dbPTM

RARA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RARA_MOUSE
UniProt AC	P11416
Protein Name	Retinoic acid receptor alpha
Gene Name	Rara
Organism	Mus musculus (Mouse).
Sequence Length	462
Subcellular Localization	Nucleus. Cytoplasm. Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus is dependent on activation of PKC and the downstream MAPK phosphorylation.
Protein Description	Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function..
Protein Sequence	MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTSLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFDVGMSKESVRNDRNKKKKEAPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDKVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQSGGGTRDGGGLAPPPGSCSPSLSPSSHRSSPATQSP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
74 (in isoform 2)	Phosphorylation	-	38.25	25338131
77	Phosphorylation	EIVPSPPSPPPLPRI CCCCCCCCCCCCCCC	54.12	9230306
96	Phosphorylation	FVCQDKSSGYHYGVS EEEECCCCCCEEEEH	49.46	-
109	Methylation	VSACEGCKGFFRRSI EHHCCCCCHHHHHHH	70.39	18781795
171	Methylation	KKKKEAPKPECSESY HCCCCCCCCCCCCCE	61.57	18781795
177	Phosphorylation	PKPECSESYTLTPEV CCCCCCCCEECCHHH	13.71	27600695
178	Phosphorylation	KPECSESYTLTPEVG CCCCCCCEECCHHHH	11.17	27600695
179	Phosphorylation	PECSESYTLTPEVGE CCCCCCEECCHHHHH	33.17	27600695
181	Phosphorylation	CSESYTLTPEVGELI CCCCEECCHHHHHHH	15.03	27600695
219	Phosphorylation	NSSEQRVSLDIDLWD CCCCCEEEEECCHHH	23.63	-
232	Phosphorylation	WDKFSELSTKCIIKT HHHHHHHHHHHHHHH	23.05	25338131
233	Phosphorylation	DKFSELSTKCIIKTV HHHHHHHHHHHHHHH	42.43	25338131
347	Methylation	QDLEQPDKVDMLQEP CCCCCCCCCCCHHHH	46.98	17205979
347	"N6,N6,N6-trimethyllysine"	QDLEQPDKVDMLQEP CCCCCCCCCCCHHHH	46.98	-
369	Phosphorylation	YVRKRRPSRPHMFPK HHHHHCCCCCCCCHH	57.54	17205979
397	Phosphorylation	KGAERVITLKMEIPG CCCCEEEEEEEECCC	19.91	-
443	Phosphorylation	GLAPPPGSCSPSLSP CCCCCCCCCCCCCCC	19.73	28973931
445	Phosphorylation	APPPGSCSPSLSPSS CCCCCCCCCCCCCCC	21.15	9230306
447	Phosphorylation	PPGSCSPSLSPSSHR CCCCCCCCCCCCCCC	25.78	30635358
449	Phosphorylation	GSCSPSLSPSSHRSS CCCCCCCCCCCCCCC	27.37	9230306
451	Phosphorylation	CSPSLSPSSHRSSPA CCCCCCCCCCCCCCC	35.09	30635358
452	Phosphorylation	SPSLSPSSHRSSPAT CCCCCCCCCCCCCCC	26.72	30635358
456	Phosphorylation	SPSSHRSSPATQSP- CCCCCCCCCCCCCC-	20.64	9230306
461	Phosphorylation	RSSPATQSP------ CCCCCCCCC------	28.37	9230306

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
77	S	Phosphorylation	Kinase	CDK1	P06493	PSP
77	S	Phosphorylation	Kinase	CDK7	P50613	PSP
77	S	Phosphorylation	Kinase	CDK7	Q03147	Uniprot
96	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
219	S	Phosphorylation	Kinase	PKA	-	Uniprot
369	S	Phosphorylation	Kinase	PRKACA	P05132	GPS
369	S	Phosphorylation	Kinase	RPS6KA5	Q8C050	Uniprot
369	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
369	S	Phosphorylation	Kinase	PKA	-	Uniprot
461	S	Phosphorylation	Kinase	CDK1	P06493	PSP
461	S	Phosphorylation	Kinase	CDK7	P50613	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
77	S	Phosphorylation	9230306
On retinoic acid stimulation, phosphorylation on Ser-369 by RPS6KA5 promotes interaction with GTF2H3 and the CDK7-mediated phosphorylation of Ser-77.
77	S	Phosphorylation	9230306
Phosphorylation on Ser-77 is crucial for the N-terminal AF1 transcriptional activity.
166	K	Sumoylation	-
On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171.
171	K	Sumoylation	-
On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171.
181	T	Phosphorylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.
181	T	ubiquitylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.
369	S	Phosphorylation	19078967
On retinoic acid stimulation, phosphorylation on Ser-369 by RPS6KA5 promotes interaction with GTF2H3 and the CDK7-mediated phosphorylation of Ser-77.
399	K	Sumoylation	-
Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding.
445	S	Phosphorylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.
445	S	ubiquitylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.
461	S	Phosphorylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.
461	S	ubiquitylation	9230306
Under stress conditions, MAPK8 enhances phosphorylation on Thr-181, Ser-445 and Ser-461 leading to RARA ubiquitination and degradation.

