AiPD: Autoinhibited Protein Database

Q14653

Gene name	IRF3
Protein name	Interferon regulatory factor 3
Names	IRF-3
Species	Homo sapiens (Human)
KEGG Pathway	hsa:3661
EC number
Protein Class	INTERFERON REGULATORY FACTOR (PTHR11949)

Descriptions

IRF3 is a key transcriptional regulator of type I interferon (IFN)-dependent immune responses and is present in an inactive cytoplasmic form. The C-terminal domain of IRF-3 residues participates in the autoinhibition of IRF-3 activity via an intramolecular association with the N-terminal region. Activation of IRF3 depends on the kinase binding sites within the C-terminal region of the autoinhibitory region. The IRF3 N-terminal and C-terminal segments interact with each other to conceal the H3 and H4 helices in the IFN association domain; the hydrophobic residues in H3 and H4 are involved in DNA binding following AD translocation after IRF3 activation. The C-terminal autoinhibitory region contains phosphorylation sites and the phosphorylation of the sites converts IRF3 into a constitutively active form.

Autoinhibitory domains (AIDs)

Target domain	190-384 (IFN association domain)
Relief mechanism	PTM
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

380-427 (C-terminal autoinhibitory region)

Target domain

190-384 (IFN association domain)

Relief mechanism

PTM (Phosphorylation in autoinhibitory region)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Lin R et al. (1999) "Structural and functional analysis of interferon regulatory factor 3: localization of the transactivation and autoinhibitory domains", Molecular and cellular biology, 19, 2465-74

Shah M et al. (2015) "In silico mechanistic analysis of IRF3 inactivation and high-risk HPV E6 species-dependent drug response", Scientific reports, 5, 13446

Liu S et al. (2015) "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation", Science (New York, N.Y.), 347, aaa2630

Qin BY et al. (2003) "Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation", Nature structural biology, 10, 913-21

Autoinhibited structure

Activated structure

19 structures for Q14653

Entry ID	Method	Resolution	Chain	Position	Source
1J2F	X-ray	230 A	A/B	175-427	PDB
1QWT	X-ray	210 A	A/B	173-427	PDB
1T2K	X-ray	300 A	A/B	1-112	PDB
1ZOQ	X-ray	237 A	A/B	196-386	PDB
2O61	X-ray	280 A	A	9-111	PDB
2O6G	X-ray	310 A	E/F/G/H	1-123	PDB
2PI0	X-ray	231 A	A/B/C/D	1-113	PDB
3A77	X-ray	180 A	A/B/C/D	189-427	PDB
3QU6	X-ray	230 A	A/B/C	1-113	PDB
5JEJ	X-ray	200 A	A/B	189-427	PDB
5JEK	X-ray	240 A	A/B	189-427	PDB
5JEL	X-ray	160 A	A	189-427	PDB
5JEM	X-ray	250 A	A/B/E/G	189-398	PDB
5JEO	X-ray	172 A	A	189-427	PDB
5JER	X-ray	291 A	A/C/E/G	189-427	PDB
6SIV	X-ray	175 A	A	137-148	PDB
6SJA	X-ray	150 A	A	137-148	PDB
7JFL	X-ray	168 A	A/B	189-398	PDB
AF-Q14653-F1	Predicted				AlphaFoldDB

