dbPTM

NFKB1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	NFKB1_MOUSE
UniProt AC	P25799
Protein Name	Nuclear factor NF-kappa-B p105 subunit
Gene Name	Nfkb1
Organism	Mus musculus (Mouse).
Sequence Length	971
Subcellular Localization	Nucleus. Cytoplasm. Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). Isoform 5: Cytoplasm. Isoform 6: Nucleus. Cytoplasm. Isoform 7: Nucleus.
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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. Plays a role in the regulation of apoptosis. Isoform 5, isoform 6 and isoform 7 act as inhibitors of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105..
Protein Sequence	MADDDPYGTGQMFHLNTALTHSIFNAELYSPEIPLSTDGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGVCTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHSDLAYLQAEGGGDRQLTDREKEIIRQAAVQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDVNITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGSTGSPGPGYGYSNYGFPPYGGITFHPGVTKSNAGVTHGTINTKFKNGPKDCAKSDDEESLTLPEKETEGEGPSLPMACTKTEPIALASTMEDKEQDMGFQDNLFLEKALQLARRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHAQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRVGADLSLLDRWGNSVLHLAAKEGHDRILSILLKSRKAAPLIDHPNGEGLNAIHIAVMSNSLPCLLLLVAAGAEVNAQEQKSGRTALHLAVEYDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWEKAGEDEGVVPGTTPLDMAANWQVFDILNGKPYEPVFTSDDILPQGDMKQLTEDTRLQLCKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTIKELMEALQQMGYTEAIEVIQAAFRTPATTASSPVTTAQVHCLPLSSSSTRQHIDELRDSDSVCDSGVETSFRKLSFTESLTGDSPLLSLNKMPHGYGQEGPIEGKI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
59	S-nitrosocysteine	GFRFRYVCEGPSHGG CCCEEEEECCCCCCC	3.57	-
59	Glutathionylation	GFRFRYVCEGPSHGG CCCEEEEECCCCCCC	3.57	11714266
59	Other	GFRFRYVCEGPSHGG CCCEEEEECCCCCCC	3.57	-
59	S-nitrosylation	GFRFRYVCEGPSHGG CCCEEEEECCCCCCC	3.57	-
63	Phosphorylation	RYVCEGPSHGGLPGA EEEECCCCCCCCCCC	45.69	20139300
71	Phosphorylation	HGGLPGASSEKNKKS CCCCCCCCCCCCCCC	44.97	20139300
72	Phosphorylation	GGLPGASSEKNKKSY CCCCCCCCCCCCCCC	52.64	20139300
238	Phosphorylation	PVVSDAIYDSKAPNA CCCCCHHCCCCCCCC	18.84	22817900
299	Phosphorylation	WEGFGDFSPTDVHRQ CCCCCCCCCCHHHHC	31.46	25338131
335	Phosphorylation	FVQLRRKSDLETSEP EEEEEEHHCCCCCCC	45.69	-
369	Phosphorylation	QKLMPNFSDSFGGGS HHHCCCCCCCCCCCC	38.70	22802335
424	Phosphorylation	FHPGVTKSNAGVTHG ECCCCCCCCCCCCCC	23.65	22802335
429	Phosphorylation	TKSNAGVTHGTINTK CCCCCCCCCCEEECC	17.42	22817900
432	Phosphorylation	NAGVTHGTINTKFKN CCCCCCCEEECCCCC	11.93	22817900
435	Phosphorylation	VTHGTINTKFKNGPK CCCCEEECCCCCCCC	33.73	22802335
438	Acetylation	GTINTKFKNGPKDCA CEEECCCCCCCCCCC	63.65	-
447	Phosphorylation	GPKDCAKSDDEESLT CCCCCCCCCCCCCCC	31.59	25521595
452	Phosphorylation	AKSDDEESLTLPEKE CCCCCCCCCCCCCCC	25.30	25521595
454	Phosphorylation	SDDEESLTLPEKETE CCCCCCCCCCCCCCC	49.93	23984901
460	Phosphorylation	LTLPEKETEGEGPSL CCCCCCCCCCCCCCC	61.43	23984901
472	Phosphorylation	PSLPMACTKTEPIAL CCCCCCCCCCCCEEE	31.31	-
489 (in isoform 6)	Phosphorylation	-	40.02	25777480
494 (in isoform 6)	Phosphorylation	-	52.09	25777480
498 (in isoform 6)	Phosphorylation	-	8.11	25777480
502 (in isoform 6)	Phosphorylation	-	6.76	25777480
504 (in isoform 6)	Phosphorylation	-	4.10	25777480
506 (in isoform 6)	Phosphorylation	-	39.24	25777480
613	Phosphorylation	LLDRWGNSVLHLAAK HHHHHCCHHHHHHHH	23.32	25293948
628	Phosphorylation	EGHDRILSILLKSRK CCHHHHHHHHHHCCC	14.60	23649490
632	Acetylation	RILSILLKSRKAAPL HHHHHHHHCCCCCCC	44.78	6566121
674	Hydroxylation	VAAGAEVNAQEQKSG HHHCCCCCHHHHHCC	27.66	-
691	Phosphorylation	ALHLAVEYDNISLAG HHHHHHCCCCEEEEE	14.00	-
695	Phosphorylation	AVEYDNISLAGCLLL HHCCCCEEEEEEEEE	20.58	-
750	Phosphorylation	VENFEPLYDLDDSWE HHCCCCCCCCCCHHH	25.77	25159016
755	Phosphorylation	PLYDLDDSWEKAGED CCCCCCCHHHHCCCC	36.48	28418008
847	Phosphorylation	LNNAFRLSPAPSKTL HCCCHHCCCCCCCCC	18.11	-
853 (in isoform 3)	Phosphorylation	-	31.49	25777480
858 (in isoform 3)	Phosphorylation	-	17.28	25777480
862 (in isoform 3)	Phosphorylation	-	42.30	25777480
866 (in isoform 3)	Phosphorylation	-	44.63	25777480
868 (in isoform 3)	Phosphorylation	-	2.97	25777480
870 (in isoform 3)	Phosphorylation	-	59.87	25777480
890	Phosphorylation	VIQAAFRTPATTASS HHHHHHCCCCCCCCC	15.72	25619855
893	Phosphorylation	AAFRTPATTASSPVT HHHCCCCCCCCCCCE	24.89	25619855
894	Phosphorylation	AFRTPATTASSPVTT HHCCCCCCCCCCCEE	27.01	25619855
896	Phosphorylation	RTPATTASSPVTTAQ CCCCCCCCCCCEECE	32.84	25619855
897	Phosphorylation	TPATTASSPVTTAQV CCCCCCCCCCEECEE	22.41	22942356
900	Phosphorylation	TTASSPVTTAQVHCL CCCCCCCEECEEEEE	21.57	25619855
901	Phosphorylation	TASSPVTTAQVHCLP CCCCCCEECEEEEEE	18.48	25619855
910	Phosphorylation	QVHCLPLSSSSTRQH EEEEEECCCCHHHHH	26.66	25619855
911	Phosphorylation	VHCLPLSSSSTRQHI EEEEECCCCHHHHHH	35.67	25619855
912	Phosphorylation	HCLPLSSSSTRQHID EEEECCCCHHHHHHH	32.14	25619855
913	Phosphorylation	CLPLSSSSTRQHIDE EEECCCCHHHHHHHH	29.56	25619855
914	Phosphorylation	LPLSSSSTRQHIDEL EECCCCHHHHHHHHH	35.97	25619855
924	Phosphorylation	HIDELRDSDSVCDSG HHHHHHHCCCCCCCC	25.92	25338131
926	Phosphorylation	DELRDSDSVCDSGVE HHHHHCCCCCCCCCH	28.70	25266776
930	Phosphorylation	DSDSVCDSGVETSFR HCCCCCCCCCHHCCE	39.34	30482847
934	Phosphorylation	VCDSGVETSFRKLSF CCCCCCHHCCEEEEC	30.66	25338131
935	Phosphorylation	CDSGVETSFRKLSFT CCCCCHHCCEEEECC	15.00	22633953
940	Phosphorylation	ETSFRKLSFTESLTG HHCCEEEECCCCCCC	32.91	27087446
942	Phosphorylation	SFRKLSFTESLTGDS CCEEEECCCCCCCCC	22.68	21082442
944	Phosphorylation	RKLSFTESLTGDSPL EEEECCCCCCCCCCC	28.33	21082442
946	Phosphorylation	LSFTESLTGDSPLLS EECCCCCCCCCCCCC	48.50	21082442
949	Phosphorylation	TESLTGDSPLLSLNK CCCCCCCCCCCCCCC	20.84	25619855
953	Phosphorylation	TGDSPLLSLNKMPHG CCCCCCCCCCCCCCC	37.26	25619855

