AiPD: Autoinhibited Protein Database

Q04206

Gene name	RELA (NFKB3)
Protein name	Transcription factor p65
Names	Nuclear factor NF-kappa-B p65 subunit, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 3
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5970
EC number
Protein Class	NUCLEAR FACTOR NF-KAPPA-B PROTEIN (PTHR24169)

Descriptions

The inducible transcription factor NF-kB (nuclear factor kB) is responsible for regulating the expression of a wide variety of genes. The most abundant form of the protein is a heterodimer of p50 and p65 subunits, in which the p65 subunit (RELA) contains the transcriptional activation domain. Full-length RELA does not bind efficiently to DNA, but a shorter fragment lacking the C-terminal sequence binds to DNA with high affinity. Binding assay revealed that the C-terminal region interacts with the N-terminal region for the autoinhibition of N-terminal domain. The C-terminal region contains a CBP binding site and the binding of CBP to RELA enhances the transcriptional activity of RELA.

Autoinhibitory domains (AIDs)

Target domain	1-194 (N-terminal region)
Relief mechanism	Partner binding, PTM
Assay	Deletion assay, Mutagenesis experiment

AID

436-550 (C-terminal autoregulatory region containing a CBP-binding site)

Target domain

1-194 (N-terminal region)

Relief mechanism

Partner binding (CBP binding to RELA), PTM (Phosphorylation of Ser near the N-terminal region by PKA)

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

No accessory elements

References

Zhong H et al. (1998) "Phosphorylation of NF-kappa B p65 by PKA stimulates transcriptional activity by promoting a novel bivalent interaction with the coactivator CBP/p300", Molecular cell, 1, 661-71

Autoinhibited structure

Activated structure

89 structures for Q04206

Entry ID	Method	Resolution	Chain	Position	Source
1NFI	X-ray	270 A	A/C	20-320	PDB
2LSP	NMR	-	A	304-316	PDB
2O61	X-ray	280 A	A	20-291	PDB
3GUT	X-ray	359 A	A/C/E/G	20-291	PDB
3QXY	X-ray	209 A	P/Q	302-316	PDB
3RC0	X-ray	219 A	P/Q	302-316	PDB
4KV1	X-ray	150 A	C/D	308-314	PDB
4KV4	X-ray	200 A	B	308-314	PDB
5U4K	NMR	-	B	521-551	PDB
5URN	NMR	-	B	521-551	PDB
6NV2	X-ray	113 A	P	39-51	PDB
6QHL	X-ray	120 A	P	38-51	PDB
6QHM	X-ray	125 A	P	275-287	PDB
6YOW	X-ray	123 A	P	39-51	PDB
6YOX	X-ray	205 A	P	39-51	PDB
6YOY	X-ray	180 A	P	39-51	PDB
6YP2	X-ray	180 A	P	39-51	PDB
6YP3	X-ray	180 A	P	39-51	PDB
6YP8	X-ray	180 A	P	39-51	PDB
6YPL	X-ray	180 A	P	39-51	PDB
6YPY	X-ray	140 A	P	39-51	PDB
6YQ2	X-ray	140 A	P	39-51	PDB
7BI3	X-ray	120 A	P	39-51	PDB
7BIQ	X-ray	120 A	P	39-51	PDB
7BIW	X-ray	120 A	P	39-51	PDB
7BIY	X-ray	180 A	P	39-51	PDB
7BJB	X-ray	180 A	P	39-51	PDB
7BJF	X-ray	140 A	P	39-51	PDB
7BJL	X-ray	140 A	P	39-51	PDB
7BJW	X-ray	140 A	P	39-51	PDB
7BKH	X-ray	140 A	P	39-51	PDB
7LET	X-ray	240 A	C	294-315	PDB
7LEU	X-ray	282 A	B/C	294-315	PDB
7LF4	X-ray	285 A	D/E	294-315	PDB
7NJ9	X-ray	140 A	P	39-51	PDB
7NJB	X-ray	140 A	P	39-51	PDB
7NK3	X-ray	140 A	P	39-51	PDB
7NK5	X-ray	140 A	P	39-51	PDB
7NLA	X-ray	140 A	P	39-51	PDB
7NLE	X-ray	140 A	P	39-51	PDB
7NM1	X-ray	140 A	P	39-51	PDB
7NM3	X-ray	140 A	P	39-51	PDB
7NM9	X-ray	170 A	P	39-51	PDB
7NMH	X-ray	140 A	P	39-51	PDB
7NQP	X-ray	124 A	P	39-51	PDB
7NR7	X-ray	140 A	P	39-51	PDB
7NSV	X-ray	133 A	P	39-51	PDB
7NV4	X-ray	120 A	P	39-51	PDB
7NVI	X-ray	120 A	P	39-51	PDB
7NWS	X-ray	120 A	P	39-51	PDB
7NXS	X-ray	120 A	P	39-51	PDB
7NXT	X-ray	120 A	P	39-51	PDB
7NXW	X-ray	120 A	P	39-51	PDB
7NXY	X-ray	120 A	P	39-51	PDB
7NY4	X-ray	140 A	P	39-51	PDB
7NYE	X-ray	140 A	P	39-51	PDB
7NYF	X-ray	140 A	P	39-51	PDB
7NYG	X-ray	140 A	P	39-51	PDB
7NZ6	X-ray	140 A	P	39-51	PDB
7NZG	X-ray	140 A	P	39-51	PDB
7NZK	X-ray	140 A	P	39-51	PDB
7NZV	X-ray	140 A	P	39-51	PDB
7O34	X-ray	120 A	P	39-51	PDB
7O3A	X-ray	120 A	P	39-51	PDB
7O3F	X-ray	140 A	P	39-51	PDB
7O3P	X-ray	140 A	P	39-51	PDB
7O3Q	X-ray	180 A	P	39-51	PDB
7O3R	X-ray	180 A	P	39-51	PDB
7O3S	X-ray	200 A	P	39-51	PDB
7O57	X-ray	140 A	P	39-51	PDB
7O59	X-ray	120 A	P	39-51	PDB
7O5A	X-ray	180 A	P	39-51	PDB
7O5C	X-ray	180 A	P	39-51	PDB
7O5D	X-ray	180 A	P	39-51	PDB
7O5F	X-ray	180 A	P	39-51	PDB
7O5G	X-ray	180 A	P	39-51	PDB
7O5O	X-ray	180 A	P	39-51	PDB
7O5P	X-ray	180 A	P	39-51	PDB
7O5S	X-ray	180 A	P	39-51	PDB
7O5U	X-ray	180 A	P	39-51	PDB
7O5X	X-ray	180 A	P	39-51	PDB
7O6F	X-ray	200 A	P	39-51	PDB
7O6G	X-ray	180 A	P	39-51	PDB
7O6I	X-ray	180 A	P	39-51	PDB
7O6J	X-ray	140 A	P	39-51	PDB
7O6K	X-ray	140 A	P	39-51	PDB
7O6M	X-ray	140 A	P	39-51	PDB
7O6O	X-ray	140 A	P	39-51	PDB
AF-Q04206-F1	Predicted				AlphaFoldDB

