IKBA_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: IKBA_MOUSE
• UniProt AC: Q9Z1E3
• Protein Name: NF-kappa-B inhibitor alpha
• Gene Name: Nfkbia
• Organism: Mus musculus (Mouse).
• Sequence Length: 314
• Subcellular Localization: Cytoplasm. Nucleus. Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export..
• Protein Description: Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription..
• Protein Sequence: MFQPAGHGQDWAMEGPRDGLKKERLVDDRHDSGLDSMKDEEYEQMVKELREIRLQPQEAPLAAEPWKQQLTEDGDSFLHLAIIHEEKPLTMEVIGQVKGDLAFLNFQNNLQQTPLHLAVITNQPGIAEALLKAGCDPELRDFRGNTPLHLACEQGCLASVAVLTQTCTPQHLHSVLQATNYNGHTCLHLASIHGYLAIVEHLVTLGADVNAQEPCNGRTALHLAVDLQNPDLVSLLLKCGADVNRVTYQGYSPYQLTWGRPSTRIQQQLGQLTLENLQMLPESEDEESYDTESEFTEDELPYDDCVFGGQRLTL

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
21	Ubiquitination	EGPRDGLKKERLVDD CCCCCCCCHHHHCCC	59.11	9990853
21	Sumoylation	EGPRDGLKKERLVDD CCCCCCCCHHHHCCC	59.11	-
22	Ubiquitination	GPRDGLKKERLVDDR CCCCCCCHHHHCCCC	53.78	9990853
32	Phosphorylation	LVDDRHDSGLDSMKD HCCCCCCCCHHHHCH	34.82	21455180
36	Phosphorylation	RHDSGLDSMKDEEYE CCCCCHHHHCHHHHH	32.54	21455180
42	Phosphorylation	DSMKDEEYEQMVKEL HHHCHHHHHHHHHHH	14.93	26026062
210	Hydroxylation	VTLGADVNAQEPCNG HHCCCCCCCCCCCCC	36.13	-
219	Phosphorylation	QEPCNGRTALHLAVD CCCCCCCCEEEEEEE	34.66	26239621
234	Phosphorylation	LQNPDLVSLLLKCGA CCCCCHHHHHHHCCC	22.16	26239621
244	Hydroxylation	LKCGADVNRVTYQGY HHCCCCCCCEEECCC	33.00	-
248	Phosphorylation	ADVNRVTYQGYSPYQ CCCCCEEECCCCCCC	9.33	-
251	Phosphorylation	NRVTYQGYSPYQLTW CCEEECCCCCCCCCC	7.31	-
252	Phosphorylation	RVTYQGYSPYQLTWG CEEECCCCCCCCCCC	24.77	-
283	Phosphorylation	NLQMLPESEDEESYD HHCCCCCCCCCCCCC	48.70	-
288	Phosphorylation	PESEDEESYDTESEF CCCCCCCCCCCCCCC	26.68	-
291	Phosphorylation	EDEESYDTESEFTED CCCCCCCCCCCCCCC	32.93	-
293	Phosphorylation	EESYDTESEFTEDEL CCCCCCCCCCCCCCC	39.85	8668171
296	Phosphorylation	YDTESEFTEDELPYD CCCCCCCCCCCCCCC	38.18	-

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
32	S	Phosphorylation	Kinase	CHUK	Q60680	GPS
32	S	Phosphorylation	Kinase	IKBKB	O88351	GPS
32	S	Phosphorylation	Kinase	IKBKE	Q9R0T8	GPS
32	S	Phosphorylation	Kinase	STK4	Q9JI11	GPS
36	S	Phosphorylation	Kinase	CHUK	Q60680	GPS
36	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
36	S	Phosphorylation	Kinase	IKBKE	Q9R0T8	GPS
36	S	Phosphorylation	Kinase	STK4	Q9JI11	GPS
36	S	Phosphorylation	Kinase	TBK1	Q9WUN2	Uniprot
283	S	Phosphorylation	Kinase	CK2	-	Uniprot
288	S	Phosphorylation	Kinase	CK2	-	Uniprot
291	T	Phosphorylation	Kinase	CK2	-	Uniprot
293	S	Phosphorylation	Kinase	CSNK2A1	Q60737	GPS
293	S	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Btrc	Q3ULA2	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxw11	Q5SRY7	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Skp2	Q9Z0Z3	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
21	K	ubiquitylation	Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3.	9990853
22	K	ubiquitylation	Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3.	9990853
32	S	Phosphorylation	Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity).	9859996
32	S	ubiquitylation	Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity).	9859996
36	S	Phosphorylation	Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity).	9859996
36	S	ubiquitylation	Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity).	9859996

Disease-associated PTM Sites based on SAP

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

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

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
P53_MOUSE	Trp53	physical	20211142
FBW1B_MOUSE	Fbxw11	physical	11896578
FBW1A_MOUSE	Btrc	physical	10097128
TF65_MOUSE	Rela	physical	16163708
TF65_MOUSE	Rela	physical	16928772
HXA9_MOUSE	Hoxa9	physical	15161102
FBW1A_MOUSE	Btrc	physical	10790373

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Ubiquitin-dependent degradation of IkappaBalpha is mediated by aubiquitin ligase Skp1/Cul 1/F-box protein FWD1.";
Hatakeyama S., Kitagawa M., Nakayama K., Shirane M., Matsumoto M.,Hattori K., Higashi H., Nakano H., Okumura K., Onoe K., Good R.A.,Nakayama K.;
Proc. Natl. Acad. Sci. U.S.A. 96:3859-3863(1999).
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND CUL1,PHOSPHORYLATION AT SER-32 AND SER-36, AND UBIQUITINATION.
PubMed: 10097128

"Signal-induced ubiquitination of IkappaBalpha by the F-box proteinSlimb/beta-TrCP.";
Spencer E., Jiang J., Chen Z.J.;
Genes Dev. 13:284-294(1999).
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND RELA,PHOSPHORYLATION AT SER-32 AND SER-36, AND UBIQUITINATION AT LYS-21 ANDLYS-22.
PubMed: 9990853

"Identification of the receptor component of the IkappaBalpha-ubiquitin ligase.";
Yaron A., Hatzubai A., Davis M., Lavon I., Amit S., Manning A.M.,Andersen J.S., Mann M., Mercurio F., Ben-Neriah Y.;
Nature 396:590-594(1998).
Cited for: INTERACTION WITH BTRC, PHOSPHORYLATION AT SER-32 AND SER-36, ANDUBIQUITINATION.
PubMed: 9859996

Ubiquitylation

"Signal-induced ubiquitination of IkappaBalpha by the F-box proteinSlimb/beta-TrCP.";
Spencer E., Jiang J., Chen Z.J.;
Genes Dev. 13:284-294(1999).
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BTRC; SKP1 AND RELA,PHOSPHORYLATION AT SER-32 AND SER-36, AND UBIQUITINATION AT LYS-21 ANDLYS-22.
PubMed: 9990853