IKKB_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: IKKB_HUMAN
• UniProt AC: O14920
• Protein Name: Inhibitor of nuclear factor kappa-B kinase subunit beta
• Gene Name: IKBKB
• Organism: Homo sapiens (Human).
• Sequence Length: 756
• 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: MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCLEIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREGAILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLENAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS

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
2	Phosphorylation	------MSWSPSLTT ------CCCCCCCCC	35.94	22199227
4	Phosphorylation	----MSWSPSLTTQT ----CCCCCCCCCCC	9.41	22199227
6	Phosphorylation	--MSWSPSLTTQTCG --CCCCCCCCCCCCC	32.60	22199227
8	Phosphorylation	MSWSPSLTTQTCGAW CCCCCCCCCCCCCCH	22.61	22199227
9	Phosphorylation	SWSPSLTTQTCGAWE CCCCCCCCCCCCCHH	27.46	28348404
11	Phosphorylation	SPSLTTQTCGAWEMK CCCCCCCCCCCHHHH	15.71	24043423
23	Phosphorylation	EMKERLGTGGFGNVI HHHHHHCCCCCCCCE	38.43	28857561
42	Ubiquitination	QETGEQIAIKQCRQE CCCCCCHHHHHHHHH	11.56	24816145
44	Ubiquitination	TGEQIAIKQCRQELS CCCCHHHHHHHHHCC	34.03	-
58	Ubiquitination	SPRNRERWCLEIQIM CCCCHHHHHHHHHHH	6.06	22817900
62	Ubiquitination	RERWCLEIQIMRRLT HHHHHHHHHHHHHCC	1.86	24816145
78	Ubiquitination	PNVVAARDVPEGMQN CCEEEECCCCHHHHH	56.44	22817900
88	Ubiquitination	EGMQNLAPNDLPLLA HHHHHCCCCCCCCHH	37.73	24816145
104	Ubiquitination	EYCQGGDLRKYLNQF HHCCCCCHHHHHHHH	6.02	22817900
106	Ubiquitination	CQGGDLRKYLNQFEN CCCCCHHHHHHHHHC	62.48	-
145	Ubiquitination	ENRIIHRDLKPENIV HCCCCCCCCCHHHEE	44.90	24816145
147	Acetylation	RIIHRDLKPENIVLQ CCCCCCCCHHHEEEE	55.35	23236377
147	Ubiquitination	RIIHRDLKPENIVLQ CCCCCCCCHHHEEEE	55.35	24816145
161	Ubiquitination	QQGEQRLIHKIIDLG EECHHHHHHHHHHHC	3.20	22817900
163	Ubiquitination	GEQRLIHKIIDLGYA CHHHHHHHHHHHCCC	34.07	16267042
169	Phosphorylation	HKIIDLGYAKELDQG HHHHHHCCCCCCCCC	23.07	-
171	Ubiquitination	IIDLGYAKELDQGSL HHHHCCCCCCCCCCC	50.77	-
177	Dephosphorylation	AKELDQGSLCTSFVG CCCCCCCCCCHHHHH	18.03	14585847
177	Phosphorylation	AKELDQGSLCTSFVG CCCCCCCCCCHHHHH	18.03	11325957
179	S-nitrosocysteine	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	-
179	Glutathionylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	22833525
179	Phosphorylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	16319058
179	S-nitrosylation	ELDQGSLCTSFVGTL CCCCCCCCHHHHHHH	2.99	15184672
180	Acetylation	LDQGSLCTSFVGTLQ CCCCCCCHHHHHHHH	30.41	147933
180	Phosphorylation	LDQGSLCTSFVGTLQ CCCCCCCHHHHHHHH	30.41	25849741
181	Dephosphorylation	DQGSLCTSFVGTLQY CCCCCCHHHHHHHHH	19.55	14585847
181	Phosphorylation	DQGSLCTSFVGTLQY CCCCCCHHHHHHHHH	19.55	9813230
188	Phosphorylation	SFVGTLQYLAPELLE HHHHHHHHHCHHHHH	14.14	12707358
191	Hydroxylation	GTLQYLAPELLEQQK HHHHHHCHHHHHCCC	30.12	17114296
199	Phosphorylation	ELLEQQKYTVTVDYW HHHHCCCCEEEEEEC	11.34	12707358
239	Phosphorylation	HSKVRQKSEVDIVVS CHHCCCCCEECEEEE	34.22	-
246	Phosphorylation	SEVDIVVSEDLNGTV CEECEEEECCCCCEE	17.94	25849741
252	Ubiquitination	VSEDLNGTVKFSSSL EECCCCCEEEECCCC	21.32	24816145
256	Phosphorylation	LNGTVKFSSSLPYPN CCCEEEECCCCCCCC	17.19	-
257	Phosphorylation	NGTVKFSSSLPYPNN CCEEEECCCCCCCCC	38.74	-
258	Phosphorylation	GTVKFSSSLPYPNNL CEEEECCCCCCCCCH	31.97	-
