ATF4
Cyclic AMP-dependent transcription factor ATF-4
Also known as: ATF4_HUMAN, CREB-2, TAXREB67, TXREB
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P18848
- Gene
- ATF4
- Ensembl
- ENSG00000128272
- Chromosome
- 22
- Canonical length
- 351 aa
- Protein class
- Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication. [provided by RefSeq, Sep 2011]
Canonical amino-acid sequenceUniProt
351 residues, UniProt reviewed canonical sequence.
>P18848|ATF4
1 MTEMSFLSSE VLVGDLMSPF DQSGLGAEES LGLLDDYLEV AKHFKPHGFS SDKAKAGSSE
61 WLAVDGLVSP SNNSKEDAFS GTDWMLEKMD LKEFDLDALL GIDDLETMPD DLLTTLDDTC
121 DLFAPLVQET NKQPPQTVNP IGHLPESLTK PDQVAPFTFL QPLPLSPGVL SSTPDHSFSL
181 ELGSEVDITE GDRKPDYTAY VAMIPQCIKE EDTPSDNDSG ICMSPESYLG SPQHSPSTRG
241 SPNRSLPSPG VLCGSARPKP YDPPGEKMVA AKVKGEKLDK KLKKMEQNKT AATRYRQKKR
301 AEQEALTGEC KELEKKNEAL KERADSLAKE IQYLKDLIEE VRKARGKKRV PLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ATF4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.66
- Highest tissue expression
- 837 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 837 nTPM
- colon: 826 nTPM
- skeletal muscle: 771 nTPM
- blood vessel: 703 nTPM
- pancreas: 621 nTPM
- urinary bladder: 580 nTPM
Single-cell type
- epididymal basal cells: 615 nCPM
- esophageal apical cells: 600 nCPM
- platelets: 502 nCPM
- breast secretory cells: 416 nCPM
- extravillous trophoblasts: 375 nCPM
- goblet cells: 319 nCPM
Immune cell
- basophil: 47 nTPM
- myeloid DC: 45 nTPM
- memory B-cell: 38 nTPM
- classical monocyte: 37 nTPM
- non-classical monocyte: 35 nTPM
- T-reg: 32 nTPM
Brain region
- white matter: 233 nTPM
- medulla oblongata: 218 nTPM
- cerebellum: 209 nTPM
- thalamus: 189 nTPM
- pons: 189 nTPM
- spinal cord: 185 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.09
- gnomAD pLI
- 0.02
- gnomAD missense Z
- -3.54
- DepMap mean gene effect
- -0.44
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- bone mineralization
- cellular response to amino acid starvation
- cellular response to glucose starvation
- cellular response to hypoxia
- cellular response to leucine starvation
- cellular response to oxidative stress
- cellular response to UV
- circadian regulation of gene expression
- embryonic hemopoiesis
- endoplasmic reticulum unfolded protein response
- gamma-aminobutyric acid signaling pathway
- gluconeogenesis
- HRI-mediated signaling
- integrated stress response signaling
- intracellular calcium ion homeostasis
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
- lens fiber cell morphogenesis
- mRNA transcription by RNA polymerase II
- negative regulation of cold-induced thermogenesis
- negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
- negative regulation of potassium ion transport
- negative regulation of transcription by RNA polymerase II
- negative regulation of translational initiation in response to stress
- neuron differentiation
- PERK-mediated unfolded protein response
- positive regulation of apoptotic process
- positive regulation of biomineral tissue development
- positive regulation of DNA-templated transcription
- positive regulation of gene expression
- positive regulation of neuron apoptotic process
- positive regulation of sodium-dependent phosphate transport
- positive regulation of transcription by RNA polymerase I
- positive regulation of transcription by RNA polymerase II
- positive regulation of vascular associated smooth muscle cell apoptotic process
- positive regulation of vascular endothelial growth factor production
- regulation of DNA-templated transcription
- regulation of osteoblast differentiation
- regulation of synaptic plasticity
- regulation of transcription by RNA polymerase II
- response to endoplasmic reticulum stress
- response to manganese-induced endoplasmic reticulum stress
- response to nutrient levels
- response to toxic substance
- transcription by RNA polymerase II
- L-asparagine metabolic process
Molecular functions
- cAMP response element binding
- cAMP response element binding protein binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- general transcription initiation factor binding
- identical protein binding
- leucine zipper domain binding
- promoter-specific chromatin binding
- protein heterodimerization activity
- protein kinase binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- RNA polymerase II transcription regulatory region sequence-specific DNA binding
- RNA polymerase II-specific DNA-binding transcription factor binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- transcription cis-regulatory region binding
Cellular components
- ATF1-ATF4 transcription factor complex
- ATF4-CREB1 transcription factor complex
- centrosome
- CHOP-ATF4 complex
- chromatin
- cytoplasm
- cytosol
- dendrite membrane
- Lewy body core
- neuron projection
- nuclear periphery
- nuclear speck
- nucleoplasm
- nucleus
- protein-containing complex
- RNA polymerase II transcription regulator complex
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ATF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ATF4 as an antibody target. Whether an autoantibody or antibody against ATF4 could matter depends on whether native ATF4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ATF4 is annotated at the cell surface, where native ATF4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ATF4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
Loading the interactive Seroatlas protein explorer...