ATF6A_RAT
ID ATF6A_RAT Reviewed; 656 AA.
AC G3V909; B5DF18;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 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).
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 (By
CC similarity). Interacts (via lumenal domain) with THBS1 (By similarity).
CC {ECO:0000250|UniProtKB:F6VAN0, ECO:0000250|UniProtKB:P18850}.
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 -!- 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 (By
CC similarity). {ECO:0000250|UniProtKB:F6VAN0,
CC 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 -!- SIMILARITY: Belongs to the bZIP family. ATF subfamily. {ECO:0000305}.
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DR EMBL; AABR06076112; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06076113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06076114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06076115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06076116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473958; EDM09246.1; -; Genomic_DNA.
DR EMBL; BC168890; AAI68890.1; -; mRNA.
DR RefSeq; NP_001100666.1; NM_001107196.1.
DR AlphaFoldDB; G3V909; -.
DR SMR; G3V909; -.
DR STRING; 10116.ENSRNOP00000032766; -.
DR ChEMBL; CHEMBL4105716; -.
DR GlyGen; G3V909; 3 sites.
DR PaxDb; G3V909; -.
DR PRIDE; G3V909; -.
DR GeneID; 304962; -.
DR KEGG; rno:304962; -.
DR CTD; 22926; -.
DR RGD; 1305471; Atf6.
DR VEuPathDB; HostDB:ENSRNOG00000024632; -.
DR eggNOG; KOG4343; Eukaryota.
DR HOGENOM; CLU_026136_1_0_1; -.
DR InParanoid; G3V909; -.
DR OMA; LCHRPDE; -.
DR OrthoDB; 696548at2759; -.
DR PhylomeDB; G3V909; -.
DR TreeFam; TF316079; -.
DR Reactome; R-RNO-381033; ATF6 (ATF6-alpha) activates chaperones.
DR PRO; PR:G3V909; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Proteomes; UP000234681; Chromosome 13.
DR Bgee; ENSRNOG00000024632; Expressed in liver and 19 other tissues.
DR Genevisible; G3V909; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
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:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
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:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
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:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IBA:GO_Central.
DR GO; GO:0001654; P:eye development; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:1903893; P:positive regulation of ATF6-mediated unfolded protein response; ISO:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; ISO:RGD.
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 2: Evidence at transcript 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_0000424338"
FT CHAIN 1..?
FT /note="Processed cyclic AMP-dependent transcription factor
FT ATF-6 alpha"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT /id="PRO_0000424339"
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 81..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 295..326
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 335..342
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 455..575
FT /note="Interaction with THBS4"
FT /evidence="ECO:0000250|UniProtKB:P18850"
FT REGION 632..656
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..127
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 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 580
FT /note="V -> G (in Ref. 3; AAI68890)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 656 AA; 72665 MW; 2FB1DE2B3EEE6E04 CRC64;
MESPFSPVLP HGPGEDWEST LFAELGYFTD TDDVQFDAAH ETYENNFDHL NFDLDLMPWE
SDIWSPSSHF CSDIKAEPQP LSPASSSCSV SSPRSTDSCS STQHVPEELD LLSSSQSPLS
LYGDSCHSPS SAEPLKEEKP VTGPGNKTEH GLTPKKKIQM SSKPSVQPKP LLLPAAPKTP
ANASVPAKTI IIQTLPALMP LAKQQSIISI QPAPTKGQTV LLSQPAVVQL QTPGVLPSAQ
PVLAVTGGAT QLPNHVVNVV PAPVVNSPVN GKLCVTKPVL QSSTRSTGSD IAVLRRQQRM
IKNRESACQS RKKKKEYMLG LEARLKAALS ENEQLKKENG SLKRQLDQVV SENQRLKVPS
PKRRAVCVMI VLAFIMLNYG PMSMLEQDSR RVKPSVSPAN QRRHLLEFSA KEVKDTSDGD
NQKNSYRYDH SVSNDKALMV LSEEPLLYIP PPPCQPLINT TESLRLNHEL RGWVHRHEVE
RTKSRRMTNS QQKTRILQGA LEQGSNSQLM AVQYTETTSI SRNSGSELQV YYASPGSYQG
FFDAIRRRGD TFYVVSFRRD HLLLPATTHN KTTRPKMSIV LPAININDNV INGQDYEVMM
QIDCQVMDTR ILHIKSSSVP PYLRDHQRNQ TSTFFGSPPT ATETTHVVST LPESVQ