261	Phosphorylation	KFSSSLPYPNNLNSV EECCCCCCCCCHHHH	24.72	-
267	Phosphorylation	PYPNNLNSVLAERLE CCCCCHHHHHHHHHH	22.98	-
276	Ubiquitination	LAERLEKWLQLMLMW HHHHHHHHHHHHHHH	4.67	24816145
278	Ubiquitination	ERLEKWLQLMLMWHP HHHHHHHHHHHHHCC	24.58	29967540
294	Phosphorylation	QRGTDPTYGPNGCFK HCCCCCCCCCCCHHH	35.65	29496907
301	Ubiquitination	YGPNGCFKALDDILN CCCCCHHHHHHHHHH	52.71	-
306	Ubiquitination	CFKALDDILNLKLVH HHHHHHHHHHHHHHH	2.47	29967540
321	Ubiquitination	ILNMVTGTIHTYPVT HHHHCCCCCEEECCC	10.54	24816145
324	Phosphorylation	MVTGTIHTYPVTEDE HCCCCCEEECCCCCH	26.18	-
325	Phosphorylation	VTGTIHTYPVTEDES CCCCCEEECCCCCHH	4.99	-
332	Phosphorylation	YPVTEDESLQSLKAR ECCCCCHHHHHHHHH	43.99	-
335	Phosphorylation	TEDESLQSLKARIQQ CCCHHHHHHHHHHHH	36.81	-
335	Ubiquitination	TEDESLQSLKARIQQ CCCHHHHHHHHHHHH	36.81	29967540
337	Ubiquitination	DESLQSLKARIQQDT CHHHHHHHHHHHHHC	40.65	29967540
344	Phosphorylation	KARIQQDTGIPEEDQ HHHHHHHCCCCHHHH	32.45	-
345	Ubiquitination	ARIQQDTGIPEEDQE HHHHHHCCCCHHHHH	41.57	24816145
359	Ubiquitination	ELLQEAGLALIPDKP HHHHHHCCCCCCCCC	4.52	29967540
363	Ubiquitination	EAGLALIPDKPATQC HHCCCCCCCCCCCEE	44.41	29967540
365	Ubiquitination	GLALIPDKPATQCIS CCCCCCCCCCCEECC	31.06	29967540
368	Phosphorylation	LIPDKPATQCISDGK CCCCCCCCEECCCCC	32.28	25849741
372	Phosphorylation	KPATQCISDGKLNEG CCCCEECCCCCCCCC	48.19	25849741
393	Phosphorylation	LVFLFDNSKITYETQ EEEEEECCEEEEEEE	27.55	-
396	Phosphorylation	LFDNSKITYETQISP EEECCEEEEEEECCC	21.02	29449344
397	Phosphorylation	FDNSKITYETQISPR EECCEEEEEEECCCC	22.06	27642862
399	Phosphorylation	NSKITYETQISPRPQ CCEEEEEEECCCCCC	22.31	29449344
402	Phosphorylation	ITYETQISPRPQPES EEEEEECCCCCCCCC	12.68	25849741
408	Ubiquitination	ISPRPQPESVSCILQ CCCCCCCCCEEEEEC	59.53	29967540
409	Phosphorylation	SPRPQPESVSCILQE CCCCCCCCEEEEECC	26.47	-
411	Phosphorylation	RPQPESVSCILQEPK CCCCCCEEEEECCCC	12.52	-
416	Ubiquitination	SVSCILQEPKRNLAF CEEEEECCCCCCCHH	49.71	29967540
418	Ubiquitination	SCILQEPKRNLAFFQ EEEECCCCCCCHHHH	53.84	29967540
426	Ubiquitination	RNLAFFQLRKVWGQV CCCHHHHHHHHHHHH	4.90	24816145
446	Ubiquitination	TLKEDCNRLQQGQRA HHHHHHHHHHHHHHH	39.96	24816145
450	Ubiquitination	DCNRLQQGQRAAMMN HHHHHHHHHHHHHHH	13.14	24816145
465	Ubiquitination	LLRNNSCLSKMKNSM HHHCCHHHHHHHHHH	5.75	29967540
467	Acetylation	RNNSCLSKMKNSMAS HCCHHHHHHHHHHHH	40.73	25953088
467	Ubiquitination	RNNSCLSKMKNSMAS HCCHHHHHHHHHHHH	40.73	29967540
469	Malonylation	NSCLSKMKNSMASMS CHHHHHHHHHHHHHH	50.00	26320211
470	Ubiquitination	SCLSKMKNSMASMSQ HHHHHHHHHHHHHHH	33.25	24816145
471	O-linked_Glycosylation	CLSKMKNSMASMSQQ HHHHHHHHHHHHHHH	15.37	30379171
471	Phosphorylation	CLSKMKNSMASMSQQ HHHHHHHHHHHHHHH	15.37	-
472	Ubiquitination	LSKMKNSMASMSQQL HHHHHHHHHHHHHHH	4.47	24816145
474	Phosphorylation	KMKNSMASMSQQLKA HHHHHHHHHHHHHHH	15.43	-
476	Phosphorylation	KNSMASMSQQLKAKL HHHHHHHHHHHHHHH	16.57	-
481	Ubiquitination	SMSQQLKAKLDFFKT HHHHHHHHHHHHHHH	26.66	24816145
488	Phosphorylation	AKLDFFKTSIQIDLE HHHHHHHHHEEECHH	26.38	-
489	Phosphorylation	KLDFFKTSIQIDLEK HHHHHHHHEEECHHH	17.06	-
496	Ubiquitination	SIQIDLEKYSEQTEF HEEECHHHHHCCCCC	62.46	24816145
501	Phosphorylation	LEKYSEQTEFGITSD HHHHHCCCCCCCCCH	29.27	24719451
505	Ubiquitination	SEQTEFGITSDKLLL HCCCCCCCCCHHHHH	3.96	24816145
507	Phosphorylation	QTEFGITSDKLLLAW CCCCCCCCHHHHHHH	30.72	25849741
