NR4A3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NR4A3_HUMAN
• UniProt AC: Q92570
• Protein Name: Nuclear receptor subfamily 4 group A member 3
• Gene Name: NR4A3
• Organism: Homo sapiens (Human).
• Sequence Length: 626
• Subcellular Localization: Nucleus .
• Protein Description: Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity). [PubMed: 20558821 In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface]
• Protein Sequence: MPCVQAQYSPSPPGSSYAAQTYSSEYTTEIMNPDYTKLTMDLGSTEITATATTSLPSISTFVEGYSSNYELKPSCVYQMQRPLIKVEEGRAPSYHHHHHHHHHHHHHHQQQHQQPSIPPASSPEDEVLPSTSMYFKQSPPSTPTTPAFPPQAGALWDEALPSAPGCIAPGPLLDPPMKAVPTVAGARFPLFHFKPSPPHPPAPSPAGGHHLGYDPTAAAALSLPLGAAAAAGSQAAALESHPYGLPLAKRAAPLAFPPLGLTPSPTASSLLGESPSLPSPPSRSSSSGEGTCAVCGDNAACQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRNRCQYCRFQKCLSVGMVKEVVRTDSLKGRRGRLPSKPKSPLQQEPSQPSPPSPPICMMNALVRALTDSTPRDLDYSRYCPTDQAAAGTDAEHVQQFYNLLTASIDVSRSWAEKIPGFTDLPKEDQTLLIESAFLELFVLRLSIRSNTAEDKFVFCNGLVLHRLQCLRGFGEWLDSIKDFSLNLQSLNLDIQALACLSALSMITERHGLKEPKRVEELCNKITSSLKDHQSKGQALEPTESKVLGALVELRKICTLGLQRIFYLKLEDLVSPPSIIDKLFLDTLPF

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
8	Phosphorylation	MPCVQAQYSPSPPGS CCCEECEECCCCCCC	26.09	-
26	Phosphorylation	AQTYSSEYTTEIMNP CEEECCCEECCCCCC	22.40	-
187	Dimethylation	VPTVAGARFPLFHFK CCCCCCCCCCEEECC	32.56	-
187	Methylation	VPTVAGARFPLFHFK CCCCCCCCCCEEECC	32.56	52718201
262	Phosphorylation	AFPPLGLTPSPTASS CCCCCCCCCCCCHHH	21.66	20873877
264	Phosphorylation	PPLGLTPSPTASSLL CCCCCCCCCCHHHHC	29.64	20873877
266	Phosphorylation	LGLTPSPTASSLLGE CCCCCCCCHHHHCCC	43.43	20873877
268	Phosphorylation	LTPSPTASSLLGESP CCCCCCHHHHCCCCC	24.81	20873877
269	Phosphorylation	TPSPTASSLLGESPS CCCCCHHHHCCCCCC	25.75	20873877
274	Phosphorylation	ASSLLGESPSLPSPP HHHHCCCCCCCCCCC	20.28	20873877
276	Phosphorylation	SLLGESPSLPSPPSR HHCCCCCCCCCCCCC	63.29	20873877
279	Phosphorylation	GESPSLPSPPSRSSS CCCCCCCCCCCCCCC	55.53	28348404
282	Phosphorylation	PSLPSPPSRSSSSGE CCCCCCCCCCCCCCC	48.45	20873877
284	Phosphorylation	LPSPPSRSSSSGEGT CCCCCCCCCCCCCCC	38.62	27251275
285	Phosphorylation	PSPPSRSSSSGEGTC CCCCCCCCCCCCCCE	27.67	27251275
286	Phosphorylation	SPPSRSSSSGEGTCA CCCCCCCCCCCCCEE	43.54	27251275
287	Phosphorylation	PPSRSSSSGEGTCAV CCCCCCCCCCCCEEE	42.69	27251275
296 (in isoform 3)	Phosphorylation	-	25.30	27251275
304	Phosphorylation	DNAACQHYGVRTCEG CCCCCCHHCCCCCCC	7.46	-
308	Phosphorylation	CQHYGVRTCEGCKGF CCHHCCCCCCCCCCH	16.71	-
325	Ubiquitination	RTVQKNAKYVCLANK HHHHHCCCEEEECCC	47.84	-
332	Ubiquitination	KYVCLANKNCPVDKR CEEEECCCCCCCCHH	55.08	-
364	Phosphorylation	MVKEVVRTDSLKGRR CEEEEEECCCCCCCC	20.52	28102081
366	Phosphorylation	KEVVRTDSLKGRRGR EEEEECCCCCCCCCC	31.22	28355574
376	Phosphorylation	GRRGRLPSKPKSPLQ CCCCCCCCCCCCCCC	67.21	16223362
377 (in isoform 3)	Phosphorylation	-	55.30	27251275
380	Phosphorylation	RLPSKPKSPLQQEPS CCCCCCCCCCCCCCC	39.09	29449344
387	Phosphorylation	SPLQQEPSQPSPPSP CCCCCCCCCCCCCCC	54.71	16223362
390	Phosphorylation	QQEPSQPSPPSPPIC CCCCCCCCCCCCCCH	41.63	29449344
393	Phosphorylation	PSQPSPPSPPICMMN CCCCCCCCCCCHHHH	46.85	29449344
488	O-linked_Glycosylation	RLSIRSNTAEDKFVF HHHHCCCCCCCCEEE	32.44	30379171
526	Phosphorylation	DFSLNLQSLNLDIQA HHCCCHHHCCCHHHH	23.53	-
538	Phosphorylation	IQALACLSALSMITE HHHHHHHHHHHHHHH	27.35	-
563	Phosphorylation	EELCNKITSSLKDHQ HHHHHHHHHHHHHHH	17.55	30108239
564	Phosphorylation	ELCNKITSSLKDHQS HHHHHHHHHHHHHHH	36.83	30108239
565	Phosphorylation	LCNKITSSLKDHQSK HHHHHHHHHHHHHHC	30.68	30108239
567	Ubiquitination	NKITSSLKDHQSKGQ HHHHHHHHHHHHCCC	55.93	-
582	Ubiquitination	ALEPTESKVLGALVE CCCCCHHHHHHHHHH	34.93	-
611	Phosphorylation	LKLEDLVSPPSIIDK EEHHHHCCCHHHHHH	38.09	21815630

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of NR4A3_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NR4A3_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of NR4A3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SIX3_HUMAN	SIX3	physical	11173923
CSN5_HUMAN	COPS5	physical	15604093
SIX3_HUMAN	SIX3	physical	15523651

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 612219: Ewing sarcoma (ES)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.