NEMO_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NEMO_MOUSE
• UniProt AC: O88522
• Protein Name: NF-kappa-B essential modulator
• Gene Name: Ikbkg
• Organism: Mus musculus (Mouse).
• Sequence Length: 412
• Subcellular Localization: Cytoplasm. Nucleus.
• Protein Description: Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination..
• Protein Sequence: MNKHPWKNQLSEMVQPSGGPAEDQDMLGEESSLGKPAMLHLPSEQGTPETLQRCLEENQELRDAIRQSNQMLRERCEELLHFQVSQREEKEFLMCKFQEARKLVERLSLEKLDLRSQREQALKELEQLKKCQQQMAEDKASVKAQVTSLLGELQESQSRLEAATKDRQALEGRIRAVSEQVRQLESEREVLQQQHSVQVDQLRMQNQSVEAALRMERQAASEEKRKLAQLQAAYHQLFQDYDSHIKSSKGMQLEDLRQQLQQAEEALVAKQELIDKLKEEAEQHKIVMETVPVLKAQADIYKADFQAERHAREKLVEKKEYLQEQLEQLQREFNKLKVGCHESARIEDMRKRHVETPQPPLLPAPAHHSFHLALSNQRRSPPEEPPDFCCPKCQYQAPDMDTLQIHVMECIE

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
31	Phosphorylation	QDMLGEESSLGKPAM HHCCCCCCCCCCCCH	26.93	-
43	Phosphorylation	PAMLHLPSEQGTPET CCHHCCCCCCCCHHH	49.24	22324799
47	Phosphorylation	HLPSEQGTPETLQRC CCCCCCCCHHHHHHH	20.04	22324799
68	Phosphorylation	LRDAIRQSNQMLRER HHHHHHHHHHHHHHH	21.12	-
85	Phosphorylation	ELLHFQVSQREEKEF HHHCCCCCHHHHHHH	16.85	20932476
108	Phosphorylation	RKLVERLSLEKLDLR HHHHHHHCHHHHCHH	40.48	29514104
147	Phosphorylation	ASVKAQVTSLLGELQ HHHHHHHHHHHHHHH	11.11	30635358
148	Phosphorylation	SVKAQVTSLLGELQE HHHHHHHHHHHHHHH	23.81	30635358
156	Phosphorylation	LLGELQESQSRLEAA HHHHHHHHHHHHHHH	22.09	30635358
158	Phosphorylation	GELQESQSRLEAATK HHHHHHHHHHHHHHH	48.38	30635358
196	Phosphorylation	EVLQQQHSVQVDQLR HHHHHHHCHHHHHHH	15.20	29514104
221	Phosphorylation	RMERQAASEEKRKLA HHHHHHCHHHHHHHH	49.67	21659604
270	Sumoylation	AEEALVAKQELIDKL HHHHHHHHHHHHHHH	36.50	-
270	Ubiquitination	AEEALVAKQELIDKL HHHHHHHHHHHHHHH	36.50	-
278	Ubiquitination	QELIDKLKEEAEQHK HHHHHHHHHHHHHHC	60.28	PubMed
302	Ubiquitination	KAQADIYKADFQAER HHHHHHHHHHHHHHH	41.64	-
302	Sumoylation	KAQADIYKADFQAER HHHHHHHHHHHHHHH	41.64	-
314	Ubiquitination	AERHAREKLVEKKEY HHHHHHHHHHHHHHH	52.89	17728323
318	Ubiquitination	AREKLVEKKEYLQEQ HHHHHHHHHHHHHHH	43.35	17728323
319	Ubiquitination	REKLVEKKEYLQEQL HHHHHHHHHHHHHHH	37.78	17728323
337	Ubiquitination	QREFNKLKVGCHESA HHHHHHCCCCHHHHH	37.88	-
343	Phosphorylation	LKVGCHESARIEDMR CCCCHHHHHCHHHHH	10.13	-
369	Phosphorylation	LPAPAHHSFHLALSN CCCCCCHHHHHHHCC	12.42	25266776
375	Phosphorylation	HSFHLALSNQRRSPP HHHHHHHCCCCCCCC	25.88	21183079
380	Phosphorylation	ALSNQRRSPPEEPPD HHCCCCCCCCCCCCC	47.17	25521595
392	Ubiquitination	PPDFCCPKCQYQAPD CCCCCCCCCCCCCCC	21.76	17728323