333 variants for Q14653

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA9580328 RCV000585897 RCV000891824 rs143769046	277	A>T	Herpes simplex encephalitis, susceptibility to, 7 [ClinVar]	Yes	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
RCV000190468 CA204455 rs750526659	285	R>Q	Herpes simplex encephalitis, susceptibility to, 7 [ClinVar]	Yes	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
rs1260438913 CA406895777	2	G>*		No	ClinGen gnomAD
CA9580620 rs747101705	6	P>T		No	ClinGen ExAC gnomAD
rs1345659199 CA406895642	10	P>S		No	ClinGen gnomAD
CA9580615 rs755933046	13	V>A		No	ClinGen ExAC gnomAD
rs777496791 CA9580616	13	V>M		No	ClinGen ExAC gnomAD
rs748010879 CA9580613	14	S>T		No	ClinGen ExAC gnomAD
rs140943712 CA9580612	15	Q>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA406895531 rs1175683484	16	L>P		No	ClinGen gnomAD
rs751073304 CA9580610	19	G>R		No	ClinGen ExAC gnomAD
rs1445438225 CA406895478	20	Q>E		No	ClinGen gnomAD
CA9580608 rs758045346	22	E>K		No	ClinGen ExAC gnomAD
rs765633565 CA9580606	24	V>L		No	ClinGen ExAC gnomAD
CA406895382 rs1205408815	25	A>S		No	ClinGen TOPMed
CA9580604 rs777197706	29	K>E		No	ClinGen ExAC TOPMed gnomAD
CA9580602 rs551453557	29	K>N		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1234152111 CA406895309	30	S>R		No	ClinGen TOPMed
rs1325444175 CA406895302	30	S>R		No	ClinGen gnomAD
rs775617534 CA9580601	30	S>T		No	ClinGen ExAC gnomAD
rs772068784 CA9580600	31	R>G		No	ClinGen ExAC gnomAD
CA406895299 rs1021169823	31	R>H		No	ClinGen TOPMed gnomAD
CA309529187 rs1021169823	31	R>L		No	ClinGen TOPMed gnomAD
CA406895287 rs1480971369	33	R>H		No	ClinGen TOPMed
rs1480971369 CA406895288	33	R>P		No	ClinGen TOPMed
CA406895223 rs147660107	39	K>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs747924831 CA9580596	41	G>D		No	ClinGen ExAC gnomAD
CA406895168 rs1400676553	43	R>Q		No	ClinGen TOPMed
CA309529136 rs765413754	45	D>N		No	ClinGen TOPMed
CA309529135 rs1056931602	45	D>V		No	ClinGen Ensembl
CA406895117 rs1265579462	46	A>T		No	ClinGen Ensembl
rs1287964859 CA406895091	47	Q>H		No	ClinGen TOPMed
CA406895106 rs1356408122	47	Q>K		No	ClinGen TOPMed
CA406895094 rs1194237221	47	Q>L		No	ClinGen TOPMed gnomAD
CA406895097 rs1194237221	47	Q>R		No	ClinGen TOPMed gnomAD
CA309529134 rs76863988	48	Q>E		No	ClinGen Ensembl
CA406895000 rs1241612941	52	G>V		No	ClinGen gnomAD
rs1287628711 CA406894993	53	I>V		No	ClinGen TOPMed gnomAD
rs1462115524 CA406894953	55	Q>*		No	ClinGen gnomAD
rs772574723 CA9580509	59	E>K		No	ClinGen ExAC TOPMed gnomAD
rs769364335 CA9580508	61	T>S		No	ClinGen ExAC gnomAD
rs1417180670 CA406894694	62	G>S		No	ClinGen gnomAD
rs1282723092 CA406894686	62	G>V		No	ClinGen TOPMed
rs747712427 CA9580507	63	A>T		No	ClinGen ExAC TOPMed gnomAD
CA9580505 rs768948848	64	Y>C		No	ClinGen ExAC TOPMed gnomAD
CA406894669 rs1483450963	64	Y>H		No	ClinGen gnomAD
CA406894656 rs1568462177	65	V>I		No	ClinGen Ensembl
rs780438084 CA9580503	66	P>S		No	ClinGen ExAC TOPMed gnomAD
CA9580501 rs746409863	67	G>R		No	ClinGen ExAC TOPMed gnomAD
CA406894608 rs1315614215	68	R>K		No	ClinGen TOPMed gnomAD
rs778822795 CA406894601	69	D>H		No	ClinGen ExAC TOPMed gnomAD
rs778822795 CA9580500	69	D>N		No	ClinGen ExAC TOPMed gnomAD
CA9580499 rs757366375	70	K>R		No	ClinGen ExAC gnomAD
rs778130760 CA9580497	73	L>P		No	ClinGen ExAC gnomAD
CA9580496 rs145341832	75	T>A		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs751364925 CA9580495	76	W>*		No	ClinGen ExAC gnomAD
