RXRA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RXRA_MOUSE
• UniProt AC: P28700
• Protein Name: Retinoic acid receptor RXR-alpha
• Gene Name: Rxra
• Organism: Mus musculus (Mouse).
• Sequence Length: 467
• Subcellular Localization: Nucleus.
• 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 RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. 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. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes..
• Protein Sequence: MDTKHFLPLDFSTQVNSSSLNSPTGRGSMAVPSLHPSLGPGIGSPLGSPGQLHSPISTLSSPINGMGPPFSVISSPMGPHSMSVPTTPTLGFGTGSPQLNSPMNPVSSTEDIKPPLGLNGVLKVPAHPSGNMASFTKHICAICGDRSSGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREAVQEERQRGKDRNENEVESTSSANEDMPVEKILEAELAVEPKTETYVEANMGLNPSSPNDPVTNICQAADKQLFTLVEWAKRIPHFSELPLDDQVILLRAGWNELLIASFSHRSIAVKDGILLATGLHVHRNSAHSAGVGAIFDRVLTELVSKMRDMQMDKTELGCLRAIVLFNPDSKGLSNPAEVEALREKVYASLEAYCKHKYPEQPGRFAKLLLRLPALRSIGLKCLEHLFFFKLIGDTPIDTFLMEMLEAPHQAT

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
4	Ubiquitination	----MDTKHFLPLDF ----CCCCCCCCCCC	28.26	-
17	Phosphorylation	DFSTQVNSSSLNSPT CCCCCCCCCCCCCCC	23.58	25619855
18	Phosphorylation	FSTQVNSSSLNSPTG CCCCCCCCCCCCCCC	33.37	25619855
19	Phosphorylation	STQVNSSSLNSPTGR CCCCCCCCCCCCCCC	31.24	25619855
22	Phosphorylation	VNSSSLNSPTGRGSM CCCCCCCCCCCCCCC	29.18	25521595
24	Phosphorylation	SSSLNSPTGRGSMAV CCCCCCCCCCCCCCC	39.05	25619855
28	Phosphorylation	NSPTGRGSMAVPSLH CCCCCCCCCCCCCCC	11.38	-
61	Phosphorylation	SPISTLSSPINGMGP CCCHHCCCCCCCCCC	32.67	10383391
75	Phosphorylation	PPFSVISSPMGPHSM CCCEEEECCCCCCCC	14.05	10383391
87	Phosphorylation	HSMSVPTTPTLGFGT CCCCCCCCCCCCCCC	14.27	10383391
134	Phosphorylation	HPSGNMASFTKHICA CCCCCHHHHHHEEEH	23.76	-
150	Acetylation	CGDRSSGKHYGVYSC CCCCCCCCEEEEEEC	35.28	-
229	Phosphorylation	ENEVESTSSANEDMP CCCCCCCCCCCCCCC	36.41	23684622
230	Phosphorylation	NEVESTSSANEDMPV CCCCCCCCCCCCCCH	34.89	23684622
264	Phosphorylation	ANMGLNPSSPNDPVT ECCCCCCCCCCCHHH	58.30	29472430
265	Phosphorylation	NMGLNPSSPNDPVTN CCCCCCCCCCCHHHH	29.04	10383391
271	Phosphorylation	SSPNDPVTNICQAAD CCCCCHHHHHHHHHH	25.01	23140645
386	Ubiquitination	VLFNPDSKGLSNPAE ECCCCCCCCCCCHHH	71.85	-
422	Ubiquitination	EQPGRFAKLLLRLPA CCCCHHHHHHHHHHH	36.63	-
432	O-linked_Glycosylation	LRLPALRSIGLKCLE HHHHHHHHHHHHHHH	23.12	30059200

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
61	S	Phosphorylation	Kinase	JNK1	Q91Y86	PSP
61	S	Phosphorylation	Kinase	JNK2	Q9WTU6	PSP
75	S	Phosphorylation	Kinase	JNK1	Q91Y86	PSP
75	S	Phosphorylation	Kinase	JNK2	Q9WTU6	PSP
87	T	Phosphorylation	Kinase	JNK1	Q91Y86	PSP
87	T	Phosphorylation	Kinase	JNK2	Q9WTU6	PSP
265	S	Phosphorylation	Kinase	JNK1	Q91Y86	PSP
265	S	Phosphorylation	Kinase	JNK2	Q9WTU6	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
22	S	Phosphorylation	Constitutively phosphorylated on Ser-22 in the presence or absence of ligand.	10383391
28	S	Phosphorylation	Phosphorylated on Ser-28, in vitro, by PKA (By similarity).	12032153
61	S	Phosphorylation	Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265.	10383391
75	S	Phosphorylation	Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265.	10383391
87	T	Phosphorylation	Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265.	10383391
265	S	Phosphorylation	Under stress conditions, hyperphosphorylated by activated JNK on Ser-61, Ser-75, Thr-87 and Ser-265.	10383391

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NR1H3_MOUSE	Nr1h3	physical	20211142
SFPQ_HUMAN	SFPQ	physical	11259580
NONO_HUMAN	NONO	physical	11259580
SIN3A_HUMAN	SIN3A	physical	11259580
NR1H4_MOUSE	Nr1h4	physical	19883617
TGIF1_MOUSE	Tgif1	physical	16428452
SMRD3_HUMAN	SMARCD3	physical	14701856
EP300_HUMAN	EP300	physical	14701856
TIF1A_MOUSE	Trim24	physical	7744009

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"The phosphorylation site located in the A region of retinoic Xreceptor alpha is required for the antiproliferative effect ofretinoic acid (RA) and the activation of RA target genes in F9cells.";
Bastien J., Adam-Stitah S., Plassat J.L., Chambon P.,Rochette-Egly C.;
J. Biol. Chem. 277:28683-28689(2002).
Cited for: PHOSPHORYLATION AT SER-22, FUNCTION, AND MUTAGENESIS OF SER-22.
PubMed: 12032153

"Hyperphosphorylation of the retinoid X receptor alpha by activated c-Jun NH2-terminal kinases.";
Adam-Stitah S., Penna L., Chambon P., Rochette-Egly C.;
J. Biol. Chem. 274:18932-18941(1999).
Cited for: PHOSPHORYLATION AT SER-22; SER-61; SER-75; THR-87 AND SER-265,FUNCTION, AND MUTAGENENESIS OF SER-22; SER-44; SER-48; SER-54; SER-61;SER-75; THR-87; SER-96; SER-101 AND SER-265.
PubMed: 10383391