358 variants for Q04206

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA279852 rs863223356 RCV000202330	110	I>T	Childhood-Onset Schizophrenia [ClinVar]	Yes	ClinGen ClinVar Ensembl dbSNP
rs750044010 CA6107009	4	L>V		No	ClinGen ExAC TOPMed
rs1402366956 CA381395187	6	P>S		No	ClinGen gnomAD
CA381395170 rs1169785805	8	I>M		No	ClinGen gnomAD
rs1462514055 CA381395167	9	F>V		No	ClinGen gnomAD
rs1263528129 CA381395161	10	P>A		No	ClinGen TOPMed
rs368784411 CA224011379	10	P>L		No	ClinGen ESP TOPMed gnomAD
CA381395159 rs1263528129	10	P>S		No	ClinGen TOPMed
rs1338619714 CA381395131	12	E>D		No	ClinGen gnomAD
CA381395119 rs1332337161	14	A>V		No	ClinGen gnomAD
rs1376292952 CA381395105	16	A>V		No	ClinGen gnomAD
rs1418277571 CA381395104	17	S>P		No	ClinGen gnomAD
CA381395087 rs1472798377	19	P>L		No	ClinGen gnomAD
CA381395090 rs1159476176	19	P>S		No	ClinGen gnomAD
CA6106985 rs765199827	20	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs1213950702 CA381395033	27	P>S		No	ClinGen gnomAD
rs753627793 CA6106983	28	K>Q		No	ClinGen ExAC gnomAD
rs1285811443 CA381394973	36	Y>H		No	ClinGen gnomAD
rs1268667021 CA381394949	39	E>Q		No	ClinGen TOPMed
rs1193259548 CA381394925	42	S>F		No	ClinGen gnomAD
CA6106979 rs764030082	45	S>N		No	ClinGen ExAC gnomAD
rs969818412 CA224011265	49	E>K		No	ClinGen gnomAD
CA381394877 rs1167688221	50	R>K		No	ClinGen gnomAD
rs770416604 CA6106977	51	S>R		No	ClinGen ExAC gnomAD
rs1565192440 COSM1744255 CA381394616	64	N>S	biliary_tract [Cosmic]	No	ClinGen cosmic curated Ensembl
CA6106949 rs368661961	65	G>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA6106947 rs779944761	69	P>S		No	ClinGen ExAC TOPMed gnomAD
CA381394549 rs1412466213	72	V>L		No	ClinGen gnomAD
CA224011109 rs151125290	73	R>C		No	ClinGen ESP TOPMed gnomAD
rs1438780274 CA381394539	73	R>H		No	ClinGen gnomAD
CA381394487 rs1178830994	78	T>N		No	ClinGen TOPMed gnomAD
rs1480907469 CA381394478	79	K>R		No	ClinGen TOPMed gnomAD
CA6106944 rs761767619	80	D>E		No	ClinGen ExAC TOPMed gnomAD
CA381394452 rs1282651820	81	P>R		No	ClinGen gnomAD
rs1484848625 CA381394456	81	P>S		No	ClinGen gnomAD
CA381394432 rs1353372476	83	H>Q		No	ClinGen gnomAD
rs752869747 CA6106942	84	R>Q		No	ClinGen ExAC gnomAD
rs1590939582 CA381394409	86	H>P		No	ClinGen Ensembl
CA224011083 rs1012952762	91	V>L		No	ClinGen TOPMed
rs1374686489 CA381394342	93	K>R		No	ClinGen gnomAD
rs11557248 CA224011078	96	R>L		No	ClinGen gnomAD
rs11557248 CA381394307	96	R>Q		No	ClinGen gnomAD
CA6106940 rs759715841	96	R>W		No	ClinGen ExAC TOPMed gnomAD
rs766963304 CA6106938	97	D>N		No	ClinGen ExAC TOPMed gnomAD
rs562262364 CA6106937	100	Y>C		No	ClinGen 1000Genomes ExAC gnomAD
CA381394270 rs1358445187	100	Y>H		No	ClinGen gnomAD
CA6106936 rs773613820	104	L>F		No	ClinGen ExAC gnomAD
CA381394226 rs773613820	104	L>V		No	ClinGen ExAC gnomAD
CA6106933 rs774014347	106	P>L		No	ClinGen ExAC TOPMed gnomAD
CA6106934 rs774014347	106	P>Q		No	ClinGen ExAC TOPMed gnomAD
rs774014347 CA381394202	106	P>R		No	ClinGen ExAC TOPMed gnomAD
rs748761373 CA381394188	108	R>C		No	ClinGen ExAC gnomAD
rs1488068046 CA381394185	108	R>H		No	ClinGen gnomAD
rs748761373 CA6106931	108	R>S		No	ClinGen ExAC gnomAD
CA6106930 rs779601305	110	I>M		No	ClinGen ExAC TOPMed gnomAD
rs769755404 CA6106929	111	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs749535863 CA6106904	123	K>R		No	ClinGen ExAC gnomAD
CA6106903 rs780140984	124	R>Q		No	ClinGen ExAC
CA381393578 rs1172744425	127	E>K		No	ClinGen gnomAD
rs1429314714 CA381393532	130	I>V		No	ClinGen gnomAD
rs750564559 CA6106901	133	R>H		No	ClinGen ExAC TOPMed gnomAD
CA6106900 rs767880564	135	Q>H		No	ClinGen ExAC gnomAD
rs757845338 CA6106899	136	T>A		No	ClinGen ExAC gnomAD
CA381393403 rs1254116157	138	N>I		No	ClinGen gnomAD
rs751905199 CA6106898	139	N>T		No	ClinGen ExAC gnomAD
rs1336819380 CA381393365	141	F>S		No	ClinGen gnomAD
rs1436789790 CA381393265	144	P>H		No	ClinGen gnomAD
rs1158346001 CA381393246	145	I>T		No	ClinGen gnomAD
rs140130811 CA224010176	145	I>V		No	ClinGen ESP TOPMed gnomAD
rs1255403640 CA381393228	146	E>G		No	ClinGen TOPMed
rs1469104216 CA381393210	147	E>G		No	ClinGen gnomAD
rs1590937041 CA381393202	148	Q>E		No	ClinGen Ensembl
