dbPTM

IKKB_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IKKB_MOUSE
UniProt AC	O88351
Protein Name	Inhibitor of nuclear factor kappa-B kinase subunit beta
Gene Name	Ikbkb
Organism	Mus musculus (Mouse).
Sequence Length	757
Subcellular Localization	Cytoplasm . Nucleus . Membrane raft . Colocalized with DPP4 in membrane rafts.
Protein Description	Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation..
Protein Sequence	MSWSPSLPTQTCGAWEMKERLGTGGFGNVIRWHNQATGEQIAIKQCRQELSPKNRNRWCLEIQIMRRLNHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRRYLNQFENCCGLREGAVLTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEKRLIHKIIDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSEVDIVVSEDLNGAVKFSSSLPFPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPQYGPNGCFRALDDILNLKLVHVLNMVTGTVHTYPVTEDESLQSLKTRIQENTGILETDQELLQKAGLVLLPDKPATQCISDSKTNEGLTLDMDLVFLLDNSKINYETQITPRPPPESVSCILQEPKRNLSFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMSLLRNNSCLSKMKNAMASTAQQLKAKLDFFKTSIQIDLEKYKEQTEFGITSDKLLLAWREMEQAVEQCGRENDVKHLVERMMALQTDIVDLQRSPMGRKQGGTLDDLEEQARELYRKLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDERTVVRLQEKRQKELWNLLKIACSKVRGPVSGSPDSMNVSRLSHPGQLMSQPSSACDSLPESDKKSEELVAEAHALCSRLESALQDTVKEQDRSFTTLDWSWLQMEDEERCSLEQACD

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSWSPSLPT ------CCCCCCCCC	35.94	26643407
4	Phosphorylation	----MSWSPSLPTQT ----CCCCCCCCCCC	9.41	26643407
6	Phosphorylation	--MSWSPSLPTQTCG --CCCCCCCCCCCCC	41.27	26643407
177	Phosphorylation	AKELDQGSLCTSFVG CCCCCCCCCCHHHHH	18.03	20710027
179	Glutathionylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	22833525
179	S-nitrosocysteine	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	-
179	S-nitrosylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	-
180	Acetylation	LDQGSLCTSFVGTLQ CCCCCCCHHHHHHHH	30.41	-
181	Phosphorylation	DQGSLCTSFVGTLQY CCCCCCHHHHHHHHH	19.55	20710027
188	Phosphorylation	SFVGTLQYLAPELLE HHHHHHHHHCHHHHH	14.14	20534585
191	Hydroxylation	GTLQYLAPELLEQQK HHHHHHCHHHHHCCC	30.12	-
199	Phosphorylation	ELLEQQKYTVTVDYW HHHHCCCCEEEEEEC	11.34	20534585
466	Phosphorylation	LRNNSCLSKMKNAMA HHCCHHHHHHHHHHH	34.72	20139300
498	Ubiquitination	QIDLEKYKEQTEFGI ECCHHHHHHHHCCCC	55.18	22790023
501	Phosphorylation	LEKYKEQTEFGITSD HHHHHHHHCCCCCCH	34.08	-
555	Ubiquitination	QRSPMGRKQGGTLDD HCCCCCCCCCCCHHH	47.79	22790023
670	Phosphorylation	SKVRGPVSGSPDSMN HHCCCCCCCCCCCCC	36.37	23684622
672	Phosphorylation	VRGPVSGSPDSMNVS CCCCCCCCCCCCCHH	20.30	25521595
675	Phosphorylation	PVSGSPDSMNVSRLS CCCCCCCCCCHHHCC	18.68	23684622
679	Phosphorylation	SPDSMNVSRLSHPGQ CCCCCCHHHCCCCCC	23.62	22942356
682	Phosphorylation	SMNVSRLSHPGQLMS CCCHHHCCCCCCHHC	26.90	26643407
689	Phosphorylation	SHPGQLMSQPSSACD CCCCCHHCCCCHHHH	47.75	29472430
692	Phosphorylation	GQLMSQPSSACDSLP CCHHCCCCHHHHCCC	23.95	29472430
693	Phosphorylation	QLMSQPSSACDSLPE CHHCCCCHHHHCCCC	39.33	29472430
697	Phosphorylation	QPSSACDSLPESDKK CCCHHHHCCCCCCHH	45.79	29472430
701	Phosphorylation	ACDSLPESDKKSEEL HHHCCCCCCHHHHHH	53.44	29472430
705	Phosphorylation	LPESDKKSEELVAEA CCCCCHHHHHHHHHH	41.88	25367039
733	Phosphorylation	TVKEQDRSFTTLDWS HHHHCCCCCEECCCH	34.92	-
740	Phosphorylation	SFTTLDWSWLQMEDE CCEECCCHHHCCCCH	19.99	-

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
177	S	Phosphorylation	Kinase	PRKAA2	Q8BRK8	GPS
177	S	Phosphorylation	Kinase	TBK1	Q9WUN2	Uniprot
177	S	Phosphorylation	Kinase	PRKCZ	Q02956	Uniprot
181	S	Phosphorylation	Kinase	TBK1	Q9WUN2	Uniprot
181	S	Phosphorylation	Kinase	PRKAA2	Q8BRK8	GPS
181	S	Phosphorylation	Kinase	PDPK1	Q9Z2A0	Uniprot
181	S	Phosphorylation	Kinase	PRKCZ	Q02956	Uniprot
181	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
188	Y	Phosphorylation	Kinase	PYK2	Q9QVP9	PSP
199	Y	Phosphorylation	Kinase	PYK2	Q9QVP9	PSP
679	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
682	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
689	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
692	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
697	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
701	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
705	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Trim21	Q62191	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
163	S	Phosphorylation	-
Ubiquitination on 'Ser-163' may modulate phosphorylation on C-terminal serine residues.
163	S	ubiquitylation	-
'Ser-163' may not serve as a monoubiquitination site.
163	S	ubiquitylation	-
Ubiquitination on 'Ser-163' may modulate phosphorylation on C-terminal serine residues.
177	S	Phosphorylation	-
Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.
177	S	Phosphorylation	-
Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity.
181	S	Phosphorylation	-
Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.
181	S	Phosphorylation	-
Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity.

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 IKKB_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CITE2_MOUSE	Cited2	genetic	21098220
NKX32_MOUSE	Nkx3-2	physical	21606193
NEMO_MOUSE	Ikbkg	physical	21606193
FBW1A_MOUSE	Btrc	physical	21606193
IKBA_MOUSE	Nfkbia	physical	21765415
IKBB_MOUSE	Nfkbib	physical	10593965
IKBA_MOUSE	Nfkbia	physical	21862579
OPTN_MOUSE	Optn	physical	21862579
IKBA_MOUSE	Nfkbia	physical	22037600
IKBB_MOUSE	Nfkbib	physical	16260493
SASH1_MOUSE	Sash1	physical	23776175
NEMO_MOUSE	Ikbkg	physical	23825957
IKKA_MOUSE	Chuk	physical	24240172
NEMO_MOUSE	Ikbkg	physical	24240172
RHOA_MOUSE	Rhoa	physical	24240172

Drug and Disease Associations

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

Regulatory Network of IKKB_MOUSE

Related Literatures of Post-Translational Modification

show

show

show

show

show

show

show