507	Ubiquitination	QTEFGITSDKLLLAW CCCCCCCCHHHHHHH	30.72	29967540
509	Ubiquitination	EFGITSDKLLLAWRE CCCCCCHHHHHHHHH	40.58	29967540
529	Ubiquitination	ELCGRENEVKLLVER HHCCCHHHHHHHHHH	35.95	24816145
531	Ubiquitination	CGRENEVKLLVERMM CCCHHHHHHHHHHHH	29.89	24816145
542	Phosphorylation	ERMMALQTDIVDLQR HHHHHHCCCHHHHHC	28.66	27251275
544	Ubiquitination	MMALQTDIVDLQRSP HHHHCCCHHHHHCCC	2.70	29967540
550	Phosphorylation	DIVDLQRSPMGRKQG CHHHHHCCCCCCCCC	13.28	28450419
553	Ubiquitination	DLQRSPMGRKQGGTL HHHCCCCCCCCCCCH	36.70	24816145
555	Ubiquitination	QRSPMGRKQGGTLDD HCCCCCCCCCCCHHH	47.79	24816145
559	Phosphorylation	MGRKQGGTLDDLEEQ CCCCCCCCHHHHHHH	33.56	-
569	Ubiquitination	DLEEQARELYRRLRE HHHHHHHHHHHHHHH	53.84	29967540
583	Phosphorylation	EKPRDQRTEGDSQEM HCCCCCCCCCCHHHH	38.39	-
587	Phosphorylation	DQRTEGDSQEMVRLL CCCCCCCHHHHHHHH	38.61	-
600	Phosphorylation	LLLQAIQSFEKKVRV HHHHHHHHHHHHHHH	29.29	22817900
601	Ubiquitination	LLQAIQSFEKKVRVI HHHHHHHHHHHHHHH	10.26	29967540
603	Acetylation	QAIQSFEKKVRVIYT HHHHHHHHHHHHHHH	55.33	25953088
603	Ubiquitination	QAIQSFEKKVRVIYT HHHHHHHHHHHHHHH	55.33	29967540
605	Ubiquitination	IQSFEKKVRVIYTQL HHHHHHHHHHHHHCC	9.77	29967540
609	Phosphorylation	EKKVRVIYTQLSKTV HHHHHHHHHCCCCCE	5.88	22817900
610	Phosphorylation	KKVRVIYTQLSKTVV HHHHHHHHCCCCCEE	16.35	-
611	Phosphorylation	KVRVIYTQLSKTVVC HHHHHHHCCCCCEEE	27.11	33259812
613	Phosphorylation	RVIYTQLSKTVVCKQ HHHHHCCCCCEEECH	19.23	32645325
616	Phosphorylation	YTQLSKTVVCKQKAL HHCCCCCEEECHHHH	5.67	33259812
626	Ubiquitination	KQKALELLPKVEEVV CHHHHHHHHCHHHHH	2.55	29967540
628	Ubiquitination	KALELLPKVEEVVSL HHHHHHHCHHHHHHH	63.35	29967540
634	Phosphorylation	PKVEEVVSLMNEDEK HCHHHHHHHCCCCCC	27.38	25849741
652	Ubiquitination	RLQEKRQKELWNLLK HHHHHHHHHHHHHHH	59.83	-
659	Acetylation	KELWNLLKIACSKVR HHHHHHHHHHHHHCC	31.27	20167786
662	Ubiquitination	WNLLKIACSKVRGPV HHHHHHHHHHCCCCC	4.63	29967540
664	Ubiquitination	LLKIACSKVRGPVSG HHHHHHHHCCCCCCC	35.52	29967540
670	Phosphorylation	SKVRGPVSGSPDSMN HHCCCCCCCCCCCCC	36.37	23401153
672	Phosphorylation	VRGPVSGSPDSMNAS CCCCCCCCCCCCCHH	20.30	19664994
675	Phosphorylation	PVSGSPDSMNASRLS CCCCCCCCCCHHHCC	19.81	22167270
676	Sulfoxidation	VSGSPDSMNASRLSQ CCCCCCCCCHHHCCC	6.73	21406390
679	Phosphorylation	SPDSMNASRLSQPGQ CCCCCCHHHCCCCCC	28.84	23927012
682	Phosphorylation	SMNASRLSQPGQLMS CCCHHHCCCCCCHHC	32.97	23927012
689	Phosphorylation	SQPGQLMSQPSTASN CCCCCHHCCCCCCCC	47.75	28450419
692	Phosphorylation	GQLMSQPSTASNSLP CCHHCCCCCCCCCCC	29.03	23927012
693	Phosphorylation	QLMSQPSTASNSLPE CHHCCCCCCCCCCCC	40.57	28450419
695	Phosphorylation	MSQPSTASNSLPEPA HCCCCCCCCCCCCCC	27.34	23401153
697	Phosphorylation	QPSTASNSLPEPAKK CCCCCCCCCCCCCCC	42.69	23927012
703	Ubiquitination	NSLPEPAKKSEELVA CCCCCCCCCCHHHHH	68.50	-
705	Phosphorylation	LPEPAKKSEELVAEA CCCCCCCCHHHHHHH	35.28	25849741
717	Phosphorylation	AEAHNLCTLLENAIQ HHHHHHHHHHHHHHH	37.23	25849741
733	O-linked_Glycosylation	TVREQDQSFTALDWS HHHHHHHCCEEECCH	32.62	32114385
733	Phosphorylation	TVREQDQSFTALDWS HHHHHHHCCEEECCH	32.62	22817900
735	Phosphorylation	REQDQSFTALDWSWL HHHHHCCEEECCHHH	31.40	-
740	Phosphorylation	SFTALDWSWLQTEEE CCEEECCHHHCCHHH	19.99	22817900
750	Phosphorylation	QTEEEEHSCLEQAS- CCHHHHHHHHHHCC-	24.55	17114296
756	Phosphorylation	HSCLEQAS------- HHHHHHCC-------	40.21	10195894

