UniProtKB - P18848 (ATF4_HUMAN)
Cyclic AMP-dependent transcription factor ATF-4
ATF4
Functioni
Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:17684156, 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 ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:32132706, PubMed:32132707).
Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity).
Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088).
Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987).
However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792).
Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity).
Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and promotes ER stress-induced neuronal cell death by regulating the expression of BBC3/PUMA in response to ER stress (PubMed:15775988).
May cooperate with the UPR transcriptional regulator QRICH1 to regulate ER protein homeostasis which is critical for cell viability in response to ER stress (PubMed:33384352).
In the absence of stress, ATF4 translation is at low levels and it is required for normal metabolic processes such as 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 similarity11 Publications(Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I.
1 PublicationGO - Molecular functioni
- cAMP response element binding protein binding Source: UniProtKB
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: ParkinsonsUK-UCL
- general transcription initiation factor binding Source: Ensembl
- identical protein binding Source: IntAct
- leucine zipper domain binding Source: ParkinsonsUK-UCL
- promoter-specific chromatin binding Source: MGI
- protein C-terminus binding Source: Ensembl
- protein heterodimerization activity Source: UniProtKB
- protein kinase binding Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ParkinsonsUK-UCL
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific DNA binding Source: ParkinsonsUK-UCL
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: ParkinsonsUK-UCL
GO - Biological processi
- bone mineralization Source: UniProtKB
- cellular calcium ion homeostasis Source: Ensembl
- cellular response to amino acid starvation Source: UniProtKB
- cellular response to dopamine Source: CAFA
- cellular response to glucose starvation Source: ParkinsonsUK-UCL
- cellular response to leucine starvation Source: MGI
- cellular response to oxidative stress Source: UniProtKB
- cellular response to oxygen-glucose deprivation Source: Ensembl
- cellular response to UV Source: UniProtKB
- circadian regulation of gene expression Source: UniProtKB
- embryonic hemopoiesis Source: UniProtKB
- endoplasmic reticulum unfolded protein response Source: UniProtKB
- gamma-aminobutyric acid signaling pathway Source: Ensembl
- gluconeogenesis Source: UniProtKB
- HRI-mediated signaling Source: UniProtKB
- integrated stress response signaling Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: UniProtKB
- L-asparagine metabolic process Source: UniProtKB
- lens fiber cell morphogenesis Source: UniProtKB
- mRNA transcription by RNA polymerase II Source: UniProtKB
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCL
- negative regulation of potassium ion transport Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- negative regulation of translational initiation in response to stress Source: UniProtKB
- neuron differentiation Source: Ensembl
- PERK-mediated unfolded protein response Source: UniProtKB
- positive regulation of apoptotic process Source: ParkinsonsUK-UCL
- positive regulation of biomineral tissue development Source: Ensembl
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of neuron apoptotic process Source: UniProtKB
- positive regulation of sodium-dependent phosphate transport Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase I Source: ParkinsonsUK-UCL
