P03069 (GCN4_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
General control protein GCN4

Alternative name(s):
Amino acid biosynthesis regulatory protein

Gene names

Name:	GCN4
Synonyms:	AAS3, ARG9
Ordered Locus Names:	YEL009C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	281 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Is a transcription factor that is responsible for the activation of more than 30 genes required for amino acid or for purine biosynthesis in response to amino acid or purine starvation. Binds and recognize the DNA sequence: 5'-TGA[CG]TCA-3'.
Subunit structure	Binds DNA as a dimer.
Subcellular location	Nucleus.
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. Ref.7 Ref.8
Post-translational modification	Phosphorylated by the cyclin-CDK PCL5-PHO85. Phosphorylation of Thr-165 induces degradation of GCN4 by the E3 ubiquitin ligase complex SCF(Cdc4). Ref.9
Sequence similarities	Belongs to the bZIP family. GCN4 subfamily. Contains 1 bZIP (basic-leucine zipper) domain.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular amino acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of ribosomal protein gene transcription from RNA polymerase II promoter in response to nutrient levels Inferred from mutant phenotype PubMed 21183953. Source: SGD nitrogen catabolite activation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 21148207. Source: SGD positive regulation of RNA polymerase II transcriptional preinitiation complex assembly Inferred from direct assay PubMed 18794364. Source: SGD positive regulation of transcription initiation from RNA polymerase II promoter Inferred from mutant phenotype PubMed 1425591. Source: SGD
Cellular_component	nucleus Inferred from direct assay PubMed 12455686PubMed 14648200. Source: SGD
Molecular_function	RNA polymerase II transcription factor binding transcription factor activity involved in negative regulation of transcription Inferred from physical interaction PubMed 21183953. Source: SGD RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Inferred from mutant phenotype PubMed 16581788PubMed 19940160. Source: SGD RNA polymerase II transcription factor recruiting transcription factor activity Inferred from mutant phenotype PubMed 16581788PubMed 19940160. Source: SGD TFIID-class binding transcription factor activity Inferred from physical interaction PubMed 20308326. Source: SGD chromatin binding Inferred from direct assay PubMed 18794364. Source: SGD sequence-specific DNA binding Inferred from direct assay PubMed 19158363PubMed 2204805PubMed 3290651PubMed 3464968Ref.7PubMed 3907851. Source: SGD sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype PubMed 16581788. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 281

281

General control protein GCN4

PRO_0000076490

Regions

Domain

225 – 281

57

bZIP

Region

89 – 100

12

Required for transcriptional activation

Region

106 – 125

20

Required for transcriptional activation

Region

231 – 251

21

Basic motif By similarity

Region

253 – 274

22

Leucine-zipper By similarity

Amino acid modifications

Modified residue

17

1

Phosphoserine Ref.10

Modified residue

165

1

Phosphothreonine; by PHO85 Ref.9 Ref.10

Modified residue

218

1

Phosphoserine Ref.10

Natural variations

Natural variant

24

1

S → P in strain: CLIB 219. Ref.3

Natural variant

62

1

P → S in strain: CLIB 630 haplotype Ha2. Ref.3

Natural variant

82

1

T → A in strain: CLIB 556 haplotype Ha1. Ref.3

Natural variant

91

1

D → A in strain: CLIB 95, CLIB 219, CLIB 382, CLIB 388, CLIB 410, CLIB 413, CLIB 556, CLIB 630, K1, R12, R13 haplotype Ha2, Sigma 1278B haplotype Ha1, YIIc12 and YIIc17. Ref.3

Natural variant

125

1

D → A in strain: CLIB 556 haplotype Ha1. Ref.3

Natural variant

196

1

D → E in strain: CLIB 388, CLIB 410, CLIB 413, CLIB 630 haplotype Ha1, K1, YIIc12 haplotype Ha2 and YIIc17 haplotype Ha1. Ref.3

Experimental info

Mutagenesis

97 – 98

2

FF → AA: Reduces transcriptional activation activity; when associated with A-107; A-110; A-113; A-120; A-123 and A-124.

Mutagenesis

107

1

M → A: Reduces transcriptional activation activity; when associated with A-97; A-98; A-110; A-113; A-120; A-123 and A-124. Ref.8

Mutagenesis

110

1

Y → A: Reduces transcriptional activation activity; when associated with A-97; A-98; A-107; A-113; A-120; A-123 and A-124. Ref.8

Mutagenesis

113

1

L → A: Reduces transcriptional activation activity; when associated with A-97; A-98; A-107; A-110; A-120; A-123 and A-124. Ref.8

Mutagenesis

120 – 124

5

WTSLF → ATSAA: Reduces transcriptional activation activity; when associated with A-97; A-98; A-107; A-110 and A-113. Ref.8

Sequence conflict

239 – 281

43

ARRSR…LVGER → PGVLVRESCKE in AAA65521. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

281

Helix Strand Turn

Details...