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	P54646	GPS
177	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
177	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
177	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
177	S	Phosphorylation	Kinase	PRKCE	Q02156	GPS
177	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP
177	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
177	S	Phosphorylation	Kinase	MAP3K14	Q99558	GPS
181	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
181	S	Phosphorylation	Kinase	TBK1	Q9UHD2	Uniprot
181	S	Phosphorylation	Kinase	SGK1	O00141	PSP
181	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
181	S	Phosphorylation	Kinase	PDPK1	O15530	Uniprot
181	S	Phosphorylation	Kinase	MAP3K14	Q99558	GPS
181	S	Phosphorylation	Kinase	PKCZ	Q05513	PSP
181	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
181	S	Phosphorylation	Kinase	PRKAA2	P54646	GPS
188	Y	Phosphorylation	Kinase	LYN	P07948	PSP
188	Y	Phosphorylation	Kinase	SRC	P12931	PSP
199	Y	Phosphorylation	Kinase	LYN	P07948	PSP
199	Y	Phosphorylation	Kinase	SRC	P12931	PSP
670	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
670	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
670	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
672	S	Phosphorylation	Kinase	IKBKB	O14920	GPS
672	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
672	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
675	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
675	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
682	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
682	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
689	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
689	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
692	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
692	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
695	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
695	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
697	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
697	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
705	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
705	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
733	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
733	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
733	S	Phosphorylation	Kinase	PLK1	P53350	PSP
740	S	Phosphorylation	Kinase	PLK1	P53350	PSP
740	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
740	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
750	S	Phosphorylation	Kinase	IKK-FAMILY	-	GPS
750	S	Phosphorylation	Kinase	IKK_GROUP	-	PhosphoELM
750	S	Phosphorylation	Kinase	PLK1	P53350	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	KEAP1	Q14145	PMID:19818716
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM21	P19474	PMID:19675099
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW11	Q9UKB1	PMID:10321728