CA381393192 rs1345639265	148	Q>R		No	ClinGen TOPMed
rs1365998197 CA381393178	149	R>C		No	ClinGen TOPMed gnomAD
CA6106876 rs761250712	149	R>H		No	ClinGen ExAC TOPMed gnomAD
CA381393172 rs761250712	149	R>L		No	ClinGen ExAC TOPMed gnomAD
CA381393085 rs1398971779	157	V>M		No	ClinGen gnomAD
rs375925395 CA6106871	158	R>Q		No	ClinGen ESP ExAC gnomAD
rs1457182302 CA381393010	164	T>S		No	ClinGen gnomAD
CA224010160 rs957917859	165	V>A		No	ClinGen TOPMed
CA6106868 rs774268451	166	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs568782744 CA6106869 COSM3810080	166	R>W	breast [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC gnomAD
CA381392942 rs1590936944	167	D>A		No	ClinGen Ensembl
CA6106867 rs769890889	167	D>H		No	ClinGen ExAC gnomAD
CA381392932 rs1416924926	168	P>A		No	ClinGen TOPMed gnomAD
CA381392924 rs1422039715	168	P>L		No	ClinGen TOPMed
rs2375676 CA224010138	169	S>A		No	ClinGen Ensembl
CA224010139 rs2375676	169	S>T		No	ClinGen Ensembl
rs746111744 CA6106866	171	R>S		No	ClinGen ExAC TOPMed gnomAD
rs746111744 CA381392875	171	R>S		No	ClinGen ExAC TOPMed gnomAD
rs1399250604 CA381392872	172	P>S		No	ClinGen gnomAD
CA381392850 rs1590936874	173	L>P		No	ClinGen Ensembl
CA381392839 COSM1561661 rs1159602684	174	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1461359004 CA381392838	174	R>H		No	ClinGen TOPMed gnomAD
CA6106863 rs747469170	176	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1301308246 CA381392803	176	P>S		No	ClinGen TOPMed
CA224010113 rs548164575	178	V>L		No	ClinGen Ensembl
CA381392713 rs1475365161	181	H>R		No	ClinGen gnomAD
rs1241103660 CA381392690	183	I>V		No	ClinGen TOPMed gnomAD
CA381391992 rs1393793185	189	P>A		No	ClinGen TOPMed
rs1308599130 CA381391945	193	E>K		No	ClinGen TOPMed gnomAD
rs1308599130 CA381391943	193	E>Q		No	ClinGen TOPMed gnomAD
CA224009282 rs11606329	197	C>R		No	ClinGen Ensembl
RCV001092067 rs1326268854	198	R>*		No	ClinVar dbSNP
CA6106838 rs145138143	199	V>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs755895938 CA6106836	201	R>Q		No	ClinGen ExAC gnomAD
rs1194237734 CA381391748	207	L>V		No	ClinGen TOPMed gnomAD
CA381391631 rs1439792199	216	C>G		No	ClinGen gnomAD
rs1439805810 CA381391453	226	V>M		No	ClinGen TOPMed
CA381391436 rs1314465477	227	Y>C		No	ClinGen TOPMed
CA6106817 rs368076224	228	F>V		No	ClinGen ESP ExAC gnomAD
rs756811835 CA6106816	229	T>M		No	ClinGen ExAC TOPMed gnomAD
rs1032578811 CA224009025	230	G>R		No	ClinGen TOPMed
rs764063700 CA6106814	231	P>L		No	ClinGen ExAC gnomAD
rs751077868 CA6106815	231	P>T		No	ClinGen ExAC TOPMed gnomAD
rs1343398488 CA381391366	232	G>A		No	ClinGen gnomAD
CA381391325 rs1363382539	234	E>G		No	ClinGen TOPMed
rs1856484601 RCV001055525	236	R>*		No	ClinVar dbSNP
CA6106811 rs765033710	236	R>Q		No	ClinGen ExAC gnomAD
CA224008981 rs926385426	242	A>G		No	ClinGen Ensembl
rs1474354942 CA381391151	244	V>G		No	ClinGen gnomAD
CA381391120 RCV000754618 rs1565190345	246	R>*		No	ClinGen ClinVar Ensembl dbSNP
CA6106806 rs774359103	250	I>T		No	ClinGen ExAC gnomAD
CA6106805 rs769190277	253	R>P		No	ClinGen ExAC TOPMed gnomAD
rs769190277 CA381390994	253	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1590935322 CA381390988	254	T>P		No	ClinGen Ensembl
CA6106802 rs770313905	258	A>T		No	ClinGen ExAC TOPMed gnomAD
rs745468574 CA381390914	259	D>A		No	ClinGen ExAC gnomAD
CA6106801 rs745468574	259	D>G		No	ClinGen ExAC gnomAD
CA6106800 rs780968051	260	P>L		No	ClinGen ExAC gnomAD
CA381390888 rs1381464457	261	S>R		No	ClinGen TOPMed gnomAD
CA381390887 rs1381464457	261	S>R		No	ClinGen TOPMed gnomAD
rs1359669742 CA381390871	263	Q>P		No	ClinGen gnomAD
CA6106799 rs770531864	264	A>T		No	ClinGen ExAC gnomAD
rs746526485 CA6106798	264	A>V		No	ClinGen ExAC TOPMed gnomAD
CA381390851 rs1393561951	265	P>A		No	ClinGen gnomAD
CA6106796 rs758298850	266	V>L		No	ClinGen ExAC TOPMed gnomAD
rs758298850 CA6106797	266	V>M		No	ClinGen ExAC TOPMed gnomAD
CA381390828 rs1420318686 COSM1223509	267	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1420318686 CA381390830	267	R>G		No	ClinGen TOPMed gnomAD
CA381390827 rs1165809846	267	R>H		No	ClinGen TOPMed gnomAD
rs866716163 CA224008912	269	S>F		No	ClinGen Ensembl
