NFKB2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NFKB2_MOUSE
• UniProt AC: Q9WTK5
• Protein Name: Nuclear factor NF-kappa-B p100 subunit
• Gene Name: Nfkb2
• Organism: Mus musculus (Mouse).
• Sequence Length: 899
• Subcellular Localization: Nucleus. Cytoplasm. Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B)..
• Protein Description: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, 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. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65 (By similarity). In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer..
• Protein Sequence: MDNCYDPGLDGIPEYDDFEFSPSIVEPKDPAPETADGPYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAKIEVDLVTHSDPPRAHAHSLVGKQCSELGVCAVSVGPKDMTAQFNNLGVLHVTKKNMMEIMIQKLQRQRLRSKPQGLTEAERRELEQEAKELKKVMDLSIVRLRFSAFLRASDGSFSLPLKPVISQPIHDSKSPGASNLKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDENGWQAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTVFLQLKRKRGGDVSDSKQFTYYPLVEDKEEVQRKRRKALPTFSQPFGGGSHMGGGSGGSAGGYGGAGGGGSLGFFSSSLAYNPYQSGAAPMGCYPGGGGGAQMAGSRRDTDAGEGAEEPRTPPEAPQGEPQALDTLQRAREYNARLFGLAQRSARALLDYGVTADARALLAGQRHLLMAQDENGDTPLHLAIIHGQTGVIEQIAHVIYHAQYLGVINLTNHLHQTPLHLAVITGQTRVVSFLLQVGADPTLLDRHGDSALHLALRAGAAAPELLQALLRSGAHAVPQILHMPDFEGLYPVHLAVHARSPECLDLLVDCGAEVEAPERQGGRTALHLATEMEELGLVTHLVTKLHANVNARTFAGNTPLHLAAGLGSPTLTRLLLKAGADIHAENEEPLCPLPSPSTSGSDSDSEGPERDTQRNFRGHTPLDLTCSTKVKTLLLNAAQNTTEPPLAPPSPAGPGLSLGDAALQNLEQLLDGPEAQGSWAELAERLGLRSLVDTYRKTPSPSGSLLRSYKLAGGDLVGLLEALSDMGLHEGVRLLKGPETRDKLPSTEVKEDSAYGSQSVEQEAEKLCPPPEPPGGLCHGHPQPQVH

