UniProt functional annotation for P03069



	UniProt functional annotation for P03069

UniProt code: P03069.

Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).

Taxonomy: Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.

Function: Master transcriptional regulator that mediates the response to amino acid starvation (PubMed:11390663, PubMed:29628310). Binds variations of the DNA sequence 5'-ATGA[CG]TCAT-3' in canonical nucleosome-depleted 5'-positioned promoters, and also within coding sequences and 3' non-coding regions (PubMed:29628310, PubMed:11390663, PubMed:1473154, PubMed:2277632, PubMed:1939099, PubMed:7664107, PubMed:2204805, PubMed:3678204, PubMed:3532321, PubMed:3530496). During nutrient starvation (low or poor amino acid, carbon or purine sources), it activates genes required for amino acid biosynthesis and transport, autophagy, cofactor biosynthesis and transport, mitochondrial transport, and additional downstream transcription factors (PubMed:11390663, PubMed:29628310, PubMed:8336737, PubMed:1939099, PubMed:10733573, PubMed:7862116). Activates transcription by recruiting multiple coactivators, including the mediator complex, the SAGA complex, and the SWI/SNF complex, to enable assembly of the pre- initiation complex at core promoters (PubMed:19940160, PubMed:9488488, PubMed:10549298). {ECO:0000269|PubMed:10549298, ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:11390663, ECO:0000269|PubMed:1473154, ECO:0000269|PubMed:1939099, ECO:0000269|PubMed:19940160, ECO:0000269|PubMed:2204805, ECO:0000269|PubMed:2277632, ECO:0000269|PubMed:29628310, ECO:0000269|PubMed:3530496, ECO:0000269|PubMed:3532321, ECO:0000269|PubMed:3678204, ECO:0000269|PubMed:7664107, ECO:0000269|PubMed:7862116, ECO:0000269|PubMed:8336737, ECO:0000269|PubMed:9488488}.

Subunit: Homodimer (PubMed:1473154, PubMed:3678204). Each subunit binds overlapping and non-identical half-sites that flank the central CG base-pair in the pseudo-palindromic motif 5'-ATGA[CG]TCAT-3' (PubMed:1473154, PubMed:7664107, PubMed:2204805, PubMed:3678204). Interacts with the mediator tail; the interaction with GAL11/MED15 is direct (PubMed:19940160, PubMed:9488488, PubMed:10549298). Interacts with the SAGA histone acetyltransferase complex (PubMed:19940160, PubMed:9488488, PubMed:10549298). Interacts with the SWI/SNF chromatin remodeling complex (PubMed:19940160, PubMed:10549298). {ECO:0000269|PubMed:10549298, ECO:0000269|PubMed:1473154, ECO:0000269|PubMed:19940160, ECO:0000269|PubMed:2204805, ECO:0000269|PubMed:3678204, ECO:0000269|PubMed:7664107, ECO:0000269|PubMed:9488488}.

Subcellular location: Nucleus {ECO:0000269|PubMed:12455686, ECO:0000269|PubMed:14648200}. Note=Localizes to the nucleus independently of cellular amino acid levels. {ECO:0000269|PubMed:12455686}.

Induction: Translation is induced by amino acid or purine starvation, or during growth in low or poor carbon sources (PubMed:6387704, PubMed:6433345, PubMed:8336737, PubMed:10733573, PubMed:9582292). Translational repression during nutrient-rich conditions is dependent on four uORFs (upstream open reading frames) present in the 5'-UTR of the mRNA; these promote ribosome dissociation (PubMed:6387704, PubMed:6433345, PubMed:3516411, PubMed:2676723, PubMed:8336737, PubMed:9582292). Translational induction occurs in conditions reducing translation machinery efficiency, leading to ribosomes scanning over the uORFs, and increased translation of the mRNA (PubMed:1986242). The rapid translational induction is followed by transcriptional induction at later time-points, independently of the uORF sequences (PubMed:9582292). {ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:1986242, ECO:0000269|PubMed:2676723, ECO:0000269|PubMed:3516411, ECO:0000269|PubMed:6387704, ECO:0000269|PubMed:6433345, ECO:0000269|PubMed:8336737, ECO:0000269|PubMed:9582292}.

Domain: Residues 89 to 100 and 106 to 125 define the N-terminal activation domain (NTAD) and the central acidic activation domain (CAAD) respectively, which can function independently to promote high- level transcription of the target genes. {ECO:0000269|PubMed:3530496, ECO:0000269|PubMed:7862116}.

Ptm: Phosphorylated by the cyclin-CDK PCL5-PHO85. Phosphorylation of Thr-165 induces degradation of GCN4 by the E3 ubiquitin ligase complex SCF(Cdc4). {ECO:0000269|PubMed:12101234}.

Disruption phenotype: Abolishes recruitment of the mediator complex to the upstream activating sequence (UAS) of amino-acid starvation responsive genes (PubMed:19940160). Decreases RNA level of genes involved in amino acid biosynthesis and cofactor biosynthesis during amino acid starvation or methyl methanesulfonate stress (PubMed:11390663, PubMed:8336737, PubMed:29628310). Growth dependent on amino acid supplementation (PubMed:10733573). Sensitive to amino acid starvation (PubMed:10549298). Sensitive to purine starvation (PubMed:8336737). Decreases cellular glycogen levels during glucose starvation (PubMed:10733573). {ECO:0000269|PubMed:10549298, ECO:0000269|PubMed:10733573, ECO:0000269|PubMed:11390663, ECO:0000269|PubMed:19940160, ECO:0000269|PubMed:29628310, ECO:0000269|PubMed:8336737}.

Similarity: Belongs to the bZIP family. GCN4 subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Taxonomy:		Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.



