dbPTM

RIPK3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RIPK3_HUMAN
UniProt AC	Q9Y572
Protein Name	Receptor-interacting serine/threonine-protein kinase 3
Gene Name	RIPK3
Organism	Homo sapiens (Human).
Sequence Length	518
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	MSCVKLWPSGAPAPLVSIEELENQELVGKGGFGTVFRAQHRKWGYDVAVKIVNSKAISREVKAMASLDNEFVLRLEGVIEKVNWDQDPKPALVTKFMENGSLSGLLQSQCPRPWPLLCRLLKEVVLGMFYLHDQNPVLLHRDLKPSNVLLDPELHVKLADFGLSTFQGGSQSGTGSGEPGGTLGYLAPELFVNVNRKASTASDVYSFGILMWAVLAGREVELPTEPSLVYEAVCNRQNRPSLAELPQAGPETPGLEGLKELMQLCWSSEPKDRPSFQECLPKTDEVFQMVENNMNAAVSTVKDFLSQLRSSNRRFSIPESGQGGTEMDGFRRTIENQHSRNDVMVSEWLNKLNLEEPPSSVPKKCPSLTKRSRAQEEQVPQAWTAGTSSDSMAQPPQTPETSTFRNQMPSPTSTGTPSPGPRGNQGAERQGMNWSCRTPEPNPVTGRPLVNIYNCSGVQVGDNNYLTMQQTTALPTWGLAPSGKGRGLQHPPPVGSQEGPKDPEAWSRPQGWYNHSGK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSCVKLWPS ------CCCEEECCC	27.84	-
5	Ubiquitination	---MSCVKLWPSGAP ---CCCEEECCCCCC	49.51	29967540
55	Ubiquitination	AVKIVNSKAISREVK EEEEECHHHHCHHHH	44.53	29967540
164	Phosphorylation	KLADFGLSTFQGGSQ EHHHHCCCEECCCCC	27.79	-
170	Phosphorylation	LSTFQGGSQSGTGSG CCEECCCCCCCCCCC	28.18	28348404
172	Phosphorylation	TFQGGSQSGTGSGEP EECCCCCCCCCCCCC	39.77	28348404
174	Phosphorylation	QGGSQSGTGSGEPGG CCCCCCCCCCCCCCC	33.16	28348404
176	Phosphorylation	GSQSGTGSGEPGGTL CCCCCCCCCCCCCCC	39.56	28348404
182	Phosphorylation	GSGEPGGTLGYLAPE CCCCCCCCCEEECCH	23.95	29883609
199	Phosphorylation	VNVNRKASTASDVYS EECCCCCCCHHHHHH	27.78	19524512
224	Phosphorylation	GREVELPTEPSLVYE CCCEECCCCCHHHHH	73.48	26657352
227	Phosphorylation	VELPTEPSLVYEAVC EECCCCCHHHHHHHH	25.00	26657352
230	Phosphorylation	PTEPSLVYEAVCNRQ CCCCHHHHHHHHCCC	11.94	28796482
241	Phosphorylation	CNRQNRPSLAELPQA HCCCCCCCHHHCCCC	36.65	23312004
252	Phosphorylation	LPQAGPETPGLEGLK CCCCCCCCCCHHHHH	26.28	23312004
267	Phosphorylation	ELMQLCWSSEPKDRP HHHHHHCCCCCCCCC	24.67	23879269
268	Phosphorylation	LMQLCWSSEPKDRPS HHHHHCCCCCCCCCC	33.16	23879269
299	Phosphorylation	NNMNAAVSTVKDFLS HCHHHHHHHHHHHHH	23.82	-
300	Phosphorylation	NMNAAVSTVKDFLSQ CHHHHHHHHHHHHHH	25.61	-
316	Phosphorylation	RSSNRRFSIPESGQG HHCCCCCCCCCCCCC	35.11	22617229
320	Phosphorylation	RRFSIPESGQGGTEM CCCCCCCCCCCCCCC	30.94	28450419
325	Phosphorylation	PESGQGGTEMDGFRR CCCCCCCCCCHHHHH	34.65	29978859
333	Phosphorylation	EMDGFRRTIENQHSR CCHHHHHHHHHCCCC	28.52	28450419
339	Phosphorylation	RTIENQHSRNDVMVS HHHHHCCCCCHHHHH	24.02	23401153
359	Phosphorylation	LNLEEPPSSVPKKCP CCCCCCCCCCCCCCC	55.47	24719451
360	Phosphorylation	NLEEPPSSVPKKCPS CCCCCCCCCCCCCCC	48.49	28348404
367	Phosphorylation	SVPKKCPSLTKRSRA CCCCCCCCCCHHHHH	59.13	26657352
372	Phosphorylation	CPSLTKRSRAQEEQV CCCCCHHHHHCHHHC	33.26	-
389	Phosphorylation	AWTAGTSSDSMAQPP HHHCCCCCCCCCCCC	33.28	21601212
401	Phosphorylation	QPPQTPETSTFRNQM CCCCCCCCCCCCCCC	33.98	-
410	Phosphorylation	TFRNQMPSPTSTGTP CCCCCCCCCCCCCCC	35.15	23401153
412	Phosphorylation	RNQMPSPTSTGTPSP CCCCCCCCCCCCCCC	43.17	26657352
413	Phosphorylation	NQMPSPTSTGTPSPG CCCCCCCCCCCCCCC	28.37	28450419
414	Phosphorylation	QMPSPTSTGTPSPGP CCCCCCCCCCCCCCC	47.77	28450419
416	Phosphorylation	PSPTSTGTPSPGPRG CCCCCCCCCCCCCCC	22.23	28450419
418	Phosphorylation	PTSTGTPSPGPRGNQ CCCCCCCCCCCCCCC	42.18	30624053
467	O-linked_Glycosylation	VGDNNYLTMQQTTAL ECCCCEEEEEEECCC	11.54	30770249
486	Methylation	LAPSGKGRGLQHPPP CCCCCCCCCCCCCCC	46.24	115389587
496	Phosphorylation	QHPPPVGSQEGPKDP CCCCCCCCCCCCCCH	25.87	28450419

