dbPTM

RIPK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	RIPK2_MOUSE
UniProt AC	P58801
Protein Name	Receptor-interacting serine/threonine-protein kinase 2
Gene Name	Ripk2
Organism	Mus musculus (Mouse).
Sequence Length	539
Subcellular Localization	Cytoplasm .
Protein Description	Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is release from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation..
Protein Sequence	MNGDAICSALPPIPYHKLADLHYLSRGASGTVSSARHADWRVRVAVKHLHIHTPLLDSERNDILREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDIAWPLRFRILHEIALGVNYLHNMNPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRSYKSAPEGGTIIYMPPENYEPGQKSRASVKHDIYSYAVIMWEVLSRKQPFEEVTNPLQIMYSVSQGHRPDTSEENLPFDIPHRGLMISLIQSGWAQNPDERPSFLKCLIELEPVLRTFEDITFLEAVIQLKKAKIQSSSSTIHLCDKKMDLSLNIPANHPPQEESCGSSLLSRNTGSPGPSRSLSAPQDKGFLSGAPQDCSSLKAHHCPGNHSWDGIVSVPPGAAFCDRRASSCSLAVISPFLVEKGSERPPIGIAQQWIQSKREAIVSQMTEACLNQSLDALLSRDLIMKEDYELISTKPTRTSKVRQLLDTSDIQGEEFAKVVVQKLKDNKQLGLQPYPEVPVLSKAPPSNFPQNKSL

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
29	Phosphorylation	HYLSRGASGTVSSAR HHHHCCCCCCCCHHH	37.51	22807455
34	Phosphorylation	GASGTVSSARHADWR CCCCCCCHHHHCCHH	25.61	22807455
168	Phosphorylation	KIADFGLSKWRMMSL EEHHHCCCHHHEECC	30.47	26824392
174	Phosphorylation	LSKWRMMSLSQSRSY CCHHHEECCHHCCCC	18.61	26824392
176	Phosphorylation	KWRMMSLSQSRSYKS HHHEECCHHCCCCCC	20.85	26824392
178	Phosphorylation	RMMSLSQSRSYKSAP HEECCHHCCCCCCCC	21.59	26824392
180	Phosphorylation	MSLSQSRSYKSAPEG ECCHHCCCCCCCCCC	42.00	30635358
181	Phosphorylation	SLSQSRSYKSAPEGG CCHHCCCCCCCCCCC	14.09	30635358
203	Ubiquitination	ENYEPGQKSRASVKH CCCCCCCCCCHHHCH	48.07	22790023
209	Ubiquitination	QKSRASVKHDIYSYA CCCCHHHCHHHHHHH	32.82	-
331	Phosphorylation	CDKKMDLSLNIPANH CCCCCCEEECCCCCC	18.33	26824392
344	Phosphorylation	NHPPQEESCGSSLLS CCCCCCCCCCCCHHH	24.03	26370283
354	Phosphorylation	SSLLSRNTGSPGPSR CCHHHCCCCCCCCCC	37.62	22324799
356	Phosphorylation	LLSRNTGSPGPSRSL HHHCCCCCCCCCCCC	25.33	25266776
360	Phosphorylation	NTGSPGPSRSLSAPQ CCCCCCCCCCCCCCC	40.18	25266776
362	Phosphorylation	GSPGPSRSLSAPQDK CCCCCCCCCCCCCCC	30.89	28833060
364	Phosphorylation	PGPSRSLSAPQDKGF CCCCCCCCCCCCCCC	38.87	26824392
373	Phosphorylation	PQDKGFLSGAPQDCS CCCCCCCCCCCCCHH	30.55	26824392
392	Phosphorylation	HHCPGNHSWDGIVSV CCCCCCCCCCCEEEE	30.75	25266776
398	Phosphorylation	HSWDGIVSVPPGAAF CCCCCEEEECCCCCC	27.30	-
411	Phosphorylation	AFCDRRASSCSLAVI CCCCCCCCCCCEEEE	30.02	25521595
412	Phosphorylation	FCDRRASSCSLAVIS CCCCCCCCCCEEEEH	13.52	25521595
414	Phosphorylation	DRRASSCSLAVISPF CCCCCCCCEEEEHHH	22.70	22942356
419	Phosphorylation	SCSLAVISPFLVEKG CCCEEEEHHHHHHCC	11.73	26060331
473	Phosphorylation	DLIMKEDYELISTKP CHHHHCCHHHCCCCC	17.46	-
481	Phosphorylation	ELISTKPTRTSKVRQ HHCCCCCCCHHHHHH	48.40	26060331
483	Phosphorylation	ISTKPTRTSKVRQLL CCCCCCCHHHHHHHH	35.06	25338131
484	Phosphorylation	STKPTRTSKVRQLLD CCCCCCHHHHHHHHC	26.34	26060331
526	Phosphorylation	YPEVPVLSKAPPSNF CCCCCCCCCCCCCCC	27.31	-
531	Phosphorylation	VLSKAPPSNFPQNKS CCCCCCCCCCCCCCC	50.47	28833060
538	Phosphorylation	SNFPQNKSL------ CCCCCCCCC------	47.03	22322096

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
-	K	Ubiquitination	E3 ubiquitin ligase	Traf6	P70196	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
48	K	ubiquitylation	30405132
Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.
209	K	ubiquitylation	30405132
Ubiquitinated on Lys-209; undergoes 'Lys-63'-linked polyubiquitination catalyzed by ITCH.

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 RIPK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
LRRK2_MOUSE	Lrrk2	physical	20949042
TRAF6_MOUSE	Traf6	physical	17947236
CYLD_MOUSE	Cyld	physical	26834734

Drug and Disease Associations

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

Regulatory Network of RIPK2_MOUSE

Related Literatures of Post-Translational Modification

show

show