Function:		Master transcriptional regulator that mediates the response to amino acid starvation (PubMed:11390663, PubMed:29628310). Binds variations of the DNA sequence 5'-ATGA[CG]TCAT-3' in canonical nucleosome-depleted 5'-positioned promoters, and also within coding sequences and 3' non-coding regions (PubMed:29628310, PubMed:11390663, PubMed:1473154, PubMed:2277632, PubMed:1939099, PubMed:7664107, PubMed:2204805, PubMed:3678204, PubMed:3532321, PubMed:3530496). During nutrient starvation (low or poor amino acid, carbon or purine sources), it activates genes required for amino acid biosynthesis and transport, autophagy, cofactor biosynthesis and transport, mitochondrial transport, and additional downstream transcription factors (PubMed:11390663, PubMed:29628310, PubMed:8336737, PubMed:1939099, PubMed:10733573, PubMed:7862116). Activates transcription by recruiting multiple coactivators, including the mediator complex, the SAGA complex, and the SWI/SNF complex, to enable assembly of the pre- initiation complex at core promoters (PubMed:19940160, PubMed:9488488, PubMed:10549298). {ECO:0000269\|PubMed:10549298, ECO:0000269\|PubMed:10733573, ECO:0000269\|PubMed:11390663, ECO:0000269\|PubMed:1473154, ECO:0000269\|PubMed:1939099, ECO:0000269\|PubMed:19940160, ECO:0000269\|PubMed:2204805, ECO:0000269\|PubMed:2277632, ECO:0000269\|PubMed:29628310, ECO:0000269\|PubMed:3530496, ECO:0000269\|PubMed:3532321, ECO:0000269\|PubMed:3678204, ECO:0000269\|PubMed:7664107, ECO:0000269\|PubMed:7862116, ECO:0000269\|PubMed:8336737, ECO:0000269\|PubMed:9488488}.


Subunit:		Homodimer (PubMed:1473154, PubMed:3678204). Each subunit binds overlapping and non-identical half-sites that flank the central CG base-pair in the pseudo-palindromic motif 5'-ATGA[CG]TCAT-3' (PubMed:1473154, PubMed:7664107, PubMed:2204805, PubMed:3678204). Interacts with the mediator tail; the interaction with GAL11/MED15 is direct (PubMed:19940160, PubMed:9488488, PubMed:10549298). Interacts with the SAGA histone acetyltransferase complex (PubMed:19940160, PubMed:9488488, PubMed:10549298). Interacts with the SWI/SNF chromatin remodeling complex (PubMed:19940160, PubMed:10549298). {ECO:0000269\|PubMed:10549298, ECO:0000269\|PubMed:1473154, ECO:0000269\|PubMed:19940160, ECO:0000269\|PubMed:2204805, ECO:0000269\|PubMed:3678204, ECO:0000269\|PubMed:7664107, ECO:0000269\|PubMed:9488488}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:12455686, ECO:0000269\|PubMed:14648200}. Note=Localizes to the nucleus independently of cellular amino acid levels. {ECO:0000269\|PubMed:12455686}.
Induction:		Translation is induced by amino acid or purine starvation, or during growth in low or poor carbon sources (PubMed:6387704, PubMed:6433345, PubMed:8336737, PubMed:10733573, PubMed:9582292). Translational repression during nutrient-rich conditions is dependent on four uORFs (upstream open reading frames) present in the 5'-UTR of the mRNA; these promote ribosome dissociation (PubMed:6387704, PubMed:6433345, PubMed:3516411, PubMed:2676723, PubMed:8336737, PubMed:9582292). Translational induction occurs in conditions reducing translation machinery efficiency, leading to ribosomes scanning over the uORFs, and increased translation of the mRNA (PubMed:1986242). The rapid translational induction is followed by transcriptional induction at later time-points, independently of the uORF sequences (PubMed:9582292). {ECO:0000269\|PubMed:10733573, ECO:0000269\|PubMed:1986242, ECO:0000269\|PubMed:2676723, ECO:0000269\|PubMed:3516411, ECO:0000269\|PubMed:6387704, ECO:0000269\|PubMed:6433345, ECO:0000269\|PubMed:8336737, ECO:0000269\|PubMed:9582292}.
Domain:		Residues 89 to 100 and 106 to 125 define the N-terminal activation domain (NTAD) and the central acidic activation domain (CAAD) respectively, which can function independently to promote high- level transcription of the target genes. {ECO:0000269\|PubMed:3530496, ECO:0000269\|PubMed:7862116}.
Ptm:		Phosphorylated by the cyclin-CDK PCL5-PHO85. Phosphorylation of Thr-165 induces degradation of GCN4 by the E3 ubiquitin ligase complex SCF(Cdc4). {ECO:0000269\|PubMed:12101234}.
Disruption phenotype:		Abolishes recruitment of the mediator complex to the upstream activating sequence (UAS) of amino-acid starvation responsive genes (PubMed:19940160). Decreases RNA level of genes involved in amino acid biosynthesis and cofactor biosynthesis during amino acid starvation or methyl methanesulfonate stress (PubMed:11390663, PubMed:8336737, PubMed:29628310). Growth dependent on amino acid supplementation (PubMed:10733573). Sensitive to amino acid starvation (PubMed:10549298). Sensitive to purine starvation (PubMed:8336737). Decreases cellular glycogen levels during glucose starvation (PubMed:10733573). {ECO:0000269\|PubMed:10549298, ECO:0000269\|PubMed:10733573, ECO:0000269\|PubMed:11390663, ECO:0000269\|PubMed:19940160, ECO:0000269\|PubMed:29628310, ECO:0000269\|PubMed:8336737}.
Similarity:		Belongs to the bZIP family. GCN4 subfamily. {ECO:0000305}.