ATF6A_MOUSE
ID ATF6A_MOUSE Reviewed; 656 AA.
AC F6VAN0; B2RU98; Q8BZ84;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 88.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [4]
RP INTERACTION WITH THBS1 AND THBS4, AND SUBCELLULAR LOCATION.
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 [5]
RP DISRUPTION PHENOTYPE.
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).
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. Endoplasmic reticulum stress promotes
CC processing of this form, releasing the transcription factor form that
CC translocates into the nucleus, where it activates transcription of
CC genes involved in the unfolded protein response (UPR).
CC {ECO:0000250|UniProtKB:P18850}.
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. Binds DNA on the 5'-
CC 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'). 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. May play a role in
CC foveal development and cone function in the retina.
CC {ECO:0000250|UniProtKB:P18850}.
CC -!- SUBUNIT: Interacts with XBP1 isoform 2; the interaction occurs in a ER
CC stress-dependent manner. Interacts with LACC1.
CC {ECO:0000250|UniProtKB:P18850}.
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
CC (PubMed:22682248). {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.
CC {ECO:0000250|UniProtKB:P18850}.
CC -!- INTERACTION:
CC F6VAN0; Q3U182: Crtc2; NbExp=2; IntAct=EBI-6171558, EBI-8018890;
CC F6VAN0; Q9Z1T2: Thbs4; NbExp=3; IntAct=EBI-6171558, EBI-6171531;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:22682248}; Single-pass type II membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:P18850};
CC Single-pass type II membrane protein {ECO:0000255}. Note=Translocates
CC from the endoplasmic reticulum to the Golgi, where it is processed.
CC {ECO:0000250|UniProtKB:P18850}.
CC -!- SUBCELLULAR LOCATION: [Processed cyclic AMP-dependent transcription
CC factor ATF-6 alpha]: Nucleus {ECO:0000269|PubMed:22682248}. Note=Under
CC ER stress the cleaved N-terminal cytoplasmic domain translocates into
CC the nucleus (PubMed:22682248). THBS4 promotes its nuclear shuttling
CC (PubMed:22682248). {ECO:0000269|PubMed:22682248}.
CC -!- DOMAIN: The basic domain functions as a nuclear localization signal.
CC {ECO:0000250|UniProtKB:P18850}.
CC -!- DOMAIN: The basic leucine-zipper domain is sufficient for association
CC with the NF-Y trimer and binding to ERSE.
CC {ECO:0000250|UniProtKB:P18850}.
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 (By
CC similarity). {ECO:0000250|UniProtKB:P18850}.
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) (By similarity). {ECO:0000250|UniProtKB:P18850}.
CC -!- PTM: Ubiquitinated by RNF186 at Lys-139, which is required for pattern
CC recognition receptor-induced unfolded protein response-associated
CC outcomes. {ECO:0000250|UniProtKB:P18850}.
CC -!- DISRUPTION PHENOTYPE: Animals have normal retinal morphology and
CC function at a young age but develop rod and cone dysfunction with
CC increasing age. {ECO:0000269|PubMed:26029869}.
CC -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC29389.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK036335; BAC29389.1; ALT_INIT; mRNA.
DR EMBL; AC113490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125021; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC141028; AAI41029.1; -; mRNA.
DR CCDS; CCDS56653.1; -.
DR RefSeq; NP_001074773.1; NM_001081304.1.
DR AlphaFoldDB; F6VAN0; -.
DR SMR; F6VAN0; -.
DR BioGRID; 230540; 4.
DR DIP; DIP-59768N; -.
DR IntAct; F6VAN0; 4.
DR STRING; 10090.ENSMUSP00000027974; -.
DR GlyConnect; 2243; 2 N-Linked glycans (1 site).
DR GlyGen; F6VAN0; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; F6VAN0; -.
DR PhosphoSitePlus; F6VAN0; -.
DR MaxQB; F6VAN0; -.
DR PaxDb; F6VAN0; -.
DR PeptideAtlas; F6VAN0; -.
DR PRIDE; F6VAN0; -.
DR ProteomicsDB; 277213; -.
DR Antibodypedia; 20515; 652 antibodies from 46 providers.
DR DNASU; 226641; -.
