dbPTM

RARA_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RARA_HUMAN
UniProt AC	P10276
Protein Name	Retinoic acid receptor alpha
Gene Name	RARA
Organism	Homo sapiens (Human).
Sequence Length	462
Subcellular Localization	Nucleus. Cytoplasm. Nuclear localization depends on ligand binding, phosphorylation and sumoylation. Transloaction to the nucleus in the absence of ligand 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 (By similarity)..
Protein Sequence	MASNSSSCPTPGGGHLNGYPVPPYAFFFPPMLGGLSPPGALTTLQHQLPVSGYSTPSPATIETQSSSSEEIVPSPPSPPPLPRIYKPCFVCQDKSSGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKESVRNDRNKKKKEVPKPECSESYTLTPEVGELIEKVRKAHQETFPALCQLGKYTTNNSSEQRVSLDIDLWDKFSELSTKCIIKTVEFAKQLPGFTTLTIADQITLLKAACLDILILRICTRYTPEQDTMTFSDGLTLNRTQMHNAGFGPLTDLVFAFANQLLPLEMDDAETGLLSAICLICGDRQDLEQPDRVDMLQEPLLEALKVYVRKRRPSRPHMFPKMLMKITDLRSISAKGAERVITLKMEIPGSMPPLIQEMLENSEGLDTLSGQPGGGGRDGGGLAPPPGSCSPSLSPSSNRSSPATHSP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2 (in isoform 2)	Phosphorylation	-	19.88	24043423
4 (in isoform 2)	Phosphorylation	-	36.05	24043423
11 (in isoform 2)	Phosphorylation	-	25.28	24043423
21 (in isoform 2)	Phosphorylation	-	5.85	24043423
72 (in isoform 2)	Phosphorylation	-	4.31	27251275
72	Phosphorylation	SSSSEEIVPSPPSPP CCCCCCCCCCCCCCC	4.31	27251275
74	Phosphorylation	SSEEIVPSPPSPPPL CCCCCCCCCCCCCCC	38.25	24275569
77	Phosphorylation	EIVPSPPSPPPLPRI CCCCCCCCCCCCCCC	54.12	16769902
96	Phosphorylation	FVCQDKSSGYHYGVS EEEECCCCCCEEEEH	49.46	16417524
105	S-palmitoylation	YHYGVSACEGCKGFF CEEEEHHCCCCCHHH	3.44	30076181
118	Ubiquitination	FFRRSIQKNMVYTCH HHHHHHHHCCEEEEC	45.39	-
166	Sumoylation	RNDRNKKKKEVPKPE HCCCCCCCCCCCCCC	56.63	19850744
166	Sumoylation	RNDRNKKKKEVPKPE HCCCCCCCCCCCCCC	56.63	-
171	Sumoylation	KKKKEVPKPECSESY CCCCCCCCCCCCCCE	59.63	19850744
171	Sumoylation	KKKKEVPKPECSESY CCCCCCCCCCCCCCE	59.63	-
174	S-palmitoylation	KEVPKPECSESYTLT CCCCCCCCCCCEEEC	8.09	30076181
181	Phosphorylation	CSESYTLTPEVGELI CCCCEEECHHHHHHH	15.03	15657432
190	Ubiquitination	EVGELIEKVRKAHQE HHHHHHHHHHHHHHH	40.10	-
208	Nitration	ALCQLGKYTTNNSSE HHHHHCCEECCCCCC	19.59	-
219	Phosphorylation	NSSEQRVSLDIDLWD CCCCCEEEEECCHHH	23.63	20215566
277	Nitration	ILRICTRYTPEQDTM HHHHHCCCCCCCCEE	14.43	-
362	Nitration	LLEALKVYVRKRRPS HHHHHHHHHHHHCCC	7.92	-
369	Phosphorylation	YVRKRRPSRPHMFPK HHHHHCCCCCCCCHH	57.54	11812818
382	Phosphorylation	PKMLMKITDLRSISA HHHHHHHHCHHHCCC	24.38	23532336
399	Sumoylation	AERVITLKMEIPGSM CCEEEEEEEECCCCC	26.32	19850744
399	Sumoylation	AERVITLKMEIPGSM CCEEEEEEEECCCCC	26.32	-
405	Phosphorylation	LKMEIPGSMPPLIQE EEEECCCCCCHHHHH	23.82	-
440	Phosphorylation	DGGGLAPPPGSCSPS CCCCCCCCCCCCCCC	40.03	24719451
443	Phosphorylation	GLAPPPGSCSPSLSP CCCCCCCCCCCCCCC	19.73	30266825
445	Phosphorylation	APPPGSCSPSLSPSS CCCCCCCCCCCCCCC	21.15	30266825
447	Phosphorylation	PPGSCSPSLSPSSNR CCCCCCCCCCCCCCC	25.78	30266825
449	Phosphorylation	GSCSPSLSPSSNRSS CCCCCCCCCCCCCCC	27.37	30266825
451	Phosphorylation	CSPSLSPSSNRSSPA CCCCCCCCCCCCCCC	36.55	29255136
452	Phosphorylation	SPSLSPSSNRSSPAT CCCCCCCCCCCCCCC	39.38	29255136
455	Phosphorylation	LSPSSNRSSPATHSP CCCCCCCCCCCCCCC	44.94	24247654
456	Phosphorylation	SPSSNRSSPATHSP- CCCCCCCCCCCCCC-	18.47	24247654
459	Phosphorylation	SNRSSPATHSP---- CCCCCCCCCCC----	26.69	28102081
461	Phosphorylation	RSSPATHSP------ CCCCCCCCC------	28.13	15657432

