dbPTM

CRTC2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CRTC2_MOUSE
UniProt AC	Q3U182
Protein Name	CREB-regulated transcription coactivator 2
Gene Name	Crtc2
Organism	Mus musculus (Mouse).
Sequence Length	692
Subcellular Localization	Cytoplasm . Nucleus . Translocated from the nucleus to the cytoplasm on interaction of the phosphorylated form with 14-3-3 protein (By similarity). In response to cAMP levels and glucagon, relocated to the nucleus (PubMed:16148943).
Protein Description	Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates gluconeogenesis as a component of the LKB1/AMPK/TORC2 signaling pathway. Regulates the expression of specific genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells (By similarity)..
Protein Sequence	MATSGANGPGSATASASNPRKFSEKIALQKQRQAEETAAFEEVMMDIGSTRLQAQKLRLAYTRSSHYGGSLPNVNQIGCGLAEFQSPLHSPLDSSRSTRHHGLVERVQRDARRMVSPLRRYPRHIDSSPYSPAYLSPPPESGWRRMMPWGNLPAEKGQLFRLPSALNRTSSDSALHTSVMNPNPQDTYPGPTPPSVLPSRRGGGFLDGEMDAKVPAIEENVVDDKHLLKPWDAKKLSSSSSRPRSCEVPGINIFPSPDQPANVPVLPPAMNTGGSLPDLTNLHFPPPLPTPLDPEETVYPSLSGGNSTTNLTHTMTHLGISGGLGLGPSYDVPGLHSPLSHPSLQSSLSNPNLQASLSSPQPQLQGSHSHPSLPASSLAHHALPTTSLGHPSLSAPALSSSSSSSSTSSPVLSAPPYPASTPGASPRHRRVPLSPLSLPAGPADARRSQQQLPKQFSPTMSPTLSSITQGVPLDTSKLPTDQRLPPYPYSPPSLVIPTHPPTPKSLQQLPSQACLVQPSGGQPPGRQPHYGALYPPGSSGHGQQPYHRPINDFSLGNLEQFNMESPSTSLVLDPPAFSEGPGFLGSEGSMSGPQDPHVLNHQNLTHCSRHGSGPNIILTGDSSPGFSKEIAAALAGVPGFEVSASGLELGLGLEDELRMEPLGLEGLTMLSDPCALLPDPAVEDSFRSDRLQ

