dbPTM

NFAC4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NFAC4_HUMAN
UniProt AC	Q14934
Protein Name	Nuclear factor of activated T-cells, cytoplasmic 4
Gene Name	NFATC4
Organism	Homo sapiens (Human).
Sequence Length	902
Subcellular Localization	Cytoplasm . Nucleus . Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sus
Protein Description	Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 and IL-4. Transcriptionally repressed by estrogen receptors; this inhibition is further enhanced by estrogen. Increases the transcriptional activity of PPARG and has a direct role in adipocyte differentiation. May play an important role in myotube differentiation. May play a critical role in cardiac development and hypertrophy. May play a role in deafferentation-induced apoptosis of sensory neurons..
Protein Sequence	MGAASCEDEELEFKLVFGEEKEAPPLGAGGLGEELDSEDAPPCCRLALGEPPPYGAAPIGIPRPPPPRPGMHSPPPRPAPSPGTWESQPARSVRLGGPGGGAGGAGGGRVLECPSIRITSISPTPEPPAALEDNPDAWGDGSPRDYPPPEGFGGYREAGGQGGGAFFSPSPGSSSLSSWSFFSDASDEAALYAACDEVESELNEAASRFGLGSPLPSPRASPRPWTPEDPWSLYGPSPGGRGPEDSWLLLSAPGPTPASPRPASPCGKRRYSSSGTPSSASPALSRRGSLGEEGSEPPPPPPLPLARDPGSPGPFDYVGAPPAESIPQKTRRTSSEQAVALPRSEEPASCNGKLPLGAEESVAPPGGSRKEVAGMDYLAVPSPLAWSKARIGGHSPIFRTSALPPLDWPLPSQYEQLELRIEVQPRAHHRAHYETEGSRGAVKAAPGGHPVVKLLGYSEKPLTLQMFIGTADERNLRPHAFYQVHRITGKMVATASYEAVVSGTKVLEMTLLPENNMAANIDCAGILKLRNSDIELRKGETDIGRKNTRVRLVFRVHVPQGGGKVVSVQAASVPIECSQRSAQELPQVEAYSPSACSVRGGEELVLTGSNFLPDSKVVFIERGPDGKLQWEEEATVNRLQSNEVTLTLTVPEYSNKRVSRPVQVYFYVSNGRRKRSPTQSFRFLPVICKEEPLPDSSLRGFPSASATPFGTDMDFSPPRPPYPSYPHEDPACETPYLSEGFGYGMPPLYPQTGPPPSYRPGLRMFPETRGTTGCAQPPAVSFLPRPFPSDPYGGRGSSFSLGLPFSPPAPFRPPPLPASPPLEGPFPSQSDVHPLPAEGYNKVGPGYGPGEGAPEQEKSRGGYSSGFRDSVPIQGITLEEVSEIIGRDLSGFPAPPGEEPPA

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3 (in isoform 11)	Phosphorylation	-	8.56	24043423
3 (in isoform 2)	Phosphorylation	-	8.56	24043423
3 (in isoform 3)	Phosphorylation	-	8.56	24043423
4 (in isoform 11)	Phosphorylation	-	14.69	24043423
4 (in isoform 2)	Phosphorylation	-	14.69	24043423
4 (in isoform 3)	Phosphorylation	-	14.69	24043423
5	Phosphorylation	---MGAASCEDEELE ---CCCCCCCCCEEE	19.94	29514088
7 (in isoform 11)	Phosphorylation	-	67.00	24043423
7 (in isoform 2)	Phosphorylation	-	67.00	24043423
7 (in isoform 3)	Phosphorylation	-	67.00	24043423
12 (in isoform 11)	Phosphorylation	-	43.97	24043423
12 (in isoform 2)	Phosphorylation	-	43.97	24043423
12 (in isoform 3)	Phosphorylation	-	43.97	24043423
15 (in isoform 11)	Phosphorylation	-	4.72	24043423
15 (in isoform 2)	Phosphorylation	-	4.72	24043423
15 (in isoform 3)	Phosphorylation	-	4.72	24043423
17 (in isoform 11)	Phosphorylation	-	17.25	24043423
17 (in isoform 2)	Phosphorylation	-	17.25	24043423
17 (in isoform 3)	Phosphorylation	-	17.25	24043423