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
31	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
43	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
85	S	Phosphorylation	Kinase	ATM	Q62388	Uniprot
147	T	Phosphorylation	Kinase	IKBKB	O88351	GPS
148	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
156	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
158	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
369	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
369	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
369	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
369	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
375	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
375	S	Phosphorylation	Kinase	IKKB	O88351	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	Malt1	Q2TBA3	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Traf6	P70196	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
27	K	ubiquitylation	Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral innate and inflammatory responses.	17728323
63	K	ubiquitylation	Polyubiquitinated on Lys-392 through 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.	-
63	K	ubiquitylation	Polyubiquitinated on Lys-278 through 'Lys-63'; the ubiquitination is mediated by NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.	-
68	S	Phosphorylation	Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.	-
85	S	ubiquitylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
85	S	Sumoylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
85	S	Phosphorylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
111	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
143	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
226	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
246	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
270	K	ubiquitylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
270	K	Phosphorylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
270	K	Sumoylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	-
270	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
270	K	ubiquitylation	Monoubiquitinated on Lys-270 and Lys-302; promotes nuclear export.	-
278	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	17728323
278	K	ubiquitylation	Polyubiquitinated on Lys-278 through 'Lys-63'; the ubiquitination is mediated by NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.	17728323
285	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
295	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	-
302	K	ubiquitylation	Monoubiquitinated on Lys-270 and Lys-302; promotes nuclear export.	19303852
302	K	ubiquitylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	19303852
302	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	19303852
302	K	Sumoylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	19303852
302	K	Phosphorylation	Sumoylated on Lys-270 and Lys-302 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.	19303852
319	K	ubiquitylation	Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation.	17728323
392	K	ubiquitylation	Polyubiquitinated on Lys-392 through 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.	17728323

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CIKS_HUMAN	TRAF3IP2	physical	10962033
NFE2_MOUSE	Nfe2	physical	20211142
TFE2_MOUSE	Tcf3	physical	20211142
TNAP3_MOUSE	Tnfaip3	physical	20211142
TS101_MOUSE	Tsg101	physical	20211142
IKBZ_MOUSE	Nfkbiz	physical	20211142
MAML1_MOUSE	Maml1	physical	20211142
TNIP1_HUMAN	TNIP1	physical	16684768
UBC_HUMAN	UBC	physical	19766637
IKKB_MOUSE	Ikbkb	physical	21606193
NKX32_MOUSE	Nkx3-2	physical	21606193
HOIL1_MOUSE	Rbck1	physical	19136968
RNF31_MOUSE	Rnf31	physical	19136968
HS71B_MOUSE	Hspa1b	physical	19136968
NLRX1_MOUSE	Nlrx1	physical	21703539
TRAF2_MOUSE	Traf2	physical	18635759
UBE2N_MOUSE	Ube2n	physical	18635759
TNR5_MOUSE	Cd40	physical	18635759
UBC_HUMAN	UBC	physical	22819327
NEMO_MOUSE	Ikbkg	physical	19830703
IKKB_MOUSE	Ikbkb	physical	16378096
IKBA_HUMAN	NFKBIA	physical	16378096
IKBA_MOUSE	Nfkbia	physical	17158449
RIPK1_MOUSE	Ripk1	physical	22037414
IKBA_MOUSE	Nfkbia	physical	10748240
IKKA_MOUSE	Chuk	physical	10748240
IKKB_MOUSE	Ikbkb	physical	10748240
IKBB_MOUSE	Nfkbib	physical	16301747
GSK3B_MOUSE	Gsk3b	physical	12808104
IKKA_MOUSE	Chuk	physical	12808104
IKKB_MOUSE	Ikbkb	physical	12808104
IKBA_MOUSE	Nfkbia	physical	11009421
IKBA_MOUSE	Nfkbia	physical	19091594
IKBB_MOUSE	Nfkbib	physical	16260493
CYLD_MOUSE	Cyld	physical	23825957
IKKA_MOUSE	Chuk	physical	23871670
IKKB_MOUSE	Ikbkb	physical	23871670
MAVS_MOUSE	Mavs	physical	23951545
TRAF2_MOUSE	Traf2	physical	23951545
IKBA_MOUSE	Nfkbia	physical	23951545
RNF31_MOUSE	Rnf31	physical	24469399
RHBD3_MOUSE	Rhbdd3	physical	24859449
TNAP3_MOUSE	Tnfaip3	physical	24859449
GDIR1_MOUSE	Arhgdia	physical	24240172
IKKA_MOUSE	Chuk	physical	24240172
NEMO_MOUSE	Ikbkg	physical	24240172
IKKB_MOUSE	Ikbkb	physical	24240172
RHOA_MOUSE	Rhoa	physical	24240172
HS71B_MOUSE	Hspa1b	physical	16697380
PADI2_MOUSE	Padi2	physical	20937835
SMN_MOUSE	Smn1	physical	28214532
TBK1_MOUSE	Tbk1	physical	27776110

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta-mediated phosphorylation.";
Prajapati S., Gaynor R.B.;
J. Biol. Chem. 277:24331-24339(2002).
Cited for: PHOSPHORYLATION AT SER-369, AND MUTAGENESIS OF SER-369 AND SER-375.
PubMed: 11971901

Ubiquitylation

"Identification of TRAF6-dependent NEMO polyubiquitination sitesthrough analysis of a new NEMO mutation causing incontinentiapigmenti.";
Sebban-Benin H., Pescatore A., Fusco F., Pascuale V., Gautheron J.,Yamaoka S., Moncla A., Ursini M.V., Courtois G.;
Hum. Mol. Genet. 16:2805-2815(2007).
Cited for: UBIQUITINATION AT LYS-278; LYS-314; LYS-318; LYS-319 AND LYS-392, ANDMUTAGENESIS OF LYS-278; LYS-314; VAL-316; LYS-318; LYS-319 ANDLYS-392.
PubMed: 17728323