dbPTM

ATF4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	ATF4_HUMAN
UniProt AC	P18848
Protein Name	Cyclic AMP-dependent transcription factor ATF-4
Gene Name	ATF4
Organism	Homo sapiens (Human).
Sequence Length	351
Subcellular Localization	Cytoplasm . Cell membrane . Nucleus . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Colocalizes with NEK6 at the centrosome (PubMed:20873783).
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. 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 endoplasmic reticulum (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. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors. [PubMed: 26086088]
Protein Sequence	MTEMSFLSSEVLVGDLMSPFDQSGLGAEESLGLLDDYLEVAKHFKPHGFSSDKAKAGSSEWLAVDGLVSPSNNSKEDAFSGTDWMLEKMDLKEFDLDALLGIDDLETMPDDLLTTLDDTCDLFAPLVQETNKQPPQTVNPIGHLPESLTKPDQVAPFTFLQPLPLSPGVLSSTPDHSFSLELGSEVDITEGDRKPDYTAYVAMIPQCIKEEDTPSDNDSGICMSPESYLGSPQHSPSTRGSPNRSLPSPGVLCGSARPKPYDPPGEKMVAAKVKGEKLDKKLKKMEQNKTAATRYRQKKRAEQEALTGECKELEKKNEALKERADSLAKEIQYLKDLIEEVRKARGKKRVP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
42	Ubiquitination	DDYLEVAKHFKPHGF HHHHHHHHHCCCCCC	55.54	22817900
45	Ubiquitination	LEVAKHFKPHGFSSD HHHHHHCCCCCCCCH	35.51	21906983
45	Ubiquitination	LEVAKHFKPHGFSSD HHHHHHCCCCCCCCH	35.51	21906983
45	Sumoylation	LEVAKHFKPHGFSSD HHHHHHCCCCCCCCH	35.51	-
45	Sumoylation	LEVAKHFKPHGFSSD HHHHHHCCCCCCCCH	35.51	-
53	Sumoylation	PHGFSSDKAKAGSSE CCCCCCHHHCCCCCC	54.45	-
53	Ubiquitination	PHGFSSDKAKAGSSE CCCCCCHHHCCCCCC	54.45	21963094
53	Sumoylation	PHGFSSDKAKAGSSE CCCCCCHHHCCCCCC	54.45	28112733
55	Ubiquitination	GFSSDKAKAGSSEWL CCCCHHHCCCCCCEE	60.05	21906983
69	Phosphorylation	LAVDGLVSPSNNSKE EEECCEECCCCCCHH	27.88	25850435
71	Phosphorylation	VDGLVSPSNNSKEDA ECCEECCCCCCHHHC	40.93	21406692
74	Phosphorylation	LVSPSNNSKEDAFSG EECCCCCCHHHCCCC	41.49	25850435
75	Ubiquitination	VSPSNNSKEDAFSGT ECCCCCCHHHCCCCC	62.83	21906983
88	Ubiquitination	GTDWMLEKMDLKEFD CCHHHHHCCCCCCCC	33.48	21906983
92	Ubiquitination	MLEKMDLKEFDLDAL HHHCCCCCCCCHHHH	52.66	22817900
107	Phosphorylation	LGIDDLETMPDDLLT HCCCCHHHCCHHHHH	41.10	-
114	Phosphorylation	TMPDDLLTTLDDTCD HCCHHHHHHHHHHHH	32.39	-
115	Phosphorylation	MPDDLLTTLDDTCDL CCHHHHHHHHHHHHH	28.32	-
