RIPK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RIPK1_MOUSE
• UniProt AC: Q60855
• Protein Name: Receptor-interacting serine/threonine-protein kinase 1
• Gene Name: Ripk1
• Organism: Mus musculus (Mouse).
• Sequence Length: 656
• Subcellular Localization: Cytoplasm. Cell membrane.
• Protein Description: Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex (By similarity). Interacts with ARHGEF2 (By similarity)..
• Protein Sequence: MQPDMSLDNIKMASSDLLEKTDLDSGGFGKVSLCYHRSHGFVILKKVYTGPNRAEYNEVLLEEGKMMHRLRHSRVVKLLGIIIEEGNYSLVMEYMEKGNLMHVLKTQIDVPLSLKGRIIVEAIEGMCYLHDKGVIHKDLKPENILVDRDFHIKIADLGVASFKTWSKLTKEKDNKQKEVSSTTKKNNGGTLYYMAPEHLNDINAKPTEKSDVYSFGIVLWAIFAKKEPYENVICTEQFVICIKSGNRPNVEEILEYCPREIISLMERCWQAIPEDRPTFLGIEEEFRPFYLSHFEEYVEEDVASLKKEYPDQSPVLQRMFSLQHDCVPLPPSRSNSEQPGSLHSSQGLQMGPVEESWFSSSPEYPQDENDRSVQAKLQEEASYHAFGIFAEKQTKPQPRQNEAYNREEERKRRVSHDPFAQQRARENIKSAGARGHSDPSTTSRGIAVQQLSWPATQTVWNNGLYNQHGFGTTGTGVWYPPNLSQMYSTYKTPVPETNIPGSTPTMPYFSGPVADDLIKYTIFNSSGIQIGNHNYMDVGLNSQPPNNTCKEESTSRHQAIFDNTTSLTDEHLNPIRENLGRQWKNCARKLGFTESQIDEIDHDYERDGLKEKVYQMLQKWLMREGTKGATVGKLAQALHQCCRIDLLNHLIRASQS

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
6	Phosphorylation	--MQPDMSLDNIKMA --CCCCCCHHHHHCC	39.69	30988283
14	Phosphorylation	LDNIKMASSDLLEKT HHHHHCCCHHHHHHC	22.38	-
15	Phosphorylation	DNIKMASSDLLEKTD HHHHCCCHHHHHHCC	23.80	-
20	Acetylation	ASSDLLEKTDLDSGG CCHHHHHHCCCCCCC	47.51	23236377
25	Phosphorylation	LEKTDLDSGGFGKVS HHHCCCCCCCCCEEE	48.38	28833060
115	Ubiquitination	IDVPLSLKGRIIVEA CCCCCCCCCCCCEEE	42.65	22790023
161	Phosphorylation	IADLGVASFKTWSKL HHHHHHCCHHHHHHH	25.52	-
166	Phosphorylation	VASFKTWSKLTKEKD HCCHHHHHHHHHHHH	24.02	27819682
169	Phosphorylation	FKTWSKLTKEKDNKQ HHHHHHHHHHHHCCC	40.68	30988283
235	Phosphorylation	PYENVICTEQFVICI CCCCEECEECEEEEE	23.00	-
304	Phosphorylation	YVEEDVASLKKEYPD HHHHHHHHHHHHCCC	40.34	-
307	Ubiquitination	EDVASLKKEYPDQSP HHHHHHHHHCCCCCH	68.71	22790023
309	Phosphorylation	VASLKKEYPDQSPVL HHHHHHHCCCCCHHH	22.46	25619855
313	Phosphorylation	KKEYPDQSPVLQRMF HHHCCCCCHHHHHHH	25.10	27087446
321	Phosphorylation	PVLQRMFSLQHDCVP HHHHHHHHCCCCCEE	20.13	25521595
332	Phosphorylation	DCVPLPPSRSNSEQP CCEECCCCCCCCCCC	46.53	25619855
334	Phosphorylation	VPLPPSRSNSEQPGS EECCCCCCCCCCCCC	49.39	27087446
336	Phosphorylation	LPPSRSNSEQPGSLH CCCCCCCCCCCCCCC	38.56	23649490
341	Phosphorylation	SNSEQPGSLHSSQGL CCCCCCCCCCCCCCC	29.59	30635358
344	Phosphorylation	EQPGSLHSSQGLQMG CCCCCCCCCCCCCCC	29.65	30635358
345	Phosphorylation	QPGSLHSSQGLQMGP CCCCCCCCCCCCCCC	19.95	30635358
356	Phosphorylation	QMGPVEESWFSSSPE CCCCCCHHCCCCCCC	21.66	30635358
361	Phosphorylation	EESWFSSSPEYPQDE CHHCCCCCCCCCCCC	22.13	23649490
383	Phosphorylation	KLQEEASYHAFGIFA HHHHHHHHHHHEEEE	12.29	29514104
415	Phosphorylation	EERKRRVSHDPFAQQ HHHHHHHCCCHHHHH	21.99	26824392
429	Acetylation	QRARENIKSAGARGH HHHHHHHHHCCCCCC	45.92	19864971
437	Phosphorylation	SAGARGHSDPSTTSR HCCCCCCCCCCCCCC	54.78	23684622
503	Phosphorylation	ETNIPGSTPTMPYFS CCCCCCCCCCCCCCC	28.79	25338131
593	Phosphorylation	CARKLGFTESQIDEI HHHHHCCCHHHHHHC	32.69	30635358
595	Phosphorylation	RKLGFTESQIDEIDH HHHCCCHHHHHHCCC	29.40	27180971
612	Ubiquitination	ERDGLKEKVYQMLQK HHCCHHHHHHHHHHH	44.66	22790023

