ATF4_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ATF4_MOUSE
• UniProt AC: Q06507
• Protein Name: Cyclic AMP-dependent transcription factor ATF-4
• Gene Name: Atf4
• Organism: Mus musculus (Mouse).
• Sequence Length: 349
• Subcellular Localization: Cytoplasm . Cell membrane . Nucleus . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Colocalizes with GABBR1 in hippocampal neuron dendritic membranes. Colocalizes with NEK6 in the centrosome (By similarity).
• Protein Description: Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production. 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. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes..
• Protein Sequence: MTEMSFLNSEVLAGDLMSPFDQSGLGAEESLGLLDDYLEVAKHLKPHGFSSDKAGSSEWPAMDDGLASASDTGKEDAFSGTDWMLEKMDLKEFDFDALFRMDDLETMPDELLTTLDDTCDLFAPLVQETNKEPPQTVNPIGHLPESLIKVDQVAPFTFLQPFPCSPGVLSSTPEHSFSLELGSEVDISEGDRKPDSAAYITLIPPCVKEEDTPSDNDSGICMSPESYLGSPQHSPSTSRAPPDNLPSPGGSRGSPRPKPYDPPGVSLTAKVKTEKLDKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKEKADSLAKEIQYLKDLIEEVRKARGKKRVP

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
60	Hydroxylation	KAGSSEWPAMDDGLA CCCCCCCCCCCCCCC	17.41	24809345
91	Ubiquitination	MLEKMDLKEFDFDAL HHHCCCCCCCCHHHE	52.66	-
212	Phosphorylation	PCVKEEDTPSDNDSG CCCCCCCCCCCCCCC	28.15	23663782
214	Phosphorylation	VKEEDTPSDNDSGIC CCCCCCCCCCCCCCC	51.65	-
218	Phosphorylation	DTPSDNDSGICMSPE CCCCCCCCCCCCCHH	35.99	23663782
223	Phosphorylation	NDSGICMSPESYLGS CCCCCCCCHHHHCCC	22.54	23663782
230	Phosphorylation	SPESYLGSPQHSPST CHHHHCCCCCCCCCC	20.84	23663782
234	Phosphorylation	YLGSPQHSPSTSRAP HCCCCCCCCCCCCCC	18.46	23663782
235	Hydroxylation	LGSPQHSPSTSRAPP CCCCCCCCCCCCCCC	39.23	24809345
247	Phosphorylation	APPDNLPSPGGSRGS CCCCCCCCCCCCCCC	39.07	25619855
251	Phosphorylation	NLPSPGGSRGSPRPK CCCCCCCCCCCCCCC	39.11	25619855
254	Phosphorylation	SPGGSRGSPRPKPYD CCCCCCCCCCCCCCC	19.34	27841257
309	Acetylation	EALTGECKELEKKNE HHHHHHHHHHHHHHH	62.12	-
341	Acetylation	DLIEEVRKARGKKRV HHHHHHHHHHCCCCC	47.84	88873
346	Acetylation	VRKARGKKRVP---- HHHHHCCCCCC----	62.54	88877

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
251	S	Phosphorylation	Kinase	KS6A3	P18654	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	Btrc	Q3ULA2	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
212	T	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
212	T	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
214	S	Phosphorylation	Phosphorylation at Ser-214 by CK2 decreases its stability (By similarity).	23663782
218	S	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
218	S	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
223	S	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
223	S	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
230	S	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
230	S	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
234	S	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
234	S	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	23663782
247	S	Phosphorylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	15109498
247	S	ubiquitylation	Phosphorylated on the betaTrCP degron motif at Ser-218, followed by phosphorylation at Thr-212, Ser-223, Ser-230, Ser-234 and Ser-247, promoting interaction with BTRC and ubiquitination.	15109498
251	S	Phosphorylation	Phosphorylation at Ser-251 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation.	15109498

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of ATF4_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DAPK3_HUMAN	DAPK3	physical	9488481
DAPK3_MOUSE	Dapk3	physical	9488481
FOS_MOUSE	Fos	physical	20211142
JUN_MOUSE	Jun	physical	20211142
GABR1_MOUSE	Gabbr1	physical	15013631
GABR2_MOUSE	Gabbr2	physical	15013631
ABRX2_MOUSE	Fam175b	physical	22974638
SATB2_MOUSE	Satb2	physical	16751105
TRIB3_MOUSE	Trib3	physical	12749859
HIF1A_MOUSE	Hif1a	physical	23649506
EGLN3_MOUSE	Egln3	physical	23649506

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.