NLRP3_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NLRP3_HUMAN
• UniProt AC: Q96P20
• Protein Name: NACHT, LRR and PYD domains-containing protein 3
• Gene Name: NLRP3
• Organism: Homo sapiens (Human).
• Sequence Length: 1036
• Subcellular Localization: Cytoplasm, cytosol . Inflammasome . Endoplasmic reticulum . Secreted . Nucleus . In macrophages, under resting conditions, mainly located in the cytosol, on the endoplasmic reticulum. After stimulation with inducers of the NLRP3 inflammasome, mitocho
• Protein Description: As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. Activation of NLRP3 inflammasome is also required for HMGB1 secretion. [PubMed: 22801494 The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33]
• Protein Sequence: MKMASTRCKLARYLEDLEDVDLKKFKMHLEDYPPQKGCIPLPRGQTEKADHVDLATLMIDFNGEEKAWAMAVWIFAAINRRDLYEKAKRDEPKWGSDNARVSNPTVICQEDSIEEEWMGLLEYLSRISICKMKKDYRKKYRKYVRSRFQCIEDRNARLGESVSLNKRYTRLRLIKEHRSQQEREQELLAIGKTKTCESPVSPIKMELLFDPDDEHSEPVHTVVFQGAAGIGKTILARKMMLDWASGTLYQDRFDYLFYIHCREVSLVTQRSLGDLIMSCCPDPNPPIHKIVRKPSRILFLMDGFDELQGAFDEHIGPLCTDWQKAERGDILLSSLIRKKLLPEASLLITTRPVALEKLQHLLDHPRHVEILGFSEAKRKEYFFKYFSDEAQARAAFSLIQENEVLFTMCFIPLVCWIVCTGLKQQMESGKSLAQTSKTTTAVYVFFLSSLLQPRGGSQEHGLCAHLWGLCSLAADGIWNQKILFEESDLRNHGLQKADVSAFLRMNLFQKEVDCEKFYSFIHMTFQEFFAAMYYLLEEEKEGRTNVPGSRLKLPSRDVTVLLENYGKFEKGYLIFVVRFLFGLVNQERTSYLEKKLSCKISQQIRLELLKWIEVKAKAKKLQIQPSQLELFYCLYEMQEEDFVQRAMDYFPKIEINLSTRMDHMVSSFCIENCHRVESLSLGFLHNMPKEEEEEEKEGRHLDMVQCVLPSSSHAACSHGLVNSHLTSSFCRGLFSVLSTSQSLTELDLSDNSLGDPGMRVLCETLQHPGCNIRRLWLGRCGLSHECCFDISLVLSSNQKLVELDLSDNALGDFGIRLLCVGLKHLLCNLKKLWLVSCCLTSACCQDLASVLSTSHSLTRLYVGENALGDSGVAILCEKAKNPQCNLQKLGLVNSGLTSVCCSALSSVLSTNQNLTHLYLRGNTLGDKGIKLLCEGLLHPDCKLQVLELDNCNLTSHCCWDLSTLLTSSQSLRKLSLGNNDLGDLGVMMFCEVLKQQSCLLQNLGLSEMYFNYETKSALETLQEEKPELTVVFEPSW