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
5	Phosphorylation	---MDNCYDPGLDGI ---CCCCCCCCCCCC	31.28	24224561
15	Phosphorylation	GLDGIPEYDDFEFSP CCCCCCCCCCCCCCC	18.56	24224561
21	Phosphorylation	EYDDFEFSPSIVEPK CCCCCCCCCCCCCCC	15.56	25338131
23	Phosphorylation	DDFEFSPSIVEPKDP CCCCCCCCCCCCCCC	37.76	-
72	Acetylation	LPGASSEKGRKTYPT CCCCCCCCCCCCCCE	67.00	7616925
161	Phosphorylation	LQRQRLRSKPQGLTE HHHHHHHCCCCCCCH	53.96	29176673
195	Phosphorylation	SIVRLRFSAFLRASD HHHHHHHHHHHCCCC	16.21	-
204	Phosphorylation	FLRASDGSFSLPLKP HHCCCCCCEECCCCC	19.36	26370283
206	Phosphorylation	RASDGSFSLPLKPVI CCCCCCEECCCCCEE	30.67	26160508
214	Phosphorylation	LPLKPVISQPIHDSK CCCCCEECCCCCCCC	30.09	26160508
220	Phosphorylation	ISQPIHDSKSPGASN ECCCCCCCCCCCCCC	22.37	26160508
222	Phosphorylation	QPIHDSKSPGASNLK CCCCCCCCCCCCCCC	32.30	25159016
226	Phosphorylation	DSKSPGASNLKISRM CCCCCCCCCCCEEEE	48.92	25159016
231	Phosphorylation	GASNLKISRMDKTAG CCCCCCEEEECCCCC	21.69	20531401
236	Phosphorylation	KISRMDKTAGSVRGG CEEEECCCCCCCCCC	31.80	20531401
239	Phosphorylation	RMDKTAGSVRGGDEV EECCCCCCCCCCCEE	13.23	20531401
247	Phosphorylation	VRGGDEVYLLCDKVQ CCCCCEEEEEECCCC	7.60	20531401
277	Phosphorylation	WQAFGDFSPTDVHKQ EEEECCCCCCCHHCC	31.46	25338131
414	Phosphorylation	MAGSRRDTDAGEGAE CCCCCCCCCCCCCCC	26.41	25619855
425	Phosphorylation	EGAEEPRTPPEAPQG CCCCCCCCCCCCCCC	54.64	27087446
439	Phosphorylation	GEPQALDTLQRAREY CCCCHHHHHHHHHHH	26.16	25619855
680	Phosphorylation	HLAAGLGSPTLTRLL HHCCCCCCHHHHHHH	21.54	26745281
682	Phosphorylation	AAGLGSPTLTRLLLK CCCCCCHHHHHHHHH	42.32	23984901
684	Phosphorylation	GLGSPTLTRLLLKAG CCCCHHHHHHHHHHC	23.04	23984901
707	Phosphorylation	EPLCPLPSPSTSGSD CCCCCCCCCCCCCCC	38.88	21659605
709	Phosphorylation	LCPLPSPSTSGSDSD CCCCCCCCCCCCCCC	39.27	30635358
710	Phosphorylation	CPLPSPSTSGSDSDS CCCCCCCCCCCCCCC	40.26	30635358
711	Phosphorylation	PLPSPSTSGSDSDSE CCCCCCCCCCCCCCC	40.41	24224561
713	Phosphorylation	PSPSTSGSDSDSEGP CCCCCCCCCCCCCCC	33.44	30635358
715	Phosphorylation	PSTSGSDSDSEGPER CCCCCCCCCCCCCCC	44.74	21659605
717	Phosphorylation	TSGSDSDSEGPERDT CCCCCCCCCCCCCCC	48.70	30635358
724	Phosphorylation	SEGPERDTQRNFRGH CCCCCCCCCCCCCCC	35.33	30635358
810	Phosphorylation	LVDTYRKTPSPSGSL HHHHHCCCCCCCCHH	21.72	27180971
812	Phosphorylation	DTYRKTPSPSGSLLR HHHCCCCCCCCHHHH	36.61	26643407
814	Phosphorylation	YRKTPSPSGSLLRSY HCCCCCCCCHHHHEE	45.40	25338131
816	Phosphorylation	KTPSPSGSLLRSYKL CCCCCCCHHHHEEEE	28.68	29514104
858	Phosphorylation	ETRDKLPSTEVKEDS CCCCCCCCCCCCCCC	47.86	30635358
859	Phosphorylation	TRDKLPSTEVKEDSA CCCCCCCCCCCCCCC	42.74	30635358
865	Phosphorylation	STEVKEDSAYGSQSV CCCCCCCCCCCCHHH	25.20	22942356
867	Phosphorylation	EVKEDSAYGSQSVEQ CCCCCCCCCCHHHHH	22.66	30635358
869	Phosphorylation	KEDSAYGSQSVEQEA CCCCCCCCHHHHHHH	13.45	30635358
871	Phosphorylation	DSAYGSQSVEQEAEK CCCCCCHHHHHHHHH	29.35	30635358

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
865	S	Phosphorylation	Kinase	MAP3K14	Q9WUL6	Uniprot
869	S	Phosphorylation	Kinase	MAP3K14	Q9WUL6	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Btrc	Q3ULA2	PMID:22199232

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NFKB2_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 NFKB2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TF65_MOUSE	Rela	physical	20211142
RELB_MOUSE	Relb	physical	20211142
IKBZ_MOUSE	Nfkbiz	physical	20211142
H33_MOUSE	H3f3a	physical	24115035

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale phosphorylation analysis of mouse liver.";
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, AND MASSSPECTROMETRY.
PubMed: 17242355