CREB1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CREB1_MOUSE
• UniProt AC: Q01147
• Protein Name: Cyclic AMP-responsive element-binding protein 1
• Gene Name: Creb1
• Organism: Mus musculus (Mouse).
• Sequence Length: 341
• Subcellular Localization: Nucleus .
• Protein Description: Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells..
• Protein Sequence: MTMESGADNQQSGDAAVTEAENQQMTVQAQPQIATLAQVSMPAAHATSSAPTVTLVQLPNGQTVQVHGVIQAAQPSVIQSPQVQTVQSSCKDLKRLFSGTQISTIAESEDSQESVDSVTDSQKRREILSRRPSYRKILNDLSSDAPGVPRIEEEKSEEETSAPAITTVTVPTPIYQTSSGQYIAITQGGAIQLANNGTDGVQGLQTLTMTNAAATQPGTTILQYAQTTDGQQILVPSNQVVVQAASGDVQTYQIRTAPTSTIAPGVVMASSPALPTQPAEEAARKREVRLMKNREAARECRRKKKEYVKCLENRVAVLENQNKTLIEELKALKDLYCHKSD

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
98	Phosphorylation	KDLKRLFSGTQISTI HHHHHHHCCCEEEEE	45.59	22581287
100	Phosphorylation	LKRLFSGTQISTIAE HHHHHCCCEEEEEEC	22.87	22581287
104	Phosphorylation	FSGTQISTIAESEDS HCCCEEEEEECCCCC	26.32	27841257
108	Phosphorylation	QISTIAESEDSQESV EEEEEECCCCCHHHH	37.37	26745281
111	Phosphorylation	TIAESEDSQESVDSV EEECCCCCHHHHHCC	31.62	26745281
114	Phosphorylation	ESEDSQESVDSVTDS CCCCCHHHHHCCCHH	24.48	26745281
117	Phosphorylation	DSQESVDSVTDSQKR CCHHHHHCCCHHHHH	25.43	22581287
119	Phosphorylation	QESVDSVTDSQKRRE HHHHHCCCHHHHHHH	33.61	23984901
121	Phosphorylation	SVDSVTDSQKRREIL HHHCCCHHHHHHHHH	28.38	22581287
128	Phosphorylation	SQKRREILSRRPSYR HHHHHHHHHCCHHHH	2.53	-
129	Phosphorylation	QKRREILSRRPSYRK HHHHHHHHCCHHHHH	31.72	18801732
133	Phosphorylation	EILSRRPSYRKILND HHHHCCHHHHHHHHH	35.44	12198546
136	Ubiquitination	SRRPSYRKILNDLSS HCCHHHHHHHHHHCC	43.22	22790023
136	Acetylation	SRRPSYRKILNDLSS HCCHHHHHHHHHHCC	43.22	126871
142	Phosphorylation	RKILNDLSSDAPGVP HHHHHHHCCCCCCCC	29.09	25521595
143	Phosphorylation	KILNDLSSDAPGVPR HHHHHHCCCCCCCCC	45.12	22324799
156	Phosphorylation	PRIEEEKSEEETSAP CCCCHHCCCCCCCCC	54.22	22581287
256	Phosphorylation	VQTYQIRTAPTSTIA CEEEEEEECCCCCCC	38.32	26239621
257	Phosphorylation	QTYQIRTAPTSTIAP EEEEEEECCCCCCCC	8.77	-
259	Phosphorylation	YQIRTAPTSTIAPGV EEEEECCCCCCCCCE	35.72	26239621
260	Phosphorylation	QIRTAPTSTIAPGVV EEEECCCCCCCCCEE	19.43	26239621
261	Phosphorylation	IRTAPTSTIAPGVVM EEECCCCCCCCCEEE	24.52	26239621
270	Phosphorylation	APGVVMASSPALPTQ CCCEEEECCCCCCCC	20.82	26060331
271	Phosphorylation	PGVVMASSPALPTQP CCEEEECCCCCCCCC	12.49	25521595
276	Phosphorylation	ASSPALPTQPAEEAA ECCCCCCCCCHHHHH	48.30	28833060
330	Ubiquitination	KTLIEELKALKDLYC HHHHHHHHHHHHHHC	55.76	22790023
340	Phosphorylation	KDLYCHKSD------ HHHHCCCCC------	25.53	27600695