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MATSGANGP ------CCCCCCCCC	15.52	-
37	O-linked_Glycosylation	KQRQAEETAAFEEVM HHHHHHHHHHHHHHH	18.13	21805467
51	Asymmetric dimethylarginine	MMDIGSTRLQAQKLR HHHHCCHHHHHHHHH	26.88	-
51	Methylation	MMDIGSTRLQAQKLR HHHHCCHHHHHHHHH	26.88	24570487
64	Phosphorylation	LRLAYTRSSHYGGSL HHHHHHCCCCCCCCC	17.42	27087446
65	Phosphorylation	RLAYTRSSHYGGSLP HHHHHCCCCCCCCCC	19.89	25619855
67	Phosphorylation	AYTRSSHYGGSLPNV HHHCCCCCCCCCCCH	25.73	25619855
70	Phosphorylation	RSSHYGGSLPNVNQI CCCCCCCCCCCHHHC	35.97	27087446
70	O-linked_Glycosylation	RSSHYGGSLPNVNQI CCCCCCCCCCCHHHC	35.97	41325
86	Phosphorylation	CGLAEFQSPLHSPLD CCHHHCCCCCCCCCC	34.45	25619855
90	Phosphorylation	EFQSPLHSPLDSSRS HCCCCCCCCCCCCCC	34.54	25619855
94	Phosphorylation	PLHSPLDSSRSTRHH CCCCCCCCCCCCCHH	35.02	25619855
95	Phosphorylation	LHSPLDSSRSTRHHG CCCCCCCCCCCCHHH	29.89	25619855
99	Methylation	LDSSRSTRHHGLVER CCCCCCCCHHHHHHH	22.50	24570487
99	Asymmetric dimethylarginine	LDSSRSTRHHGLVER CCCCCCCCHHHHHHH	22.50	-
116	Phosphorylation	RDARRMVSPLRRYPR HHHHHHHHCHHHCCC	14.63	24453211
120	Methylation	RMVSPLRRYPRHIDS HHHHCHHHCCCCCCC	54.19	24570487
120	Asymmetric dimethylarginine	RMVSPLRRYPRHIDS HHHHCHHHCCCCCCC	54.19	-
121	Phosphorylation	MVSPLRRYPRHIDSS HHHCHHHCCCCCCCC	9.74	22817900
123	Methylation	SPLRRYPRHIDSSPY HCHHHCCCCCCCCCC	30.38	24570487
123	Asymmetric dimethylarginine	SPLRRYPRHIDSSPY HCHHHCCCCCCCCCC	30.38	-
127	Phosphorylation	RYPRHIDSSPYSPAY HCCCCCCCCCCCCCC	32.39	22817900
127	O-linked_Glycosylation	RYPRHIDSSPYSPAY HCCCCCCCCCCCCCC	32.39	30831959
128	O-linked_Glycosylation	YPRHIDSSPYSPAYL CCCCCCCCCCCCCCC	24.90	30831953
128	Phosphorylation	YPRHIDSSPYSPAYL CCCCCCCCCCCCCCC	24.90	29472430
130	Phosphorylation	RHIDSSPYSPAYLSP CCCCCCCCCCCCCCC	29.27	29472430
131	Phosphorylation	HIDSSPYSPAYLSPP CCCCCCCCCCCCCCC	13.36	29472430
134	Phosphorylation	SSPYSPAYLSPPPES CCCCCCCCCCCCCCC	15.88	25777480
136	Phosphorylation	PYSPAYLSPPPESGW CCCCCCCCCCCCCCC	23.76	22942356
141	Phosphorylation	YLSPPPESGWRRMMP CCCCCCCCCCCCCCC	49.80	29472430
161	Asymmetric dimethylarginine	AEKGQLFRLPSALNR CCCCCCEECCHHHCC	55.04	-
161	Methylation	AEKGQLFRLPSALNR CCCCCCEECCHHHCC	55.04	24129315
164	Phosphorylation	GQLFRLPSALNRTSS CCCEECCHHHCCCCC	50.40	-
168	Asymmetric dimethylarginine	RLPSALNRTSSDSAL ECCHHHCCCCCCCCC	36.51	-
168	Methylation	RLPSALNRTSSDSAL ECCHHHCCCCCCCCC	36.51	24570487
169	Phosphorylation	LPSALNRTSSDSALH CCHHHCCCCCCCCCC	31.35	21082442
170	Phosphorylation	PSALNRTSSDSALHT CHHHCCCCCCCCCCC	28.98	26239621
171	O-linked_Glycosylation	SALNRTSSDSALHTS HHHCCCCCCCCCCCC	34.66	41327
171	Phosphorylation	SALNRTSSDSALHTS HHHCCCCCCCCCCCC	34.66	22942356
173	Phosphorylation	LNRTSSDSALHTSVM HCCCCCCCCCCCCCC	34.38	22942356
173	O-linked_Glycosylation	LNRTSSDSALHTSVM HCCCCCCCCCCCCCC	34.38	6460851
177	Phosphorylation	SSDSALHTSVMNPNP CCCCCCCCCCCCCCC	24.70	23984901
178	Phosphorylation	SDSALHTSVMNPNPQ CCCCCCCCCCCCCCC	14.50	26239621
187	Phosphorylation	MNPNPQDTYPGPTPP CCCCCCCCCCCCCCC	26.77	26239621
188	Phosphorylation	NPNPQDTYPGPTPPS CCCCCCCCCCCCCCC	17.93	26239621
192	Phosphorylation	QDTYPGPTPPSVLPS CCCCCCCCCCCCCCC	54.47	25777480
195	Phosphorylation	YPGPTPPSVLPSRRG CCCCCCCCCCCCCCC	37.17	25777480
199	Phosphorylation	TPPSVLPSRRGGGFL CCCCCCCCCCCCCCC	30.37	25777480
229	Acetylation	VDDKHLLKPWDAKKL CCCCCCCCCCCHHHC	50.88	23954790
275	Phosphorylation	PAMNTGGSLPDLTNL CCCCCCCCCCCCCCC	37.77	30611118
307	Phosphorylation	PSLSGGNSTTNLTHT CCCCCCCCCCCCCCC	39.62	-
369	Phosphorylation	PQLQGSHSHPSLPAS CCCCCCCCCCCCCHH	38.50	-
394	Phosphorylation	SLGHPSLSAPALSSS CCCCCCCCCCCCCCC	36.22	-
434	Phosphorylation	RHRRVPLSPLSLPAG CCCCCCCCCCCCCCC	20.09	26824392
437	Phosphorylation	RVPLSPLSLPAGPAD CCCCCCCCCCCCHHH	35.37	28833060
448	Phosphorylation	GPADARRSQQQLPKQ CHHHHHHHHHHCCCC	27.13	29899451
457	Phosphorylation	QQLPKQFSPTMSPTL HHCCCCCCCCCCCCH	19.57	27087446
459	Phosphorylation	LPKQFSPTMSPTLSS CCCCCCCCCCCCHHH	29.14	27087446
461	Phosphorylation	KQFSPTMSPTLSSIT CCCCCCCCCCHHHHC	19.74	27087446
463	Phosphorylation	FSPTMSPTLSSITQG CCCCCCCCHHHHCCC	31.78	22942356
465	Phosphorylation	PTMSPTLSSITQGVP CCCCCCHHHHCCCCC	23.36	25619855
466	Phosphorylation	TMSPTLSSITQGVPL CCCCCHHHHCCCCCC	32.54	25619855
468	Phosphorylation	SPTLSSITQGVPLDT CCCHHHHCCCCCCCC	22.63	25619855
475	Phosphorylation	TQGVPLDTSKLPTDQ CCCCCCCCCCCCCCC	35.13	28833060
476	Phosphorylation	QGVPLDTSKLPTDQR CCCCCCCCCCCCCCC	31.68	28833060
487	Phosphorylation	TDQRLPPYPYSPPSL CCCCCCCCCCCCCCE	16.92	26745281
489	Phosphorylation	QRLPPYPYSPPSLVI CCCCCCCCCCCCEEC	28.15	26239621
490	Phosphorylation	RLPPYPYSPPSLVIP CCCCCCCCCCCEECC	26.32	26824392
493	Phosphorylation	PYPYSPPSLVIPTHP CCCCCCCCEECCCCC	38.36	26745281
498	Phosphorylation	PPSLVIPTHPPTPKS CCCEECCCCCCCCHH	35.57	26745281
502	Phosphorylation	VIPTHPPTPKSLQQL ECCCCCCCCHHHHHC	48.04	25266776
612	Phosphorylation	THCSRHGSGPNIILT CCCCCCCCCCCEEEE	44.97	25521595
619	Phosphorylation	SGPNIILTGDSSPGF CCCCEEEECCCCCCC	28.65	27742792
622	Phosphorylation	NIILTGDSSPGFSKE CEEEECCCCCCCCHH	39.51	25521595
623	Phosphorylation	IILTGDSSPGFSKEI EEEECCCCCCCCHHH	33.51	27087446
627	Phosphorylation	GDSSPGFSKEIAAAL CCCCCCCCHHHHHHH	34.98	22942356
628	Acetylation	DSSPGFSKEIAAALA CCCCCCCHHHHHHHC	51.37	183505
628	Ubiquitination	DSSPGFSKEIAAALA CCCCCCCHHHHHHHC	51.37	-
674	Glutathionylation	LTMLSDPCALLPDPA EECCCCCCCCCCCHH	5.10	24333276