Helix

118 – 121

4

Helix

122 – 124

3

Helix

250 – 263

14

Turn

264 – 267

4

Helix

268 – 275

8

Turn

276 – 278

3

Sequences

	Sequence		Length	Mass (Da)
	P03069 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 2ED1B8E35D509578	FASTA	281	31,310
	10 20 30 40 50 60 MSEYQPSLFA LNPMGFSPLD GSKSTNENVS ASTSTAKPMV GQLIFDKFIK TEEDPIIKQD 70 80 90 100 110 120 TPSNLDFDFA LPQTATAPDA KTVLPIPELD DAVVESFFSS STDSTPMFEY ENLEDNSKEW 130 140 150 160 170 180 TSLFDNDIPV TTDDVSLADK AIESTEEVSL VPSNLEVSTT SFLPTPVLED AKLTQTRKVK 190 200 210 220 230 240 KPNSVVKKSH HVGKDDESRL DHLGVVAYNR KQRSIPLSPI VPESSDPAAL KRARNTEAAR 250 260 270 280 RSRARKLQRM KQLEDKVEEL LSKNYHLENE VARLKKLVGE R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evidence for translational regulation of the activator of general amino acid control in yeast." Hinnebusch A.G. Proc. Natl. Acad. Sci. U.S.A. 81:6442-6446(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"5' untranslated sequences are required for the translational control of a yeast regulatory gene." Thireos G., Penn M.D., Greer H. Proc. Natl. Acad. Sci. U.S.A. 81:5096-5100(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Differential evolution of the Saccharomyces cerevisiae DUP240 paralogs and implication of recombination in phylogeny." Leh-Louis V., Wirth B., Despons L., Wain-Hobson S., Potier S., Souciet J.-L. Nucleic Acids Res. 32:2069-2078(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-24; SER-62; ALA-82; ALA-91; ALA-125 AND GLU-196. Strain: CLIB 219, CLIB 382, CLIB 388, CLIB 410, CLIB 413, CLIB 556, CLIB 630, CLIB 95, K1, R12, R13, Sigma 1278B, YIIc12 and YIIc17.
[4]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome V." Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E., Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S., Hyman R.W. , Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X., Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y., Botstein D., Davis R.W. Nature 387:78-81(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"Construction of dimeric F(ab) useful in blood group serology." Czerwinski M., Krop-Watorek A., Lisowska E., Spitalnik S.L. Transfusion 42:257-264(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 249-281.
[7]	"Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast." Hope I.A., Struhl K. Cell 46:885-894(1986) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS.
[8]	"The transcriptional activator GCN4 contains multiple activation domains that are critically dependent on hydrophobic amino acids." Drysdale C.M., Duenas E., Jackson B.M., Reusser U., Braus G.H., Hinnebusch A.G. Mol. Cell. Biol. 15:1220-1233(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAINS, MUTAGENESIS OF 97-PHE-PHE-98; MET-107; TYR-110; LEU-113 AND 120-TRP--PHE-124.
[9]	"Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5." Shemer R., Meimoun A., Holtzman T., Kornitzer D. Mol. Cell. Biol. 22:5395-5404(2002) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-165.
[10]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; THR-165 AND SER-218, MASS SPECTROMETRY.
[11]	"X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil." O'Shea E.K., Klemm J.D., Kim P.S., Alber T. Science 254:539-544(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 250-281.
[12]	"The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex." Ellenberger T.E., Brandl C.J., Struhl K., Harrison S.C. Cell 71:1223-1237(1992) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 226-281.
[13]	"Crystal structure of GCN4-pIQI, a trimeric coiled coil with buried polar residues." Eckert D.M., Malashkevich V.N., Kim P.S. J. Mol. Biol. 284:859-865(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 249-281.
[14]	"The solution structure of a leucine-zipper motif peptide." Saudek V., Pastore A., Morelli M.A., Frank R., Gausepohl H., Gibson T. Protein Eng. 4:519-529(1991) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 237-281.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K02205 Genomic DNA. Translation: AAA34640.1.
K02649 Genomic DNA. Translation: AAA65521.1.
AJ585686 Genomic DNA. Translation: CAE52206.1.
AJ585687 Genomic DNA. Translation: CAE52207.1.
AJ585688 Genomic DNA. Translation: CAE52208.1.
AJ585689 Genomic DNA. Translation: CAE52209.1.
AJ585690 Genomic DNA. Translation: CAE52210.1.
AJ585691 Genomic DNA. Translation: CAE52211.1.
AJ585692 Genomic DNA. Translation: CAE52212.1.
AJ585693 Genomic DNA. Translation: CAE52213.1.
AJ585694 Genomic DNA. Translation: CAE52214.1.
AJ585695 Genomic DNA. Translation: CAE52215.1.
AJ585696 Genomic DNA. Translation: CAE52216.1.
AJ585697 Genomic DNA. Translation: CAE52217.1.
AJ585698 Genomic DNA. Translation: CAE52218.1.
AJ585699 Genomic DNA. Translation: CAE52219.1.
AJ585700 Genomic DNA. Translation: CAE52220.1.
AJ585701 Genomic DNA. Translation: CAE52221.1.
AJ585702 Genomic DNA. Translation: CAE52222.1.
AJ585703 Genomic DNA. Translation: CAE52223.1.
AJ585704 Genomic DNA. Translation: CAE52224.1.
AF416613 mRNA. Translation: AAL09032.1.
U18530 Genomic DNA. Translation: AAB64486.1.
BK006939 Genomic DNA. Translation: DAA07643.1.