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	CDK7	P50613	Uniprot
96	S	Phosphorylation	Kinase	AKT1	P31749	Uniprot
157	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
157	S	Phosphorylation	Kinase	PRKCG	P05129	GPS
181	T	Phosphorylation	Kinase	MAPK8	P45983	GPS
219	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
219	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
219	S	Phosphorylation	Kinase	PKA	-	Uniprot
369	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
369	S	Phosphorylation	Kinase	RPS6KA5	O75582	GPS
369	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
369	S	Phosphorylation	Kinase	PKA	-	Uniprot
445	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
461	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	MDM2	Q00987	PMID:26776160
-	K	Ubiquitination	E3 ubiquitin ligase	HACE1	Q8IYU2	PMID:19350571

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
77	S	Phosphorylation	16417524
Phosphorylation on Ser-77 is crucial for transcriptional activity (By similarity).
166	K	Sumoylation	19850744
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	19850744
On all-trans retinoic acid (ATRA) binding, a confromational change may occur that allows sumoylation on two additional site, Lys-166 and Lys-171.
219	S	Phosphorylation	20215566
This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling.
369	S	Phosphorylation	20215566
This phosphorylation on Ser-219 and Ser-369 is critical for ligand binding, nuclear localization and transcriptional activity in response to FSH signaling.
399	K	Sumoylation	19850744
Sumoylated with SUMO2, mainly on Lys-399 which is also required for SENP6 binding.