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
6	S	Phosphorylation	Kinase	IKKA	Q60680	Uniprot
6	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
25	S	Phosphorylation	Kinase	IKKA	Q60680	Uniprot
25	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
161	S	Phosphorylation	Kinase	RIPK3	Q9QZL0	Uniprot
166	S	Phosphorylation	Kinase	RIPK1	Q60855	PSP
321	S	Phosphorylation	Kinase	TAK1	O43318	PSP
321	S	Phosphorylation	Kinase	TAK1	Q62073	PSP
321	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
321	S	Phosphorylation	Kinase	MAPKAPK2	P49138	PSP
332	S	Phosphorylation	Kinase	TAK1	Q62073	PSP
334	S	Phosphorylation	Kinase	TAK1	Q62073	PSP
336	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
336	S	Phosphorylation	Kinase	MAPKAPK2	P49138	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
11	K	ubiquitylation	Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (By similarity).	28701375
25	S	Phosphorylation	Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death.	30988283
48	K	ubiquitylation	Polyubiquitinated with 'Lys-48' by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B (By similarity).	28701375
48	K	ubiquitylation	Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (By similarity).	28701375
63	K	ubiquitylation	Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (By similarity).	28701375
161	S	Phosphorylation	Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex (By similarity).	30988283
321	S	Phosphorylation	Phosphorylated at Ser-321 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2.	21183079
321	S	Phosphorylation	Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7.	21183079
321	S	ubiquitylation	Phosphorylated at Ser-321 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2.	21183079
321	S	ubiquitylation	Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7.	21183079
376	K	Phosphorylation	Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7.	31519887
376	K	ubiquitylation	Ubiquitination at Lys-376 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-321 mediated by MAP3K7.	31519887

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of RIPK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NEMO_MOUSE	Ikbkg	physical	17981138
TNAP3_MOUSE	Tnfaip3	physical	21765415
TNAP3_MOUSE	Tnfaip3	physical	18246070
ITCH_MOUSE	Itch	physical	18246070
TRAF6_MOUSE	Traf6	physical	18246070
TAXB1_MOUSE	Tax1bp1	physical	18239685
TNAP3_MOUSE	Tnfaip3	physical	18239685
M3K8_MOUSE	Map3k8	physical	16291755

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"The phagosomal proteome in interferon-gamma-activated macrophages.";
Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,Thibault P.;
Immunity 30:143-154(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-313, AND MASSSPECTROMETRY.
PubMed: 19144319