RIPK3_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RIPK3_MOUSE
• UniProt AC: Q9QZL0
• Protein Name: Receptor-interacting serine/threonine-protein kinase 3
• Gene Name: Ripk3
• Organism: Mus musculus (Mouse).
• Sequence Length: 486
• Subcellular Localization: Cytoplasm, cytosol . Cell membrane. Mitochondrion .
• Protein Description: Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production..
• Protein Sequence: MSSVKLWPTGASAVPLVSREELKKLEFVGKGGFGVVFRAHHRTWNHDVAVKIVNSKKISWEVKAMVNLRNENVLLLLGVTEDLQWDFVSGQALVTRFMENGSLAGLLQPECPRPWPLLCRLLQEVVLGMCYLHSLNPPLLHRDLKPSNILLDPELHAKLADFGLSTFQGGSQSGSGSGSGSRDSGGTLAYLDPELLFDVNLKASKASDVYSFGILVWAVLAGREAELVDKTSLIRETVCDRQSRPPLTELPPGSPETPGLEKLKELMIHCWGSQSENRPSFQDCEPKTNEVYNLVKDKVDAAVSEVKHYLSQHRSSGRNLSAREPSQRGTEMDCPRETMVSKMLDRLHLEEPSGPVPGKCPERQAQDTSVGPATPARTSSDPVAGTPQIPHTLPFRGTTPGPVFTETPGPHPQRNQGDGRHGTPWYPWTPPNPMTGPPALVFNNCSEVQIGNYNSLVAPPRTTASSSAKYDQAQFGRGRGWQPFHK