CA6106794 rs778642588	273	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA381390754 rs1417895912	273	R>W		No	ClinGen gnomAD
CA13419741 rs1252847592	274	R>W		No	ClinGen gnomAD
rs149254469 CA6106789	278	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6106790 rs761995751	278	R>W		No	ClinGen ExAC gnomAD
rs763514130 CA6106788	280	L>H		No	ClinGen ExAC TOPMed gnomAD
CA6106787 rs763514130	280	L>R		No	ClinGen ExAC TOPMed gnomAD
rs776162117 CA6106786	281	S>G		No	ClinGen ExAC gnomAD
rs1370194169 CA381390665	281	S>T		No	ClinGen gnomAD
CA381390603 rs1323750358	285	E>D		No	ClinGen gnomAD
rs929817187 CA224008883	285	E>K		No	ClinGen TOPMed
CA381390528 rs1237054467	291	D>A		No	ClinGen TOPMed
rs61759893 CA6106785	291	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6106784 rs759945679	292	T>A		No	ClinGen ExAC gnomAD
rs1172994773 CA381390513	293	D>N		No	ClinGen gnomAD
rs374605673 CA381389858	294	D>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs374605673 CA6106756	294	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
CA6106755 rs749182844	295	R>C		No	ClinGen ExAC gnomAD
CA6106754 rs150601443	295	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA381389832 rs1565189032	296	H>L		No	ClinGen Ensembl
CA6106752 COSM930488 rs142033286	297	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ESP ExAC TOPMed gnomAD
rs755884402 CA6106753	297	R>W		No	ClinGen ExAC TOPMed gnomAD
rs377717312 CA224006623	301	K>T		No	ClinGen ESP
CA224006622 rs368638080	302	R>C		No	ClinGen Ensembl
CA381389744 rs1565188999	303	K>*		No	ClinGen Ensembl
rs1254886027 CA381389731	304	R>K		No	ClinGen gnomAD
rs138034120 CA6106748	306	Y>C		No	ClinGen ESP ExAC TOPMed gnomAD
CA381389676 rs1260736909	308	T>N		No	ClinGen TOPMed gnomAD
rs755476416 CA6106747	312	I>T		No	ClinGen ExAC gnomAD
CA6106746 rs12721572	313	M>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1191351823 CA381389610	314	K>E		No	ClinGen TOPMed
CA381389590 rs1334453316	316	S>G		No	ClinGen gnomAD
rs1291631162 CA381389577	317	P>T		No	ClinGen gnomAD
CA6106744 rs760929899	318	F>S		No	ClinGen ExAC gnomAD
CA381389551 rs1466629537	319	S>N		No	ClinGen TOPMed
rs767155175 CA6106742	320	G>R		No	ClinGen ExAC TOPMed gnomAD
CA381389541 rs767155175	320	G>R		No	ClinGen ExAC TOPMed gnomAD
CA381389469 rs1196982543	321	P>L		No	ClinGen gnomAD
rs999556978 CA224006460	321	P>T		No	ClinGen Ensembl
CA6106716 rs770882250	322	T>A		No	ClinGen ExAC gnomAD
CA6106715 rs375929528	322	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs749325969 CA6106712	323	D>E		No	ClinGen ExAC gnomAD
rs138794116 CA6106713	323	D>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs780241287 CA6106711	324	P>L		No	ClinGen ExAC gnomAD
rs762060621 CA381389408	325	R>L		No	ClinGen ExAC TOPMed gnomAD
rs762060621 CA6106710	325	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1161370675 CA381389414	325	R>W		No	ClinGen TOPMed
rs750957760 CA6106709	326	P>A		No	ClinGen ExAC TOPMed gnomAD
CA381389406 rs750957760	326	P>T		No	ClinGen ExAC TOPMed gnomAD
CA381389377 rs1432792806	327	P>L		No	ClinGen TOPMed gnomAD
CA381389343 rs1193014025	329	R>G		No	ClinGen gnomAD
rs1282218073 CA381389336	329	R>Q		No	ClinGen TOPMed
COSM1223508 CA381389330 rs1478374154	330	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1232341468 CA381389322 COSM930486	330	R>H	endometrium [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1180352560 CA381389311	331	I>V		No	ClinGen TOPMed gnomAD
CA381389256 rs1484150455	334	P>S		No	ClinGen TOPMed gnomAD
CA6106707 rs757592217	335	S>C		No	ClinGen ExAC gnomAD
CA381389234 rs757592217	335	S>F		No	ClinGen ExAC gnomAD
rs751960651 CA6106706	336	R>C		No	ClinGen ExAC TOPMed gnomAD
rs1246637051 CA381389221	336	R>H		No	ClinGen gnomAD
CA381389212 rs1384344058	337	S>C		No	ClinGen TOPMed gnomAD
rs1384344058 CA381389214	337	S>G		No	ClinGen TOPMed gnomAD
rs1219333291 CA381389208	337	S>I		No	ClinGen TOPMed gnomAD
rs1219333291 CA381389211	337	S>N		No	ClinGen TOPMed gnomAD
rs762722479 CA6106704	339	A>V		No	ClinGen ExAC gnomAD
rs1411351659 CA381389157	340	S>P		No	ClinGen gnomAD
CA381389135 rs1312067163	341	V>I		No	ClinGen TOPMed gnomAD
rs371744052 CA6106701	343	K>N		No	ClinGen ESP ExAC gnomAD
CA6106702 rs764810980	343	K>R		No	ClinGen ExAC gnomAD