CA406894454 COSM168888 rs1456700189	81	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed
CA309528339 rs781555332	86	R>C		No	ClinGen gnomAD
rs764584136 CA9580491	86	R>H		No	ClinGen ExAC TOPMed gnomAD
CA9580490 rs761324173	88	E>D		No	ClinGen ExAC gnomAD
CA9580488 rs369809017	89	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs369809017 CA9580489	89	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA309528333 rs948324206	89	G>V		No	ClinGen Ensembl
COSM172881 CA9580487 rs377410193	91	R>C	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA9580486 rs377410193	91	R>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs1211971325 CA406894347	91	R>H		No	ClinGen TOPMed gnomAD
rs1485127801 CA406894341	92	L>V		No	ClinGen gnomAD
rs768917315 CA309528322	95	D>Y		No	ClinGen Ensembl
RCV000959577 rs968457 CA9580484	96	R>Q		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA9580485 rs772522569	96	R>W		No	ClinGen ExAC TOPMed gnomAD
CA406894260 rs1256594274	97	S>R		No	ClinGen TOPMed
CA406894212 rs1568461744	101	H>D		No	ClinGen Ensembl
rs1331847619 CA406894207	101	H>R		No	ClinGen gnomAD
rs1331290327 CA406894191	102	D>G		No	ClinGen gnomAD
rs771402454 CA9580482	102	D>N		No	ClinGen ExAC TOPMed gnomAD
CA309528315 rs1008835152	104	H>R		No	ClinGen TOPMed gnomAD
rs749372314 CA9580481	104	H>Y		No	ClinGen ExAC gnomAD
CA406894123 rs1403849112	106	I>M		No	ClinGen gnomAD
rs778036856 CA9580480	106	I>V		No	ClinGen ExAC gnomAD
rs34745118 CA9580479	107	Y>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA406894119 rs1242144936	107	Y>H		No	ClinGen TOPMed gnomAD
CA406894093 rs1599866688	108	E>D		No	ClinGen Ensembl
CA406894103 rs1477763512	108	E>K		No	ClinGen TOPMed gnomAD
rs1378402095 CA406894081	109	F>S		No	ClinGen gnomAD
CA406894040 rs1472189397	111	N>K		No	ClinGen TOPMed
rs892151580 CA309528171	114	V>A		No	ClinGen Ensembl
rs1357087110 CA406892891	119	Q>*		No	ClinGen gnomAD
rs1052178630 CA309528162	119	Q>H		No	ClinGen Ensembl
CA406892811 rs1448585210	124	P>L		No	ClinGen TOPMed gnomAD
rs978180939 CA309528157	125	D>N		No	ClinGen TOPMed gnomAD
CA309528154 rs878998137	127	N>K		No	ClinGen Ensembl
CA9580454 rs137902370	127	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs763532111 CA9580453	129	G>A		No	ClinGen ExAC gnomAD
CA406892711 rs1383697578	131	S>N		No	ClinGen TOPMed gnomAD
CA9580451 rs368164543	132	T>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA309528153 rs368164543	132	T>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs767197034 CA9580450	134	D>H		No	ClinGen ExAC
CA9580448 rs759148455	136	Q>R		No	ClinGen ExAC gnomAD
rs199550479 CA9580430	146	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA406892291 rs1365720630	148	V>G		No	ClinGen gnomAD
CA406892259 rs1482030256	150	A>T		No	ClinGen TOPMed gnomAD
CA9580429 rs752222408	150	A>V		No	ClinGen ExAC gnomAD
rs1352050612 CA406892226	151	P>L		No	ClinGen gnomAD
rs1392253605 CA406892239	151	P>S		No	ClinGen TOPMed
rs1167051116 CA406892200	152	L>P		No	ClinGen TOPMed
CA309527785 rs79173361	154	D>H		No	ClinGen 1000Genomes
CA309527777 rs1027603553	155	P>L		No	ClinGen gnomAD
rs888606062 CA309527782	155	P>T		No	ClinGen TOPMed
CA406892123 rs1160692267	156	G>E		No	ClinGen TOPMed gnomAD
CA406892111 rs1479197190	157	P>S		No	ClinGen gnomAD
rs754607113 CA9580427	158	P>L		No	ClinGen ExAC
CA406892073 rs1424011322	159	S>G		No	ClinGen gnomAD