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NRBF2_HUMAN	NRBF2	physical	10786636
ZBT16_HUMAN	ZBTB16	physical	14521715
RXRG_HUMAN	RXRG	physical	16189514
RXRB_HUMAN	RXRB	physical	16189514
NRIP1_HUMAN	NRIP1	physical	14581481
KAT2B_HUMAN	KAT2B	physical	14581481
HDAC3_HUMAN	HDAC3	physical	12943985
HDAC4_HUMAN	HDAC4	physical	12943985
NCOA6_HUMAN	NCOA6	physical	10823961
PML_HUMAN	PML	physical	10610177
TRIP4_HUMAN	TRIP4	physical	10454579
KDM5A_HUMAN	KDM5A	physical	11358960
BAG1_HUMAN	BAG1	physical	9642262
TADA3_HUMAN	TADA3	physical	12235159
TADA3_HUMAN	TADA3	genetic	12235159
NCOR1_HUMAN	NCOR1	physical	10336495
IRX4_HUMAN	IRX4	physical	11382777
NRIP1_HUMAN	NRIP1	physical	8887632
SP1_HUMAN	SP1	physical	10361124
NPAS2_HUMAN	NPAS2	physical	11439184
CLOCK_HUMAN	CLOCK	physical	11439184
BMAL1_HUMAN	ARNTL	physical	11439184
RXRA_HUMAN	RXRA	physical	1314167
CCND3_HUMAN	CCND3	physical	12482873
NCOA2_HUMAN	NCOA2	physical	12612084
SRC_HUMAN	SRC	physical	12612084
AJUBA_HUMAN	AJUBA	physical	20133701
LIMD1_HUMAN	LIMD1	physical	20133701
WTIP_HUMAN	WTIP	physical	20133701
SKI_HUMAN	SKI	physical	19341714
HAIR_HUMAN	HR	physical	20211142
RXRA_HUMAN	RXRA	physical	15171703
SUV91_HUMAN	SUV39H1	physical	16449642
SP1_HUMAN	SP1	physical	19401466
SKI_HUMAN	SKI	physical	16424870
NCOA2_HUMAN	NCOA2	physical	12503607
NRIP1_HUMAN	NRIP1	physical	12503607
PRS8_HUMAN	PSMC5	physical	12503607
EP300_HUMAN	EP300	physical	11980644
PARP1_HUMAN	PARP1	physical	15808511
MED6_HUMAN	MED6	physical	15808511
RXRA_HUMAN	RXRA	physical	15528208
TOP2B_HUMAN	TOP2B	physical	18212063
SP130_HUMAN	SAP130	physical	18212063
HNRPU_HUMAN	HNRNPU	physical	18212063
RFC4_HUMAN	RFC4	physical	18212063
NPM_HUMAN	NPM1	physical	18212063
MRT4_HUMAN	MRTO4	physical	18212063
SNR40_HUMAN	SNRNP40	physical	18212063
NCOR1_HUMAN	NCOR1	physical	15336696
MED1_HUMAN	MED1	physical	10760302
NCOA1_HUMAN	NCOA1	physical	10760302
HMGA1_HUMAN	HMGA1	physical	10428834
SIAH1_HUMAN	SIAH1	physical	18073335
RARA_HUMAN	RARA	physical	18073335
HDAC2_HUMAN	HDAC2	physical	18073335
NCOR1_HUMAN	NCOR1	physical	9486655
KAT2B_HUMAN	KAT2B	physical	9445475
RXRA_HUMAN	RXRA	physical	9415406
NCOR2_HUMAN	NCOR2	physical	9415406
NCOA1_HUMAN	NCOA1	physical	9192892
NCOA2_HUMAN	NCOA2	physical	9192892
NCOA3_HUMAN	NCOA3	physical	9192892
LRIF1_HUMAN	LRIF1	physical	17455211
HDAC2_HUMAN	HDAC2	physical	21383775
TADA3_HUMAN	TADA3	physical	20413580
SPI1_HUMAN	SPI1	physical	20159610
PML_HUMAN	PML	physical	20159610
PDIA3_RAT	Pdia3	physical	20130111
RARA_HUMAN	RARA	physical	20807888
RXRA_HUMAN	RXRA	physical	15604093
PRDX6_HUMAN	PRDX6	physical	15604093
RXRG_HUMAN	RXRG	physical	15604093
NR1H2_HUMAN	NR1H2	physical	15604093
ITBP2_HUMAN	ITGB1BP2	physical	15604093
RXRB_HUMAN	RXRB	physical	15604093
MED25_HUMAN	MED25	physical	17641689
SRC_HUMAN	SRC	physical	17641689
MED1_HUMAN	MED1	physical	17641689
PRS8_HUMAN	PSMC5	physical	8598193
TIF1A_HUMAN	TRIM24	physical	8598193
NCOA3_HUMAN	NCOA3	physical	9346901
MK01_HUMAN	MAPK1	physical	12048211
TRI32_HUMAN	TRIM32	physical	21984809
PRS8_HUMAN	PSMC5	physical	19144644
NCOA3_HUMAN	NCOA3	physical	19144644
NCOA3_HUMAN	NCOA3	physical	16456540
NCOR1_HUMAN	NCOR1	physical	9121466
SQSTM_HUMAN	SQSTM1	physical	21187718
UBQL1_HUMAN	UBQLN1	physical	20693704
NCOR2_HUMAN	NCOR2	physical	9380707
ARI5A_HUMAN	ARID5A	physical	15941852
RXRA_HUMAN	RXRA	physical	16540467
PRAM_HUMAN	PRAM1	physical	21803845
TNR6_HUMAN	FAS	physical	21803845
PRAME_HUMAN	PRAME	physical	16179254
NCOR1_HUMAN	NCOR1	physical	16469706
TBL1R_HUMAN	TBL1XR1	physical	16469706
PRS8_HUMAN	PSMC5	physical	8603043
SUZ12_HUMAN	SUZ12	physical	17560333
NCOA2_HUMAN	NCOA2	physical	9430642
UBP7_HUMAN	USP7	physical	23208507
NCOR2_HUMAN	NCOR2	physical	16219912
TMM54_HUMAN	TMEM54	physical	22982681
AKT1_HUMAN	AKT1	physical	16417524
RXRA_HUMAN	RXRA	physical	9582446
RXRB_HUMAN	RXRB	physical	21988832
RXRA_HUMAN	RXRA	physical	21988832
RXRG_HUMAN	RXRG	physical	21988832
NCOR1_HUMAN	NCOR1	physical	7566114
E2F1_HUMAN	E2F1	physical	24608861
MBD3_HUMAN	MBD3	physical	24821728
MTA2_HUMAN	MTA2	physical	24821728
CBX5_HUMAN	CBX5	physical	24821728
NCOA1_HUMAN	NCOA1	physical	23975195
RXRG_HUMAN	RXRG	physical	25416956
NRIP1_HUMAN	NRIP1	physical	25416956
TEKT4_HUMAN	TEKT4	physical	25416956
CBP_HUMAN	CREBBP	physical	18443043
RXRA_HUMAN	RXRA	physical	21478865
MED1_HUMAN	MED1	physical	21478865
SNW1_HUMAN	SNW1	physical	19934264
SIR1_HUMAN	SIRT1	physical	19934264
SQSTM_HUMAN	SQSTM1	physical	25973309
ACTN4_HUMAN	ACTN4	physical	22351778
NCOA1_HUMAN	NCOA1	physical	10454579
SMRD3_HUMAN	SMARCD3	physical	17363140
NCOA3_HUMAN	NCOA3	physical	20413580
KLF5_HUMAN	KLF5	physical	18466769
SRF_HUMAN	SRF	physical	11641790
RXRA_HUMAN	RXRA	physical	9121466
NCOA1_HUMAN	NCOA1	physical	9121466
RXRA_HUMAN	RXRA	physical	14521715
RXRG_HUMAN	RXRG	physical	21516116
KLF5_HUMAN	KLF5	physical	16224062
RXRA_HUMAN	RXRA	physical	16224062
KLF5_HUMAN	KLF5	physical	16102021
MDM2_HUMAN	MDM2	physical	26776160
RARB_HUMAN	RARB	physical	28514442
RXRB_HUMAN	RXRB	physical	28514442