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
100	S	Phosphorylation	Kinase	NIK	Q99558	PSP
107	S	Phosphorylation	Kinase	ATM	Q62388	PSP
107	S	Phosphorylation	Kinase	ATR	Q9JKK8	PSP
114	S	Phosphorylation	Kinase	MAP3K14	Q99558	GPS
119	S	Phosphorylation	Kinase	AKT2	Q60823	Uniprot
119	S	Phosphorylation	Kinase	CAMK2	-	Uniprot
119	S	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
119	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
119	S	Phosphorylation	Kinase	NIK	Q9WUL6	PSP
119	S	Phosphorylation	Kinase	RPS6KA5	Q8C050	Uniprot
119	S	Phosphorylation	Kinase	MSK1	O75582	PSP
119	S	Phosphorylation	Kinase	RPS6KA4	Q9Z2B9	Uniprot
119	S	Phosphorylation	Kinase	RPS6KA3	P18654	Uniprot
119	S	Phosphorylation	Kinase	P90RSK	P18653	PSP
119	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
119	S	Phosphorylation	Kinase	CAMK4	P08414	Uniprot
119	S	Phosphorylation	Kinase	CAMK1	Q91YS8	Uniprot
121	S	Phosphorylation	Kinase	ATR	Q9JKK8	GPS
121	S	Phosphorylation	Kinase	ATM	Q62388	GPS
128	S	Phosphorylation	Kinase	CAMK2	-	Uniprot
128	S	Phosphorylation	Kinase	NIK	Q99558	PSP
133	S	Phosphorylation	Kinase	RPS6KA3	P18654	GPS
133	S	Phosphorylation	Kinase	RSK_GROUP	-	PhosphoELM
133	S	Phosphorylation	Kinase	RSK-SUBFAMILY	-	GPS
133	S	Phosphorylation	Kinase	CAMK1-FAMILY	-	GPS
133	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
133	S	Phosphorylation	Kinase	SGK1	Q9WVC6	GPS
133	S	Phosphorylation	Kinase	MAPKAPK2	P49137	GPS
133	S	Phosphorylation	Kinase	CAMK2B	P28652	GPS
133	S	Phosphorylation	Kinase	RPS6KA5	Q8C050	GPS
133	S	Phosphorylation	Kinase	CAMK4	P08414	GPS
133	S	Phosphorylation	Kinase	RPS6KA4	Q9Z2B9	GPS
133	S	Phosphorylation	Kinase	RPS6KA1	P18653	GPS
142	S	Phosphorylation	Kinase	MAP3K14	Q99558	GPS
257	S	Phosphorylation	Kinase	HIPK2	Q9QZR5	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
119	S	Phosphorylation	CREBL2 positively regulates phosphorylation at Ser-119 thereby stimulating CREB1 transcriptional activity.	8552098
119	S	Phosphorylation	In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations.	8552098
119	S	Phosphorylation	In the retina, only phosphorylation of Ser-119 can be detected upon light exposure.	8552098
119	S	Phosphorylation	Phosphorylated at Ser-119 by RPS6KA3, RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli.	8552098
119	S	Phosphorylation	Phosphorylated by TSSK4 on Ser-119 (By similarity).	8552098
119	S	Phosphorylation	Phosphorylated upon calcium influx by CaMK4 and CaMK2 on Ser-119.	8552098
119	S	Phosphorylation	Phosphorylation of Ser-119 allows CREBBP binding.	8552098
119	S	Phosphorylation	Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated.	8552098
119	S	Phosphorylation	Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation.	8552098
128	S	Phosphorylation	In the SCN, phosphorylation of Ser-128 and Ser-119 are stimulated by light exposure and submitted to circadian oscillations.	11970866
128	S	Phosphorylation	Phosphorylated Ser-128 can be detected in the suprachiasmatic nucleus (SCN), the amygdala, the cortex, and the hippocampus but not in the striatum nor in the cerebellum.	11970866
128	S	Phosphorylation	Phosphorylated by CaMK2 on Ser-128.	11970866
128	S	Phosphorylation	Phosphorylation of Ser-128 blocks CREB-mediated transcription even when Ser-119 is phosphorylated.	11970866
128	S	Phosphorylation	Phosphorylation of both Ser-119 and Ser-128 in the SCN regulates the activity of CREB and participates in circadian rhythm generation.	11970866
271	S	Phosphorylation	Phosphorylation of Ser-271 by HIPK2 in response to genotoxic stress promotes CREB1 activity, facilitating the recruitment of the coactivator CBP (By similarity).	18690222
271	K	Sumoylation	Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein.	-
290	K	Sumoylation	Sumoylation on Lys-290, but not on Lys-271, is required for nuclear localization of this protein.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CREB1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SP1_MOUSE	Sp1	physical	21262356
JUN_MOUSE	Jun	physical	21262356
CREB1_MOUSE	Creb1	physical	21262356
MECP2_MOUSE	Mecp2	physical	18511691
BSH_MOUSE	Bsx	physical	17550780
SOX9_MOUSE	Sox9	physical	19113914
EP300_MOUSE	Ep300	physical	17525731
CRTC2_MOUSE	Crtc2	physical	17525731
TRAF3_MOUSE	Traf3	physical	26755589

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"The kinases MSK1 and MSK2 act as negative regulators of Toll-likereceptor signaling.";
Ananieva O., Darragh J., Johansen C., Carr J.M., McIlrath J.,Park J.M., Wingate A., Monk C.E., Toth R., Santos S.G., Iversen L.,Arthur J.S.;
Nat. Immunol. 9:1028-1036(2008).
Cited for: PHOSPHORYLATION AT SER-133, AND MUTAGENESIS OF SER-133.
PubMed: 18690222

"Phosphorylation of CREB Ser142 regulates light-induced phase shiftsof the circadian clock.";
Gau D., Lemberger T., von Gall C., Kretz O., Le Minh N., Gass P.,Schmid W., Schibler U., Korf H.W., Schuetz G.;
Neuron 34:245-253(2002).
Cited for: PHOSPHORYLATION AT SER-133 AND SER-142, MUTAGENESIS OF SER-142, ANDFUNCTION.
PubMed: 11970866

"Phosphorylation of CREB at Ser-133 induces complex formation withCREB-binding protein via a direct mechanism.";
Parker D., Ferreri K., Nakajima T., LaMorte V.J., Evans R.,Koerber S.C., Hoeger C., Montminy M.R.;
Mol. Cell. Biol. 16:694-703(1996).
Cited for: INTERACTION WITH CREBBP, PHOSPHORYLATION AT SER-133, AND MUTAGENESISOF 137-ILE-LEU-138.
PubMed: 8552098