35 (in isoform 11)	Phosphorylation	-	8.37	25332170
35 (in isoform 2)	Phosphorylation	-	8.37	25332170
35 (in isoform 3)	Phosphorylation	-	8.37	25332170
43 (in isoform 11)	Phosphorylation	-	1.73	25332170
43 (in isoform 2)	Phosphorylation	-	1.73	25332170
43 (in isoform 3)	Phosphorylation	-	1.73	25332170
44 (in isoform 11)	Phosphorylation	-	5.01	25332170
44 (in isoform 2)	Phosphorylation	-	5.01	25332170
44 (in isoform 3)	Phosphorylation	-	5.01	25332170
52	Phosphorylation	RLALGEPPPYGAAPI CHHCCCCCCCCCCCC	30.37	32142685
73	Phosphorylation	PPRPGMHSPPPRPAP CCCCCCCCCCCCCCC	30.15	26329039
110	Phosphorylation	GGAGGGRVLECPSIR CCCCCCCEEECCCEE	6.29	32142685
115	Phosphorylation	GRVLECPSIRITSIS CCEEECCCEEEEEEC	35.84	28555341
119	Phosphorylation	ECPSIRITSISPTPE ECCCEEEEEECCCCC	15.34	27251275
120	Phosphorylation	CPSIRITSISPTPEP CCCEEEEEECCCCCC	20.78	27251275
122	Phosphorylation	SIRITSISPTPEPPA CEEEEEECCCCCCCC	23.61	19690332
124	Phosphorylation	RITSISPTPEPPAAL EEEEECCCCCCCCHH	33.23	30576142
136 (in isoform 3)	Phosphorylation	-	62.30	27251275
142	Phosphorylation	PDAWGDGSPRDYPPP CCCCCCCCCCCCCCC	22.85	28842319
143	Phosphorylation	DAWGDGSPRDYPPPE CCCCCCCCCCCCCCC	38.40	32142685
147	Phosphorylation	DGSPRDYPPPEGFGG CCCCCCCCCCCCCCC	42.11	32142685
156	Phosphorylation	PEGFGGYREAGGQGG CCCCCCCCCCCCCCC	30.48	32142685
168	Phosphorylation	QGGGAFFSPSPGSSS CCCCCCCCCCCCCCC	20.29	11997522
170	Phosphorylation	GGAFFSPSPGSSSLS CCCCCCCCCCCCCCC	40.47	11997522
173	Phosphorylation	FFSPSPGSSSLSSWS CCCCCCCCCCCCCCC	21.82	-
185	Phosphorylation	SWSFFSDASDEAALY CCCCCCCCCCHHHHH	20.06	32142685
185 (in isoform 3)	Phosphorylation	-	20.06	24719451
194	Phosphorylation	DEAALYAACDEVESE CHHHHHHHHHHHHHH	6.42	32142685
201	Phosphorylation	ACDEVESELNEAASR HHHHHHHHHHHHHHH	41.95	32142685
205	Phosphorylation	VESELNEAASRFGLG HHHHHHHHHHHHCCC	15.06	32142685
213	Phosphorylation	ASRFGLGSPLPSPRA HHHHCCCCCCCCCCC	28.45	25463755
214	Phosphorylation	SRFGLGSPLPSPRAS HHHCCCCCCCCCCCC	46.63	32142685
217	Phosphorylation	GLGSPLPSPRASPRP CCCCCCCCCCCCCCC	34.40	25463755
219	Phosphorylation	GSPLPSPRASPRPWT CCCCCCCCCCCCCCC	52.62	32142685
221	Phosphorylation	PLPSPRASPRPWTPE CCCCCCCCCCCCCCC	23.79	28450419
226	Phosphorylation	RASPRPWTPEDPWSL CCCCCCCCCCCCCHH	21.34	28450419
232	Phosphorylation	WTPEDPWSLYGPSPG CCCCCCCHHCCCCCC	19.66	27732954
234	Phosphorylation	PEDPWSLYGPSPGGR CCCCCHHCCCCCCCC	22.83	19651622
237	Phosphorylation	PWSLYGPSPGGRGPE CCHHCCCCCCCCCCC	31.64	21712546
241	Phosphorylation	YGPSPGGRGPEDSWL CCCCCCCCCCCCCEE	64.51	32142685
246	Phosphorylation	GGRGPEDSWLLLSAP CCCCCCCCEEEEECC	20.26	26074081
251	Phosphorylation	EDSWLLLSAPGPTPA CCCEEEEECCCCCCC	32.18	30576142
252	Phosphorylation	DSWLLLSAPGPTPAS CCEEEEECCCCCCCC	17.03	32142685
256	Phosphorylation	LLSAPGPTPASPRPA EEECCCCCCCCCCCC	37.08	28450419
259	Phosphorylation	APGPTPASPRPASPC CCCCCCCCCCCCCCC	23.73	21712546