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
DB00459	Acitretin
DB00210	Adapalene
DB00523	Alitretinoin
DB00982	Isotretinoin
DB04942	Tamibarotene
DB00799	Tazarotene

Regulatory Network of RARA_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Activity of retinoic acid receptor-alpha is directly regulated at itsprotein kinase A sites in response to follicle-stimulating hormonesignaling."; Santos N.C., Kim K.H.; Endocrinology 151:2361-2372(2010). Cited for: PHOSPHORYLATION AT SER-219 AND SER-369, INTERACTION WITH RXRA ANDPRKAR1A, FUNCTION, AND MUTAGENESIS OF SER-219 AND SER-369.	20215566 [Abstract]
"Akt phosphorylates and suppresses the transactivation of retinoicacid receptor alpha."; Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L.,Weigel N.L., Brown P.H., Kurie J.M.; Biochem. J. 395:653-662(2006). Cited for: PHOSPHORYLATION AT SER-96, FUNCTION, INTERACTION WITH AKT1, ANDMUTAGENESIS OF SER-95; SER-96; SER-154 AND SER-157.	16417524 [Abstract]
Sumoylation
Reference	PubMed
"Small ubiquitin-like modifier-2 modification of retinoic acidreceptor-alpha regulates its subcellular localization andtranscriptional activity."; Zhu L., Santos N.C., Kim K.H.; Endocrinology 150:5586-5595(2009). Cited for: SUMOYLATION AT LYS-166; LYS-171 AND LYS-399, FUNCTION, SUBCELLULARLOCATION, AND MUTAGENESIS OF LYS-147; LYS-166; LYS-171 AND LYS-399.	19850744 [Abstract]

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