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance Source: ParkinsonsUK-UCL
- positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
- positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: ParkinsonsUK-UCL
- positive regulation of transcription from RNA polymerase II promoter in response to stress Source: ParkinsonsUK-UCL
- positive regulation of vascular associated smooth muscle cell apoptotic process Source: Ensembl
- positive regulation of vascular endothelial growth factor production Source: ParkinsonsUK-UCL
- regulation of osteoblast differentiation Source: UniProtKB
- regulation of synaptic plasticity Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- response to endoplasmic reticulum stress Source: UniProtKB
- response to manganese-induced endoplasmic reticulum stress Source: Ensembl
- response to nutrient levels Source: UniProtKB
- response to toxic substance Source: Ensembl
- transcription by RNA polymerase II Source: UniProtKB
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P18848 |
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 |
SignaLinki | P18848 |
SIGNORi | P18848 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyclic AMP-dependent transcription factor ATF-4CuratedShort 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 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:786, ATF4 |
MIMi | 604064, gene |
neXtProti | NX_P18848 |
VEuPathDBi | HostDB:ENSG00000128272 |
Subcellular locationi
Nucleus
- Nucleus 4 Publications
- Nucleus speckle 1 Publication
Plasma membrane
- Cell membrane By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytoskeleton
- centrosome 1 Publication
Note: Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Colocalizes with NEK6 at the centrosome (PubMed:20873783). Recruited to nuclear speckles following interaction with EP300/p300 (PubMed:16219772).By similarity2 Publications
Cytoskeleton
- microtubule organizing center Source: UniProtKB-SubCell
Nucleus
- ATF1-ATF4 transcription factor complex Source: ParkinsonsUK-UCL
- ATF4-CREB1 transcription factor complex Source: ParkinsonsUK-UCL
- CHOP-ATF4 complex Source: ParkinsonsUK-UCL
- nuclear periphery Source: ParkinsonsUK-UCL
- nuclear speck Source: UniProtKB-SubCell
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
- RNA polymerase II transcription regulator complex Source: ComplexPortal
Plasma Membrane
- dendrite membrane Source: Ensembl
Other locations
- chromatin Source: NTNU_SB
- cytoplasm Source: ParkinsonsUK-UCL
- Lewy body core Source: ParkinsonsUK-UCL
- neuron projection Source: ParkinsonsUK-UCL
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 156 | P → A: Increased stability in low oxygen conditions; when associated with A-162, A-164, A-167 and A-174. 1 Publication | 1 | |
Mutagenesisi | 162 | P → A: Increased stability in low oxygen conditions; when associated with A-156, A-164, A-167 and A-174. 1 Publication | 1 | |
Mutagenesisi | 164 | P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-167 and A-174. 1 Publication | 1 | |
Mutagenesisi | 167 | P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-174. 1 Publication | 1 | |
Mutagenesisi | 174 | P → A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-167. 1 Publication | 1 | |
Mutagenesisi | 213 | T → A: Does not affect phosphorylation by CK2. 1 Publication | 1 | |
Mutagenesisi | 215 | S → A: Abolished phosphorylation by CK2 leading to increased stability. 1 Publication | 1 | |
Mutagenesisi | 219 | S → N: Abolished phosphorylation on the betaTrCP degron motif, interaction with BTRC and subsequent ubiquitination. 1 Publication | 1 | |
Mutagenesisi | 245 | S → A: Abolished phosphorylation by RPS6KA3/RSK2. 1 Publication | 1 | |