rs751198728 CA9580426	159	S>R		No	ClinGen ExAC gnomAD
rs763424189 CA9580424	163	A>S		No	ClinGen ExAC TOPMed gnomAD
CA9580425 rs763424189	163	A>T		No	ClinGen ExAC TOPMed gnomAD
CA309527736 rs543870297	164	P>H		No	ClinGen 1000Genomes ExAC
rs543870297 CA9580422	164	P>L		No	ClinGen 1000Genomes ExAC
rs1465258864 CA406891988	164	P>S		No	ClinGen gnomAD
rs202051433 CA9580421 COSM1731271	166	P>S	liver [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs897364474 CA309527717	167	C>R		No	ClinGen gnomAD
CA406891923 rs1278183717	167	C>Y		No	ClinGen gnomAD
CA406891886 rs776725625	169	Q>L		No	ClinGen ExAC gnomAD
CA9580420 rs776725625	169	Q>R		No	ClinGen ExAC gnomAD
CA406891865 rs1295801861	170	P>H		No	ClinGen gnomAD
rs1370021596 CA406891868	170	P>S		No	ClinGen gnomAD
rs895293920 CA309527712	171	L>P		No	ClinGen TOPMed gnomAD
CA406891850 rs895293920	171	L>Q		No	ClinGen TOPMed gnomAD
CA406891843 rs200723078	172	R>G		No	ClinGen TOPMed gnomAD
CA9580419 rs768649559	172	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs200723078 CA309527703	172	R>W		No	ClinGen TOPMed gnomAD
rs1176166934 CA406891819	173	S>I		No	ClinGen gnomAD
rs1176166934 CA406891825	173	S>N		No	ClinGen gnomAD
rs1358001164 CA406891832	173	S>R		No	ClinGen gnomAD
rs775706732 CA9580417	174	P>L		No	ClinGen ExAC gnomAD
rs747188367 CA9580418	174	P>S		No	ClinGen ExAC TOPMed gnomAD
rs186551702 CA9580416	175	S>G		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA406891774 rs1449902203	175	S>I		No	ClinGen TOPMed gnomAD
CA406891780 rs1449902203	175	S>N		No	ClinGen TOPMed gnomAD
rs372603167 CA9580415	176	L>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA406891718 rs1181752337	177	D>N		No	ClinGen gnomAD
rs1049794743 CA309527687	178	N>S		No	ClinGen TOPMed gnomAD
rs1210942913 CA406891598	181	P>T		No	ClinGen gnomAD
CA406891516 rs1228104876	185	L>V		No	ClinGen TOPMed gnomAD
CA309527669 rs947514397	189	E>K		No	ClinGen Ensembl
CA406891326 rs1354834745	191	P>L		No	ClinGen gnomAD
rs780709450 CA9580411	191	P>S		No	ClinGen ExAC gnomAD
CA9580410 rs754446634	192	L>M		No	ClinGen ExAC gnomAD
CA9580409 rs751165530	194	R>G		No	ClinGen ExAC gnomAD
CA9580408 rs2230667	194	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs751165530 CA406891277	194	R>W		No	ClinGen ExAC gnomAD
rs758189741 CA9580407	196	L>V		No	ClinGen ExAC gnomAD
CA406891209 rs1599859589	197	V>G		No	ClinGen Ensembl
CA9580406 rs368547797	198	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA406891186 rs1391716043	198	P>S		No	ClinGen gnomAD
rs762343935 CA9580404	199	G>A		No	ClinGen ExAC gnomAD
rs767604581 CA406890932	203	E>*		No	ClinGen ExAC gnomAD
CA9580379 rs767604581	203	E>Q		No	ClinGen ExAC gnomAD
CA309527573 rs199969901	205	E>K		No	ClinGen TOPMed gnomAD
rs1599858704 CA406890806	206	V>G		No	ClinGen Ensembl
rs1020274254 CA309527571	207	T>I		No	ClinGen gnomAD
rs1020274254 CA406890785	207	T>R		No	ClinGen gnomAD
CA9580378 rs759711645	208	A>D		No	ClinGen ExAC gnomAD
CA9580377 rs774557325	209	F>C		No	ClinGen ExAC TOPMed gnomAD
CA406890698 rs1295080156	210	Y>C		No	ClinGen gnomAD
rs909093042 CA309527554	211	R>G		No	ClinGen TOPMed
CA309527542 rs983339367	211	R>Q		No	ClinGen TOPMed gnomAD
rs909093042 CA406890679	211	R>W		No	ClinGen TOPMed
rs776555644 CA9580374	212	G>R		No	ClinGen ExAC gnomAD
rs768444988 CA9580373	213	R>C		No	ClinGen ExAC TOPMed gnomAD
rs369466676 CA309527522	213	R>H		No	ClinGen ESP TOPMed gnomAD
rs746990215 CA9580372	214	Q>E		No	ClinGen ExAC gnomAD