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
2	Phosphorylation	------MSSVKLWPT ------CCCCCCCCC	43.78	26643407
3	Phosphorylation	-----MSSVKLWPTG -----CCCCCCCCCC	23.21	26643407
5	Ubiquitination	---MSSVKLWPTGAS ---CCCCCCCCCCCC	46.94	-
9	Phosphorylation	SSVKLWPTGASAVPL CCCCCCCCCCCCCCC	33.52	26643407
12	Phosphorylation	KLWPTGASAVPLVSR CCCCCCCCCCCCCCH	31.01	26643407
18	Phosphorylation	ASAVPLVSREELKKL CCCCCCCCHHHHHCC	41.48	26643407
165	Phosphorylation	KLADFGLSTFQGGSQ HHHHCCCCCCCCCCC	27.79	23612963
171	Phosphorylation	LSTFQGGSQSGSGSG CCCCCCCCCCCCCCC	28.18	24068923
173	Phosphorylation	TFQGGSQSGSGSGSG CCCCCCCCCCCCCCC	36.30	24068923
175	Phosphorylation	QGGSQSGSGSGSGSR CCCCCCCCCCCCCCC	34.72	29550500
177	Phosphorylation	GSQSGSGSGSGSRDS CCCCCCCCCCCCCCC	31.33	24068923
179	Phosphorylation	QSGSGSGSGSRDSGG CCCCCCCCCCCCCCC	34.98	24068923
181	Phosphorylation	GSGSGSGSRDSGGTL CCCCCCCCCCCCCCE	34.31	24068923
184	Phosphorylation	SGSGSRDSGGTLAYL CCCCCCCCCCCEEEC	37.70	21659605
187	Phosphorylation	GSRDSGGTLAYLDPE CCCCCCCCEEECCHH	16.25	29550500
204	Phosphorylation	FDVNLKASKASDVYS EEEECCCCCCCCHHH	27.45	-
231	Phosphorylation	EAELVDKTSLIRETV CCCCCCCCHHHHHHH	25.05	26824392
232	Phosphorylation	AELVDKTSLIRETVC CCCCCCCHHHHHHHC	27.78	22265413
257	Phosphorylation	LPPGSPETPGLEKLK CCCCCCCCCCHHHHH	26.49	23612963
264	Ubiquitination	TPGLEKLKELMIHCW CCCHHHHHHHHHHHC	60.93	-
304	Phosphorylation	DKVDAAVSEVKHYLS HHHHHHHHHHHHHHH	31.76	23612963
321	Phosphorylation	RSSGRNLSAREPSQR HCCCCCCCCCCHHHC	28.91	25266776
326	Phosphorylation	NLSAREPSQRGTEMD CCCCCCHHHCCCCCC	27.96	25266776
330	Phosphorylation	REPSQRGTEMDCPRE CCHHHCCCCCCCCHH	30.26	25266776
334	Glutathionylation	QRGTEMDCPRETMVS HCCCCCCCCHHHHHH	3.10	24333276
338	Phosphorylation	EMDCPRETMVSKMLD CCCCCHHHHHHHHHH	24.93	23612963
341	Phosphorylation	CPRETMVSKMLDRLH CCHHHHHHHHHHHHC	11.09	25266776
353	Phosphorylation	RLHLEEPSGPVPGKC HHCCCCCCCCCCCCC	60.03	23612963
360	Glutathionylation	SGPVPGKCPERQAQD CCCCCCCCCHHHCCC	5.40	24333276
369	Phosphorylation	ERQAQDTSVGPATPA HHHCCCCCCCCCCCC	33.11	23612963
374	Phosphorylation	DTSVGPATPARTSSD CCCCCCCCCCCCCCC	22.18	26824392
378	Phosphorylation	GPATPARTSSDPVAG CCCCCCCCCCCCCCC	34.39	23970565
379	Phosphorylation	PATPARTSSDPVAGT CCCCCCCCCCCCCCC	27.47	23970565
380	Phosphorylation	ATPARTSSDPVAGTP CCCCCCCCCCCCCCC	45.37	27180971
386	Phosphorylation	SSDPVAGTPQIPHTL CCCCCCCCCCCCCCC	11.41	25266776
392	Phosphorylation	GTPQIPHTLPFRGTT CCCCCCCCCCCCCCC	30.67	23612963
398	Phosphorylation	HTLPFRGTTPGPVFT CCCCCCCCCCCCEEE	26.09	28507225
399	Phosphorylation	TLPFRGTTPGPVFTE CCCCCCCCCCCEEEC	29.13	25168779
405	Phosphorylation	TTPGPVFTETPGPHP CCCCCEEECCCCCCC	38.90	25168779
407	Phosphorylation	PGPVFTETPGPHPQR CCCEEECCCCCCCCC	30.41	25168779
477	Methylation	YDQAQFGRGRGWQPF CCHHHHCCCCCCCCC	32.69	24129315
477	Dimethylation	YDQAQFGRGRGWQPF CCHHHHCCCCCCCCC	32.69	-
479	Methylation	QAQFGRGRGWQPFHK HHHHCCCCCCCCCCC	41.64	31136415
479	Dimethylation	QAQFGRGRGWQPFHK HHHHCCCCCCCCCCC	41.64	-

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
231	T	Phosphorylation	Kinase	RIPK3	Q9Y572	PSP
231	T	Phosphorylation	Kinase	RIPK3	Q9QZL0	PSP
232	S	Phosphorylation	Kinase	RIPK3	Q9Y572	PSP
232	S	Phosphorylation	Kinase	RIPK3	Q9QZL0	PSP
399	T	Phosphorylation	Kinase	MAPK1	P63085	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
48	K	ubiquitylation	Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.	-
187	T	Phosphorylation	Phosphorylation at Thr-187 is important for its kinase activity, interaction with PELI1 and for its ability to mediate TNF-induced necroptosis (By similarity).	27819682
204	S	Phosphorylation	Phosphorylation of Ser-204 plays a role in the necroptotic function of RIPK3 (By similarity).	27819682
231	T	Phosphorylation	Autophosphorylates at Thr-231 and Ser-232 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL.	23612963
232	S	Phosphorylation	Autophosphorylates at Thr-231 and Ser-232 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL.	22265413

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of RIPK3_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SQSTM_HUMAN	SQSTM1	physical	25450619

Drug and Disease Associations

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