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
163	S	Phosphorylation	According to PubMed:16267042, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues.	16267042
163	S	ubiquitylation	According to PubMed:16267042, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues.	16267042
163	S	ubiquitylation	According to PubMed:19675099, 'Ser-163' does not serve as a monoubiquitination site.	1967509
177	S	Phosphorylation	Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.	9346484
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.	9346484
180	T	Acetylation	(Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.	17116858
180	T	Phosphorylation	(Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.	17116858
181	S	Phosphorylation	Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.	9346484
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.	9346484

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_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PPM1B_HUMAN	PPM1B	physical	14585847
NFKB1_HUMAN	NFKB1	physical	11158290
FBW1A_HUMAN	BTRC	physical	11158290
M3K13_HUMAN	MAP3K13	physical	12492477
PRDX3_HUMAN	PRDX3	physical	12492477
IRS1_HUMAN	IRS1	physical	12351658
IKKA_HUMAN	CHUK	physical	9346241
NEMO_HUMAN	IKBKG	physical	11864612
CDC37_HUMAN	CDC37	physical	11864612
IKKA_HUMAN	CHUK	physical	11864612
TNR1A_HUMAN	TNFRSF1A	physical	10755617
IKBA_HUMAN	NFKBIA	physical	9891086
FANCA_HUMAN	FANCA	physical	12210728
IKKA_HUMAN	CHUK	physical	12210728
E2AK2_HUMAN	EIF2AK2	physical	10848580
CASP8_HUMAN	CASP8	physical	11002417
NEMO_HUMAN	IKBKG	physical	11971985
NCOA3_HUMAN	NCOA3	physical	11971985
TNAP3_HUMAN	TNFAIP3	physical	11594795
IKBA_HUMAN	NFKBIA	physical	9346485
IKBB_HUMAN	NFKBIB	physical	9346485
M3K14_HUMAN	MAP3K14	physical	9346485
IKKA_HUMAN	CHUK	physical	9346485
IKKB_HUMAN	IKBKB	physical	9346485
NEMO_HUMAN	IKBKG	physical	11057907
M3K7_HUMAN	MAP3K7	physical	10807933
IKKB_HUMAN	IKBKB	physical	10807933
PEBP1_RAT	Pebp1	physical	11585904
IKKA_HUMAN	CHUK	physical	11585904
IKKB_HUMAN	IKBKB	physical	11585904
TRAF2_HUMAN	TRAF2	physical	19150425
KPCT_HUMAN	PRKCQ	physical	15802604
IKBA_HUMAN	NFKBIA	physical	12054687
CUED2_HUMAN	CUEDC2	physical	18362886
TRAF2_HUMAN	TRAF2	physical	18362886
PP1A_HUMAN	PPP1CA	physical	18362886
PR15A_HUMAN	PPP1R15A	physical	18362886
TF65_HUMAN	RELA	physical	15489227
AKT1_HUMAN	AKT1	physical	15856005
IKKA_HUMAN	CHUK	physical	9346484
KPCA_HUMAN	PRKCA	physical	10022904
KPCI_HUMAN	PRKCI	physical	10022904
KPCD_HUMAN	PRKCD	physical	10022904
NEMO_HUMAN	IKBKG	physical	19820708
P53_HUMAN	TP53	physical	19196987
KEAP1_HUMAN	KEAP1	physical	19818716
HD_HUMAN	HTT	physical	20026656
CSN3_HUMAN	COPS3	physical	19656241
CSN4_HUMAN	COPS4	physical	19656241
CSN5_HUMAN	COPS5	physical	19656241
CSN7A_HUMAN	COPS7A	physical	19656241
CUL1_HUMAN	CUL1	physical	19656241
FBW1A_HUMAN	BTRC	physical	19656241