rs775100883 CA9580371	218	Q>L		No	ClinGen ExAC gnomAD
CA9580370 rs556480330	219	T>S		No	ClinGen 1000Genomes ExAC gnomAD
rs139855390 CA309527509	220	I>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs139855390 CA9580368	220	I>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1330679227 CA406890489	220	I>V		No	ClinGen TOPMed gnomAD
rs757004304 CA9580367	222	C>Y		No	ClinGen ExAC gnomAD
rs749588629 CA9580366	223	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1172652095 CA406890350	227	R>Q		No	ClinGen TOPMed
rs767516716 CA9580362	227	R>W		No	ClinGen ExAC gnomAD
rs751692759 CA9580360	229	V>G		No	ClinGen ExAC gnomAD
rs1370844626 CA406890330	229	V>M		No	ClinGen TOPMed
rs1430776249 CA406890298	230	G>A		No	ClinGen TOPMed
CA9580359 rs766505491	231	S>A		No	ClinGen ExAC
CA9580358 rs763276449	231	S>F		No	ClinGen ExAC gnomAD
CA9580356 rs369780780	232	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA406890264 rs369780780	232	E>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA406890223 rs1448104659	233	V>A		No	ClinGen TOPMed gnomAD
CA9580353 rs772194735	235	D>E		No	ClinGen ExAC gnomAD
rs1306643767 CA406890192	235	D>N		No	ClinGen TOPMed gnomAD
CA9580352 rs375866058	236	R>S		No	ClinGen ESP ExAC TOPMed gnomAD
CA9580351 rs371387640	237	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
CA9580349 rs748995672	240	G>A		No	ClinGen ExAC gnomAD
rs949318539 CA309527444	243	V>I		No	ClinGen Ensembl
CA309527438 rs1009839902	249	G>C		No	ClinGen TOPMed
rs1225883677 CA406889757	252	L>V		No	ClinGen TOPMed gnomAD
CA406889722 rs1393674428	253	T>I		No	ClinGen TOPMed gnomAD
CA9580343 rs755544427	256	G>R		No	ClinGen ExAC TOPMed gnomAD
rs916501770 CA309527419	257	V>A		No	ClinGen Ensembl
CA406889537 rs1395567382	258	M>R		No	ClinGen gnomAD
CA309527410 rs990449697	261	V>M		No	ClinGen TOPMed
CA406889283 rs1389871899	264	V>M		No	ClinGen TOPMed gnomAD
CA9580338 rs763925335	267	C>Y		No	ClinGen ExAC gnomAD
rs775493705 CA9580336	269	G>S		No	ClinGen ExAC TOPMed gnomAD
CA406889154 rs142339594	270	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs142339594 CA9580334	270	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
COSM3672975 rs142339594 CA9580335	270	G>W	prostate [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
rs1216555760 CA406889063	273	A>S		No	ClinGen TOPMed
rs1419306610 CA406889025	274	L>P		No	ClinGen gnomAD
CA9580330 rs138165581	276	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs566321486 CA9580331	276	R>W		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1354132030 CA406888899	277	A>V		No	ClinGen gnomAD
rs748503863 CA9580327	278	G>R		No	ClinGen ExAC TOPMed gnomAD
CA406888871 rs1341217972	279	Q>R		No	ClinGen gnomAD
CA9580326 rs781576099	280	W>*		No	ClinGen ExAC gnomAD
rs1408174391 CA406888806	281	L>F		No	ClinGen TOPMed gnomAD
rs769128818 CA9580325	281	L>H		No	ClinGen ExAC TOPMed gnomAD
rs1568457452 CA406888784	282	W>*		No	ClinGen Ensembl
CA406888679 rs750526659	285	R>P		No	ClinGen ExAC TOPMed gnomAD
rs758520295 CA9580321	285	R>W		No	ClinGen ExAC gnomAD
rs1419315525 CA406888641	286	L>R		No	ClinGen gnomAD
CA9580320 rs779273657	286	L>V		No	ClinGen ExAC gnomAD
rs767445736 CA9580318	287	G>A		No	ClinGen ExAC TOPMed gnomAD
rs767445736 CA9580319	287	G>E		No	ClinGen ExAC TOPMed gnomAD
CA406888639 rs1420648122	287	G>R		No	ClinGen TOPMed
rs767445736 CA9580317	287	G>V		No	ClinGen ExAC TOPMed gnomAD