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
240	S	Phosphorylation	Kinase	CHK1	O14757	PSP
246	S	Phosphorylation	Kinase	CHK1	O14757	PSP
326	S	Phosphorylation	Kinase	CHK1	O14757	PSP
326	S	Phosphorylation	Kinase	PKACA	P17612	PSP
335	S	Phosphorylation	Kinase	CHK1	O14757	PSP
335	S	Phosphorylation	Kinase	PKACA	P17612	PSP
335	S	Phosphorylation	Kinase	PKA	-	Uniprot
910	S	Phosphorylation	Kinase	GSK3-BETA	Q9WV60	Uniprot
930	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
935	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Btrc	Q3ULA2	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
59	C	S-nitrosylation	-
S-nitrosylation of Cys-59 affects DNA binding.
930	S	Phosphorylation	-
Phosphorylation at 'Ser-930' and 'Ser-935' are required for BTRC/BTRCP-mediated proteolysis.
935	S	Phosphorylation	-
Phosphorylation at 'Ser-930' and 'Ser-935' are required for BTRC/BTRCP-mediated proteolysis.

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 NFKB1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HDAC1_MOUSE	Hdac1	physical	11931769
REL_HUMAN	REL	genetic	12504005
NFKB2_MOUSE	Nfkb2	physical	20211142
RELB_MOUSE	Relb	physical	20211142
ZN276_MOUSE	Zfp276	physical	20211142
IKBZ_MOUSE	Nfkbiz	physical	20211142
GMEB2_MOUSE	Gmeb2	physical	20211142
HDAC6_MOUSE	Hdac6	physical	12372765
IKBA_MOUSE	Nfkbia	physical	21098220
M3K8_MOUSE	Map3k8	physical	18270204
FM1AA_MOUSE	Fem1a	physical	18270204
IKBA_MOUSE	Nfkbia	physical	16928772
M3K8_MOUSE	Map3k8	physical	16291755
NFKB1_MOUSE	Nfkb1	physical	23538752
TF65_MOUSE	Rela	physical	23538752

Drug and Disease Associations

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

Regulatory Network of NFKB1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry."; Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.; J. Proteome Res. 7:5314-5326(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, AND MASSSPECTROMETRY.	19367708 [Abstract]

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