UniProt Accession

 ATF4_HUMAN; P18848; Q9UH31 

Genbank Protein ID

 D90209; M86842; AL022312; BC008090; BC011994; BC024775; BC073990 

Genbank Nucleotide ID

 BAA14234.1; AAA52071.1; CAB45284.1; AAH08090.1; AAH11994.1; AAH24775.1; AAH73990.1 

Protein Name

 Cyclic AMP-dependent transcription factor ATF-4 

Protein Synonyms/Alias

 cAMP-dependent transcription factor ATF-4; Activating transcription factor 4; Cyclic AMP-responsive element-binding protein 2; CREB-2; cAMP-responsive element-binding protein 2; DNA-binding protein TAXREB67; Tax-responsive enhancer element-binding protein 67; TaxREB67 

Gene Name

 ATF4 

Gene Synonyms/Alias

 CREB2; TXREB 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
45	LEVAKHFKPHGFSSD	ubiquitination	[1, 2, 3]
53	PHGFSSDKAKAGSSE	ubiquitination	[2, 4]
55	GFSSDKAKAGSSEWL	ubiquitination	[1, 2, 3]
75	VSPSNNSKEDAFSGT	ubiquitination	[1, 2, 3, 4]
88	GTDWMLEKMDLKEFD	ubiquitination	[1, 3, 4]
259	LCGSARPKPYDPPGE	ubiquitination	[2]
267	PYDPPGEKMVAAKVK	acetylation	[5, 6]
267	PYDPPGEKMVAAKVK	ubiquitination	[2, 3]
299	ATRYRQKKRAEQEAL	ubiquitination	[2]
311	EALTGECKELEKKNE	acetylation	[7]
311	EALTGECKELEKKNE	ubiquitination	[2]
329	ERADSLAKEIQYLKD	ubiquitination	[1, 2, 3]
335	AKEIQYLKDLIEEVR	ubiquitination	[1, 2, 3]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] p300 modulates ATF4 stability and transcriptional activity independently of its acetyltransferase domain.
 Lassot I, Estrabaud E, Emiliani S, Benkirane M, Benarous R, Margottin-Goguet F.
 J Biol Chem. 2005 Dec 16;280(50):41537-45. [PMID: 16219772] 

Functional Description

 Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to ER stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. 

Sequence Annotation

 DOMAIN 278 341 bZIP.
 REGION 280 300 Basic motif (By similarity).
 REGION 305 341 Interaction with GABBR1 (By similarity).
 REGION 306 334 Leucine-zipper (By similarity).  

Keyword

 3D-structure; Activator; Cell membrane; Coiled coil; Complete proteome; Cytoplasm; Cytoskeleton; DNA-binding; Lipoprotein; Membrane; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transcription; Transcription regulation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 351 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; ISS:UniProtKB.
 GO:0032590; C:dendrite membrane; IEA:Compara.
 GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005667; C:transcription factor complex; IEA:Compara.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:UniProtKB.
 GO:0006987; P:activation of signaling protein activity involved in unfolded protein response; TAS:Reactome.
 GO:0006520; P:cellular amino acid metabolic process; TAS:UniProtKB.
 GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
 GO:0007214; P:gamma-aminobutyric acid signaling pathway; IEA:Compara.
 GO:0006094; P:gluconeogenesis; ISS:UniProtKB.
 GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
 GO:0043267; P:negative regulation of potassium ion transport; IEA:Compara.
 GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0006366; P:transcription from RNA polymerase II promoter; ISS:UniProtKB. 

Interpro

 IPR004827; bZIP. 

Pfam

 PF00170; bZIP_1 

SMART

 SM00338; BRLZ 

PROSITE

 PS50217; BZIP
 PS00036; BZIP_BASIC 

PRINTS