dbPTM

IKKA_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IKKA_HUMAN
UniProt AC	O15111
Protein Name	Inhibitor of nuclear factor kappa-B kinase subunit alpha
Gene Name	CHUK
Organism	Homo sapiens (Human).
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. [PubMed: 15084260]
Protein Sequence	MERPPGLRPGAGGPWEMRERLGTGGFGNVCLYQHRELDLKIAIKSCRLELSTKNRERWCHEIQIMKKLNHANVVKACDVPEELNILIHDVPLLAMEYCSGGDLRKLLNKPENCCGLKESQILSLLSDIGSGIRYLHENKIIHRDLKPENIVLQDVGGKIIHKIIDLGYAKDVDQGSLCTSFVGTLQYLAPELFENKPYTATVDYWSFGTMVFECIAGYRPFLHHLQPFTWHEKIKKKDPKCIFACEEMSGEVRFSSHLPQPNSLCSLVVEPMENWLQLMLNWDPQQRGGPVDLTLKQPRCFVLMDHILNLKIVHILNMTSAKIISFLLPPDESLHSLQSRIERETGINTGSQELLSETGISLDPRKPASQCVLDGVRGCDSYMVYLFDKSKTVYEGPFASRSLSDCVNYIVQDSKIQLPIIQLRKVWAEAVHYVSGLKEDYSRLFQGQRAAMLSLLRYNANLTKMKNTLISASQQLKAKLEFFHKSIQLDLERYSEQMTYGISSEKMLKAWKEMEEKAIHYAEVGVIGYLEDQIMSLHAEIMELQKSPYGRRQGDLMESLEQRAIDLYKQLKHRPSDHSYSDSTEMVKIIVHTVQSQDRVLKELFGHLSKLLGCKQKIIDLLPKVEVALSNIKEADNTVMFMQGKRQKEIWHLLKIACTQSSARSLVGSSLEGAVTPQTSAWLPPTSAEHDHSLSCVVTPQDGETSAQMIEENLNCLGHLSTIIHEANEEQGNSMMNLDWSWLTE