PIR

RGBYA2. A03605.

RefSeq

NP_010907.3. NM_001178824.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CE9	X-ray	1.80	A/B/C/D	253-281	[»]
1DGC	X-ray	3.00	A	220-281	[»]
1ENV	X-ray	2.60	A	254-280	[»]
1FAV	X-ray	3.00	A	254-280	[»]
1FMH	NMR	-	A/B	249-279	[»]
1GCL	X-ray	2.10	A/B/C/D	249-281	[»]
1GCM	X-ray	1.80	A/B/C	249-281	[»]
1GK6	X-ray	1.90	A/B	249-279	[»]
1GZL	X-ray	1.80	A/B	249-276	[»]
1IHQ	NMR	-	A/B	264-281	[»]
1IJ0	X-ray	1.86	A/B/C	249-281	[»]
1IJ1	X-ray	1.86	A/B/C	249-281	[»]
1IJ2	X-ray	1.70	A/B/C	249-281	[»]
1IJ3	X-ray	1.80	A/B/C	249-281	[»]
1KQL	X-ray	2.70	A/B	255-278	[»]
1LD4	electron microscopy	11.40	E/F/G/H/I/J/K/L	225-281	[»]
1LLM	X-ray	1.50	C/D	253-281	[»]
1NKN	X-ray	2.50	A/B/C/D	250-281	[»]
1PIQ	X-ray	1.80	A	249-277	[»]
1RB4	X-ray	1.90	A/B/C	249-281	[»]
1RB5	X-ray	1.90	A/B/C	249-281	[»]
1RB6	X-ray	1.90	A/B/C	249-281	[»]
1SWI	X-ray	2.60	A/B/C	249-281	[»]
1TMZ	NMR	-	A/B	264-281	[»]
1UNT	X-ray	2.07	A/B	249-281	[»]
1UNU	X-ray	2.07	A/B	249-281	[»]
1UNV	X-ray	2.14	A/B	249-281	[»]
1UNW	X-ray	2.20	A/B	249-281	[»]
1UNX	X-ray	2.40	A/B	249-281	[»]
1UNY	X-ray	2.30	A/B	249-281	[»]
1UNZ	X-ray	2.30	A/B	249-281	[»]
1UO0	X-ray	2.40	A/B	249-281	[»]
1UO1	X-ray	2.50	A/B	249-281	[»]
1UO2	X-ray	1.99	A/B	249-281	[»]
1UO3	X-ray	1.92	A/B	249-281	[»]
1UO4	X-ray	1.70	A/B	249-281	[»]
1UO5	X-ray	2.07	A/B	249-281	[»]
1W5G	X-ray	2.16	A/B	249-281	[»]
1W5H	X-ray	2.50	A/B	249-281	[»]
1W5I	X-ray	2.30	A/B	249-281	[»]
1W5J	X-ray	2.20	A/B/C/D	249-273	[»]
1W5K	X-ray	1.92	A/B/C/D	249-263	[»]
1W5L	X-ray	2.17	A/B	249-281	[»]
1YSA	X-ray	2.90	C/D	226-281	[»]
1ZII	X-ray	1.80	A/B	249-281	[»]
1ZIJ	X-ray	2.00	A/B/C	249-281	[»]
1ZIK	X-ray	1.80	A/B	249-281	[»]
1ZIL	X-ray	2.25	A/B	249-281	[»]
1ZIM	X-ray	2.00	A/B/C	249-281	[»]
1ZTA	NMR	-	A	247-281	[»]
2AHP	X-ray	2.00	A/B	249-281	[»]
2B1F	X-ray	1.50	A/B/C/D	251-281	[»]
2B22	X-ray	2.00	A	251-281	[»]
2BNI	X-ray	1.50	A/B/C/D	249-281	[»]
2CCE	X-ray	1.90	A/B	249-281	[»]
2CCF	X-ray	1.70	A/B	249-281	[»]
2CCN	X-ray	1.60	A/B	249-281	[»]
2D3E	X-ray	2.60	A/B/C/D	254-277	[»]
2DGC	X-ray	2.20	A	220-281	[»]
2EFR	X-ray	1.80	A/B/C/D	249-277	[»]
2EFS	X-ray	2.00	A/B/C/D	249-277	[»]
2G9J	NMR	-	A/B	264-281	[»]
2HY6	X-ray	1.25	A/B/C/D/E/F/G	251-281	[»]
2IPZ	X-ray	1.35	A/B/C/D	251-281	[»]
2LPB	NMR	-	B	101-134	[»]
2NRN	X-ray	1.40	A/B/C/D	251-281	[»]
2O7H	X-ray	1.86	A/B/C/D/E/F	249-281	[»]
2OVN	NMR	-	A	264-280	[»]
2WG5	X-ray	2.10	A/B/C/D/E/F/G/H/I/J/K/L	249-272	[»]
2WG6	X-ray	2.50	A/B/C/D/E/F/G/H/I/J/K/L	249-272	[»]
2WPY	X-ray	1.75	A	249-281	[»]
2WPZ	X-ray	1.25	A/B/C	249-281	[»]
2WQ0	X-ray	1.12	A	249-281	[»]
2WQ1	X-ray	1.08	A	249-281	[»]
2WQ2	X-ray	1.36	A	249-281	[»]
2WQ3	X-ray	1.22	A	249-281	[»]
2YNY	X-ray	1.35	A/B/C	250-277	[»]
2YNZ	X-ray	1.40	A/B/C	250-277	[»]
2YO0	X-ray	2.80	A	250-277	[»]
2YO1	X-ray	3.10	A/B/C	250-277	[»]
2YO2	X-ray	2.00	A	250-277	[»]
2YO3	X-ray	2.00	A/B/C	251-277	[»]
2Z5H	X-ray	2.89	A/B/C/D/E/F/G/H	259-278	[»]
			I	267-278	[»]
2Z5I	X-ray	2.10	A/B/C/D/E/F/G/H	259-278	[»]
			I/J	267-278	[»]
2ZTA	X-ray	1.80	A/B	249-281	[»]
3AZD	X-ray	0.98	A/B	264-281	[»]
3BAS	X-ray	2.30	A/B	250-281	[»]
3BAT	X-ray	2.30	A/B/C/D	250-281	[»]
3CK4	X-ray	1.70	A/B/C/D/E/F/G/H/I/J/K/L	251-281	[»]
3CRP	X-ray	1.70	A/B/C/D/E	251-281	[»]
3G9R	X-ray	2.00	A/B/C/D/E/F	258-263	[»]
3GJP	X-ray	2.00	A/B/C	249-281	[»]
3I1G	X-ray	1.60	A	249-281	[»]
3I5C	X-ray	1.94	A/B	249-278	[»]
3K7Z	X-ray	1.90	A/B/C	249-281	[»]
3M48	X-ray	1.45	A	249-281	[»]
3P8M	X-ray	2.90	C/D	250-281	[»]
3ZMF	X-ray	1.85	A/B/C	250-277	[»]
4G2K	X-ray	1.90	A/B/C	250-277	[»]