264	Phosphorylation	PASPRPASPCGKRRY CCCCCCCCCCCCCCC	24.33	22617229
271	Phosphorylation	SPCGKRRYSSSGTPS CCCCCCCCCCCCCCC	19.55	30087585
272	Phosphorylation	PCGKRRYSSSGTPSS CCCCCCCCCCCCCCC	19.06	21712546
273	Phosphorylation	CGKRRYSSSGTPSSA CCCCCCCCCCCCCCC	24.69	28450419
274	Phosphorylation	GKRRYSSSGTPSSAS CCCCCCCCCCCCCCC	40.52	26699800
276	Phosphorylation	RRYSSSGTPSSASPA CCCCCCCCCCCCCHH	23.19	27732954
276 (in isoform 3)	Phosphorylation	-	23.19	24719451
277	Phosphorylation	RYSSSGTPSSASPAL CCCCCCCCCCCCHHH	29.79	32142685
278	Phosphorylation	YSSSGTPSSASPALS CCCCCCCCCCCHHHH	38.07	28450419
279	Phosphorylation	SSSGTPSSASPALSR CCCCCCCCCCHHHHC	33.69	28450419
280	Phosphorylation	SSGTPSSASPALSRR CCCCCCCCCHHHHCC	24.70	32142685
280 (in isoform 3)	Phosphorylation	-	24.70	24719451
281	Phosphorylation	SGTPSSASPALSRRG CCCCCCCCHHHHCCC	16.80	27732954
284 (in isoform 3)	Phosphorylation	-	4.67	27251275
285	Phosphorylation	SSASPALSRRGSLGE CCCCHHHHCCCCCCC	23.26	27732954
289	Phosphorylation	PALSRRGSLGEEGSE HHHHCCCCCCCCCCC	31.24	30266825
289 (in isoform 3)	Phosphorylation	-	31.24	24719451
295	Phosphorylation	GSLGEEGSEPPPPPP CCCCCCCCCCCCCCC	50.65	30278072
299	Phosphorylation	EEGSEPPPPPPLPLA CCCCCCCCCCCCCCC	65.82	32142685
311	Phosphorylation	PLARDPGSPGPFDYV CCCCCCCCCCCCCCC	31.88	21712546
317	Phosphorylation	GSPGPFDYVGAPPAE CCCCCCCCCCCCCHH	10.93	27251789
322 (in isoform 3)	Phosphorylation	-	48.39	24719451
325	Phosphorylation	VGAPPAESIPQKTRR CCCCCHHHCCCCCCC	41.49	22199227
327	Phosphorylation	APPAESIPQKTRRTS CCCHHHCCCCCCCCC	38.60	32142685
327 (in isoform 3)	Phosphorylation	-	38.60	24719451
330	Phosphorylation	AESIPQKTRRTSSEQ HHHCCCCCCCCCHHH	21.82	23882029
333	Phosphorylation	IPQKTRRTSSEQAVA CCCCCCCCCHHHCCC	33.06	23403867
334	Phosphorylation	PQKTRRTSSEQAVAL CCCCCCCCHHHCCCC	30.02	23911959
335	Phosphorylation	QKTRRTSSEQAVALP CCCCCCCHHHCCCCC	32.87	21712546
335 (in isoform 3)	Phosphorylation	-	32.87	24719451
337 (in isoform 3)	Phosphorylation	-	42.98	27251275
339 (in isoform 3)	Phosphorylation	-	5.85	27251275
344	Phosphorylation	QAVALPRSEEPASCN HCCCCCCCCCCCCCC	44.35	28112733
344 (in isoform 3)	Phosphorylation	-	44.35	24719451
349	Phosphorylation	PRSEEPASCNGKLPL CCCCCCCCCCCCCCC	20.87	28555341
352	Phosphorylation	EEPASCNGKLPLGAE CCCCCCCCCCCCCCC	36.89	32142685
352 (in isoform 3)	Phosphorylation	-	36.89	24719451
368	Phosphorylation	SVAPPGGSRKEVAGM CCCCCCCCHHHCCCC	46.20	28555341
374	Phosphorylation	GSRKEVAGMDYLAVP CCHHHCCCCEEEECC	18.05	32142685
374 (in isoform 3)	Phosphorylation	-	18.05	24719451
382	Phosphorylation	MDYLAVPSPLAWSKA CEEEECCCCCCHHCC	26.41	22199227
387	Phosphorylation	VPSPLAWSKARIGGH CCCCCCHHCCCCCCC	15.72	30576142
395	Phosphorylation	KARIGGHSPIFRTSA CCCCCCCCCCCCCCC	23.98	28555341
397 (in isoform 3)	Phosphorylation	-	4.01	24719451
