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Entry version 222 (02 Dec 2020)
Sequence version 3 (17 Oct 2006)
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Protein

Cyclic AMP-dependent transcription factor ATF-4

Gene

ATF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and acts both as a regulator of normal metabolic and redox processes, and as a master transcription factor during the integrated stress response (ISR) (PubMed:1847461, PubMed:16682973, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress, such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:32132707). During the ISR, ATF4 protein is translated in response to eIF-2-alpha/EIF2S1 phosphorylation caused by stress, and acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:32132707). Protects cells against metabolic consequences of ER oxidation by promoting expression of genes linked to amino acid sufficiency and resistance to oxidative stress (By similarity). Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to amino acid deprivation or endoplasmic reticulum (ER) stress (PubMed:11960987). Together with DDIT3/CHOP, mediates ER-mediated cell death by promoting expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the unfolded protein response (UPR) in response to ER stress (By similarity). ATF4 and DDIT3/CHOP activate the transcription of TRIB3 and promote ER stress-induced neuronal cell-death by regulating the expression of BBC3/PUMA (PubMed:15775988, PubMed:18940792). During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed:26086088). Activates expression of genes required to promote cell recovery in response to mitochondrial stress (PubMed:32132706, PubMed:32132707). Independently of the ISR, also required for normal metabolic processes: plays a key role in embryonic lens formation, fetal liver hematopoiesis, bone development and synaptic plasticity (By similarity). Acts as a regulator of osteoblast differentiation in response to phosphorylation by RPS6KA3/RSK2: phosphorylation in osteoblasts enhances transactivation activity and promotes expression of osteoblast-specific genes and post-transcriptionally regulates the synthesis of Type I collagen, the main constituent of the bone matrix (PubMed:15109498). Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). Activates transcription of SIRT4 (By similarity). Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4 (By similarity). Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes (By similarity). Mainly acts as a transcriptional activator in cellular stress adaptation, but it can also act as a transcriptional repressor: acts as a regulator of synaptic plasticity by repressing transcription, thereby inhibiting induction and maintenance of long-term memory (By similarity). Regulates synaptic functions via interaction with DISC1 in neurons, which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (PubMed:31444471).By similarity10 Publications
(Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I.1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
P18848

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-380994, ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381042, PERK regulates gene expression
R-HSA-381183, ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency

SIGNOR Signaling Network Open Resource

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SIGNORi
P18848

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Cyclic AMP-dependent transcription factor ATF-4Curated
Short name:
cAMP-dependent transcription factor ATF-4Curated
Alternative name(s):
Activating transcription factor 41 Publication
Cyclic AMP-responsive element-binding protein 21 Publication
Short name:
CREB-21 Publication
Short name:
cAMP-responsive element-binding protein 21 Publication
Tax-responsive enhancer element-binding protein 671 Publication
Short name:
TaxREB671 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ATF41 PublicationImported
Synonyms:CREB21 Publication, TXREB1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 22

Organism-specific databases

Eukaryotic Pathogen and Host Database Resources

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EuPathDBi
HostDB:ENSG00000128272.14

Human Gene Nomenclature Database

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HGNCi
HGNC:786, ATF4

Online Mendelian Inheritance in Man (OMIM)

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MIMi
604064, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P18848

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi156P → A: Increased stability in low oxygen conditions; when associated with A-162, A-164, A-167 and A-174. 1 Publication1
Mutagenesisi162P → A: Increased stability in low oxygen conditions; when associated with A-156, A-164, A-167 and A-174. 1 Publication1
Mutagenesisi164P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-167 and A-174. 1 Publication1
Mutagenesisi167P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-174. 1 Publication1
Mutagenesisi174P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-167. 1 Publication1
Mutagenesisi213T → A: Does not affect phosphorylation by CK2. 1 Publication1
Mutagenesisi215S → A: Abolished phosphorylation by CK2 leading to increased stability. 1 Publication1
Mutagenesisi219S → N: Abolished phosphorylation on the betaTrCP degron motif, interaction with BTRC and subsequent ubiquitination. 1 Publication1
Mutagenesisi245S → A: Abolished phosphorylation by RPS6KA3/RSK2. 1 Publication1
Mutagenesisi311K → R: Decreased acetylation without affecting ubiquitination by SCF(BTRC). 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
468