CA406888609 rs759355126	288	H>D		No	ClinGen ExAC TOPMed gnomAD
CA9580316 rs759355126	288	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs1389511631 CA406888551	290	H>Y		No	ClinGen TOPMed
rs1433098917 CA406888522	291	T>K		No	ClinGen TOPMed
rs1361576344 CA406888389	294	A>V		No	ClinGen TOPMed
rs1336881907 CA406888338	297	E>K		No	ClinGen gnomAD
rs1295157537 CA406888325	298	E>K		No	ClinGen gnomAD
rs1289280913 CA406888200	301	P>L		No	ClinGen gnomAD
rs372478931 CA9580312	301	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1444807578 CA406888178	302	N>H		No	ClinGen gnomAD
rs769404615 CA9580311	303	S>G		No	ClinGen ExAC TOPMed gnomAD
CA9580309 rs368333462	304	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1241122010 CA406888091	305	H>N		No	ClinGen TOPMed
CA9580306 rs375519678	310	E>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9580305 rs772523709	311	V>I		No	ClinGen ExAC TOPMed gnomAD
CA406887798 rs1187896216	313	K>R		No	ClinGen TOPMed
rs745931564 CA9580304	314	D>G		No	ClinGen ExAC gnomAD
rs745931564 CA406887778	314	D>V		No	ClinGen ExAC gnomAD
COSM3835392 rs1469737120 CA406887708	317	G>E	breast [Cosmic]	No	ClinGen cosmic curated gnomAD
CA9580303 rs779185798	318	G>D		No	ClinGen ExAC TOPMed gnomAD
rs949205599 CA309527271	318	G>S		No	ClinGen Ensembl
CA406887698 rs779185798	318	G>V		No	ClinGen ExAC TOPMed gnomAD
rs1599856065 CA406887653	319	V>A		No	ClinGen Ensembl
rs1599856065 CA406887662	319	V>G		No	ClinGen Ensembl
CA9580302 rs757508350	319	V>M		No	ClinGen ExAC TOPMed gnomAD
rs754148669 CA9580301	321	D>E		No	ClinGen ExAC TOPMed gnomAD
CA406887500 rs1365784017	323	G>A		No	ClinGen gnomAD
rs1466759704 CA406887461	324	P>L		No	ClinGen TOPMed
CA406887479 rs1568456795	324	P>S		No	ClinGen Ensembl
CA9580299 rs754811594	325	F>C		No	ClinGen ExAC gnomAD
CA9580297 rs766332611	326	I>T		No	ClinGen ExAC TOPMed gnomAD
CA406885957 rs1237122603	331	T>A		No	ClinGen gnomAD
CA406885949 rs1211946448	331	T>I		No	ClinGen gnomAD
rs779760743 CA9580279	333	T>M		No	ClinGen ExAC TOPMed gnomAD
rs750392569 CA9580277	334	E>A		No	ClinGen ExAC TOPMed gnomAD
rs1226124645 CA406885878 COSM1481331	335	G>E	breast [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
CA406885832 rs1416297269	337	G>A		No	ClinGen gnomAD
CA9580275 rs561346823	337	G>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs561346823 CA9580274	337	G>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA9580273 rs763772455	338	R>C		No	ClinGen ExAC gnomAD
CA9580272 rs750741168	338	R>H		No	ClinGen ExAC TOPMed gnomAD
CA406885795 rs774859762	339	S>*		No	ClinGen ExAC TOPMed gnomAD
rs774859762 CA9580271	339	S>L		No	ClinGen ExAC TOPMed gnomAD
rs760057796 CA9580269	341	R>C		No	ClinGen ExAC TOPMed gnomAD
CA9580268 rs148237208	341	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA309526526 rs1057506192	342	Y>C		No	ClinGen TOPMed gnomAD
rs896047044 CA309526525	344	L>F		No	ClinGen TOPMed gnomAD
CA406885648 rs1249836290	346	F>I		No	ClinGen gnomAD
CA406885613 rs1204912777	347	C>F		No	ClinGen gnomAD
CA406885586 rs1481127701	348	V>G		No	ClinGen gnomAD
CA9580266 COSM1161285 rs749370315	350	E>K	haematopoietic_and_lymphoid_tissue [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA406885431 rs1234547568	352	W>*		No	ClinGen gnomAD
rs1348265621 CA406885399	353	P>L		No	ClinGen gnomAD
CA309526521 rs773201962	354	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs773201962 CA406885376	354	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs1291555795 CA406885353	355	D>A		No	ClinGen TOPMed gnomAD