438	Phosphorylation	AHYETEGSRGAVKAA HEECCCCCCCCHHCC	22.70	23403867
445 (in isoform 3)	Phosphorylation	-	9.50	24719451
468	Ubiquitination	PLTLQMFIGTADERN CEEEEEEEECCCCCC	3.93	29967540
510	Phosphorylation	GTKVLEMTLLPENNM CCEEEEEEECCCCCC	18.77	22210691
526	Ubiquitination	ANIDCAGILKLRNSD CCCCCEEEHHHHCCC	1.31	29967540
532	Phosphorylation	GILKLRNSDIELRKG EEHHHHCCCCEECCC	33.27	28450419
538	Ubiquitination	NSDIELRKGETDIGR CCCCEECCCCCCCCC	73.96	29967540
592	Phosphorylation	LPQVEAYSPSACSVR CCCCEEECCCCEEEC	21.30	28555341
595 (in isoform 3)	Phosphorylation	-	7.93	24719451
601	Ubiquitination	SACSVRGGEELVLTG CCEEECCCCEEEEEC	18.03	29967540
653	Phosphorylation	LTLTVPEYSNKRVSR EEEECCCCCCCCCCC	16.09	-
654	Phosphorylation	TLTVPEYSNKRVSRP EEECCCCCCCCCCCC	33.92	-
676	Phosphorylation	SNGRRKRSPTQSFRF ECCCCCCCCCCCEEE	35.02	15657420
689	Sumoylation	RFLPVICKEEPLPDS EEEEEEECCCCCCCC	54.72	28112733
716	Phosphorylation	FGTDMDFSPPRPPYP CCCCCCCCCCCCCCC	29.72	24719451
772	Phosphorylation	FPETRGTTGCAQPPA CCCCCCCCCCCCCCC	32.84	-
788	Ubiquitination	SFLPRPFPSDPYGGR EECCCCCCCCCCCCC	40.27	29967540
819	Phosphorylation	RPPPLPASPPLEGPF CCCCCCCCCCCCCCC	25.72	26074081
846	Ubiquitination	GYNKVGPGYGPGEGA CCCCCCCCCCCCCCC	33.82	29967540
858	Ubiquitination	EGAPEQEKSRGGYSS CCCCHHHHCCCCCCC	45.18	29967540
921	Ubiquitination	-------------------------- --------------------------		29967540

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
168	S	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
168	S	Phosphorylation	Kinase	MAPK7	Q13164	Uniprot
170	S	Phosphorylation	Kinase	MK14	Q16539	PhosphoELM
170	S	Phosphorylation	Kinase	MAPK7	Q13164	Uniprot
213	S	Phosphorylation	Kinase	MAPK9	Q9WTU6	GPS
213	S	Phosphorylation	Kinase	JNK1	P45983	PSP
213	S	Phosphorylation	Kinase	MAPK8	Q91Y86	GPS
213	S	Phosphorylation	Kinase	JNK2	P45984	PSP
217	S	Phosphorylation	Kinase	MAPK9	Q9WTU6	GPS
217	S	Phosphorylation	Kinase	JNK1	P45983	PSP
217	S	Phosphorylation	Kinase	MAPK8	Q91Y86	GPS
217	S	Phosphorylation	Kinase	JNK2	P45984	PSP
259	S	Phosphorylation	Kinase	CDK3	Q00526	PSP
281	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
285	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
289	S	Phosphorylation	Kinase	RSK2	P51812	PSP
344	S	Phosphorylation	Kinase	RSK2	P51812	PSP
676	S	Phosphorylation	Kinase	MAPK3	P27361	GPS
676	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
676	S	Phosphorylation	Kinase	RPS6KA3	P51812	GPS
676	S	Phosphorylation	Kinase	RSK-SUBFAMILY	-	GPS
676	S	Phosphorylation	Kinase	RSK_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
48	K	ubiquitylation	19026640
Polyubiquitin linkage mainly occurs through 'Lys-48'.
168	S	Phosphorylation	11997522
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.
168	S	Phosphorylation	11997522
Phosphorylation at Ser-168 and Ser-170 is stimulated by UV irradiation.