CA6106699 rs771045696	344	P>A		No	ClinGen ExAC gnomAD
CA224005990 rs997637338	347	Q>H		No	ClinGen TOPMed gnomAD
CA381388428 rs1196154107	348	P>S		No	ClinGen gnomAD
rs1267397579 CA381388399	350	P>T		No	ClinGen gnomAD
rs1481868107 CA381388369	352	T>A		No	ClinGen gnomAD
CA6106650 rs774079396	352	T>M		No	ClinGen ExAC TOPMed gnomAD
CA381388329 rs1347094026	354	S>F		No	ClinGen gnomAD
rs1235283948 CA381388311	356	S>G		No	ClinGen gnomAD
rs759766423 CA6106648	357	T>I		No	ClinGen ExAC gnomAD
rs1302055993 CA381388274	360	Y>C		No	ClinGen gnomAD
rs1310254235 CA381388252	361	D>E		No	ClinGen gnomAD
rs1348785979 CA381388266	361	D>N		No	ClinGen gnomAD
rs1410768522 CA381388212	364	P>L		No	ClinGen gnomAD
rs1402154056 CA381388205	365	T>I		No	ClinGen TOPMed gnomAD
CA381388184 rs1171374836	366	M>T		No	ClinGen gnomAD
rs12721575 CA224005933	368	F>L		No	ClinGen Ensembl
rs12721575 CA224005931	368	F>L		No	ClinGen Ensembl
rs1468006702 CA381388140	369	P>L		No	ClinGen gnomAD
rs771032052 CA6106646	370	S>A		No	ClinGen ExAC gnomAD
CA6106645 rs747467496	371	G>E		No	ClinGen ExAC TOPMed gnomAD
CA381388124 rs1157690704	371	G>R		No	ClinGen gnomAD
CA6106644 rs773748330	373	I>M		No	ClinGen ExAC gnomAD
rs772497103 CA6106643	375	Q>E		No	ClinGen ExAC
rs1485245702 CA381388049	376	A>D		No	ClinGen gnomAD
rs748545913 CA6106642	377	S>L		No	ClinGen ExAC gnomAD
rs1483533790 CA381388033	378	A>T		No	ClinGen gnomAD
CA6106640 rs754622774	380	A>D		No	ClinGen ExAC
rs1290399583 CA381387994	381	P>L		No	ClinGen gnomAD
CA381387957 rs1332591254	384	P>R		No	ClinGen gnomAD
rs1405172010 CA381387961	384	P>S		No	ClinGen TOPMed
rs755660407 CA6106637	385	Q>H		No	ClinGen ExAC gnomAD
rs779659272 CA6106638	385	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs1413493308 CA381387901	388	P>L		No	ClinGen TOPMed gnomAD
rs1283746730 CA381387907	388	P>S		No	ClinGen gnomAD
rs1366570652 CA381387878	390	A>V		No	ClinGen TOPMed gnomAD
rs1346474543 CA381387872	391	P>S		No	ClinGen TOPMed
rs1189280546 CA381387866	392	A>T		No	ClinGen gnomAD
CA381387852 rs1260899484	393	P>S		No	ClinGen gnomAD
rs1208220510 CA381387835	395	P>R		No	ClinGen gnomAD
rs1463629801 CA381387830	396	A>T		No	ClinGen gnomAD
CA381387811 rs1209657498	397	P>L		No	ClinGen gnomAD
rs749937116 CA6106636	397	P>S		No	ClinGen ExAC gnomAD
rs1355903094 CA381387808	398	A>S		No	ClinGen gnomAD
CA381387803 rs1282808983	398	A>V		No	ClinGen gnomAD
CA381387791 rs1341628692	399	M>I		No	ClinGen gnomAD
rs560604471 CA381387782	400	V>I		No	ClinGen gnomAD
rs560604471 CA224005827	400	V>L		No	ClinGen gnomAD
CA381387752 rs1263055359	403	L>V		No	ClinGen TOPMed
rs1390278423 CA381387743	404	A>P		No	ClinGen TOPMed gnomAD
CA381387744 rs1390278423	404	A>T		No	ClinGen TOPMed gnomAD
rs781182014 CA6106634	406	A>T		No	ClinGen ExAC gnomAD
rs1590931358 CA381387696	407	P>L		No	ClinGen Ensembl
CA6106632 rs751310615	408	A>G		No	ClinGen ExAC gnomAD
CA381387677 rs1210908822	409	P>L		No	ClinGen TOPMed
CA381387611 rs1451237617	415	P>L		No	ClinGen TOPMed gnomAD
CA381387620 rs1186645003	415	P>S		No	ClinGen TOPMed gnomAD
CA6106628 rs754083713	418	P>S		No	ClinGen ExAC gnomAD
rs375768034 CA381387551	420	A>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA6106626 rs375768034	420	A>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1287948980 CA381387546	421	V>L		No	ClinGen TOPMed gnomAD
rs1012204019 CA224005761	422	A>V		No	ClinGen TOPMed
rs1211831291 CA381387505	426	P>L		No	ClinGen gnomAD
rs773234750 CA6106624	427	K>Q		No	ClinGen ExAC gnomAD
CA381387481 rs1590931266	429	T>A		No	ClinGen Ensembl
rs1297711254 CA381387464	430	Q>R		No	ClinGen TOPMed gnomAD
rs55766259 CA224005732	431	A>G		No	ClinGen Ensembl
rs774718207 CA6106622	433	E>K		No	ClinGen ExAC TOPMed gnomAD
CA381387414 rs1329027216	434	G>A		No	ClinGen gnomAD
CA6106621 rs555785944	435	T>M		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6106619 rs749716796	437	S>*		No	ClinGen ExAC gnomAD
CA381387370 rs1431554156	438	E>G		No	ClinGen gnomAD
CA381387356 rs1390663138	439	A>D		No	ClinGen gnomAD
rs1390663138 CA381387354	439	A>V		No	ClinGen gnomAD
CA381387333 rs1168603207	442	Q>*		No	ClinGen gnomAD
rs11608099 CA224005727	442	Q>H		No	ClinGen Ensembl