DR Ensembl; ENSMUST00000027974; ENSMUSP00000027974; ENSMUSG00000026663.
DR GeneID; 226641; -.
DR KEGG; mmu:226641; -.
DR UCSC; uc007dmj.1; mouse.
DR CTD; 22926; -.
DR MGI; MGI:1926157; Atf6.
DR VEuPathDB; HostDB:ENSMUSG00000026663; -.
DR eggNOG; KOG4343; Eukaryota.
DR GeneTree; ENSGT00940000159221; -.
DR HOGENOM; CLU_026136_1_0_1; -.
DR InParanoid; F6VAN0; -.
DR OMA; LCHRPDE; -.
DR OrthoDB; 696548at2759; -.
DR PhylomeDB; F6VAN0; -.
DR TreeFam; TF316079; -.
DR Reactome; R-MMU-381033; ATF6 (ATF6-alpha) activates chaperones.
DR BioGRID-ORCS; 226641; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Atf6; mouse.
DR PRO; PR:F6VAN0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; F6VAN0; protein.
DR Bgee; ENSMUSG00000026663; Expressed in myocardium of ventricle and 248 other tissues.
DR Genevisible; F6VAN0; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR GO; GO:0001654; P:eye development; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903893; P:positive regulation of ATF6-mediated unfolded protein response; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; ISS: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; DNA-binding; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Isopeptide bond; Membrane; Nucleus; Reference proteome;
KW Signal-anchor; Transcription; Transcription regulation; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Unfolded protein response.
FT CHAIN 1..656
FT /note="Cyclic AMP-dependent transcription factor ATF-6
FT alpha"
FT /id="PRO_0000424336"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-dependent transcription factor
FT ATF-6 alpha"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT /id="PRO_0000424337"
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..656
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 293..356
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..137
FT /note="Transcription activation"
FT /evidence="ECO:0000305"
FT REGION 75..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..326
FT /note="Basic motif"
FT REGION 335..342
FT /note="Leucine-zipper"
FT REGION 391..429
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..575
FT /note="Interaction with THBS4"
FT /evidence="ECO:0000269|PubMed:22682248"
FT REGION 632..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..132
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..156
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 406..407
FT /note="Cleavage; by MBTPS1"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 629
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 75
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT CONFLICT 141
FT /note="V -> I (in Ref. 3; AAI41029)"
FT /evidence="ECO:0000305"
FT CONFLICT 237
FT /note="S -> P (in Ref. 3; AAI41029)"
FT /evidence="ECO:0000305"
FT CONFLICT 441
FT /note="L -> P (in Ref. 1; BAC29389)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 656 AA; 72694 MW; C3ADCF7DF2CB3EC9 CRC64;
MESPFSPVLP HGPDEDWEST LFAELGYFTD TDDVHFDAAH EAYENNFDHL NFDLDLMPWE
SDLWSPGSHF CSDMKAEPQP LSPASSSCSI SSPRSTDSCS STQHVPEELD LLSSSQSPLS
LYGDSCNSPS SVEPLKEEKP VTGPGNKTEH GLTPKKKIQM SSKPSVQPKP LLLPAAPKTQ
TNASVPAKAI IIQTLPALMP LAKQQSIISI QPAPTKGQTV LLSQPTVVQL QSPAVLSSAQ
PVLAVTGGAA QLPNHVVNVL PAPVVSSPVN GKLSVTKPVL QSATRSMGSD IAVLRRQQRM
IKNRESACQS RKKKKEYMLG LEARLKAALS ENEQLKKENG SLKRQLDEVV SENQRLKVPS
PKRRAVCVMI VLAFIMLNYG PMSMLEQESR RVKPSVSPAN QRRHLLEFSA KEVKDTSDGD
NQKDSYSYDH SVSNDKALMV LSEEPLLYMP PPPCQPLINT TESLRLNHEL RGWVHRHEVE
RTKSRRMTNS QQKARILQGA LEQGSNSQLM AVQYTETTSI SRNSGSELQV YYASPGSYQG
FFDAIRRRGD TFYVVSFRRD HLLLPATTHN KTTRPKMSIV LPAININDNV INGQDYEVMM
QIDCQVMDTR ILHIKSSSVP PYLRDHQRNQ TSTFFGSPPT TTETTHVVST IPESLQ