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
23	Phosphorylation	EMRERLGTGGFGNVC HHHHHHCCCCCCCEE	38.43	18515365
44	Ubiquitination	LDLKIAIKSCRLELS CHHHHHHHHCCEEEC	34.19	29967540
45	Phosphorylation	DLKIAIKSCRLELST HHHHHHHHCCEEECC	9.80	23090842
51	Phosphorylation	KSCRLELSTKNRERW HHCCEEECCCCHHHH	28.14	23090842
52	Phosphorylation	SCRLELSTKNRERWC HCCEEECCCCHHHHH	44.99	23090842
53	Ubiquitination	CRLELSTKNRERWCH CCEEECCCCHHHHHH	51.11	27667366
67	Ubiquitination	HEIQIMKKLNHANVV HHHHHHHHCCCCCCH	36.82	-
105	Ubiquitination	CSGGDLRKLLNKPEN CCCHHHHHHHCCCCC	65.70	29967540
109	Ubiquitination	DLRKLLNKPENCCGL HHHHHHCCCCCCCCC	54.39	29967540
117	Ubiquitination	PENCCGLKESQILSL CCCCCCCCHHHHHHH	40.37	29967540
119	Phosphorylation	NCCGLKESQILSLLS CCCCCCHHHHHHHHH	22.42	27732954
119	Acetylation	NCCGLKESQILSLLS CCCCCCHHHHHHHHH	22.42	147937
123	Phosphorylation	LKESQILSLLSDIGS CCHHHHHHHHHHCCC	28.97	27732954
126	Phosphorylation	SQILSLLSDIGSGIR HHHHHHHHHCCCCHH	32.26	27732954
130	Phosphorylation	SLLSDIGSGIRYLHE HHHHHCCCCHHHHHH	31.23	27732954
139	Ubiquitination	IRYLHENKIIHRDLK HHHHHHCCEECCCCC	39.80	29967540
146	Ubiquitination	KIIHRDLKPENIVLQ CEECCCCCHHHEEEE	55.35	29967540
158	Ubiquitination	VLQDVGGKIIHKIID EEEECCCHHHHHHHH	32.34	29967540
168	Phosphorylation	HKIIDLGYAKDVDQG HHHHHHCCCCCCCCC	20.13	-
176	Phosphorylation	AKDVDQGSLCTSFVG CCCCCCCCHHHHHHH	18.03	18515365
179	Acetylation	VDQGSLCTSFVGTLQ CCCCCHHHHHHHHHH	30.41	81051399
179	Phosphorylation	VDQGSLCTSFVGTLQ CCCCCHHHHHHHHHH	30.41	-
180	Phosphorylation	DQGSLCTSFVGTLQY CCCCHHHHHHHHHHH	19.55	18515365
211	Ubiquitination	YWSFGTMVFECIAGY ECCHHHHHHHHHHCC	3.52	27667366
296	Ubiquitination	GPVDLTLKQPRCFVL CCCCEEECCCCEEEE	53.68	21906983
322	Acetylation	ILNMTSAKIISFLLP HHCCCCCCHHHHHCC	40.10	30589471
333	Phosphorylation	FLLPPDESLHSLQSR HHCCCCHHHHHHHHH	38.47	22210691
366	Ubiquitination	GISLDPRKPASQCVL CCCCCCCCCHHHHHH	50.77	29967540
389	Ubiquitination	YMVYLFDKSKTVYEG EEEEEEECCCCEEEC	46.66	22505724
391	Ubiquitination	VYLFDKSKTVYEGPF EEEEECCCCEEECCC	47.99	27667366
415	Ubiquitination	NYIVQDSKIQLPIIQ HHHHCCCCCCCCHHH	42.64	-
425	Malonylation	LPIIQLRKVWAEAVH CCHHHHHHHHHHHHH	51.20	26320211
433	Phosphorylation	VWAEAVHYVSGLKED HHHHHHHHHHCCHHH	6.96	24114839
435	Phosphorylation	AEAVHYVSGLKEDYS HHHHHHHHCCHHHHH	31.10	24114839
438	Acetylation	VHYVSGLKEDYSRLF HHHHHCCHHHHHHHH	52.65	11794729
463	Phosphorylation	LRYNANLTKMKNTLI HHHHCCHHHHHHHHH	28.97	-
473	Phosphorylation	KNTLISASQQLKAKL HHHHHHHHHHHHHHH	16.21	22817900
500	Phosphorylation	RYSEQMTYGISSEKM HHHHHHHHCCCHHHH	13.71	-
506	Ubiquitination	TYGISSEKMLKAWKE HHCCCHHHHHHHHHH	52.02	29967540
569	Acetylation	QRAIDLYKQLKHRPS HHHHHHHHHHCCCCC	57.35	25953088
569	Ubiquitination	QRAIDLYKQLKHRPS HHHHHHHHHHCCCCC	57.35	29967540
572	Ubiquitination	IDLYKQLKHRPSDHS HHHHHHHCCCCCCCC	34.77	29967540
576	Phosphorylation	KQLKHRPSDHSYSDS HHHCCCCCCCCCCCC	48.16	29116813
579	Phosphorylation	KHRPSDHSYSDSTEM CCCCCCCCCCCCHHE	31.18	27251275
581	Phosphorylation	RPSDHSYSDSTEMVK CCCCCCCCCCHHEEE	28.27	23312004
593	Phosphorylation	MVKIIVHTVQSQDRV EEEEHHHHHHCHHHH	14.89	24670416
602	Ubiquitination	QSQDRVLKELFGHLS HCHHHHHHHHHHHHH	49.90	29967540
615	Ubiquitination	LSKLLGCKQKIIDLL HHHHHCCHHHHHHHH	53.48	27667366
617	Ubiquitination	KLLGCKQKIIDLLPK HHHCCHHHHHHHHHH	27.42	29967540
624	Ubiquitination	KIIDLLPKVEVALSN HHHHHHHHHHHHHHC	51.50	-
645	Acetylation	TVMFMQGKRQKEIWH EEEEECCCHHHHHHH	34.46	25953088
722	Acetylation	NCLGHLSTIIHEANE HHHHHHHHHHHHHCH	30.25	147941