CA6106617 rs1477765782	442	Q>L		No	ClinGen TOPMed gnomAD
CA381387330 rs1477765782	442	Q>P		No	ClinGen TOPMed gnomAD
rs1490573963 CA381387309	444	Q>R		No	ClinGen gnomAD
rs1485728798 CA381387277	446	D>E		No	ClinGen TOPMed
CA381387278 rs1430719920	446	D>V		No	ClinGen gnomAD
rs769633553 CA381387263	447	D>E		No	ClinGen ExAC TOPMed gnomAD
rs780580304 CA6106613	449	D>E		No	ClinGen ExAC TOPMed gnomAD
CA381387246 rs1344961447	449	D>H		No	ClinGen gnomAD
rs1219124903 CA381387207	452	A>V		No	ClinGen gnomAD
rs757149780 CA6106611	455	G>V		No	ClinGen ExAC gnomAD
rs758168856 CA6106608	458	T>I		No	ClinGen ExAC TOPMed gnomAD
rs758168856 CA6106609	458	T>R		No	ClinGen ExAC TOPMed gnomAD
rs367873849 CA6106607	460	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1411388720 CA381387088	462	V>M		No	ClinGen TOPMed gnomAD
CA381387067 rs1333488473	463	F>L		No	ClinGen gnomAD
rs766584902 CA6106606	463	F>Y		No	ClinGen ExAC gnomAD
CA6106605 rs760866901	464	T>A		No	ClinGen ExAC gnomAD
CA381387024 rs1174324125	467	A>V		No	ClinGen gnomAD
CA6106600 rs769322382	470	D>H		No	ClinGen ExAC TOPMed gnomAD
CA381386972 rs1366985822	471	N>S		No	ClinGen TOPMed
CA6106598 rs535576789	473	E>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1177462012 CA381386950	473	E>K		No	ClinGen gnomAD
rs769429371 CA6106597	475	Q>E		No	ClinGen ExAC gnomAD
rs1393696800 CA381386915	476	Q>H		No	ClinGen TOPMed
CA6106596 rs745510018	481	G>C		No	ClinGen ExAC TOPMed gnomAD
CA381386874 rs1267463921	482	I>V		No	ClinGen TOPMed
CA6106595 rs374751242	485	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
CA6106594 rs566890727	486	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA6106592 rs777658303	487	H>P		No	ClinGen ExAC gnomAD
rs546654982 CA224005622	487	H>Q		No	ClinGen 1000Genomes gnomAD
rs1283377121 CA381386754	492	M>L		No	ClinGen TOPMed gnomAD
rs747928226 CA6106590	493	L>M		No	ClinGen ExAC gnomAD
CA6106588 rs756297857	495	E>D		No	ClinGen ExAC gnomAD
rs778695678 CA6106589	495	E>G		No	ClinGen ExAC TOPMed gnomAD
rs1387957052 CA381386666	499	A>S		No	ClinGen TOPMed gnomAD
CA381386660 rs1157278470	500	I>V		No	ClinGen gnomAD
CA6106586 rs767826580	502	R>C		No	ClinGen ExAC gnomAD
rs1181568528 CA381386640	502	R>H		No	ClinGen gnomAD
rs1239685921 CA381386613	505	T>S		No	ClinGen gnomAD
CA381386606 rs1565187728	506	G>A		No	ClinGen Ensembl
CA6106584 rs751753627	506	G>R		No	ClinGen ExAC TOPMed gnomAD
rs540158560 CA6106583	507	A>V		No	ClinGen 1000Genomes ExAC gnomAD
rs1363246020 CA381386585	509	R>S		No	ClinGen TOPMed
CA381386570 rs1463059248	512	D>N		No	ClinGen TOPMed
rs1463059248 CA381386571	512	D>Y		No	ClinGen TOPMed
CA381386559 rs1381286744	513	P>L		No	ClinGen gnomAD
CA381386561 rs1381286744	513	P>Q		No	ClinGen gnomAD
rs200767506 CA381386562	513	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs200767506 CA6106580	513	P>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs369008511 CA224005573	514	A>G		No	ClinGen ESP TOPMed
rs1590930882 CA381386539	517	P>T		No	ClinGen Ensembl
rs1364620549 CA381386516	519	G>A		No	ClinGen gnomAD
CA6106577 rs776126630	520	A>T		No	ClinGen ExAC gnomAD
rs1345948863 CA381386493	521	P>L		No	ClinGen gnomAD
rs746519095 CA6106575	525	N>S		No	ClinGen ExAC TOPMed gnomAD
CA6106574 rs201037601	528	L>F		No	ClinGen ExAC TOPMed gnomAD
CA6106573 rs201037601	528	L>I		No	ClinGen ExAC TOPMed gnomAD
rs1184817070 CA381386411	529	S>P		No	ClinGen gnomAD
rs778642669 CA6106571	530	G>V		No	ClinGen ExAC gnomAD
rs754755213 CA6106570	532	E>D		No	ClinGen ExAC TOPMed gnomAD
CA381386352 rs1189873448	532	E>G		No	ClinGen gnomAD
CA224005537 rs767319473	533	D>E		No	ClinGen TOPMed gnomAD
CA381386323 rs767319473	533	D>E		No	ClinGen TOPMed gnomAD
rs1382122315 CA381386274	537	I>V		No	ClinGen TOPMed gnomAD
rs199846198 CA6106568	538	A>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs754554427 CA224005517	540	M>T		No	ClinGen Ensembl
rs375525158 CA6106565	540	M>V		No	ClinGen ESP ExAC gnomAD
CA381386156 rs1227655115	542	F>L		No	ClinGen gnomAD
rs758932077 CA6106563	544	A>T		No	ClinGen ExAC gnomAD
CA224005501 rs372036028	546	L>M		No	ClinGen ESP
rs951877648 CA224005490	548	Q>H		No	ClinGen TOPMed gnomAD
rs759788260 CA6106560	550	S>T		No	ClinGen ExAC gnomAD

