ATF4_DANRE
ID ATF4_DANRE Reviewed; 339 AA.
AC Q6NW59;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Cyclic AMP-dependent transcription factor ATF-4;
DE Short=cAMP-dependent transcription factor ATF-4;
DE AltName: Full=Activating transcription factor 4;
GN Name=atf4; Synonyms=atf4a {ECO:0000312|ZFIN:ZDB-GENE-040426-2340};
GN ORFNames=zgc:85951;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000312|EMBL:AAH67714.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH67714.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcription factor that binds the cAMP response element
CC (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological
CC functions, as regulator of metabolic and redox processes under normal
CC cellular conditions, and as master transcription factor during
CC integrated stress response (ISR) (By similarity). Binds to asymmetric
CC CRE's as a heterodimer and to palindromic CRE's as a homodimer (By
CC similarity). Core effector of the ISR, which is required for adaptation
CC to various stress such as endoplasmic reticulum (ER) stress, amino acid
CC starvation, mitochondrial stress or oxidative stress. During ISR, atf4
CC translation is induced via an alternative ribosome translation re-
CC initiation mechanism in response to eif2s1/eIF-2-alpha phosphorylation,
CC and stress-induced atf4 acts as a master transcription factor of
CC stress-responsive genes in order to promote cell recovery (By
CC similarity). Promotes the transcription of genes linked to amino acid
CC sufficiency and resistance to oxidative stress to protect cells against
CC metabolic consequences of ER oxidation (By similarity). In the absence
CC of stress, atf4 translation is at low levels and it is required for
CC normal metabolic processes such as embryonic lens formation, fetal
CC liver hematopoiesis, bone development and synaptic plasticity (By
CC similarity). Acts as a regulator of osteoblast differentiation by
CC promoting expression of osteoblast-specific genes (By similarity).
CC Regulates the circadian expression of the core clock components. Mainly
CC acts as a transcriptional activator in cellular stress adaptation, but
CC it can also act as a transcriptional repressor (By similarity).
CC {ECO:0000250|UniProtKB:P18848, ECO:0000250|UniProtKB:Q06507}.
CC -!- SUBUNIT: Binds DNA as a homodimer and as a heterodimer.
CC {ECO:0000250|UniProtKB:P18848}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P18848}.
CC -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
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DR EMBL; BC067714; AAH67714.1; -; mRNA.
DR RefSeq; NP_998398.1; NM_213233.1.
DR AlphaFoldDB; Q6NW59; -.
DR SMR; Q6NW59; -.
DR STRING; 7955.ENSDARP00000042969; -.
DR PaxDb; Q6NW59; -.
DR Ensembl; ENSDART00000191678; ENSDARP00000145766; ENSDARG00000111939.
DR GeneID; 406514; -.
DR KEGG; dre:406514; -.
DR CTD; 406514; -.
DR ZFIN; ZDB-GENE-040426-2340; atf4a.
DR eggNOG; KOG4571; Eukaryota.
DR GeneTree; ENSGT00530000063801; -.
DR HOGENOM; CLU_055748_0_0_1; -.
DR InParanoid; Q6NW59; -.
DR OMA; WMTEKID; -.
DR OrthoDB; 1524842at2759; -.
DR PhylomeDB; Q6NW59; -.
DR TreeFam; TF316136; -.
DR PRO; PR:Q6NW59; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 6.
DR Bgee; ENSDARG00000111939; Expressed in granulocyte and 27 other tissues.
DR GO; GO:1990590; C:ATF1-ATF4 transcription factor complex; IBA:GO_Central.
DR GO; GO:1990589; C:ATF4-CREB1 transcription factor complex; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008140; F:cAMP response element binding protein binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISS:UniProtKB.
DR GO; GO:0140468; P:HRI-mediated signaling; ISS:UniProtKB.
DR GO; GO:0140467; P:integrated stress response signaling; ISS:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0070309; P:lens fiber cell morphogenesis; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR InterPro; IPR029811; ATF4.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR PANTHER; PTHR13044:SF2; PTHR13044:SF2; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 2: Evidence at transcript level;
KW Activator; Biological rhythms; DNA-binding; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..339
FT /note="Cyclic AMP-dependent transcription factor ATF-4"
FT /id="PRO_0000258023"
FT DOMAIN 266..329
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 14..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 153..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..288
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 294..322
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT COMPBIAS 34..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..237
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..313
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 339 AA; 36605 MW; C3C40B2D17D24CD2 CRC64;
MSLCVGDAGA LLLGPWPLTA DPQGPLLDQD EESSVLEGSW SPSSSSLSSF SPPASGDAPS
ELLSLSWQPS DVLLTEQSTA GDVFPGMDWM TEKLDLNDFD LDSLIGSCDS EDSPGSPEDL
LACLDSSMDL DLDSLPFGSA DLDLPLGLDL PLPEEIKSEP LSPAPSVPSP PEEAPQDEHT
EVPVLHPAGI MLSLSPSHIV VLLTPKEEQN ISDCSDSDSG ISVSGSPAHQ SDLEPSSRAK
PYSRPDPEAS PALKGRVKTS SGAPKVEKKL KKMEQNKTAA TRYRQKKRVE QESLNSECSE
LEKKNRELSE KADSLSREIQ YLRDLLEEMR TAKQRKSKR