Mutagenesisi | 311 | K → R: Decreased acetylation without affecting ubiquitination by SCF(BTRC). 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 468 |
OpenTargetsi | ENSG00000128272 |
PharmGKBi | PA25086 |
Miscellaneous databases
Pharosi | P18848, Tbio |
Chemistry databases
DrugBanki | DB00852, Pseudoephedrine |
Genetic variation databases
BioMutai | ATF4 |
DMDMi | 116241262 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076584 | 1 – 351 | Cyclic AMP-dependent transcription factor ATF-4Add BLAST | 351 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 53 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 213 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 215 | Phosphoserine; by CK21 Publication | 1 | |
Modified residuei | 219 | PhosphoserineBy similarity | 1 | |
Modified residuei | 224 | PhosphoserineBy similarity | 1 | |
Modified residuei | 231 | PhosphoserineBy similarity | 1 | |
Modified residuei | 235 | PhosphoserineBy similarity | 1 | |
Modified residuei | 236 | 4-hydroxyprolineBy similarity | 1 | |
Modified residuei | 245 | Phosphoserine; by RPS6KA31 Publication | 1 | |
Modified residuei | 248 | PhosphoserineBy similarity | 1 | |
Cross-linki | 259 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 267 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 272 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 311 | N6-acetyllysine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P18848 |
jPOSTi | P18848 |
MassIVEi | P18848 |
PaxDbi | P18848 |
PeptideAtlasi | P18848 |
PRIDEi | P18848 |
ProteomicsDBi | 53615 |
PTM databases
iPTMneti | P18848 |
PhosphoSitePlusi | P18848 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000128272, Expressed in lower esophagus and 125 other tissues |
Genevisiblei | P18848, HS |
Organism-specific databases
HPAi | ENSG00000128272, Low tissue specificity |
Interactioni
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 PublicationsBinary interactionsi
P18848
GO - Molecular functioni
- cAMP response element binding protein binding Source: UniProtKB
- general transcription initiation factor binding Source: Ensembl
- identical protein binding Source: IntAct
- leucine zipper domain binding Source: ParkinsonsUK-UCL
- protein C-terminus binding Source: Ensembl
- protein heterodimerization activity Source: UniProtKB
- protein kinase binding Source: UniProtKB
- RNA polymerase II-specific DNA-binding transcription factor binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 106958, 90 interactors |
ComplexPortali | CPX-6385, bZIP transcription factor complex, ATF3-ATF4 CPX-6408, bZIP transcription factor complex, ATF2-ATF4 CPX-6521, bZIP transcription factor complex, ATF4-ATF4 CPX-6522, bZIP transcription factor complex, ATF4-BATF CPX-6523, bZIP transcription factor complex, ATF4-BATF2 CPX-6524, bZIP transcription factor complex, ATF4-BATF3 CPX-6525, bZIP transcription factor complex, ATF4-CEBPA CPX-6526, bZIP transcription factor complex, ATF4-CEBPB CPX-6527, bZIP transcription factor complex, ATF4-CEBPG CPX-6528, bZIP transcription factor complex, ATF4-CEBPD CPX-6529, bZIP transcription factor complex, ATF4-CEBPE CPX-6541, bZIP transcription factor complex, ATF4-CREB3 CPX-6542, bZIP transcription factor complex, ATF4-CREBZF CPX-6543, bZIP transcription factor complex, ATF4-DDIT3 CPX-6562, bZIP transcription factor complex, ATF4-JUN CPX-6563, bZIP transcription factor complex, ATF4-JUNB CPX-6564, bZIP transcription factor complex, ATF4-FOS CPX-6565, bZIP transcription factor complex, ATF4-FOSL1 CPX-6566, bZIP transcription factor complex, ATF4-MAF CPX-6567, bZIP transcription factor complex, ATF4-MAFB CPX-6568, bZIP transcription factor complex, ATF4-NFE2 CPX-6569, bZIP transcription factor complex, ATF4-NFE2L1 CPX-6570, bZIP transcription factor complex, ATF4-NFE2L2 CPX-6572, bZIP transcription factor complex, ATF4-NFE2L3 CPX-8, bZIP transcription factor complex, ATF4-CREB1 CPX-9, bZIP transcription factor complex, ATF1-ATF4 |