170	S	Phosphorylation	11997522
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.
170	S	Phosphorylation	11997522
Phosphorylation at Ser-168 and Ser-170 is stimulated by UV irradiation.
213	S	Phosphorylation	17875713
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.
217	S	Phosphorylation	17875713
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.
289	S	Phosphorylation	17213202
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.
344	S	Phosphorylation	17213202
Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3.

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 NFAC4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LPIN1_HUMAN	LPIN1	physical	20385772
CEBPA_HUMAN	CEBPA	physical	20385772
MK08_HUMAN	MAPK8	physical	17875713
MK09_HUMAN	MAPK9	physical	17875713
NR1I2_HUMAN	NR1I2	physical	21988832
MK14_HUMAN	MAPK14	physical	25241761

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
There are no disease associations of PTM sites.

Regulatory Network of NFAC4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Integration of protein kinases mTOR and extracellular signal-regulated kinase 5 in regulating nucleocytoplasmic localization ofNFATc4."; Yang T.T.C., Yu R.Y.L., Agadir A., Gao G.-J., Campos-Gonzalez R.,Tournier C., Chow C.-W.; Mol. Cell. Biol. 28:3489-3501(2008). Cited for: SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-168 AND SER-170.	18347059 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis."; Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III; J. Proteome Res. 7:1346-1351(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-272 AND SER-334, ANDMASS SPECTROMETRY.	18220336 [Abstract]
"RSK2 mediates muscle cell differentiation through regulation ofNFAT3."; Cho Y.-Y., Yao K., Bode A.M., Bergen H.R. III, Madden B.J., Oh S.-M.,Ermakova S., Kang B.S., Choi H.S., Shim J.-H., Dong Z.; J. Biol. Chem. 282:8380-8392(2007). Cited for: FUNCTION, INTERACTION WITH RPS6KA3, AND PHOSPHORYLATION AT SER-289 ANDSER-344.	17213202 [Abstract]
"Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 induced cell transformation."; Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y.,Bode A.M., Dong Z.; Cancer Res. 67:8725-8735(2007). Cited for: INTERACTION WITH MAPK8 AND MAPK9, PHOSPHORYLATION AT SER-213 ANDSER-217, AND MUTAGENESIS OF SER-213 AND SER-217.	17875713 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289, AND MASSSPECTROMETRY.	17081983 [Abstract]
"Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases."; Yang T.T.C., Xiong Q., Enslen H., Davis R.J., Chow C.-W.; Mol. Cell. Biol. 22:3892-3904(2002). Cited for: FUNCTION, PHOSPHORYLATION AT SER-168 AND SER-170, AND MUTAGENESIS OFSER-168 AND SER-170.	11997522 [Abstract]

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