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	P31749	Uniprot
23	T	Phosphorylation	Kinase	AKT2	P31751	PSP
23	T	Phosphorylation	Kinase	SGK1	O00141	Uniprot
23	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
23	T	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
176	S	Phosphorylation	Kinase	NIK	Q99558	PSP
180	S	Phosphorylation	Kinase	MAP3K14	Q99558	GPS
180	S	Phosphorylation	Kinase	SGK1	O00141	Uniprot
473	S	Phosphorylation	Kinase	ATM	Q13315	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW11	Q9UKB1	PMID:10321728
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:19109186

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
179	T	Acetylation	17116858
(Microbial infection) Acetylation of Thr-179 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.
179	T	Phosphorylation	17116858
(Microbial infection) Acetylation of Thr-179 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.

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 IKKA_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PPM1B_HUMAN	PPM1B	physical	14585847
M3K14_HUMAN	MAP3K14	physical	9244310
TRAF2_HUMAN	TRAF2	physical	9244310
M3K8_HUMAN	MAP3K8	physical	10072079
IKBA_HUMAN	NFKBIA	physical	9252186
IRS1_HUMAN	IRS1	physical	12351658
NALP4_HUMAN	NLRP4	physical	12093792
CDC37_HUMAN	CDC37	physical	11864612
PRKDC_HUMAN	PRKDC	physical	9632806
IKKA_HUMAN	CHUK	physical	10755617
M3K14_HUMAN	MAP3K14	physical	10887201
E2AK2_HUMAN	EIF2AK2	physical	10848580
CASP8_HUMAN	CASP8	physical	11002417
NCOA3_HUMAN	NCOA3	physical	11971985
IKKB_HUMAN	IKBKB	physical	10968790
IKBA_HUMAN	NFKBIA	physical	9346485
IKBB_HUMAN	NFKBIB	physical	9346485
IKKA_HUMAN	CHUK	physical	9346485
IKKB_HUMAN	IKBKB	physical	9346485
NEMO_HUMAN	IKBKG	physical	11057907
IKKB_HUMAN	IKBKB	physical	11057907
M3K7_HUMAN	MAP3K7	physical	10094049
M3K14_HUMAN	MAP3K14	physical	10094049
PEBP1_RAT	Pebp1	physical	11585904
IKKA_HUMAN	CHUK	physical	11585904
CUL1_HUMAN	CUL1	physical	17914462
P73_HUMAN	TP73	physical	17452332
AKT1_HUMAN	AKT1	physical	15800029
TF65_HUMAN	RELA	physical	16382138
NCOR2_HUMAN	NCOR2	physical	16382138
IKBA_HUMAN	NFKBIA	physical	12054687
NCOR2_HUMAN	NCOR2	physical	15494311
TF65_HUMAN	RELA	physical	15489227
H32_HUMAN	HIST2H3C	physical	17643371
IKKB_HUMAN	IKBKB	physical	9346484
IKKB_HUMAN	IKBKB	physical	9751060
NEMO_HUMAN	IKBKG	physical	9751060
M3K7_HUMAN	MAP3K7	physical	9742107
KPCA_HUMAN	PRKCA	physical	10022904
KPCI_HUMAN	PRKCI	physical	10022904
KPCD_HUMAN	PRKCD	physical	10022904
HD_HUMAN	HTT	physical	20026656
CSN5_HUMAN	COPS5	physical	19656241
IKBA_HUMAN	NFKBIA	physical	20932476