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
136	S	Phosphorylation	Kinase	MTOR	P42345	PSP
171	S	Phosphorylation	Kinase	AMPK	-	Uniprot
171	S	Phosphorylation	Kinase	PRKAA1	P54645	GPS
171	S	Phosphorylation	Kinase	MARK-SUBFAMILY	-	GPS
171	S	Phosphorylation	Kinase	AMPK-FAMILY	-	GPS
171	S	Phosphorylation	Kinase	QIK	Q8CFH6	PSP
171	S	Phosphorylation	Kinase	SIK2	Q9H0K1	GPS
171	S	Phosphorylation	Kinase	SIK1	Q60670	Uniprot
171	S	Phosphorylation	Kinase	SIK	P57059	PSP
171	S	Phosphorylation	Kinase	MARK4	Q96L34	PSP
171	S	Phosphorylation	Kinase	MARK2	Q05512	Uniprot
171	S	Phosphorylation	Kinase	MARK2	Q7KZI7	PSP
275	S	Phosphorylation	Kinase	MARK4	Q96L34	PSP
275	S	Phosphorylation	Kinase	SIK	P57059	PSP
275	S	Phosphorylation	Kinase	MARK3	P27448	PSP
275	S	Phosphorylation	Kinase	MARK2	Q7KZI7	PSP
307	S	Phosphorylation	Kinase	MARK4	Q96L34	PSP
307	S	Phosphorylation	Kinase	SIK	P57059	PSP
307	S	Phosphorylation	Kinase	MARK2	Q7KZI7	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	Det1#Cop1	Q9D0A0#Q9R1A8	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
171	S	Phosphorylation	16148943
Following adenylyl cyclase activation, dephosphorylated at Ser-171 by PPP3CA/calcineurin A resulting in CRTC2 dissociation from 14-3-3 proteins and PPP3CA.
171	S	Phosphorylation	16148943
Phosphorylation/dephosphorylation states of Ser-171 are required for regulating transduction of CREB activity.
275	S	Phosphorylation	28235073
Phosphorylation at Ser-275 by MARK2 is induced under low glucose conditions and dephosphorylated in response to glucose influx (By similarity).
275	S	Phosphorylation	28235073
Phosphorylation at Ser-275 promotes interaction with 14-3-3 proteins and translocation to the cytoplasm (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 CRTC2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
1433B_HUMAN	YWHAB	physical	18626018