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
182	T	Phosphorylation	Kinase	RIPK3	Q9Y572	PSP
199	S	Phosphorylation	Kinase	RIPK3	Q9Y572	GPS
227	S	Phosphorylation	Kinase	RIPK3	Q9Y572	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	BIRC2	Q13490	PMID:21931591
-	K	Ubiquitination	E3 ubiquitin ligase	BIRC3	Q13489	PMID:21931591

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
48	K	ubiquitylation	21931591
Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.
182	T	Phosphorylation	29883609
Phosphorylation at Thr-182 is important for its kinase activity, interaction with PELI1 and PELI1-mediated 'Lys-48'-linked polyubiquitination and for its ability to mediate TNF-induced necroptosis.
182	T	ubiquitylation	29883609
Phosphorylation at Thr-182 is important for its kinase activity, interaction with PELI1 and PELI1-mediated 'Lys-48'-linked polyubiquitination and for its ability to mediate TNF-induced necroptosis.
199	S	Phosphorylation	11734559
Phosphorylation of Ser-199 plays a role in the necroptotic function of RIPK3.
227	S	Phosphorylation	22265413
Autophosphorylates at Ser-227 following activation by ZBP1: phosphorylation at these sites is a hallmark of necroptosis and is required for binding MLKL.

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 RIPK3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RIPK1_HUMAN	RIPK1	physical	10339433
TCAM1_HUMAN	TICAM1	physical	15064760
TNR1A_HUMAN	TNFRSF1A	physical	10339433
CTND1_HUMAN	CTNND1	physical	21903422
CDC37_HUMAN	CDC37	physical	21903422
FKBP4_HUMAN	FKBP4	physical	21903422
FKBP5_HUMAN	FKBP5	physical	21903422
INP5K_HUMAN	INPP5K	physical	21903422
PYGL_HUMAN	PYGL	physical	21903422
RIPK1_HUMAN	RIPK1	physical	21903422
STIP1_HUMAN	STIP1	physical	21903422
RIPK1_HUMAN	RIPK1	physical	22864571
FADD_HUMAN	FADD	physical	22864571
EPHA4_HUMAN	EPHA4	physical	26186194
ZG16B_HUMAN	ZG16B	physical	26186194
PTPRK_HUMAN	PTPRK	physical	26186194
DAXX_HUMAN	DAXX	physical	23260419
RIPK1_HUMAN	RIPK1	physical	25882049
RIPK1_HUMAN	RIPK1	physical	24098568
RIPK1_HUMAN	RIPK1	physical	26786097
FADD_HUMAN	FADD	physical	26786097
RIPK3_HUMAN	RIPK3	physical	27045108
EPHA4_HUMAN	EPHA4	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
There are no disease associations of PTM sites.

Regulatory Network of RIPK3_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Receptor interacting protein kinase-3 determines cellular necroticresponse to TNF-alpha."; He S., Wang L., Miao L., Wang T., Du F., Zhao L., Wang X.; Cell 137:1100-1111(2009). Cited for: FUNCTION, PHOSPHORYLATION AT SER-199, AND INTERACTION WITH RIPK1.	19524512 [Abstract]
"Identification of a novel homotypic interaction motif required forthe phosphorylation of receptor-interacting protein (RIP) by RIP3."; Sun X., Yin J., Starovasnik M.A., Fairbrother W.J., Dixit V.M.; J. Biol. Chem. 277:9505-9511(2002). Cited for: RIP HOMOTYPIC INTERACTION MOTIF, PHOSPHORYLATION AT SER-199, ANDINTERACTION WITH RIPK1.	11734559 [Abstract]

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