IRF5_HUMAN	IRF5	physical	19786094
TRI40_HUMAN	TRIM40	physical	21474709
NEMO_HUMAN	IKBKG	physical	19815509
CDC37_HUMAN	CDC37	physical	21903422
IKKB_HUMAN	IKBKB	physical	21903422
NEMO_HUMAN	IKBKG	physical	21903422
TF65_HUMAN	RELA	physical	21903422
NCOA3_HUMAN	NCOA3	physical	15383283
TRAF6_HUMAN	TRAF6	physical	15836773
TAB2_HUMAN	TAB2	physical	15836773
IKBA_HUMAN	NFKBIA	physical	18501560
NEMO_HUMAN	IKBKG	physical	16497931
IKBA_HUMAN	NFKBIA	physical	15590691
RB6I2_HUMAN	ERC1	physical	15218148
NEMO_HUMAN	IKBKG	physical	11485410
IKBB_HUMAN	NFKBIB	physical	11485410
P63_HUMAN	TP63	physical	20145131
M3K14_HUMAN	MAP3K14	physical	17563756
IKBA_HUMAN	NFKBIA	physical	9914500
IKKB_HUMAN	IKBKB	physical	9914500
IKKE_HUMAN	IKBKE	physical	9914500
IKBA_HUMAN	NFKBIA	physical	12138192
IKBA_HUMAN	NFKBIA	physical	9689078
IKBB_HUMAN	NFKBIB	physical	9689078
IKBA_HUMAN	NFKBIA	physical	12190313
TNIP2_HUMAN	TNIP2	physical	21784860
IKKB_HUMAN	IKBKB	physical	21784860
SRC_HUMAN	SRC	physical	12707358
NALP2_HUMAN	NLRP2	physical	15456791
IKKB_HUMAN	IKBKB	physical	10733566
M3K1_HUMAN	MAP3K1	physical	9819420
IKBA_HUMAN	NFKBIA	physical	17053167
TRI27_HUMAN	TRIM27	physical	16393995
P73_HUMAN	TP73	physical	21482671
IKBA_HUMAN	NFKBIA	physical	17384642
CTNB1_HUMAN	CTNNB1	physical	12589056
FOXO3_HUMAN	FOXO3	physical	15084260
TNR1A_HUMAN	TNFRSF1A	physical	21724995
IKBA_HUMAN	NFKBIA	physical	17379600
NFKB1_HUMAN	NFKB1	physical	11976329
IKBA_HUMAN	NFKBIA	physical	9721103
IKKB_HUMAN	IKBKB	physical	9721103
IKKA_HUMAN	CHUK	physical	9721103
IKBA_HUMAN	NFKBIA	physical	16354686
TRAF1_HUMAN	TRAF1	physical	12709429
IKBA_HUMAN	NFKBIA	physical	20133937
IKKB_HUMAN	IKBKB	physical	11080499
NEMO_HUMAN	IKBKG	physical	11080499
IKBA_HUMAN	NFKBIA	physical	11080499
CBP_HUMAN	CREBBP	physical	14597638
TRADD_HUMAN	TRADD	physical	10980203
RIPK1_HUMAN	RIPK1	physical	10980203
IKBA_HUMAN	NFKBIA	physical	11113112
BCL10_HUMAN	BCL10	physical	11113112
NEMO_HUMAN	IKBKG	physical	17000764
IKBA_HUMAN	NFKBIA	physical	20449947
IKBA_HUMAN	NFKBIA	physical	18074035
IKBA_HUMAN	NFKBIA	physical	15670770
IKBA_HUMAN	NFKBIA	physical	12411322
CAR11_HUMAN	CARD11	physical	18625728
ESR1_HUMAN	ESR1	physical	15808510
NCOA3_HUMAN	NCOA3	physical	15808510
M3K7_HUMAN	MAP3K7	physical	16893890
MYC_HUMAN	MYC	physical	21575199
IKKB_HUMAN	IKBKB	physical	21575199
NCOR1_HUMAN	NCOR1	physical	17630505
IKBA_HUMAN	NFKBIA	physical	12486103
IKKB_HUMAN	IKBKB	physical	12486103
ASC_HUMAN	PYCARD	physical	12486103
NEMO_HUMAN	IKBKG	physical	12486103
IKBA_HUMAN	NFKBIA	physical	17363905
IKBA_HUMAN	NFKBIA	physical	20434986
IKBA_HUMAN	NFKBIA	physical	16286467