JUN_HUMAN	JUN	physical	19656241
RB6I2_HUMAN	ERC1	physical	20932476
NEMO_HUMAN	IKBKG	physical	20932476
M3K7_HUMAN	MAP3K7	physical	20932476
IKKA_HUMAN	CHUK	physical	20932476
TNAP3_HUMAN	TNFAIP3	physical	21220427
IKBA_HUMAN	NFKBIA	physical	20797629
FBW1A_HUMAN	BTRC	physical	20797629
HNRPU_HUMAN	HNRNPU	physical	20797629
TRI40_HUMAN	TRIM40	physical	21474709
NEMO_HUMAN	IKBKG	physical	19815509
IKBA_HUMAN	NFKBIA	physical	22022389
CDC37_HUMAN	CDC37	physical	21903422
FKBP4_HUMAN	FKBP4	physical	21903422
FKBP5_HUMAN	FKBP5	physical	21903422
IKKA_HUMAN	CHUK	physical	21903422
NEMO_HUMAN	IKBKG	physical	21903422
PYGL_HUMAN	PYGL	physical	21903422
CSK2B_HUMAN	CSNK2B	physical	20797629
MK14_HUMAN	MAPK14	physical	20797629
NLRX1_HUMAN	NLRX1	physical	21703539
IKKA_HUMAN	CHUK	physical	12244103
MUC1_HUMAN	MUC1	physical	18037881
NEMO_HUMAN	IKBKG	physical	18037881
RB6I2_HUMAN	ERC1	physical	15218148
IKBA_HUMAN	NFKBIA	physical	15218148
NEMO_HUMAN	IKBKG	physical	17977820
P63_HUMAN	TP63	physical	20145131
HOME3_HUMAN	HOMER3	physical	20693425
IKBA_HUMAN	NFKBIA	physical	9914500
IKKB_HUMAN	IKBKB	physical	9914500
IKKE_HUMAN	IKBKE	physical	9914500
IKBA_HUMAN	NFKBIA	physical	18981174
NED4L_HUMAN	NEDD4L	physical	18981174
NEMO_HUMAN	IKBKG	physical	16906147
PELI1_HUMAN	PELI1	physical	21204785
IKBA_HUMAN	NFKBIA	physical	9689078
IKBB_HUMAN	NFKBIB	physical	9689078
BRAP_HUMAN	BRAP	physical	21670849
BCL10_HUMAN	BCL10	physical	17213322
TNIP2_HUMAN	TNIP2	physical	21784860
KEAP1_HUMAN	KEAP1	physical	20600852
IKBA_HUMAN	NFKBIA	physical	16611882
SRC_HUMAN	SRC	physical	12707358
NALP2_HUMAN	NLRP2	physical	15456791
HS90A_HUMAN	HSP90AA1	physical	19786027
EGLN3_HUMAN	EGLN3	physical	19786027
M3K1_HUMAN	MAP3K1	physical	9819420
TRI27_HUMAN	TRIM27	physical	16393995
P73_HUMAN	TP73	physical	21482671
TPPC9_HUMAN	TRAPPC9	physical	15951441
FAF1_HUMAN	FAF1	physical	17684021
TF65_HUMAN	RELA	physical	16046471
MEOX2_HUMAN	MEOX2	physical	20421348
TRAF1_HUMAN	TRAF1	physical	20856938
FOXO3_HUMAN	FOXO3	physical	15084260
IKKB_HUMAN	IKBKB	physical	12890679
CSF2R_HUMAN	CSF2RA	physical	12637324
TNR1A_HUMAN	TNFRSF1A	physical	21724995
NFKB1_HUMAN	NFKB1	physical	11976329
IKBA_HUMAN	NFKBIA	physical	9721103
IKKB_HUMAN	IKBKB	physical	9721103
IKKB_HUMAN	IKBKB	physical	12709429
IKBA_HUMAN	NFKBIA	physical	12709429
TRAF1_HUMAN	TRAF1	physical	12709429
TSC1_HUMAN	TSC1	physical	17693255
IKKA_HUMAN	CHUK	physical	17693255
NEMO_HUMAN	IKBKG	physical	17693255
IKBA_HUMAN	NFKBIA	physical	11080499
CBP_HUMAN	CREBBP	physical	14597638
IKKB_HUMAN	IKBKB	physical	17079871
IKBA_HUMAN	NFKBIA	physical	17079871
NAA20_HUMAN	NAA20	physical	19716809
IKBA_HUMAN	NFKBIA	physical	12943667
NEMO_HUMAN	IKBKG	physical	17000764
IKBA_HUMAN	NFKBIA	physical	20449947
IKBA_HUMAN	NFKBIA	physical	12411322
NEMO_HUMAN	IKBKG	physical	19422324
IKKA_HUMAN	CHUK	physical	21575199
IKBA_HUMAN	NFKBIA	physical	22990857
NEMO_HUMAN	IKBKG	physical	22990857