2 associated diseases with Q04206

[MIM: 618287]: Mucocutaneous ulceration, chronic (CMCU)

An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections. {ECO:0000269|PubMed:28600438}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal dominant, mucocutaneous disease characterized by chronic mucosal lesions, in absence of recurrent infections. {ECO:0000269|PubMed:28600438}. Note=The disease may be caused by variants affecting the gene represented in this entry.

6 regional properties for Q04206

Type	Name	Position	InterPro Accession
domain	IPT domain	193 - 289	IPR002909
domain	Rel homology domain, DNA-binding domain	16 - 190	IPR011539
conserved_site	Rel homology domain, conserved site	34 - 40	IPR030492
domain	Transcription factor p65, RHD domain, N-terminal	19 - 187	IPR030495
domain	Rel homology dimerisation domain	195 - 291	IPR032397
domain	NFkappaB IPT domain	194 - 290	IPR033926

Functions

		Description
EC Number
Subcellular Localization	Nucleus Cytoplasm	Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) (PubMed:1493333) Colocalized with DDX1 in the nucleus upon TNF-alpha induction (PubMed:19058135) Colocalizes with GFI1 in the nucleus after LPS stimulation (PubMed:20547752) Translocation to the nucleus is impaired in L monocytogenes infection (PubMed:20855622)
PANTHER Family	PTHR24169	NUCLEAR FACTOR NF-KAPPA-B PROTEIN
PANTHER Subfamily	PTHR24169:SF1	TRANSCRIPTION FACTOR P65
PANTHER Protein Class	DNA-binding transcription factor Rel homology transcription factor immunoglobulin fold transcription factor
PANTHER Pathway Category	Inflammation mediated by chemokine and cytokine signaling pathway NFkappaB Gonadotropin-releasing hormone receptor pathway p65 Toll receptor signaling pathway NFkappaB Apoptosis signaling pathway NFkappaB

9 GO annotations of cellular component

Name	Definition
chromatin	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
glutamatergic synapse	A synapse that uses glutamate as a neurotransmitter.
NF-kappaB complex	A protein complex that consists of a homo- or heterodimer of members of a family of structurally related proteins that contain a conserved N-terminal region called the Rel homology domain (RHD). In the nucleus, NF-kappaB complexes act as transcription factors. In unstimulated cells, NF-kappaB dimers are sequestered in the cytoplasm by IkappaB monomers; signals that induce NF-kappaB activity cause degradation of IkappaB, allowing NF-kappaB dimers to translocate to the nucleus and induce gene expression.
NF-kappaB p50/p65 complex	A heterodimer of NF-kappa B p50 and p65 subunits.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
transcription regulator complex	A protein complex that is capable of associating with DNA by direct binding, or via other DNA-binding proteins or complexes, and regulating transcription.

26 GO annotations of molecular function

Name	Definition
actinin binding	Binding to actinin, any member of a family of proteins that crosslink F-actin.
ankyrin repeat binding	Binding to an ankyrin repeat of a protein. Ankyrin repeats are tandemly repeated modules of about 33 amino acids; each repeat folds into a helix-loop-helix structure with a beta-hairpin/loop region projecting out from the helices at a 90-degree angle, and repeats stack to form an L-shaped structure.
chromatin binding	Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
chromatin DNA binding	Binding to DNA that is assembled into chromatin.
DNA binding	Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
DNA-binding transcription activator activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.
DNA-binding transcription factor activity	A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.
DNA-binding transcription factor activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.
DNA-binding transcription factor binding	Binding to a DNA-binding transcription factor, a protein that interacts with a specific DNA sequence (sometimes referred to as a motif) within the regulatory region of a gene to modulate transcription.
DNA-binding transcription repressor activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that represses or decreases the transcription of specific gene sets transcribed by RNA polymerase II.
enzyme binding	Binding to an enzyme, a protein with catalytic activity.
general transcription initiation factor binding	Binding to a general transcription initiation factor, a protein that contributes to transcription start site selection and transcription initiation.
histone deacetylase binding	Binding to histone deacetylase.
identical protein binding	Binding to an identical protein or proteins.
NF-kappaB binding	Binding to NF-kappaB, a transcription factor for eukaryotic RNA polymerase II promoters.
peptide binding	Binding to a peptide, an organic compound comprising two or more amino acids linked by peptide bonds.
phosphate ion binding	Binding to a phosphate ion.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein N-terminus binding	Binding to a protein N-terminus, the end of any peptide chain at which the 2-amino (or 2-imino) function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
RNA polymerase II core promoter sequence-specific DNA binding	Binding to a DNA sequence that is part of the core promoter of a RNA polymerase II-transcribed gene.
RNA polymerase II transcription regulatory region sequence-specific DNA binding	Binding to a specific sequence of DNA that is part of a regulatory region that controls the transcription of a gene or cistron by RNA polymerase II.
transcription cis-regulatory region binding	Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon.
transcription coactivator binding	Binding to a transcription coactivator, a protein involved in positive regulation of transcription via protein-protein interactions with transcription factors and other proteins that positively regulate transcription. Transcription coactivators do not bind DNA directly, but rather mediate protein-protein interactions between activating transcription factors and the basal transcription machinery.
ubiquitin protein ligase binding	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

