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Protein

Cyclic AMP-dependent transcription factor ATF-6 alpha

Gene

Atf6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. 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. May play a role in foveal development and cone function in the retina (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation, Unfolded protein response

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-RNO-381033. ATF6 (ATF6-alpha) activates chaperones.

Names & Taxonomyi

Protein namesi
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:
Gene namesi
Name:Atf6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 13

Organism-specific databases

RGDi1305471. Atf6.

Subcellular locationi

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.

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei378 – 398Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini399 – 656LumenalSequence analysisAdd BLAST258

GO - Cellular componenti

  • Golgi apparatus Source: Ensembl
  • integral component of endoplasmic reticulum membrane Source: Ensembl
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004243381 – 656Cyclic AMP-dependent transcription factor ATF-6 alphaAdd BLAST656
ChainiPRO_00004243391 – ?Processed cyclic AMP-dependent transcription factor ATF-6 alphaBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi459N-linked (GlcNAc...)Sequence analysis1
Glycosylationi570N-linked (GlcNAc...)Sequence analysis1
Glycosylationi629N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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 (By similarity).By similarity
N-glycosylated. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR) (By similarity).By similarity
Phosphorylated in vitro by MAPK14/P38MAPK.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei406 – 407Cleavage; by PS1By similarity2

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiG3V909.

Expressioni

Gene expression databases

BgeeiENSRNOG00000024632.
GenevisibleiG3V909. RN.

Interactioni

Subunit structurei

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. Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation. Interacts with XBP1; the interaction occurs in a ER stress-dependent manner (By similarity).By similarity

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000032766.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini293 – 356bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 137Transcription activationBy similarityAdd BLAST137
Regioni295 – 326Basic motifPROSITE-ProRule annotationAdd BLAST32
Regioni335 – 342Leucine-zipperPROSITE-ProRule annotation8
Regioni455 – 575Interaction with THBS4By similarityAdd BLAST121

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi61 – 131Ser-richAdd BLAST71
Compositional biasi450 – 453Poly-Pro4

Domaini

The basic domain functions as a nuclear localization signal.By similarity
The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE.By similarity

Sequence similaritiesi

Belongs to the bZIP family. ATF subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4343. Eukaryota.
ENOG410ZAAP. LUCA.
GeneTreeiENSGT00530000063762.
HOGENOMiHOG000253938.
HOVERGENiHBG108357.
InParanoidiG3V909.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
PhylomeDBiG3V909.
TreeFamiTF316079.

Family and domain databases

InterProiIPR029801. ATF6A.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF116. PTHR22952:SF116. 2 hits.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

G3V909-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESPFSPVLP HGPGEDWEST LFAELGYFTD TDDVQFDAAH ETYENNFDHL
60 70 80 90 100
NFDLDLMPWE SDIWSPSSHF CSDIKAEPQP LSPASSSCSV SSPRSTDSCS
110 120 130 140 150
STQHVPEELD LLSSSQSPLS LYGDSCHSPS SAEPLKEEKP VTGPGNKTEH
160 170 180 190 200
GLTPKKKIQM SSKPSVQPKP LLLPAAPKTP ANASVPAKTI IIQTLPALMP
210 220 230 240 250
LAKQQSIISI QPAPTKGQTV LLSQPAVVQL QTPGVLPSAQ PVLAVTGGAT
260 270 280 290 300
QLPNHVVNVV PAPVVNSPVN GKLCVTKPVL QSSTRSTGSD IAVLRRQQRM
310 320 330 340 350
IKNRESACQS RKKKKEYMLG LEARLKAALS ENEQLKKENG SLKRQLDQVV
360 370 380 390 400
SENQRLKVPS PKRRAVCVMI VLAFIMLNYG PMSMLEQDSR RVKPSVSPAN
410 420 430 440 450
QRRHLLEFSA KEVKDTSDGD NQKNSYRYDH SVSNDKALMV LSEEPLLYIP
460 470 480 490 500
PPPCQPLINT TESLRLNHEL RGWVHRHEVE RTKSRRMTNS QQKTRILQGA
510 520 530 540 550
LEQGSNSQLM AVQYTETTSI SRNSGSELQV YYASPGSYQG FFDAIRRRGD
560 570 580 590 600
TFYVVSFRRD HLLLPATTHN KTTRPKMSIV LPAININDNV INGQDYEVMM
610 620 630 640 650
QIDCQVMDTR ILHIKSSSVP PYLRDHQRNQ TSTFFGSPPT ATETTHVVST

LPESVQ
Length:656
Mass (Da):72,665
Last modified:November 16, 2011 - v1
Checksum:i2FB1DE2B3EEE6E04
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti580V → G in AAI68890 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06076112 Genomic DNA. No translation available.
AABR06076113 Genomic DNA. No translation available.
AABR06076114 Genomic DNA. No translation available.
AABR06076115 Genomic DNA. No translation available.
AABR06076116 Genomic DNA. No translation available.
CH473958 Genomic DNA. Translation: EDM09246.1.
BC168890 mRNA. Translation: AAI68890.1.
RefSeqiNP_001100666.1. NM_001107196.1.
UniGeneiRn.15235.

Genome annotation databases

EnsembliENSRNOT00000029202; ENSRNOP00000032766; ENSRNOG00000024632.
GeneIDi304962.
KEGGirno:304962.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06076112 Genomic DNA. No translation available.
AABR06076113 Genomic DNA. No translation available.
AABR06076114 Genomic DNA. No translation available.
AABR06076115 Genomic DNA. No translation available.
AABR06076116 Genomic DNA. No translation available.
CH473958 Genomic DNA. Translation: EDM09246.1.
BC168890 mRNA. Translation: AAI68890.1.
RefSeqiNP_001100666.1. NM_001107196.1.
UniGeneiRn.15235.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000032766.

Proteomic databases

PaxDbiG3V909.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000029202; ENSRNOP00000032766; ENSRNOG00000024632.
GeneIDi304962.
KEGGirno:304962.

Organism-specific databases

CTDi22926.
RGDi1305471. Atf6.

Phylogenomic databases

eggNOGiKOG4343. Eukaryota.
ENOG410ZAAP. LUCA.
GeneTreeiENSGT00530000063762.
HOGENOMiHOG000253938.
HOVERGENiHBG108357.
InParanoidiG3V909.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
PhylomeDBiG3V909.
TreeFamiTF316079.

Enzyme and pathway databases

ReactomeiR-RNO-381033. ATF6 (ATF6-alpha) activates chaperones.

Miscellaneous databases

PROiG3V909.

Gene expression databases

BgeeiENSRNOG00000024632.
GenevisibleiG3V909. RN.

Family and domain databases

InterProiIPR029801. ATF6A.
IPR004827. bZIP.
[Graphical view]
PANTHERiPTHR22952:SF116. PTHR22952:SF116. 2 hits.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATF6A_RAT
AccessioniPrimary (citable) accession number: G3V909
Secondary accession number(s): B5DF18
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2013
Last sequence update: November 16, 2011
Last modified: November 30, 2016
This is version 43 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.