CORUMi | P18848 |
DIPi | DIP-354N |
ELMi | P18848 |
IntActi | P18848, 80 interactors |
MINTi | P18848 |
STRINGi | 9606.ENSP00000336790 |
Miscellaneous databases
RNActi | P18848, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P18848 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P18848 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 278 – 341 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 210 – 268 | DisorderedSequence analysisAdd BLAST | 59 | |
Regioni | 280 – 300 | Basic motifPROSITE-ProRule annotationAdd BLAST | 21 | |
Regioni | 305 – 341 | Interaction with GABBR1By similarityAdd BLAST | 37 | |
Regioni | 306 – 334 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 29 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 280 – 340 | Add BLAST | 61 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 215 – 224 | BetaTrCP degron motif1 Publication | 10 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 217 – 245 | Polar residuesSequence analysisAdd BLAST | 29 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG4571, Eukaryota |
GeneTreei | ENSGT00530000063801 |
HOGENOMi | CLU_055748_1_0_1 |
InParanoidi | P18848 |
OMAi | IVNPIGH |
OrthoDBi | 1524842at2759 |
PhylomeDBi | P18848 |
TreeFami | TF316136 |
Family and domain databases
InterProi | View protein in InterPro IPR029811, ATF4 IPR004827, bZIP |
PANTHERi | PTHR13044:SF32, PTHR13044:SF32, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A6Q8PG17 | A0A6Q8PG17_HUMAN | Activating transcription factor 4 | ATF4 | 322 | Annotation score: | ||
B4DJD4 | B4DJD4_HUMAN | Activating transcription factor 4 | ATF4 | 267 | Annotation score: | ||
A0A6Q8PFH6 | A0A6Q8PFH6_HUMAN | Cyclic AMP-dependent transcription ... | ATF4 | 126 | Annotation score: | ||
A0A6Q8PGY1 | A0A6Q8PGY1_HUMAN | Cyclic AMP-dependent transcription ... | ATF4 | 189 | Annotation score: | ||
A0A6Q8PHB3 | A0A6Q8PHB3_HUMAN | Cyclic AMP-dependent transcription ... | ATF4 | 121 | Annotation score: | ||
A0A7P0Z4J5 | A0A7P0Z4J5_HUMAN | Cyclic AMP-dependent transcription ... | ATF4 | 97 | Annotation score: | ||
A0A6Q8PF56 | A0A6Q8PF56_HUMAN | Cyclic AMP-dependent transcription ... | ATF4 | 59 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 284 | K → R no nucleotide entry (PubMed:2516827).Curated | 1 | |
Sequence conflicti | 290 | T → R no nucleotide entry (PubMed:2516827).Curated | 1 | |
Sequence conflicti | 329 – 331 | KEI → REK no nucleotide entry (PubMed:2516827).Curated | 3 | |
Sequence conflicti | 338 | I → L no nucleotide entry (PubMed:2516827).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_028253 | 22 | Q → P3 PublicationsCorresponds to variant dbSNP:rs4894Ensembl. | 1 | |
Natural variantiVAR_029259 | 258 | P → A. Corresponds to variant dbSNP:rs1803323EnsemblClinVar. | 1 | |
Natural variantiVAR_014768 | 322 | E → D. Corresponds to variant dbSNP:rs1803324EnsemblClinVar. | 1 |
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 |
CCDSi | CCDS13996.1 |
PIRi | A45377 |
RefSeqi | NP_001666.2, NM_001675.4 NP_877962.1, NM_182810.2 XP_016884296.1, XM_017028807.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS13996.1 |
PIRi | A45377 |
RefSeqi | NP_001666.2, NM_001675.4 NP_877962.1, NM_182810.2 XP_016884296.1, XM_017028807.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1CI6 | X-ray | 2.60 | A | 280-341 | [»] | |
SMRi | P18848 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106958, 90 interactors |