NEMO_HUMAN	IKBKG	physical	12486103
IKBA_HUMAN	NFKBIA	physical	17363905
IKBA_HUMAN	NFKBIA	physical	20434986
NLRC5_HUMAN	NLRC5	physical	20434986
IKBA_HUMAN	NFKBIA	physical	16286467
IKKA_HUMAN	CHUK	physical	16286467
IKBA_HUMAN	NFKBIA	physical	16319058
IKBA_HUMAN	NFKBIA	physical	15125834
AURKA_HUMAN	AURKA	physical	17939994
IKKB_HUMAN	IKBKB	physical	17939994
PP1A_HUMAN	PPP1CA	physical	18949366
CSN5_HUMAN	COPS5	physical	23636414
CSN3_HUMAN	COPS3	physical	23636414
SASH1_HUMAN	SASH1	physical	23776175
AP2C_HUMAN	TFAP2C	physical	21988832
IKKB_HUMAN	IKBKB	physical	23792959
IKBA_HUMAN	NFKBIA	physical	24611898
IKKB_HUMAN	IKBKB	physical	24611898
IKBA_HUMAN	NFKBIA	physical	24469399
IKBA_HUMAN	NFKBIA	physical	23816567
NEMO_HUMAN	IKBKG	physical	23506214
IKBA_HUMAN	NFKBIA	physical	24912152
IKKB_HUMAN	IKBKB	physical	24912152
MTOR_HUMAN	MTOR	physical	18490760
IKBA_HUMAN	NFKBIA	physical	18519641
TF65_HUMAN	RELA	physical	18519641
SNP23_MOUSE	Snap23	physical	18692471
IKBA_HUMAN	NFKBIA	physical	15125833
RPTOR_HUMAN	RPTOR	physical	23872070
NEMO_HUMAN	IKBKG	physical	21455180
IKBA_HUMAN	NFKBIA	physical	19959994
IKKA_HUMAN	CHUK	physical	25852190
DHC24_HUMAN	DHCR24	physical	25852190
NEMO_HUMAN	IKBKG	physical	25852190
RAN_HUMAN	RAN	physical	25852190
CMC2_HUMAN	SLC25A13	physical	25852190
GHC1_HUMAN	SLC25A22	physical	25852190
IKBA_HUMAN	NFKBIA	physical	24618592
NEMO_HUMAN	IKBKG	physical	25400026
MAVS_HUMAN	MAVS	physical	25636800
IKKB_HUMAN	IKBKB	physical	25486864
CBP_HUMAN	CREBBP	physical	25241761
IKKA_HUMAN	CHUK	physical	25241761
CLH1_HUMAN	CLTC	physical	25241761
CSF2R_HUMAN	CSF2RA	physical	25241761
FOXO3_HUMAN	FOXO3	physical	25241761
TF65_HUMAN	RELA	physical	25241761
NFKB1_HUMAN	NFKB1	physical	25241761
CTNB1_HUMAN	CTNNB1	physical	25241761
TRAF2_HUMAN	TRAF2	physical	25241761
IKBA_HUMAN	NFKBIA	physical	26740240
IKBA_HUMAN	NFKBIA	physical	25595906
LATS2_HUMAN	LATS2	physical	25946971
M3K7_HUMAN	MAP3K7	physical	25946971
GLI1_HUMAN	GLI1	physical	26603838
ITCH_HUMAN	ITCH	physical	26603838
IKBA_HUMAN	NFKBIA	physical	26802121
UBP18_HUMAN	USP18	physical	26240016
IKBA_HUMAN	NFKBIA	physical	26221961
TWST1_HUMAN	TWIST1	physical	23375009
AKT1_HUMAN	AKT1	physical	22689577
IKBA_HUMAN	NFKBIA	physical	18375836
IKBA_HUMAN	NFKBIA	physical	18202307
IKBA_HUMAN	NFKBIA	physical	18593939
IKBA_HUMAN	NFKBIA	physical	15919917
IKBA_HUMAN	NFKBIA	physical	12624112
IKBA_HUMAN	NFKBIA	physical	15456896
IKBA_HUMAN	NFKBIA	physical	15217903
IKBA_HUMAN	NFKBIA	physical	28214532
KLH21_HUMAN	KLHL21	physical	27387502
TRAF2_HUMAN	TRAF2	physical	27387502
M3K7_HUMAN	MAP3K7	physical	27387502
IKBA_HUMAN	NFKBIA	physical	27387502
IKBA_HUMAN	NFKBIA	physical	27497262
IKKA_HUMAN	CHUK	physical	28514442
NEMO_HUMAN	IKBKG	physical	26500060
HIF1A_HUMAN	HIF1A	physical	26500060
EPAS1_HUMAN	EPAS1	physical	26500060
IKBA_HUMAN	NFKBIA	physical	22904686
IKKB_HUMAN	IKBKB	physical	29111346