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 RARA_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NCOA1_MOUSE	Ncoa1	physical	8855229
NRIP1_MOUSE	Nrip1	physical	20211142
ELOB_MOUSE	Tceb2	physical	9869640
ELOC_MOUSE	Tceb1	physical	9869640
GRIP1_MOUSE	Grip1	physical	17389641
KAT2B_MOUSE	Kat2b	physical	17389641
NRIP1_MOUSE	Nrip1	physical	17389641
PURA_MOUSE	Pura	physical	18495661
PABP1_MOUSE	Pabpc1	physical	18495661
SFPQ_MOUSE	Sfpq	physical	18495661
NONO_MOUSE	Nono	physical	18495661
HNRPU_MOUSE	Hnrnpu	physical	18495661
1433Z_MOUSE	Ywhaz	physical	18495661
PURB_MOUSE	Purb	physical	18495661
NR1H4_MOUSE	Nr1h4	physical	18495661
THOC4_MOUSE	Alyref	physical	18495661
EIF3A_MOUSE	Eif3a	physical	18495661
EIF3B_MOUSE	Eif3b	physical	18495661
RS3_MOUSE	Rps3	physical	18495661
RS4X_MOUSE	Rps4x	physical	18495661
RS5_MOUSE	Rps5	physical	18495661
RS6_MOUSE	Rps6	physical	18495661
RS13_MOUSE	Rps13	physical	18495661
RS16_MOUSE	Rps16	physical	18495661
RS17_MOUSE	Rps17	physical	18495661
RS19_MOUSE	Rps19	physical	18495661
RS25_MOUSE	Rps25	physical	18495661
RS26_MOUSE	Rps26	physical	18495661
RL23_MOUSE	Rpl23	physical	18495661
RSSA_MOUSE	Rpsa	physical	18495661
HS71B_MOUSE	Hspa1b	physical	18495661
DDX1_MOUSE	Ddx1	physical	18495661
DDX3X_MOUSE	Ddx3x	physical	18495661
ROAA_MOUSE	Hnrnpab	physical	18495661
HNRPD_MOUSE	Hnrnpd	physical	18495661
HNRPQ_MOUSE	Syncrip	physical	18495661
EWS_MOUSE	Ewsr1	physical	18495661
FUS_MOUSE	Fus	physical	18495661
RBM3_MOUSE	Rbm3	physical	18495661
G3BP1_MOUSE	G3bp1	physical	18495661
SOSB1_MOUSE	Nabp2	physical	18495661
AP2A1_MOUSE	Ap2a1	physical	18495661
AP2A2_MOUSE	Ap2a2	physical	18495661
AP2B1_MOUSE	Ap2b1	physical	18495661
AP2M1_MOUSE	Ap2m1	physical	18495661
VIME_MOUSE	Vim	physical	18495661
DESM_MOUSE	Des	physical	18495661
TBA3_MOUSE	Tuba3a	physical	18495661
ACTB_MOUSE	Actb	physical	18495661
TMOD1_MOUSE	Tmod1	physical	18495661
TERA_MOUSE	Vcp	physical	18495661
1433B_MOUSE	Ywhab	physical	18495661
1433G_MOUSE	Ywhag	physical	18495661
KCND2_MOUSE	Kcnd2	physical	18495661
SND1_MOUSE	Snd1	physical	18495661
NDKA_MOUSE	Nme1	physical	18495661
EP300_MOUSE	Ep300	physical	21722948
SIR1_MOUSE	Sirt1	physical	19934264
SNW1_MOUSE	Snw1	physical	19934264
SMRD3_MOUSE	Smarcd3	physical	17363140

Drug and Disease Associations

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

Regulatory Network of RARA_MOUSE

Related Literatures of Post-Translational Modification

Methylation
Reference	PubMed
"Lysine trimethylation of retinoic acid receptor-alpha: a novel meansto regulate receptor function."; Huq M.D., Tsai N.-P., Khan S.A., Wei L.-N.; Mol. Cell. Proteomics 6:677-688(2007). Cited for: PROTEIN SEQUENCE OF 340-359, METHYLATION AT LYS-347, FUNCTION,INTERACTION WITH RXRA AND NCOR1, MASS SPECTROMETRY, AND MUTAGENESIS OFLYS-347.	17205979 [Abstract]
Phosphorylation
Reference	PubMed
"A coordinated phosphorylation cascade initiated by p38MAPK/MSK1directs RARalpha to target promoters."; Bruck N., Vitoux D., Ferry C., Duong V., Bauer A., de The H.,Rochette-Egly C.; EMBO J. 28:34-47(2009). Cited for: PHOSPHORYLATION AT SER-77 AND SER-369, FUNCTION, INTERACTION WITHGTF2H3, AND MUTAGENESIS OF SER-77 AND SER-369.	19078967 [Abstract]
"Stimulation of RAR alpha activation function AF-1 through binding tothe general transcription factor TFIIH and phosphorylation by CDK7."; Rochette-Egly C., Adam S., Rossignol M., Egly J.-M., Chambon P.; Cell 90:97-107(1997). Cited for: INTERACTION WITH CDK7 AND GTF2H3, PHOSPHORYLATION AT SER-77, FUNCTION,AND MUTAGENESIS OF SER-74; SER-77; SER-449; SER-456 AND SER-461.	9230306 [Abstract]

show

show

show

show

show

show

show

show

show

show

show

show