IKBA_HUMAN	NFKBIA	physical	16319058
TRAF4_HUMAN	TRAF4	physical	22547678
RIPK2_HUMAN	RIPK2	physical	22547678
ERBIN_HUMAN	ERBB2IP	physical	22547678
NEMO_HUMAN	IKBKG	physical	22547678
BCL10_HUMAN	BCL10	physical	22547678
M3K4_HUMAN	MAP3K4	physical	22547678
PP1A_HUMAN	PPP1CA	physical	18949366
NEMO_HUMAN	IKBKG	physical	18949366
IKBA_HUMAN	NFKBIA	physical	18949366
IKBA_HUMAN	NFKBIA	physical	18003900
PIAS1_HUMAN	PIAS1	physical	23032264
A16L2_HUMAN	ATG16L2	physical	23563314
CSN5_HUMAN	COPS5	physical	23636414
CSN3_HUMAN	COPS3	physical	23636414
SASH1_HUMAN	SASH1	physical	23776175
RL27_HUMAN	RPL27	physical	21988832
PAX8_HUMAN	PAX8	physical	21988832
CDC73_HUMAN	CDC73	physical	22863883
ML12A_HUMAN	MYL12A	physical	22863883
PAF1_HUMAN	PAF1	physical	22863883
IKBA_HUMAN	NFKBIA	physical	24270572
ROA1_HUMAN	HNRNPA1	physical	24720748
PSMD9_HUMAN	PSMD9	physical	24720748
MTOR_HUMAN	MTOR	physical	18490760
IKBA_HUMAN	NFKBIA	physical	18519641
TF65_HUMAN	RELA	physical	18519641
CBP_HUMAN	CREBBP	physical	17434128
NFKB2_HUMAN	NFKB2	physical	16651533
NEMO_HUMAN	IKBKG	physical	21455180
IKBA_HUMAN	NFKBIA	physical	19959994
IKBA_HUMAN	NFKBIA	physical	11940602
IKBA_HUMAN	NFKBIA	physical	24618592
IKBA_HUMAN	NFKBIA	physical	15310755
IKKB_HUMAN	IKBKB	physical	25748427
UBP18_HUMAN	USP18	physical	26240016
AKT1_HUMAN	AKT1	physical	15710601
IKBA_HUMAN	NFKBIA	physical	16219905
IKBA_HUMAN	NFKBIA	physical	12624112
KLH21_HUMAN	KLHL21	physical	27387502
BCL3_HUMAN	BCL3	physical	28689659
NEMO_HUMAN	IKBKG	physical	26500060

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
613630	Cocoon syndrome (COCOS)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB06151	Acetylcysteine
DB00233	Aminosalicylic Acid
DB00244	Mesalazine
DB00795	Sulfasalazine

Regulatory Network of IKKA_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulatesNF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2Aand NR2B expression."; Tai D.J., Su C.C., Ma Y.L., Lee E.H.; J. Biol. Chem. 284:4073-4089(2009). Cited for: PHOSPHORYLATION AT THR-23 AND SER-180 BY SGK1.	19088076 [Abstract]
"NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation ofSer-176."; Ling L., Cao Z., Goeddel D.V.; Proc. Natl. Acad. Sci. U.S.A. 95:3792-3797(1998). Cited for: PHOSPHORYLATION AT SER-176, AND MUTAGENESIS OF SER-176; THR-179 ANDSER-180.	9520446 [Abstract]
"NF-kappaB activation by tumour necrosis factor requires the Aktserine-threonine kinase."; Ozes O.N., Mayo L.D., Gustin J.A., Pfeffer S.R., Pfeffer L.M.,Donner D.B.; Nature 401:82-85(1999). Cited for: PHOSPHORYLATION AT THR-23, AND MUTAGENESIS OF THR-23.	10485710 [Abstract]

show

show