62 GO annotations of biological process

Name	Definition
animal organ morphogenesis	Morphogenesis of an animal organ. An organ is defined as a tissue or set of tissues that work together to perform a specific function or functions. Morphogenesis is the process in which anatomical structures are generated and organized. Organs are commonly observed as visibly distinct structures, but may also exist as loosely associated clusters of cells that work together to perform a specific function or functions.
cellular defense response	A defense response that is mediated by cells.
cellular response to angiotensin	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an angiotensin stimulus. Angiotensin is any of three physiologically active peptides (angiotensin II, III, or IV) processed from angiotensinogen.
cellular response to hepatocyte growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hepatocyte growth factor stimulus.
cellular response to hydrogen peroxide	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
cellular response to interleukin-1	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
cellular response to interleukin-6	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-6 stimulus.
cellular response to lipopolysaccharide	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria.
cellular response to lipoteichoic acid	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipoteichoic acid stimulus; lipoteichoic acid is a major component of the cell wall of gram-positive bacteria and typically consists of a chain of glycerol-phosphate repeating units linked to a glycolipid anchor.
cellular response to nicotine	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nicotine stimulus.
cellular response to peptidoglycan	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptidoglycan stimulus. Peptidoglycan is a bacterial cell wall macromolecule.
cellular response to tumor necrosis factor	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a tumor necrosis factor stimulus.
cellular response to vascular endothelial growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vascular endothelial growth factor stimulus.
chromatin organization	The assembly or remodeling of chromatin composed of DNA complexed with histones, other associated proteins, and sometimes RNA.
cytokine-mediated signaling pathway	The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
defense response to virus	Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
hair follicle development	The process whose specific outcome is the progression of the hair follicle over time, from its formation to the mature structure. A hair follicle is a tube-like opening in the epidermis where the hair shaft develops and into which the sebaceous glands open.
I-kappaB kinase/NF-kappaB signaling	The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription.
inflammatory response	The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
innate immune response	Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
interleukin-1-mediated signaling pathway	The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
liver development	The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes.
negative regulation of apoptotic process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
negative regulation of extrinsic apoptotic signaling pathway	Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway.
negative regulation of NIK/NF-kappaB signaling	Any process that stops, prevents or reduces the frequency, rate or extent of NIK/NF-kappaB signaling.
negative regulation of pri-miRNA transcription by RNA polymerase II	Any process that stops, prevents or reduces the frequency, rate or extent of microRNA (miRNA) gene transcription.
negative regulation of protein catabolic process	Any process that stops, prevents or reduces the frequency, rate or extent of protein catabolic process.
negative regulation of protein sumoylation	Any process that stops, prevents, or reduces the frequency, rate or extent of the addition of SUMO groups to a protein.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
negative regulation of transcription, DNA-templated	Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
neuropeptide signaling pathway	A G protein-coupled receptor signaling pathway initiated by a neuropeptide binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process.
NIK/NF-kappaB signaling	The process in which a signal is passed on to downstream components within the cell through the NIK-dependent processing and activation of NF-KappaB. Begins with activation of the NF-KappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-Kappa B2 protein (p100) leading to p100 processing and release of an active NF-KappaB (p52).
nucleotide-binding oligomerization domain containing 2 signaling pathway	The series of molecular signals initiated by the binding of a ligand (such as a bacterial peptidoglycan) to a cytoplasmic nucleotide-binding oligomerization domain containing 2 (NOD2) protein receptor, and ending with regulation of a downstream cellular process.
positive regulation of amyloid-beta formation	Any process that activates or increases the frequency, rate or extent of amyloid-beta formation.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of I-kappaB kinase/NF-kappaB signaling	Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling.
positive regulation of interleukin-12 production	Any process that activates or increases the frequency, rate, or extent of interleukin-12 production.
positive regulation of interleukin-8 production	Any process that activates or increases the frequency, rate, or extent of interleukin-8 production.
positive regulation of leukocyte adhesion to vascular endothelial cell	Any process that activates or increases the frequency, rate or extent of leukocyte adhesion to vascular endothelial cell.
positive regulation of miRNA metabolic process	Any process that activates or increases the frequency, rate or extent of miRNA metabolic process.
positive regulation of NF-kappaB transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB.
positive regulation of NIK/NF-kappaB signaling	Any process that activates or increases the frequency, rate or extent of NIK/NF-kappaB signaling.
positive regulation of pri-miRNA transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of microRNA (miRNA) gene transcription.
positive regulation of T cell receptor signaling pathway	Any process that activates or increases the frequency, rate or extent of signaling pathways initiated by the cross-linking of an antigen receptor on a T cell.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	Any positive regulation of transcription from RNA polymerase II promoter that is involved in cellular response to chemical stimulus.
positive regulation of transcription, DNA-templated	Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription.
postsynapse to nucleus signaling pathway	The series of molecular signals that conveys information from the postsynapse to the nucleus via cytoskeletal transport of a protein from a postsynapse to the component to the nucleus where it affects biochemical processes that occur in the nucleus (e.g DNA transcription, mRNA splicing, or DNA/histone modifications).
regulation of DNA-templated transcription in response to stress	Modulation of the frequency, rate or extent of transcription from a DNA template as a result of a stimulus indicating the organism is under stress. The stress is usually, but not necessarily, exogenous (e.g. temperature, humidity, ionizing radiation).
regulation of inflammatory response	Any process that modulates the frequency, rate or extent of the inflammatory response, the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents.
regulation of NIK/NF-kappaB signaling	Any process that modulates the frequency, rate or extent of NIK/NF-kappaB signaling.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
regulation of transcription, DNA-templated	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
response to cytokine	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus.
response to interleukin-1	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus.
response to muramyl dipeptide	Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a muramyl dipeptide stimulus. Muramyl dipeptide is derived from peptidoglycan.
response to muscle stretch	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a myofibril being extended beyond its slack length.
response to organic substance	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic substance stimulus.
response to UV-B	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a UV-B radiation stimulus. UV-B radiation (UV-B light) spans the wavelengths 280 to 315 nm.
transcription, DNA-templated	The synthesis of an RNA transcript from a DNA template.
tumor necrosis factor-mediated signaling pathway	The series of molecular signals initiated by tumor necrosis factor binding to its receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription.

6 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q94527	Rel	Nuclear factor NF-kappa-B p110 subunit	Drosophila melanogaster (Fruit fly)	EV
Q00653	NFKB2	Nuclear factor NF-kappa-B p100 subunit	Homo sapiens (Human)	SS
P19838	NFKB1	Nuclear factor NF-kappa-B p105 subunit	Homo sapiens (Human)	SS
Q04207	Rela	Transcription factor p65	Mus musculus (Mouse)	SS
Q9WTK5	Nfkb2	Nuclear factor NF-kappa-B p100 subunit [Cleaved into: Nuclear factor NF-kappa-B p52 subunit]	Mus musculus (Mouse)	EV
P25799	Nfkb1	Nuclear factor NF-kappa-B p105 subunit [Cleaved into: Nuclear factor NF-kappa-B p50 subunit]	Mus musculus (Mouse)	EV

10	20	30	40	50	60
MDELFPLIFP	AEPAQASGPY	VEIIEQPKQR	GMRFRYKCEG	RSAGSIPGER	STDTTKTHPT
70	80	90	100	110	120
IKINGYTGPG	TVRISLVTKD	PPHRPHPHEL	VGKDCRDGFY	EAELCPDRCI	HSFQNLGIQC
130	140	150	160	170	180
VKKRDLEQAI	SQRIQTNNNP	FQVPIEEQRG	DYDLNAVRLC	FQVTVRDPSG	RPLRLPPVLS
190	200	210	220	230	240
HPIFDNRAPN	TAELKICRVN	RNSGSCLGGD	EIFLLCDKVQ	KEDIEVYFTG	PGWEARGSFS
250	260	270	280	290	300
QADVHRQVAI	VFRTPPYADP	SLQAPVRVSM	QLRRPSDREL	SEPMEFQYLP	DTDDRHRIEE
310	320	330	340	350	360
KRKRTYETFK	SIMKKSPFSG	PTDPRPPPRR	IAVPSRSSAS	VPKPAPQPYP	FTSSLSTINY
370	380	390	400	410	420
DEFPTMVFPS	GQISQASALA	PAPPQVLPQA	PAPAPAPAMV	SALAQAPAPV	PVLAPGPPQA
430	440	450	460	470	480
VAPPAPKPTQ	AGEGTLSEAL	LQLQFDDEDL	GALLGNSTDP	AVFTDLASVD	NSEFQQLLNQ
490	500	510	520	530	540
GIPVAPHTTE	PMLMEYPEAI	TRLVTGAQRP	PDPAPAPLGA	PGLPNGLLSG	DEDFSSIADM
550
DFSALLSQIS	S