Drug and Disease Associations

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

Regulatory Network of CRTC2_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-169; THR-177 ANDSER-612, AND MASS SPECTROMETRY.	17242355 [Abstract]
"Insulin modulates gluconeogenesis by inhibition of the coactivatorTORC2."; Dentin R., Liu Y., Koo S.-H., Hedrick S., Vargas T., Heredia J.,Yates J. III, Montminy M.; Nature 449:366-369(2007). Cited for: INTERACTION WITH RFWD2, PHOSPHORYLATION AT SER-171, SUBCELLULARLOCATION, AND MUTAGENESIS OF SER-171; VAL-214; PRO-215 AND LYS-628.	17805301 [Abstract]
"The kinase LKB1 mediates glucose homeostasis in liver and therapeuticeffects of metformin."; Shaw R.J., Lamia K.A., Vasquez D., Koo S.-H., Bardeesy N.,Depinho R.A., Montminy M., Cantley L.C.; Science 310:1642-1646(2005). Cited for: FUNCTION, PHOSPHORYLATION AT SER-171, AND SUBCELLULAR LOCATION.	16308421 [Abstract]
"The CREB coactivator TORC2 is a key regulator of fasting glucosemetabolism."; Koo S.-H., Flechner L., Qi L., Zhang X., Screaton R.A., Jeffries S.,Hedrick S., Xu W., Boussouar F., Brindle P., Takemori H., Montminy M.; Nature 437:1109-1111(2005). Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-171, AND TISSUESPECIFICITY.	16148943 [Abstract]

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