119	Phosphorylation	LLTTLDDTCDLFAPL HHHHHHHHHHHHHHH	13.95	-
166	Phosphorylation	FLQPLPLSPGVLSST EEEECCCCCCCCCCC	20.05	26074081
213	Phosphorylation	QCIKEEDTPSDNDSG HHHCCCCCCCCCCCC	28.15	-
215	Phosphorylation	IKEEDTPSDNDSGIC HCCCCCCCCCCCCCC	51.65	23123191
219	Phosphorylation	DTPSDNDSGICMSPE CCCCCCCCCCCCCHH	35.99	11238952
224	Phosphorylation	NDSGICMSPESYLGS CCCCCCCCHHHHCCC	22.54	22817900
231	Phosphorylation	SPESYLGSPQHSPST CHHHHCCCCCCCCCC	20.84	-
235	Phosphorylation	YLGSPQHSPSTRGSP HCCCCCCCCCCCCCC	18.46	-
236	Hydroxylation	LGSPQHSPSTRGSPN CCCCCCCCCCCCCCC	37.28	-
245	Phosphorylation	TRGSPNRSLPSPGVL CCCCCCCCCCCCCCC	51.80	22817900
248	Phosphorylation	SPNRSLPSPGVLCGS CCCCCCCCCCCCCCC	39.31	30108239
259	Ubiquitination	LCGSARPKPYDPPGE CCCCCCCCCCCCCCC	51.13	-
259	Sumoylation	LCGSARPKPYDPPGE CCCCCCCCCCCCCCC	51.13	28112733
267	Sumoylation	PYDPPGEKMVAAKVK CCCCCCCCCEEEHHH	44.59	28112733
267	Ubiquitination	PYDPPGEKMVAAKVK CCCCCCCCCEEEHHH	44.59	23503661
267	Sumoylation	PYDPPGEKMVAAKVK CCCCCCCCCEEEHHH	44.59	-
267	Acetylation	PYDPPGEKMVAAKVK CCCCCCCCCEEEHHH	44.59	23749302
272	Sumoylation	GEKMVAAKVKGEKLD CCCCEEEHHHHHHHH	34.44	28112733
272	Acetylation	GEKMVAAKVKGEKLD CCCCEEEHHHHHHHH	34.44	26051181
272	Ubiquitination	GEKMVAAKVKGEKLD CCCCEEEHHHHHHHH	34.44	23503661
274	Acetylation	KMVAAKVKGEKLDKK CCEEEHHHHHHHHHH	61.72	26051181
277	Acetylation	AAKVKGEKLDKKLKK EEHHHHHHHHHHHHH	71.32	26051181
277	Ubiquitination	AAKVKGEKLDKKLKK EEHHHHHHHHHHHHH	71.32	-
290	Phosphorylation	KKMEQNKTAATRYRQ HHHHHHHHHHHHHHH	29.13	29978859
293	Phosphorylation	EQNKTAATRYRQKKR HHHHHHHHHHHHHHH	26.26	24719451
295	Phosphorylation	NKTAATRYRQKKRAE HHHHHHHHHHHHHHH	17.03	24719451
299	Ubiquitination	ATRYRQKKRAEQEAL HHHHHHHHHHHHHHH	48.80	-
311	Ubiquitination	EALTGECKELEKKNE HHHHHHHHHHHHHHH	62.12	-
311	Acetylation	EALTGECKELEKKNE HHHHHHHHHHHHHHH	62.12	16219772
326	Phosphorylation	ALKERADSLAKEIQY HHHHHHHHHHHHHHH	29.28	28122231
329	Ubiquitination	ERADSLAKEIQYLKD HHHHHHHHHHHHHHH	61.72	23503661
335	Ubiquitination	AKEIQYLKDLIEEVR HHHHHHHHHHHHHHH	45.62	22817900
343	Acetylation	DLIEEVRKARGKKRV HHHHHHHHHHCCCCC	47.84	88871
348	Acetylation	VRKARGKKRVP---- HHHHHCCCCCC----	62.54	88875