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 615592: Immunodeficiency 15 (IMD15)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• DB06151: Acetylcysteine
• DB00945: Acetylsalicylic acid
• DB01169: Arsenic trioxide
• DB00995: Auranofin
• DB00244: Mesalazine
• DB00795: Sulfasalazine

Related Literatures of Post-Translational Modification

Phosphorylation

"3-Phosphoinositide-dependent protein kinase-1-mediated IkappaB kinasebeta (IkkB) phosphorylation activates NF-kappaB signaling.";
Tanaka H., Fujita N., Tsuruo T.;
J. Biol. Chem. 280:40965-40973(2005).
Cited for: PHOSPHORYLATION AT SER-181 BY PDPK1, AND INTERACTION WITH PDPK1.
PubMed: 16207722

"NAK is an IkappaB kinase-activating kinase.";
Tojima Y., Fujimoto A., Delhase M., Chen Y., Hatakeyama S.,Nakayama K., Kaneko Y., Nimura Y., Motoyama N., Ikeda K., Karin M.,Nakanishi M.;
Nature 404:778-782(2000).
Cited for: PHOSPHORYLATION AT SER-177 AND SER-181 BY TBK1, AND MUTAGENESIS OF177-SER--SER-181.
PubMed: 10783893

"Positive and negative regulation of IkappaB kinase activity throughIKKbeta subunit phosphorylation.";
Delhase M., Hayakawa M., Chen Y., Karin M.;
Science 284:309-313(1999).
Cited for: PHOSPHORYLATION AT SER-177; SER-181; SER-670; SER-672; SER-675;SER-682; SER-689; SER-692; SER-695; SER-697; SER-705; SER-733; SER-740AND SER-750.
PubMed: 10195894

"Activation of IkappaB kinase beta by protein kinase C isoforms.";
Lallena M.J., Diaz-Meco M.T., Bren G., Paya C.V., Moscat J.;
Mol. Cell. Biol. 19:2180-2188(1999).
Cited for: PHOSPHORYLATION AT SER-177 AND SER-181.
PubMed: 10022904

S-nitrosylation

"Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation.";
Reynaert N.L., Ckless K., Korn S.H., Vos N., Guala A.S., Wouters E.F.,van der Vliet A., Janssen-Heininger Y.M.;
Proc. Natl. Acad. Sci. U.S.A. 101:8945-8950(2004).
Cited for: S-NITROSYLATION AT CYS-179.
PubMed: 15184672

Ubiquitylation

"Site-specific monoubiquitination of IkappaB kinase IKKbeta regulatesits phosphorylation and persistent activation.";
Carter R.S., Pennington K.N., Arrate P., Oltz E.M., Ballard D.W.;
J. Biol. Chem. 280:43272-43279(2005).
Cited for: UBIQUITINATION AT LYS-163.
PubMed: 16267042