ATF4
entrez
468
canonical
uniprot
P18848
canonical
ensembl
ENSG00000128272
resolver
ensp
ENSP00000336790
resolver
ensp
ENSP00000379912
resolver
ensp
ENSP00000384587
resolver
ensp
ENSP00000501783
resolver
ensp
ENSP00000501863
resolver
ensp
ENSP00000502400
resolver
ensp
ENSP00000502610
resolver
ensp
ENSP00000505360
resolver
ensp
ENSP00000591583
resolver
ensp
ENSP00000591584
resolver
ensp
ENSP00000591585
resolver
ensp
ENSP00000591586
resolver
ensp
ENSP00000591587
resolver
ensp
ENSP00000591588
resolver
ensp
ENSP00000630483
resolver
ensp
ENSP00000630484
resolver
ensp
ENSP00000630485
resolver
enst
ENST00000337304
resolver
enst
ENST00000396680
resolver
enst
ENST00000404241
resolver
enst
ENST00000674568
resolver
enst
ENST00000674835
resolver
enst
ENST00000674920
resolver
enst
ENST00000676346
resolver
enst
ENST00000679776
resolver
enst
ENST00000921524
resolver
enst
ENST00000921525
resolver
enst
ENST00000921526
resolver
enst
ENST00000921527
resolver
enst
ENST00000921528
resolver
enst
ENST00000921529
resolver
enst
ENST00000960424
resolver
enst
ENST00000960425
resolver
enst
ENST00000960426
resolver
genesymbol
ATF4
resolver
genesymbol_syn
CREB2
resolver
genesymbol_syn
TXREB
resolver
hgnc
HGNC:786
resolver
uniprot
Q96AQ3
resolver
uniprot
Q9UH31
resolver
uniprot_entry
ATF4_HUMAN
resolver
uniprot_sec
Q96AQ3
resolver
uniprot_sec
Q9UH31
resolver
amino_acid_sequence
MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFSSDKAKAGSSEWLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALLGIDDLETMPDDLLTTLDDTCDLFAPLVQETNKQPPQTVNPIGHLPESLTKPDQVAPFTFLQPLPLSPGVLSSTPDHSFSLELGSEVDITEGDRKPDYTAYVAMIPQCIKEEDTPSDNDSGICMSPESYLGSPQHSPSTRGSPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGEKLDKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRVP
uniprot
proteins
function
FUNCTION: 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:16682973, PubMed:17684156, PubMed:31023583, 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:31023583, 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:31023583, 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). Activates the expression of COX7A2L/SCAF1 downstream of the EIF2AK3/PERK-mediated unfolded protein response, thereby promoting formation of respiratory chain supercomplexes and increasing mitochondrial oxidative phosphorylation (PubMed:31023583). 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). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:11960987, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:17684156, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:26086088, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:31444471, ECO:0000269|PubMed:32132706, ECO:0000269|PubMed:32132707, ECO:0000269|PubMed:33384352}.; FUNCTION: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. {ECO:0000269|PubMed:1847461}.
uniprot
proteins
mass_dalton
38590
uniprot
proteins
mutagenesis
MUTAGEN 156; /note="P->A: Increased stability in low oxygen conditions; when associated with A-162, A-164, A-167 and A-174."; /evidence="ECO:0000269|PubMed:17684156"; MUTAGEN 162; /note="P->A: Increased stability in low oxygen conditions; when associated with A-156, A-164, A-167 and A-174."; /evidence="ECO:0000269|PubMed:17684156"; MUTAGEN 164; /note="P->A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-167 and A-174."; /evidence="ECO:0000269|PubMed:17684156"; MUTAGEN 167; /note="P->A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-174."; /evidence="ECO:0000269|PubMed:17684156"; MUTAGEN 174; /note="P->A: Increased stability in low oxygen conditions; when associated with A-156, A-162, A-164 and A-167."; /evidence="ECO:0000269|PubMed:17684156"; MUTAGEN 213; /note="T->A: Does not affect phosphorylation by CK2."; /evidence="ECO:0000269|PubMed:23123191"; MUTAGEN 215; /note="S->A: Abolished phosphorylation by CK2 leading to increased stability."; /evidence="ECO:0000269|PubMed:23123191"; MUTAGEN 219; /note="S->N: Abolished phosphorylation on the betaTrCP degron motif, interaction with BTRC and subsequent ubiquitination."; /evidence="ECO:0000269|PubMed:16219772"; MUTAGEN 245; /note="S->A: Abolished phosphorylation by RPS6KA3/RSK2."; /evidence="ECO:0000269|PubMed:15109498"; MUTAGEN 311; /note="K->R: Decreased acetylation without affecting ubiquitination by SCF(BTRC)."; /evidence="ECO:0000269|PubMed:16219772
uniprot
proteins
post_translational_modification
PTM: 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). {ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:16219772}.; PTM: 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). {ECO:0000250|UniProtKB:Q06507, ECO:0000269|PubMed:15109498, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:23123191}.; PTM: Hydroxylated by PHD3, leading to decreased protein stability. {ECO:0000305|PubMed:17684156}.
uniprot
proteins
protein_family
BZIP family
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
11018027
uniprot
proteins
pubmed
11238952
uniprot
proteins
pubmed
11960987
uniprot
proteins
pubmed
15109498
uniprot
proteins
pubmed
1534408
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15775988
uniprot
proteins
pubmed
15911876
uniprot
proteins
pubmed
16219772
uniprot
proteins
pubmed
16682973
uniprot
proteins
pubmed
17684156
uniprot
proteins
pubmed
1847461
uniprot
proteins
pubmed
18940792
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20873783
uniprot
proteins
pubmed
21408167
uniprot
proteins
pubmed
22974638
uniprot
proteins
pubmed
23123191
uniprot
proteins
pubmed
2516827
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
26086088
uniprot
proteins
pubmed
27629041
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
31023583
uniprot
proteins
pubmed
31444471
uniprot
proteins
pubmed
32132706
uniprot
proteins
pubmed
32132707
uniprot
proteins
pubmed
33384352
uniprot
proteins
sequence_length
351
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16682973, ECO:0000269|PubMed:22974638, ECO:0000269|PubMed:23123191, ECO:0000269|PubMed:31444471}. Nucleus speckle {ECO:0000269|PubMed:16219772}. Cytoplasm {ECO:0000250|UniProtKB:Q9ES19}. Cell membrane {ECO:0000250|UniProtKB:Q9ES19}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:20873783}. 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). {ECO:0000250|UniProtKB:Q9ES19, ECO:0000269|PubMed:16219772, ECO:0000269|PubMed:20873783}.
uniprot
proteins