DisProt

DP00083.

ProteinModelPortal

P03069.

SMR

P03069. Positions 101-134, 229-277.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-591N.

IntAct

P03069. 5 interactions.

MINT

MINT-395967.

Proteomic databases

PaxDb

P03069.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YEL009C; YEL009C; YEL009C.

GeneID

856709.

KEGG

sce:YEL005C.
sce:YEL009C.

Organism-specific databases

CYGD

YEL009c.

SGD

S000000735. GCN4.

Phylogenomic databases

eggNOG

NOG329891.

KO

K09464.

OMA

RKLQRMN.

OrthoDB

EOG46QB3F.

Gene expression databases

Genevestigator

P03069.

GermOnline

YEL009C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR004827. bZIP.
[Graphical view]

Pfam

PF00170. bZIP_1. 1 hit.
[Graphical view]

SMART

SM00338. BRLZ. 1 hit.
[Graphical view]

PROSITE

PS50217. BZIP. 1 hit.
PS00036. BZIP_BASIC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P03069.

NextBio

982781.

Entry information

Entry name

GCN4_YEAST

Accession

Primary (citable) accession number: P03069
Secondary accession number(s): D3DLN9 , P03068, Q70D88, Q70D91, Q70D96, Q70D99, Q70DA0, Q96UT3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 148 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program