Open Targets

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OpenTargetsi
ENSG00000128272

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA25086

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P18848, Tbio

Chemistry databases

Drug and drug target database

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DrugBanki
DB00852, Pseudoephedrine

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
ATF4

Domain mapping of disease mutations (DMDM)

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DMDMi
116241262

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000765841 – 351Cyclic AMP-dependent transcription factor ATF-4Add BLAST351

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki53Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei213PhosphothreonineBy similarity1
Modified residuei215Phosphoserine; by CK21 Publication1
Modified residuei219PhosphoserineBy similarity1
Modified residuei224PhosphoserineBy similarity1
Modified residuei231PhosphoserineBy similarity1
Modified residuei235PhosphoserineBy similarity1
Modified residuei2364-hydroxyprolineBy similarity1
Modified residuei245Phosphoserine; by RPS6KA31 Publication1
Modified residuei248PhosphoserineBy similarity1
Cross-linki259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki267Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki272Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei311N6-acetyllysine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4 (PubMed:11238952). Interaction with EP300/p300 inhibits ubiquitination by SCF(BTRC) (PubMed:16219772).2 Publications
Phosphorylation at Ser-245 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation (PubMed:15109498). Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity). Phosphorylation is promoted by mTORC1 (By similarity). Phosphorylation at Ser-215 by CK2 decreases its stability (PubMed:23123191). Phosphorylated by NEK6 (PubMed:20873783).By similarity3 Publications
Hydroxylated by PHD3, leading to decreased protein stability.1 Publication

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
P18848

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P18848

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P18848

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P18848

PeptideAtlas

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PeptideAtlasi
P18848

PRoteomics IDEntifications database

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PRIDEi
P18848

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
53615

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P18848

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P18848

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Specifically produced in response to various stress, such as endoplasmic reticulum (ER) stress, amino acid starvation, or oxidative stress (PubMed:27629041). In absence of stress, some upstream open reading frame (uORF) of this transcript is translated, thereby preventing its translation (PubMed:27629041). In response to stress and subsequent eIF-2-alpha/EIF2S1 phosphorylation, preferentially translated (PubMed:27629041).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000128272, Expressed in lower esophagus and 124 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P18848, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000128272, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Binds DNA as a homodimer and as a heterodimer (PubMed:11018027). Heterodimer; heterodimerizes with CEBPB (PubMed:11018027). Heterodimer; heterodimerizes with DDIT3/CHOP (PubMed:18940792).

Interacts with CEP290 (via an N-terminal region) (PubMed:16682973).

Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3 (PubMed:20873783, PubMed:21408167).

Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (By similarity).

Forms a heterodimer with TXLNG in osteoblasts (PubMed:15911876).

Interacts (via its DNA binding domain) with FOXO1 (C-terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production (By similarity).

Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (By similarity).

Interacts with ABRAXAS2 (PubMed:22974638).

Interacts with TRIB3, inhibiting the transactivation activity of ATF4 (By similarity).

Interacts with DISC1; which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (By similarity).

Interacts with EP300/p300; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (PubMed:16219772).

By similarity8 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
106958, 87 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-8, ATF4-CREB1 transcription factor complex
CPX-9, ATF1-ATF4 transcription factor complex

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
P18848

Database of interacting proteins

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DIPi
DIP-354N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P18848

Protein interaction database and analysis system

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IntActi
P18848, 62 interactors

Molecular INTeraction database

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MINTi
P18848

STRING: functional protein association networks

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STRINGi
9606.ENSP00000336790

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
P18848, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1351
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P18848

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
P18848

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini278 – 341bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni280 – 300Basic motifPROSITE-ProRule annotationAdd BLAST21
Regioni305 – 341Interaction with GABBR1By similarityAdd BLAST37
Regioni306 – 334Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili280 – 340Add BLAST61

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi215 – 224BetaTrCP degron motif1 Publication10

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the bZIP family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG4571, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00530000063801

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_055748_1_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P18848