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
5	Phosphorylation	---MKMASTRCKLAR ---CCCHHHHHHHHH		-
13	Phosphorylation	TRCKLARYLEDLEDV HHHHHHHHHHCHHCC		-
161	Phosphorylation	RNARLGESVSLNKRY HCCCCCCCCCCCHHH		-
163	Phosphorylation	ARLGESVSLNKRYTR CCCCCCCCCCHHHHH		-
198	Phosphorylation	GKTKTCESPVSPIKM CCCCCCCCCCCCCEE		-
233	Phosphorylation	GAAGIGKTILARKMM CCCCCCHHHHHHHHH		-
295	Phosphorylation	HKIVRKPSRILFLMD HHHCCCCCCEEEEEC		-
320	Phosphorylation	EHIGPLCTDWQKAER CCCHHCCCCHHHHHC		24719451
334	Phosphorylation	RGDILLSSLIRKKLL CCCHHHHHHHHHHHC		24719451
387	Phosphorylation	EYFFKYFSDEAQARA HHHHHHCCHHHHHHH		-
436	Phosphorylation	GKSLAQTSKTTTAVY CCCHHHHCCCHHHHH		-
496	Ubiquitination	LRNHGLQKADVSAFL HHHCCCCHHHHHHHH		-
524	Phosphorylation	FYSFIHMTFQEFFAA HHHHHHHHHHHHHHH		23532336
728	Phosphorylation	VNSHLTSSFCRGLFS CCHHHCHHHHHHHHH		-
861	Phosphorylation	SHSLTRLYVGENALG CCCCCEEECCCCCCC		-
975	Phosphorylation	SQSLRKLSLGNNDLG CHHHHHHCCCCCCHH		-
1006	Phosphorylation	LLQNLGLSEMYFNYE HHHHCCCCHHHHCHH		24043423
1009	Phosphorylation	NLGLSEMYFNYETKS HCCCCHHHHCHHHHH		24043423
1012	Phosphorylation	LSEMYFNYETKSALE CCHHHHCHHHHHHHH		24043423
1014	Phosphorylation	EMYFNYETKSALETL HHHHCHHHHHHHHHH		24043423

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
198	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
295	S	Phosphorylation	Kinase	PKACA	P17612	PSP
295	S	Phosphorylation	Kinase	PRKACA	P05132	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	FBXL2	Q9UKC9	PMID:26037928

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
48	K	ubiquitylation	Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination.	22948162

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of NLRP3_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SGT1_HUMAN	SUGT1	physical	17435760
HS90A_HUMAN	HSP90AA1	physical	17435760
FAF1_HUMAN	FAF1	physical	17046979
MCFD2_HUMAN	MCFD2	physical	26344197
FBXL2_HUMAN	FBXL2	physical	26037928
H15_HUMAN	HIST1H1B	physical	26496610
HNRPC_HUMAN	HNRNPC	physical	26496610
RBBP7_HUMAN	RBBP7	physical	26496610
RSMB_HUMAN	SNRPB	physical	26496610
SPAST_HUMAN	SPAST	physical	26496610
TOP1_HUMAN	TOP1	physical	26496610
LTBP4_HUMAN	LTBP4	physical	26496610
SMCA5_HUMAN	SMARCA5	physical	26496610
GEMI2_HUMAN	GEMIN2	physical	26496610
YBOX3_HUMAN	YBX3	physical	26496610
AP3B1_HUMAN	AP3B1	physical	26496610
PHF14_HUMAN	PHF14	physical	26496610
NPA1P_HUMAN	URB1	physical	26496610
DNJA2_HUMAN	DNAJA2	physical	26496610
CBX3_HUMAN	CBX3	physical	26496610
FBX28_HUMAN	FBXO28	physical	26496610
CBX5_HUMAN	CBX5	physical	26496610
MTCH1_HUMAN	MTCH1	physical	26496610
NECT3_HUMAN	PVRL3	physical	26496610
FBXL6_HUMAN	FBXL6	physical	26496610
QCR8_HUMAN	UQCRQ	physical	26496610
CSN7A_HUMAN	COPS7A	physical	26496610
LC7L3_HUMAN	LUC7L3	physical	26496610
FEM1A_HUMAN	FEM1A	physical	26496610
LUC7L_HUMAN	LUC7L	physical	26496610
DMAP1_HUMAN	DMAP1	physical	26496610
PHRF1_HUMAN	PHRF1	physical	26496610
CCD86_HUMAN	CCDC86	physical	26496610
PCGF5_HUMAN	PCGF5	physical	26496610
ZC3H8_HUMAN	ZC3H8	physical	26496610
K2013_HUMAN	KIAA2013	physical	26496610
NALP5_HUMAN	NLRP5	physical	26496610
ULK1_HUMAN	ULK1	physical	26347139
CHIP_HUMAN	STUB1	physical	25594175
MARH7_HUMAN	MARCH7	physical	25594175
UBR5_HUMAN	UBR5	physical	25594175
HDAC6_HUMAN	HDAC6	physical	26471297
ARI2_HUMAN	ARIH2	physical	29021376

Drug and Disease Associations

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