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
107	T	Phosphorylation	Kinase	RET	P07949	PSP
114	T	Phosphorylation	Kinase	RET	P07949	PSP
115	T	Phosphorylation	Kinase	RET	P07949	PSP
119	T	Phosphorylation	Kinase	RET	P07949	PSP
215	S	Phosphorylation	Kinase	CK2A1	P68400	PSP
215	S	Phosphorylation	Kinase	CK2B	P67870	PSP
215	S	Phosphorylation	Kinase	CK2	-	Uniprot
245	S	Phosphorylation	Kinase	KS6A3	P51812	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:11238952

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
213	T	Phosphorylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
213	T	ubiquitylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
215	S	Phosphorylation	23123191
Phosphorylation at Ser-215 by CK2 decreases its stability.
219	S	Phosphorylation	16219772
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
219	S	ubiquitylation	16219772
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
224	S	Phosphorylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
224	S	ubiquitylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
231	S	Phosphorylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
231	S	ubiquitylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
235	S	Phosphorylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
235	S	ubiquitylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
245	S	Phosphorylation	15109498
Phosphorylation at Ser-245 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation.
248	S	Phosphorylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).
248	S	ubiquitylation	23123191
Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity).

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of ATF4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GPS2_HUMAN	GPS2	physical	16189514
LDOC1_HUMAN	LDOC1	physical	16189514
TREX2_HUMAN	TREX2	physical	16189514
PTCD3_HUMAN	PTCD3	physical	16189514
TTHY_HUMAN	TTR	physical	16189514
RPB3_HUMAN	POLR2C	physical	12860379
TRIB3_HUMAN	TRIB3	physical	12743605
CEBPB_MOUSE	Cebpb	physical	11018027
EIF2A_HUMAN	EIF2A	physical	15475356
TBP_HUMAN	TBP	physical	9295363
T2FB_HUMAN	GTF2F2	physical	9295363
TF2B_HUMAN	GTF2B	physical	9295363
CBP_HUMAN	CREBBP	physical	9295363
JUN_HUMAN	JUN	physical	1827203
ATF3_HUMAN	ATF3	physical	19164757
TRIB3_HUMAN	TRIB3	physical	18276110
EP300_HUMAN	EP300	physical	16219772
ZN226_HUMAN	ZNF226	physical	20211142
TIF1A_HUMAN	TRIM24	physical	20211142
TF2AY_HUMAN	GTF2A1L	physical	20211142
KAT2B_HUMAN	KAT2B	physical	17726049
FBW1A_HUMAN	BTRC	physical	11238952
CEBPE_HUMAN	CEBPE	physical	17042743
EGLN3_HUMAN	EGLN3	physical	17684156
A4_HUMAN	APP	physical	21832049
ZN212_HUMAN	ZNF212	physical	18255255
SRA1_HUMAN	SRA1	physical	20398657
NF2L2_HUMAN	NFE2L2	physical	23661758
MAF_HUMAN	MAF	physical	23661758
BATF3_HUMAN	BATF3	physical	23661758
BATF_HUMAN	BATF	physical	23661758
ATF3_HUMAN	ATF3	physical	23661758
ATF4_HUMAN	ATF4	physical	23661758
FOSL1_HUMAN	FOSL1	physical	23661758
FOS_HUMAN	FOS	physical	23661758
JUN_HUMAN	JUN	physical	23661758
ATF2_HUMAN	ATF2	physical	23661758
CEBPE_HUMAN	CEBPE	physical	23661758
CEBPA_HUMAN	CEBPA	physical	23661758
DDIT3_HUMAN	DDIT3	physical	23661758
EP300_HUMAN	EP300	physical	14630807
MPZL2_HUMAN	MPZL2	physical	21988832
TGM2_HUMAN	TGM2	physical	21988832
REPS1_HUMAN	REPS1	physical	21988832
FBW1A_HUMAN	BTRC	physical	21988832
RS6_HUMAN	RPS6	physical	21988832
HXK3_HUMAN	HK3	physical	21988832
JUNB_HUMAN	JUNB	physical	21988832
LMNB1_HUMAN	LMNB1	physical	21988832
MDM2_HUMAN	MDM2	physical	21988832
MP2K7_HUMAN	MAP2K7	physical	21988832
SNP29_HUMAN	SNAP29	physical	21988832
CKAP4_HUMAN	CKAP4	physical	21988832
EP300_HUMAN	EP300	physical	17872950
CEBPG_HUMAN	CEBPG	physical	25416956
GOGA1_HUMAN	GOLGA1	physical	25416956
GPS2_HUMAN	GPS2	physical	25416956
BFSP2_HUMAN	BFSP2	physical	25416956
FBW1A_HUMAN	BTRC	physical	25416956
NDC80_HUMAN	NDC80	physical	25416956
LDOC1_HUMAN	LDOC1	physical	25416956
CC106_HUMAN	CCDC106	physical	25416956
TRIB3_HUMAN	TRIB3	physical	25416956
GCC1_HUMAN	GCC1	physical	25416956
FBW1A_HUMAN	BTRC	physical	21516116
JUN_HUMAN	JUN	physical	25241761
FOS_HUMAN	FOS	physical	25241761
CBP_HUMAN	CREBBP	physical	25241761
EP300_HUMAN	EP300	physical	12471036
TBC25_HUMAN	TBC1D25	physical	28514442
MDM2_HUMAN	MDM2	physical	27264869

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00852	Pseudoephedrine

Regulatory Network of ATF4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69, AND MASSSPECTROMETRY.	19413330 [Abstract]

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