Identification of Orthologs from Complete Genome Data

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OMAi
IVNPIGH

Database of Orthologous Groups

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OrthoDBi
1524842at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P18848

TreeFam database of animal gene trees

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TreeFami
TF316136

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR029811, ATF4
IPR004827, bZIP

The PANTHER Classification System

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PANTHERi
PTHR13044:SF32, PTHR13044:SF32, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF00170, bZIP_1, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00338, BRLZ, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS50217, BZIP, 1 hit
PS00036, BZIP_BASIC, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P18848-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTEMSFLSSE VLVGDLMSPF DQSGLGAEES LGLLDDYLEV AKHFKPHGFS
60 70 80 90 100
SDKAKAGSSE WLAVDGLVSP SNNSKEDAFS GTDWMLEKMD LKEFDLDALL
110 120 130 140 150
GIDDLETMPD DLLTTLDDTC DLFAPLVQET NKQPPQTVNP IGHLPESLTK
160 170 180 190 200
PDQVAPFTFL QPLPLSPGVL SSTPDHSFSL ELGSEVDITE GDRKPDYTAY
210 220 230 240 250
VAMIPQCIKE EDTPSDNDSG ICMSPESYLG SPQHSPSTRG SPNRSLPSPG
260 270 280 290 300
VLCGSARPKP YDPPGEKMVA AKVKGEKLDK KLKKMEQNKT AATRYRQKKR
310 320 330 340 350
AEQEALTGEC KELEKKNEAL KERADSLAKE IQYLKDLIEE VRKARGKKRV

P
Length:351
Mass (Da):38,590
Last modified:October 17, 2006 - v3
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3BBB7379DC3B0D07
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A6Q8PF56A0A6Q8PF56_HUMAN
Cyclic AMP-dependent transcription ...
ATF4
59Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PFH6A0A6Q8PFH6_HUMAN
Cyclic AMP-dependent transcription ...
ATF4
126Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PG17A0A6Q8PG17_HUMAN
Cyclic AMP-dependent transcription ...
ATF4
100Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PGY1A0A6Q8PGY1_HUMAN
Cyclic AMP-dependent transcription ...
ATF4
189Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A6Q8PHB3A0A6Q8PHB3_HUMAN
Cyclic AMP-dependent transcription ...
ATF4
121Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti284K → R no nucleotide entry (PubMed:2516827).Curated1
Sequence conflicti290T → R no nucleotide entry (PubMed:2516827).Curated1
Sequence conflicti329 – 331KEI → REK no nucleotide entry (PubMed:2516827).Curated3
Sequence conflicti338I → L no nucleotide entry (PubMed:2516827).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_02825322Q → P3 PublicationsCorresponds to variant dbSNP:rs4894Ensembl.1
Natural variantiVAR_029259258P → A. Corresponds to variant dbSNP:rs1803323EnsemblClinVar.1
Natural variantiVAR_014768322E → D. Corresponds to variant dbSNP:rs1803324EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
D90209 mRNA Translation: BAA14234.1
M86842 mRNA Translation: AAA52071.1
CR456384 mRNA Translation: CAG30270.1
AL022312 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60341.1
CH471095 Genomic DNA Translation: EAW60342.1
BC008090 mRNA Translation: AAH08090.1
BC011994 mRNA Translation: AAH11994.1
BC016855 mRNA Translation: AAH16855.1
BC022088 mRNA Translation: AAH22088.1
BC024775 mRNA Translation: AAH24775.1
BC044895 mRNA Translation: AAH44895.1
BC073754 mRNA Translation: AAH73754.1
BC073990 mRNA Translation: AAH73990.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS13996.1

Protein sequence database of the Protein Information Resource

More...
PIRi
A45377

NCBI Reference Sequences

More...
RefSeqi
NP_001666.2, NM_001675.4
NP_877962.1, NM_182810.2
XP_016884296.1, XM_017028807.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000337304; ENSP00000336790; ENSG00000128272
ENST00000396680; ENSP00000379912; ENSG00000128272
ENST00000404241; ENSP00000384587; ENSG00000128272