CA406885340 rs1291555795	355	D>G		No	ClinGen TOPMed gnomAD
rs770031770 CA9580264	355	D>H		No	ClinGen ExAC gnomAD
CA406885338 rs1291555795	355	D>V		No	ClinGen TOPMed gnomAD
CA9580263 rs200830423	357	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1165785204 CA406885207	359	T>I		No	ClinGen gnomAD
rs1181819640 CA406885129	362	L>F		No	ClinGen gnomAD
rs1599848627 CA406885083	363	V>G		No	ClinGen Ensembl
rs148672096 CA406885099	363	V>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA9580260 rs148672096	363	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1189813077 CA406885007	364	M>I		No	ClinGen gnomAD
rs973508874 CA309526517	364	M>V		No	ClinGen Ensembl
CA406884981 rs1599848565	365	V>G		No	ClinGen Ensembl
CA9580232 rs374065879	368	V>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs963871762 COSM439989 CA309526371	370	T>M	breast [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs1193302131 CA406884228	373	R>G		No	ClinGen gnomAD
CA309526369 rs1049486	377	E>K		No	ClinGen Ensembl
CA9580229 rs187335764	379	A>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs147691115 CA9580226	380	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
CA9580227 rs768844517	380	R>W		No	ClinGen ExAC TOPMed gnomAD
rs774095875 CA9580225	382	G>E		No	ClinGen ExAC TOPMed gnomAD
rs1282254086 CA406883908	382	G>R		No	ClinGen gnomAD
CA406883790 rs1270637498	385	S>P		No	ClinGen gnomAD
rs1568450467 CA406883594	390	T>I		No	ClinGen Ensembl
rs770719440 CA9580224	393	L>V		No	ClinGen ExAC TOPMed gnomAD
CA9580223 rs749194762	394	H>R		No	ClinGen ExAC TOPMed gnomAD
CA9580221 rs147048613	397	N>K		No	ClinGen ESP ExAC TOPMed gnomAD
CA9580222 rs372996527	397	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs747576150 CA9580220	398	S>I		No	ClinGen ExAC gnomAD
rs1030559815 CA309526366	398	S>R		No	ClinGen gnomAD
rs141496153 CA9580218	401	L>V		No	ClinGen ESP ExAC TOPMed gnomAD
rs1475349908 CA406883203	404	T>N		No	ClinGen gnomAD
rs780497970 CA9580216	405	S>T		No	ClinGen ExAC gnomAD
rs377085289 CA9580214	406	D>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs753813852 CA9580211	415	L>S		No	ClinGen ExAC gnomAD
rs1263796041 CA406882955	416	V>G		No	ClinGen gnomAD
rs1388596714 CA406882966	416	V>M		No	ClinGen Ensembl
CA406882891 rs1413758072	419	M>I		No	ClinGen Ensembl
CA406882897 rs1356360289	419	M>T		No	ClinGen gnomAD
CA406882903 rs1454802716	419	M>V		No	ClinGen TOPMed
CA309526364 rs891691722	420	D>H		No	ClinGen Ensembl
CA9580210 rs764192287	423	G>V		No	ClinGen ExAC gnomAD
rs775706485 CA9580208	425	G>E		No	ClinGen ExAC TOPMed gnomAD
CA406882769 rs748641459	426	E>*		No	ClinGen TOPMed gnomAD
rs748641459 CA309526363	426	E>K		No	ClinGen TOPMed gnomAD
rs7251 CA309526362	427	S>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs7251 CA9580207	427	S>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
VAR_084069	49	E>-	decreased IFNB induction upon Sendai virus infection [UniProt]	No	UniProt
VAR_084070	145	G>-	decreased IFNB induction upon Sendai virus infection [UniProt]	No	UniProt
VAR_084071	146	N>K	decreased IFNB induction upon Sendai virus infection [UniProt]	No	UniProt
VAR_084072	227	R>Q	no effect on IFNB induction upon Sendai virus infection [UniProt]	No	UniProt
VAR_084073	401	L>V	no effect on IFNB induction upon Sendai virus infection [UniProt]	No	UniProt

