Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cyclic AMP-dependent transcription factor ATF-6 alpha

Gene

Atf6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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-MMU-381033. 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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1926157. Atf6.

Subcellular locationi

Processed 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 377377CytoplasmicSequence analysisAdd
BLAST
Transmembranei378 – 39821Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini399 – 656258LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum Source: ParkinsonsUK-UCL
  • Golgi apparatus Source: MGI
  • integral component of endoplasmic reticulum membrane Source: MGI
  • membrane Source: MGI
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Animals have normal retinal morphology and function at a young age but develop rod and cone dysfunction with increasing age.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 656656Cyclic AMP-dependent transcription factor ATF-6 alphaPRO_0000424336Add
BLAST
Chaini1 – ?Processed cyclic AMP-dependent transcription factor ATF-6 alphaPRO_0000424337

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi459 – 4591N-linked (GlcNAc...)Sequence analysis
Glycosylationi570 – 5701N-linked (GlcNAc...)Sequence analysis
Glycosylationi629 – 6291N-linked (GlcNAc...)Sequence analysis

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei406 – 4072Cleavage; by PS1By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiF6VAN0.
PaxDbiF6VAN0.
PeptideAtlasiF6VAN0.

PTM databases

iPTMnetiF6VAN0.
PhosphoSiteiF6VAN0.

Expressioni

Gene expression databases

BgeeiENSMUSG00000026663.
GenevisibleiF6VAN0. MM.

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 with XBP1 isoform 2; the interaction occurs in a ER stress-dependent manner (By similarity). Interacts (via lumenal domain) with THBS1 (PubMed:22682248). Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation (PubMed:22682248).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Thbs4Q9Z1T23EBI-6171558,EBI-6171531

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230540. 1 interaction.
DIPiDIP-59768N.
IntActiF6VAN0. 3 interactions.
STRINGi10090.ENSMUSP00000027974.

Structurei

3D structure databases

ProteinModelPortaliF6VAN0.
SMRiF6VAN0. Positions 301-344.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini293 – 35664bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 137137Transcription activationBy similarityAdd
BLAST
Regioni295 – 32632Basic motifAdd
BLAST
Regioni335 – 3428Leucine-zipper
Regioni455 – 575121Interaction with THBS4Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi94 – 14451Ser-richAdd
BLAST

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.
InParanoidiF6VAN0.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
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.

F6VAN0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESPFSPVLP HGPDEDWEST LFAELGYFTD TDDVHFDAAH EAYENNFDHL
60 70 80 90 100
NFDLDLMPWE SDLWSPGSHF CSDMKAEPQP LSPASSSCSI SSPRSTDSCS
110 120 130 140 150
STQHVPEELD LLSSSQSPLS LYGDSCNSPS SVEPLKEEKP VTGPGNKTEH
160 170 180 190 200
GLTPKKKIQM SSKPSVQPKP LLLPAAPKTQ TNASVPAKAI IIQTLPALMP
210 220 230 240 250
LAKQQSIISI QPAPTKGQTV LLSQPTVVQL QSPAVLSSAQ PVLAVTGGAA
260 270 280 290 300
QLPNHVVNVL PAPVVSSPVN GKLSVTKPVL QSATRSMGSD IAVLRRQQRM
310 320 330 340 350
IKNRESACQS RKKKKEYMLG LEARLKAALS ENEQLKKENG SLKRQLDEVV
360 370 380 390 400
SENQRLKVPS PKRRAVCVMI VLAFIMLNYG PMSMLEQESR RVKPSVSPAN
410 420 430 440 450
QRRHLLEFSA KEVKDTSDGD NQKDSYSYDH SVSNDKALMV LSEEPLLYMP
460 470 480 490 500
PPPCQPLINT TESLRLNHEL RGWVHRHEVE RTKSRRMTNS QQKARILQGA
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 TTETTHVVST

IPESLQ
Length:656
Mass (Da):72,694
Last modified:October 3, 2012 - v2
Checksum:iC3ADCF7DF2CB3EC9
GO

Sequence cautioni

The sequence BAC29389 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti141 – 1411V → I in AAI41029 (PubMed:15489334).Curated
Sequence conflicti237 – 2371S → P in AAI41029 (PubMed:15489334).Curated
Sequence conflicti441 – 4411L → P in BAC29389 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036335 mRNA. Translation: BAC29389.1. Different initiation.
AC113490 Genomic DNA. No translation available.
AC125021 Genomic DNA. No translation available.
BC141028 mRNA. Translation: AAI41029.1.
CCDSiCCDS56653.1.
RefSeqiNP_001074773.1. NM_001081304.1.
UniGeneiMm.377046.

Genome annotation databases

EnsembliENSMUST00000027974; ENSMUSP00000027974; ENSMUSG00000026663.
GeneIDi226641.
KEGGimmu:226641.
UCSCiuc007dmj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036335 mRNA. Translation: BAC29389.1. Different initiation.
AC113490 Genomic DNA. No translation available.
AC125021 Genomic DNA. No translation available.
BC141028 mRNA. Translation: AAI41029.1.
CCDSiCCDS56653.1.
RefSeqiNP_001074773.1. NM_001081304.1.
UniGeneiMm.377046.

3D structure databases

ProteinModelPortaliF6VAN0.
SMRiF6VAN0. Positions 301-344.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi230540. 1 interaction.
DIPiDIP-59768N.
IntActiF6VAN0. 3 interactions.
STRINGi10090.ENSMUSP00000027974.

PTM databases

iPTMnetiF6VAN0.
PhosphoSiteiF6VAN0.

Proteomic databases

MaxQBiF6VAN0.
PaxDbiF6VAN0.
PeptideAtlasiF6VAN0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027974; ENSMUSP00000027974; ENSMUSG00000026663.
GeneIDi226641.
KEGGimmu:226641.
UCSCiuc007dmj.1. mouse.

Organism-specific databases

CTDi22926.
MGIiMGI:1926157. Atf6.

Phylogenomic databases

eggNOGiKOG4343. Eukaryota.
ENOG410ZAAP. LUCA.
GeneTreeiENSGT00530000063762.
HOGENOMiHOG000253938.
HOVERGENiHBG108357.
InParanoidiF6VAN0.
KOiK09054.
OMAiIIIQTVP.
OrthoDBiEOG091G0JCT.
TreeFamiTF316079.

Enzyme and pathway databases

ReactomeiR-MMU-381033. ATF6-alpha activates chaperones.

Miscellaneous databases

ChiTaRSiAtf6. mouse.
PROiF6VAN0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026663.
GenevisibleiF6VAN0. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: F6VAN0
Secondary accession number(s): B2RU98, Q8BZ84
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2013
Last sequence update: October 3, 2012
Last modified: September 7, 2016
This is version 49 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.