Reviewed, UniProtKB/Swiss-Prot P03069 (GCN4_YEAST)

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 (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	281 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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).
Sequence similarities	Belongs to the bZIP family. GCN4 subfamily. Contains 1 bZIP 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
Gene Ontology (GO)
Biological process	amino acid biosynthetic process Traceable author statement. Source: SGD positive regulation of gene-specific transcription involved in unfolded protein response Inferred from mutant phenotype. Source: SGD
Cellular component	nucleus Inferred from physical interaction. Source: SGD
Molecular function	transcription factor activity Inferred from direct assay. 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

253 – 274

22

Leucine-zipper

DNA binding

231 – 249

19

Basic motif

Region

89 – 100

12

Required for transcriptional activation

Region

106 – 125

20

Required for transcriptional activation

Amino acid modifications

Modified residue

17

1

Phosphoserine

Modified residue

165

1

Phosphothreonine; by PHO85

Modified residue

218

1

Phosphoserine

Natural variations

Natural variant

24

1

S → P in strain: CLIB 219.

Natural variant

62

1

P → S in strain: CLIB 630 haplotype Ha2.

Natural variant

82

1

T → A in strain: CLIB 556 haplotype Ha1.

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.

Natural variant

125

1

D → A in strain: CLIB 556 haplotype Ha1.

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.

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

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

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

Mutagenesis

120 – 124

5

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

Sequence conflict

239 – 281

43

ARRSR…LVGER → PGVLVRESCKE in AAA65521. Ref.2

Secondary structure

1

.

.

.

.

.

281

Helix Strand Turn

Details...

Helix

230 – 248

19

Helix

251 – 280

30

Sequences

	Sequence		Length	Mass (Da)
	P03069-1 [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: 6387704] [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: 6433345] [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: 15087486] [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: 9169868] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[5]	"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: 11896344] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 249-281.
[6]	"Functional dissection of a eukaryotic transcriptional activator protein, GCN4 of yeast." Hope I.A., Struhl K. Cell 46:885-894(1986) [PubMed: 3530496] [Abstract] Cited for: DOMAINS.
[7]	"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: 7862116] [Abstract] Cited for: DOMAINS, MUTAGENESIS OF 97-PHE-PHE-98; MET-107; TYR-110; LEU-113 AND 120-TRP--PHE-124.
[8]	"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: 12101234] [Abstract] Cited for: PHOSPHORYLATION AT THR-165.
[9]	"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: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; THR-165 AND SER-218, MASS SPECTROMETRY.
[10]	"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: 1948029] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 250-281.
[11]	"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: 1473154] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 226-281.
[12]	"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: 9837709] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 249-281.
[13]	"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: 1891459] [Abstract] Cited for: STRUCTURE BY NMR OF 237-281.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

RGBYA2. A03605.

RefSeq

NP_010907.1.

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CE9	X-ray	1.80	A/B/C/D	251-281	[»]
1DGC	X-ray	3.00	A	220-281	[»]
1FAV	X-ray	3.00	A	-	[»]
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	249-280	[»]
1GZL	X-ray	1.80	A/B	-	[»]
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	255-281	[»]
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	249-279	[»]
1RB1	X-ray	1.90	A/B/C	249-281	[»]
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	249-281	[»]
1W5K	X-ray	1.92	A/B/C/D	249-281	[»]
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	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	253-278	[»]
2DGC	X-ray	2.20	A	220-281	[»]
2EFR	X-ray	1.80	A/B/C/D	248-277	[»]
2EFS	X-ray	2.00	A/B/C/D	248-277	[»]
2G9J	NMR	-	A/B	264-281	[»]
2IPZ	X-ray	1.35	A	251-281	[»]
2NRN	X-ray	1.40	A/B/C/D	251-281	[»]
2O7H	X-ray	1.86	A/B/C/D/E/F	249-281	[»]
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	[»]

DisProt

DP00083.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:591N.

IntAct

P03069.

Genome annotation databases

Ensembl

YEL009C. Saccharomyces cerevisiae. [Contig view]

GeneID

856709.

GenomeReviews

Gene locus YEL009C in contig U00092_GR.

KEGG

sce:YEL009C.

NMPDR

fig|4932.3.peg.1964.

Organism-specific databases

CYGD

YEL009c.

SGD

S000000735. GCN4.

Yeast-GFP

Search...

Gene expression databases

ArrayExpress

P03069.

GermOnline

YEL009C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR011616. bZIP_1.
IPR004827. TF_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]

BLOCKS

Search...

ProtoNet

Search...

Other Resources

LinkHub

P03069.

NextBio

982781.

Entry information

Entry name	GCN4_YEAST
Accession	Primary (citable) accession number: P03069 Secondary accession number(s): P03068