IKKA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: IKKA_MOUSE
• UniProt AC: Q60680
• Protein Name: Inhibitor of nuclear factor kappa-B kinase subunit alpha
• Gene Name: Chuk
• Organism: Mus musculus (Mouse).
• Sequence Length: 745
• Subcellular Localization: Cytoplasm . Nucleus . Shuttles between the cytoplasm and the nucleus.
• 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 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. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor..
• Protein Sequence: MERPPGLRPGAGGPWEMRERLGTGGFGNVSLYQHRELDLKIAIKSCRLELSSKNRERWCHEIQIMKKLDHANVVKACDVPEELNFLINDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKTIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMTGEVRFSSHLPQPNSLCSLIVEPMESWLQLMLNWDPQQRGGPIDLTLKQPRCFALMDHILNLKIVHILNMTSAKIISFLLPCDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFRKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYSEVGVIGYLEDQIMSLHTEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPPDHLYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGTVTPPVSAWLPPTLADREHPLTCVVTPQDGETLAQMIEENLNCLGHLSTIIREANEDQSSSLMSLDWSWLAE

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
23	Phosphorylation	EMRERLGTGGFGNVS HHHHHHCCCCCCCCE	38.43	29514104
176	Phosphorylation	AKDVDQGSLCTSFVG CCCCCCCCHHHHHHH	18.03	20710027
180	Phosphorylation	DQGSLCTSFVGTLQY CCCCHHHHHHHHHHH	19.55	15935065
345	Phosphorylation	QSRIERETGINTGSQ HHHHHHHHCCCCCCH	49.97	25338131
499	Phosphorylation	ERYSEQMTYGISSEK HHHHHHHHHCCCHHH	20.49	-
506	Ubiquitination	TYGISSEKMLKAWKE HHCCCHHHHHHHHHH	52.02	-
665	Phosphorylation	CTQSSARSLVGSSLE HCHHHHHHHCCCCCC	27.42	25338131
669	Phosphorylation	SARSLVGSSLEGTVT HHHHHCCCCCCCCCC	25.03	25338131
670	Phosphorylation	ARSLVGSSLEGTVTP HHHHCCCCCCCCCCC	25.22	25338131
676	Phosphorylation	SSLEGTVTPPVSAWL CCCCCCCCCCHHHCC	23.01	25338131
734	Phosphorylation	ANEDQSSSLMSLDWS CCCCCCCCCCCCCHH	33.08	25338131

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
23	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
23	T	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
176	S	Phosphorylation	Kinase	MAP3K14	Q9WUL6	Uniprot
180	S	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of IKKA_MOUSE !!

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TAXB1_MOUSE	Tax1bp1	physical	21765415
PRGC2_MOUSE	Ppargc1b	genetic	22351927
IKBB_MOUSE	Nfkbib	physical	22351927
IKBB_MOUSE	Nfkbib	physical	10593965
IKKB_MOUSE	Ikbkb	physical	12070292
NEMO_MOUSE	Ikbkg	physical	12070292
IKBB_MOUSE	Nfkbib	physical	16260493
A16L2_MOUSE	Atg16l2	physical	23563314
SMN_MOUSE	Smn1	physical	28214532

Drug and Disease Associations

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