DR GenomeRNAi; 22926; -.
DR Pharos; P18850; Tbio.
DR PRO; PR:P18850; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P18850; protein.
DR Bgee; ENSG00000118217; Expressed in corpus epididymis and 208 other tissues.
DR Genevisible; P18850; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005635; C:nuclear envelope; TAS:ProtInc.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal.
DR GO; GO:0035497; F:cAMP response element binding; IEA:InterPro.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0036500; P:ATF6-mediated unfolded protein response; TAS:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR GO; GO:0036503; P:ERAD pathway; IC:ComplexPortal.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903893; P:positive regulation of ATF6-mediated unfolded protein response; IDA:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR029801; ATF6A.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR PANTHER; PTHR46164:SF1; PTHR46164:SF1; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Activator; Disease variant; DNA-binding; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Isopeptide bond; Membrane; Nucleus;
KW Reference proteome; Signal-anchor; Transcription; Transcription regulation;
KW Transmembrane; Transmembrane helix; Ubl conjugation;
KW Unfolded protein response.
FT CHAIN 1..670
FT /note="Cyclic AMP-dependent transcription factor ATF-6
FT alpha"
FT /id="PRO_0000076589"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-dependent transcription factor
FT ATF-6 alpha"
FT /evidence="ECO:0000305|PubMed:11163209"
FT /id="PRO_0000296200"
FT TOPO_DOM 1..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..670
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 306..369
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..150
FT /note="Transcription activation"
FT /evidence="ECO:0000305"
FT REGION 91..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 308..339
FT /note="Basic motif"
FT REGION 348..355
FT /note="Leucine-zipper"
FT REGION 468..589
FT /note="Interaction with THBS4"
FT /evidence="ECO:0000269|PubMed:22682248"
FT COMPBIAS 92..146
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 419..420
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000305|PubMed:11163209"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14699159"
FT CARBOHYD 584
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14699159"
FT CARBOHYD 643
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:14699159"
FT CROSSLNK 87
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 152
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:34623328"
FT VARIANT 67
FT /note="M -> L (in dbSNP:rs1058405)"
FT /evidence="ECO:0000269|PubMed:9271374"
FT /id="VAR_022455"
FT VARIANT 67
FT /note="M -> V (in dbSNP:rs1058405)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_022456"
FT VARIANT 145
FT /note="A -> P (in dbSNP:rs2070150)"
FT /evidence="ECO:0000269|PubMed:9271374,
FT ECO:0000269|PubMed:9837962"
FT /id="VAR_022457"
FT VARIANT 157
FT /note="P -> S (in dbSNP:rs1135983)"
FT /evidence="ECO:0000269|PubMed:9271374,
FT ECO:0000269|PubMed:9837962"
FT /id="VAR_022458"
FT VARIANT 324
FT /note="R -> C (in ACHM7; reduced ATF6-mediated unfolded
FT protein response; dbSNP:rs761357250)"
FT /evidence="ECO:0000269|PubMed:26029869"
FT /id="VAR_075681"
FT VARIANT 567
FT /note="Y -> N (in ACHM7; dbSNP:rs796065053)"
FT /evidence="ECO:0000269|PubMed:26029869"
FT /id="VAR_075682"
FT MUTAGEN 152
FT /note="K->R: Almost complete loss of RNF186-mediated
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:34623328"
FT MUTAGEN 391
FT /note="N->F: Loss of proteolytic cleavage; when associated
FT with L-394."
FT /evidence="ECO:0000269|PubMed:11163209"
FT MUTAGEN 394
FT /note="P->L: Loss of proteolytic cleavage; when associated
FT with F-391."
FT /evidence="ECO:0000269|PubMed:11163209"
FT MUTAGEN 415..416
FT /note="RR->AA: Reduces proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:11163209"
FT MUTAGEN 419
FT /note="L->V: Reduces proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:11163209"
FT MUTAGEN 474
FT /note="T->I: Loss of glycosylation at Asn-472 and increase
FT of Golgi translocation rate."
FT /evidence="ECO:0000269|PubMed:14699159"
FT MUTAGEN 586
FT /note="T->I: Loss of glycosylation at Asn-584 and increase
FT of Golgi translocation rate. Higher increase in Golgi
FT translocation rate; when associated with Ile-645."
FT /evidence="ECO:0000269|PubMed:14699159"
FT MUTAGEN 645
FT /note="T->I: Loss of glycosylation at Asn-643 and increase
FT of Golgi translocation rate. Higher increase in Golgi
FT translocation rate; when associated with Ile-586."
FT /evidence="ECO:0000269|PubMed:14699159"
FT CONFLICT 195
FT /note="N -> I (in Ref. 4; AAH14969/AAH71997)"
FT /evidence="ECO:0000305"
FT CONFLICT 198..201
FT /note="VPAK -> IPPQ (in Ref. 4; AAH14969/AAH71997)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="L -> I (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="T -> R (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 366..369
FT /note="NQRL -> LRNS (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="S -> G (in Ref. 1; AAB64434)"
FT /evidence="ECO:0000305"
FT CONFLICT 513..514
FT /note="AL -> VV (in Ref. 1; AAB64434)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 670 AA; 74585 MW; 5EBD08CF4121D41A CRC64;
MGEPAGVAGT MESPFSPGLF HRLDEDWDSA LFAELGYFTD TDELQLEAAN ETYENNFDNL
DFDLDLMPWE SDIWDINNQI CTVKDIKAEP QPLSPASSSY SVSSPRSVDS YSSTQHVPEE
LDLSSSSQMS PLSLYGENSN SLSSAEPLKE DKPVTGPRNK TENGLTPKKK IQVNSKPSIQ
PKPLLLPAAP KTQTNSSVPA KTIIIQTVPT LMPLAKQQPI ISLQPAPTKG QTVLLSQPTV
VQLQAPGVLP SAQPVLAVAG GVTQLPNHVV NVVPAPSANS PVNGKLSVTK PVLQSTMRNV
GSDIAVLRRQ QRMIKNRESA CQSRKKKKEY MLGLEARLKA ALSENEQLKK ENGTLKRQLD
EVVSENQRLK VPSPKRRVVC VMIVLAFIIL NYGPMSMLEQ DSRRMNPSVS PANQRRHLLG
FSAKEAQDTS DGIIQKNSYR YDHSVSNDKA LMVLTEEPLL YIPPPPCQPL INTTESLRLN
HELRGWVHRH EVERTKSRRM TNNQQKTRIL QGALEQGSNS QLMAVQYTET TSSISRNSGS
ELQVYYASPR SYQDFFEAIR RRGDTFYVVS FRRDHLLLPA TTHNKTTRPK MSIVLPAINI
NENVINGQDY EVMMQIDCQV MDTRILHIKS SSVPPYLRDQ QRNQTNTFFG SPPAATEATH
VVSTIPESLQ