ComplexPortali | CPX-6385, bZIP transcription factor complex, ATF3-ATF4 CPX-6408, bZIP transcription factor complex, ATF2-ATF4 CPX-6521, bZIP transcription factor complex, ATF4-ATF4 CPX-6522, bZIP transcription factor complex, ATF4-BATF CPX-6523, bZIP transcription factor complex, ATF4-BATF2 CPX-6524, bZIP transcription factor complex, ATF4-BATF3 CPX-6525, bZIP transcription factor complex, ATF4-CEBPA CPX-6526, bZIP transcription factor complex, ATF4-CEBPB CPX-6527, bZIP transcription factor complex, ATF4-CEBPG CPX-6528, bZIP transcription factor complex, ATF4-CEBPD CPX-6529, bZIP transcription factor complex, ATF4-CEBPE CPX-6541, bZIP transcription factor complex, ATF4-CREB3 CPX-6542, bZIP transcription factor complex, ATF4-CREBZF CPX-6543, bZIP transcription factor complex, ATF4-DDIT3 CPX-6562, bZIP transcription factor complex, ATF4-JUN CPX-6563, bZIP transcription factor complex, ATF4-JUNB CPX-6564, bZIP transcription factor complex, ATF4-FOS CPX-6565, bZIP transcription factor complex, ATF4-FOSL1 CPX-6566, bZIP transcription factor complex, ATF4-MAF CPX-6567, bZIP transcription factor complex, ATF4-MAFB CPX-6568, bZIP transcription factor complex, ATF4-NFE2 CPX-6569, bZIP transcription factor complex, ATF4-NFE2L1 CPX-6570, bZIP transcription factor complex, ATF4-NFE2L2 CPX-6572, bZIP transcription factor complex, ATF4-NFE2L3 CPX-8, bZIP transcription factor complex, ATF4-CREB1 CPX-9, bZIP transcription factor complex, ATF1-ATF4 |
CORUMi | P18848 |
DIPi | DIP-354N |
ELMi | P18848 |
IntActi | P18848, 80 interactors |
MINTi | P18848 |
STRINGi | 9606.ENSP00000336790 |
Chemistry databases
DrugBanki | DB00852, Pseudoephedrine |
PTM databases
iPTMneti | P18848 |
PhosphoSitePlusi | P18848 |
Genetic variation databases
BioMutai | ATF4 |
DMDMi | 116241262 |
Proteomic databases
EPDi | P18848 |
jPOSTi | P18848 |
MassIVEi | P18848 |
PaxDbi | P18848 |
PeptideAtlasi | P18848 |
PRIDEi | P18848 |
ProteomicsDBi | 53615 |
Protocols and materials databases
ABCDi | P18848, 1 sequenced antibody |
Antibodypediai | 12687, 1126 antibodies from 46 providers |
DNASUi | 468 |
Genome annotation databases
Organism-specific databases
CTDi | 468 |
DisGeNETi | 468 |
GeneCardsi | ATF4 |
HGNCi | HGNC:786, ATF4 |
HPAi | ENSG00000128272, Low tissue specificity |
MIMi | 604064, gene |
neXtProti | NX_P18848 |
OpenTargetsi | ENSG00000128272 |
PharmGKBi | PA25086 |
VEuPathDBi | HostDB:ENSG00000128272 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4571, Eukaryota |
GeneTreei | ENSGT00530000063801 |
HOGENOMi | CLU_055748_1_0_1 |
InParanoidi | P18848 |
OMAi | IVNPIGH |
OrthoDBi | 1524842at2759 |
PhylomeDBi | P18848 |
TreeFami | TF316136 |
Enzyme and pathway databases
PathwayCommonsi | P18848 |
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 |
SignaLinki | P18848 |
SIGNORi | P18848 |
Miscellaneous databases
BioGRID-ORCSi | 468, 443 hits in 1039 CRISPR screens |
ChiTaRSi | ATF4, human |
EvolutionaryTracei | P18848 |
GeneWikii | ATF4 |
GenomeRNAii | 468 |
Pharosi | P18848, Tbio |
PROi | PR:P18848 |
RNActi | P18848, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000128272, Expressed in lower esophagus and 125 other tissues |
Genevisiblei | P18848, HS |
Family and domain databases
InterProi | View protein in InterPro IPR029811, ATF4 IPR004827, bZIP |
PANTHERi | PTHR13044:SF32, PTHR13044:SF32, 1 hit |
Pfami | View protein in Pfam PF00170, bZIP_1, 1 hit |
SMARTi | View protein in SMART SM00338, BRLZ, 1 hit |
PROSITEi | View protein in PROSITE PS50217, BZIP, 1 hit PS00036, BZIP_BASIC, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ATF4_HUMAN | |
Accessioni | P18848Primary (citable) accession number: P18848 Secondary accession number(s): Q96AQ3, Q9UH31 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1990 |
Last sequence update: | October 17, 2006 | |
Last modified: | February 23, 2022 | |
This is version 227 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families