IKKB_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: IKKB_RAT
• UniProt AC: Q9QY78
• Protein Name: Inhibitor of nuclear factor kappa-B kinase subunit beta
• Gene Name: Ikbkb
• Organism: Rattus norvegicus (Rat).
• 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: MSWSPSLPTQTCGAWEMKERLGTGGFGNVIRWHNQVTGEQIAIKQCRQELSPKNRDRWCLEIQIMRRLNHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRRYLNQFENCCGLREGAILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEKRLIHKIIDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSEVDIVVSEDLNGTVKFSSSSPFPNNLNSVLAERLEKWLQLMLTWQPRQRGVDPQYGPNGCFRALDDILNLKLVHILNMVTGTIHTYPVMEDESLQSLKTRIREDTGILETDQELLQEAGLVLLPDKPATQCISDSKTNEGLTLDMDLVFLFDNSKMSYETQITPRPQPESVSCVLQEPKRNLSFFQMRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNAMASTAQQLKAKLDFFKTSIQIDLEKYREQTEFGITSDKLLLAWREMEQAVEQCGRENDVKVLVERMMALQTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQDMVRLLLQAIQSFEKKVRVIYSQLSKTVVCKQKALELLPKVEEVVRLMNEDEKTVVRLQEKRQKELWNLLKIACSKVRGPVSGSPDSMNVSRLSHPGHLMSQPSSACDSLPDSDKKSEELVAEAHALCSRLESALQDTVKQQDRSFTTLDWSWLQMEDEERCGLEQACD

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
177	Phosphorylation	AKELDQGSLCTSFVG CCCCCCCCCCHHHHH	18.03	22817900
179	S-nitrosocysteine	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	-
179	S-nitrosylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	-
181	Phosphorylation	DQGSLCTSFVGTLQY CCCCCCHHHHHHHHH	19.55	15935065
191	Hydroxylation	GTLQYLAPELLEQQK HHHHHHCHHHHHCCC	30.12	-
670	Phosphorylation	SKVRGPVSGSPDSMN HHCCCCCCCCCCCCC	36.37	27097102
672	Phosphorylation	VRGPVSGSPDSMNVS CCCCCCCCCCCCCHH	20.30	21738781
675	Phosphorylation	PVSGSPDSMNVSRLS CCCCCCCCCCHHHCC	18.68	27097102
679	Phosphorylation	SPDSMNVSRLSHPGH CCCCCCHHHCCCCCC	23.62	28689409
682	Phosphorylation	SMNVSRLSHPGHLMS CCCHHHCCCCCCCCC	26.90	25575281
689	Phosphorylation	SHPGHLMSQPSSACD CCCCCCCCCCCCHHH	45.35	25575281
692	Phosphorylation	GHLMSQPSSACDSLP CCCCCCCCCHHHCCC	23.95	25575281
693	Phosphorylation	HLMSQPSSACDSLPD CCCCCCCCHHHCCCC	39.33	25575281
697	Phosphorylation	QPSSACDSLPDSDKK CCCCHHHCCCCCCHH	41.51	25575281
701	Phosphorylation	ACDSLPDSDKKSEEL HHHCCCCCCHHHHHH	49.76	25575281
705	Phosphorylation	LPDSDKKSEELVAEA CCCCCHHHHHHHHHH	41.88	25575281
733	Phosphorylation	TVKQQDRSFTTLDWS HHHHCCCCCEECCCH	34.92	-
740	Phosphorylation	SFTTLDWSWLQMEDE CCEECCCHHEECCCH	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	PRKCZ	P09217	Uniprot
177	S	Phosphorylation	Kinase	TBK1	-	Uniprot
181	S	Phosphorylation	Kinase	PRKCZ	P09217	Uniprot
181	S	Phosphorylation	Kinase	PDPK1	O55173	Uniprot
181	S	Phosphorylation	Kinase	TBK1	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	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.

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

Protein-Protein Interaction

Oops, there are no PPI records of IKKB_RAT !!

Drug and Disease Associations

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