1 associated diseases with Q14653

[MIM: 616532]: Encephalopathy, acute, infection-induced, 7, herpes-specific (IIAE7)

A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:26216125}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Without disease ID

A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:26216125}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

3 regional properties for Q14653

Type	Name	Position	InterPro Accession
domain	Interferon regulatory factor, DNA-binding domain	1 - 112	IPR001346
domain	Interferon regulatory factor-3	201 - 380	IPR019471
conserved_site	Interferon regulatory factor, conserved site	26 - 58	IPR019817

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Nucleus Mitochondrion	Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect (PubMed:10805757, PubMed:35922005) When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm (PubMed:10805757) Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection (PubMed:25609812)
PANTHER Family	PTHR11949	INTERFERON REGULATORY FACTOR
PANTHER Subfamily	PTHR11949:SF1	INTERFERON REGULATORY FACTOR 3
PANTHER Protein Class	DNA-binding transcription factor helix-turn-helix transcription factor winged helix/forkhead transcription factor
PANTHER Pathway Category	Toll receptor signaling pathway IRF3

6 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.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
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.

11 GO annotations of molecular function

Name	Definition
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, 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 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.
identical protein binding	Binding to an identical protein or proteins.
promoter-specific chromatin binding	Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
protein domain specific binding	Binding to a specific domain of a protein.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
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.
sequence-specific DNA binding	Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
sequence-specific double-stranded DNA binding	Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding.

21 GO annotations of biological process

Name	Definition
apoptotic process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died.
cellular response to DNA damage 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 stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to exogenous dsRNA	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 exogenous double-stranded RNA stimulus.
cellular response to virus	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 stimulus from a virus.
defense response to virus	Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
immune system process	Any process involved in the development or functioning of the immune system, an organismal system for calibrated responses to potential internal or invasive threats.
lipopolysaccharide-mediated signaling pathway	The series of molecular signals initiated by the binding of a lipopolysaccharide (LPS) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Lipopolysaccharides are major components of the outer membrane of Gram-negative bacteria, making them prime targets for recognition by the immune system.
macrophage apoptotic process	Any apoptotic process in a macrophage, a mononuclear phagocyte present in a variety of tissues.
MDA-5 signaling pathway	The series of molecular signals initiated by viral RNA binding of a cytoplasmic pattern recognition receptor (PRR) MDA-5 (also known as IFIH1). MDA-5 is a cytoplasmic receptor that detects RNA synthesized during viral replication and triggers a signaling pathway to protect the host against viral infection, for example by inducing the expression of antiviral cytokines.
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 interferon-alpha production	Any process that activates or increases the frequency, rate, or extent of interferon-alpha production.
positive regulation of interferon-beta production	Any process that activates or increases the frequency, rate, or extent of interferon-beta production.
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 type I interferon production	Any process that activates or increases the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
positive regulation of type I interferon-mediated signaling pathway	Any process that increases the rate, frequency or extent of a type I interferon-mediated signaling pathway.
programmed necrotic cell death	A necrotic cell death process that results from the activation of endogenous cellular processes, such as signaling involving death domain receptors or Toll-like receptors.
regulation of apoptotic process	Any process that modulates the occurrence or rate of cell death by apoptotic process.
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 transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
TRIF-dependent toll-like receptor signaling pathway	The series of molecular signals initiated by a ligand binding to a toll-like receptor where the TRIF adaptor mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response.
type I interferon signaling pathway	The series of molecular signals initiated by type I interferon binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.

8 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q4JF28	IRF3	Interferon regulatory factor 3	Bos taurus (Bovine)	SS
Q00978	IRF9	Interferon regulatory factor 9	Homo sapiens (Human)	PR
Q13568	IRF5	Interferon regulatory factor 5	Homo sapiens (Human)	EV
Q15306	IRF4	Interferon regulatory factor 4	Homo sapiens (Human)	SS
Q92985	IRF7	Interferon regulatory factor 7	Homo sapiens (Human)	EV
Q02556	IRF8	Interferon regulatory factor 8	Homo sapiens (Human)	PR
P70671	Irf3	Interferon regulatory factor 3	Mus musculus (Mouse)	SS
Q764M6	IRF3	Interferon regulatory factor 3	Sus scrofa (Pig)	SS

10	20	30	40	50	60
MGTPKPRILP	WLVSQLDLGQ	LEGVAWVNKS	RTRFRIPWKH	GLRQDAQQED	FGIFQAWAEA
70	80	90	100	110	120
TGAYVPGRDK	PDLPTWKRNF	RSALNRKEGL	RLAEDRSKDP	HDPHKIYEFV	NSGVGDFSQP
130	140	150	160	170	180
DTSPDTNGGG	STSDTQEDIL	DELLGNMVLA	PLPDPGPPSL	AVAPEPCPQP	LRSPSLDNPT
190	200	210	220	230	240
PFPNLGPSEN	PLKRLLVPGE	EWEFEVTAFY	RGRQVFQQTI	SCPEGLRLVG	SEVGDRTLPG
250	260	270	280	290	300
WPVTLPDPGM	SLTDRGVMSY	VRHVLSCLGG	GLALWRAGQW	LWAQRLGHCH	TYWAVSEELL
310	320	330	340	350	360
PNSGHGPDGE	VPKDKEGGVF	DLGPFIVDLI	TFTEGSGRSP	RYALWFCVGE	SWPQDQPWTK
370	380	390	400	410	420
RLVMVKVVPT	CLRALVEMAR	VGGASSLENT	VDLHISNSHP	LSLTSDQYKA	YLQDLVEGMD

FQGPGES