Database of genes from NCBI RefSeq genomes

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GeneIDi
468

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:468

UCSC genome browser

More...
UCSCi
uc003axz.4, human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D90209 mRNA Translation: BAA14234.1
M86842 mRNA Translation: AAA52071.1
CR456384 mRNA Translation: CAG30270.1
AL022312 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW60341.1
CH471095 Genomic DNA Translation: EAW60342.1
BC008090 mRNA Translation: AAH08090.1
BC011994 mRNA Translation: AAH11994.1
BC016855 mRNA Translation: AAH16855.1
BC022088 mRNA Translation: AAH22088.1
BC024775 mRNA Translation: AAH24775.1
BC044895 mRNA Translation: AAH44895.1
BC073754 mRNA Translation: AAH73754.1
BC073990 mRNA Translation: AAH73990.1
CCDSiCCDS13996.1
PIRiA45377
RefSeqiNP_001666.2, NM_001675.4
NP_877962.1, NM_182810.2
XP_016884296.1, XM_017028807.1

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CI6X-ray2.60A280-341[»]
SMRiP18848
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi106958, 87 interactors
ComplexPortaliCPX-8, ATF4-CREB1 transcription factor complex
CPX-9, ATF1-ATF4 transcription factor complex
CORUMiP18848
DIPiDIP-354N
ELMiP18848
IntActiP18848, 62 interactors
MINTiP18848
STRINGi9606.ENSP00000336790

Chemistry databases

DrugBankiDB00852, Pseudoephedrine

PTM databases

iPTMnetiP18848
PhosphoSitePlusiP18848

Polymorphism and mutation databases

BioMutaiATF4
DMDMi116241262

Proteomic databases

EPDiP18848
jPOSTiP18848
MassIVEiP18848
PaxDbiP18848
PeptideAtlasiP18848
PRIDEiP18848
ProteomicsDBi53615

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...
ABCDi
P18848, 1 sequenced antibody

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
12687, 1053 antibodies

The DNASU plasmid repository

More...
DNASUi
468

Genome annotation databases

EnsembliENST00000337304; ENSP00000336790; ENSG00000128272
ENST00000396680; ENSP00000379912; ENSG00000128272
ENST00000404241; ENSP00000384587; ENSG00000128272
GeneIDi468
KEGGihsa:468
UCSCiuc003axz.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
468
DisGeNETi468
EuPathDBiHostDB:ENSG00000128272.14

GeneCards: human genes, protein and diseases

More...
GeneCardsi
ATF4
HGNCiHGNC:786, ATF4
HPAiENSG00000128272, Low tissue specificity
MIMi604064, gene
neXtProtiNX_P18848
OpenTargetsiENSG00000128272
PharmGKBiPA25086

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4571, Eukaryota
GeneTreeiENSGT00530000063801
HOGENOMiCLU_055748_1_0_1
InParanoidiP18848
OMAiIVNPIGH
OrthoDBi1524842at2759
PhylomeDBiP18848
TreeFamiTF316136

Enzyme and pathway databases

PathwayCommonsiP18848
ReactomeiR-HSA-380994, ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381042, PERK regulates gene expression
R-HSA-381183, ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-9633012, Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-9648895, Response of EIF2AK1 (HRI) to heme deficiency
SIGNORiP18848

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
468, 436 hits in 849 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
ATF4, human
EvolutionaryTraceiP18848

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
ATF4

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
468
PharosiP18848, Tbio

Protein Ontology

More...
PROi
PR:P18848
RNActiP18848, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000128272, Expressed in lower esophagus and 124 other tissues
GenevisibleiP18848, HS

Family and domain databases

InterProiView protein in InterPro
IPR029811, ATF4
IPR004827, bZIP
PANTHERiPTHR13044:SF32, PTHR13044:SF32, 1 hit
PfamiView protein in Pfam
PF00170, bZIP_1, 1 hit
SMARTiView protein in SMART
SM00338, BRLZ, 1 hit
PROSITEiView protein in PROSITE
PS50217, BZIP, 1 hit
PS00036, BZIP_BASIC, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiATF4_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P18848
Secondary accession number(s): Q96AQ3, Q9UH31
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: October 17, 2006
Last modified: December 2, 2020
This is version 222 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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