dbPTM

IRF1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	IRF1_HUMAN
UniProt AC	P10914
Protein Name	Interferon regulatory factor 1
Gene Name	IRF1
Organism	Homo sapiens (Human).
Sequence Length	325
Subcellular Localization	Nucleus. Cytoplasm. MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1.
Protein Description	Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells..
Protein Sequence	MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQRKERKSKSSRDAKSKAKRKSCGDSSPDTFSDGLSSSTLPDDHSSYTVPGYMQDLEVEQALTPALSPCAVSSTLPDWHIPVEVVPDSTSDLYNFQVSPMPSTSEATTDEDEEGKLPEDIMKLLEQSEWQPTNVDGKGYLLNEPGVQPTSVYGDFSCKEEPEIDSPGGDIGLSLQRVFTDLKNMDATWLDSLLTPVRLPSIQAIPCAP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
39	Ubiquitination	MIFQIPWKHAAKHGW EEEECCHHHHHHHCC	20.29	-
43	Ubiquitination	IPWKHAAKHGWDINK CCHHHHHHHCCCCCC	43.35	-
50	Ubiquitination	KHGWDINKDACLFRS HHCCCCCCCCHHHHH	47.22	-
57	Phosphorylation	KDACLFRSWAIHTGR CCCHHHHHHHHHCCC	17.33	20068231
62	Phosphorylation	FRSWAIHTGRYKAGE HHHHHHHCCCCCCCC	19.76	20068231
65	Phosphorylation	WAIHTGRYKAGEKEP HHHHCCCCCCCCCCC	13.41	20068231
76	Phosphorylation	EKEPDPKTWKANFRC CCCCCCCHHHHHHHH	37.27	-
78	Sumoylation	EPDPKTWKANFRCAM CCCCCHHHHHHHHHH	38.39	-
78	Sumoylation	EPDPKTWKANFRCAM CCCCCHHHHHHHHHH	38.39	22367195
78	Ubiquitination	EPDPKTWKANFRCAM CCCCCHHHHHHHHHH	38.39	22367195
78	Acetylation	EPDPKTWKANFRCAM CCCCCHHHHHHHHHH	38.39	22367195
95	Ubiquitination	LPDIEEVKDQSRNKG CCCHHHHHHHHCCCC	54.02	-
109	Phosphorylation	GSSAVRVYRMLPPLT CCHHHHHHHCCCCCC	4.63	22817900
117	Ubiquitination	RMLPPLTKNQRKERK HCCCCCCHHHHHHHH	59.78	-
126	Methylation	QRKERKSKSSRDAKS HHHHHHCCHHHHHHH	56.33	116054221
180	Phosphorylation	LEVEQALTPALSPCA CCHHHHHCCCCCCCE	14.99	-
184	Phosphorylation	QALTPALSPCAVSST HHHCCCCCCCEECCC	21.75	-
215	Phosphorylation	DLYNFQVSPMPSTSE CCCCEEECCCCCCCC	12.51	-
219	Phosphorylation	FQVSPMPSTSEATTD EEECCCCCCCCCCCC	38.01	-
221	Phosphorylation	VSPMPSTSEATTDED ECCCCCCCCCCCCCC	29.57	-
254	Ubiquitination	QPTNVDGKGYLLNEP CCCCCCCCCEECCCC	39.66	-
275	Ubiquitination	VYGDFSCKEEPEIDS ECCCCCCCCCCCCCC	65.01	PubMed
275	Sumoylation	VYGDFSCKEEPEIDS ECCCCCCCCCCCCCC	65.01	-
275	Sumoylation	VYGDFSCKEEPEIDS ECCCCCCCCCCCCCC	65.01	-
282	Phosphorylation	KEEPEIDSPGGDIGL CCCCCCCCCCCCHHH	30.98	26657352
290	Phosphorylation	PGGDIGLSLQRVFTD CCCCHHHHHHHHHHC	19.76	24719451
299	Sumoylation	QRVFTDLKNMDATWL HHHHHCHHCCCCHHH	53.70	-
299	Sumoylation	QRVFTDLKNMDATWL HHHHHCHHCCCCHHH	53.70	-
299	Ubiquitination	QRVFTDLKNMDATWL HHHHHCHHCCCCHHH	53.70	PubMed
308	Phosphorylation	MDATWLDSLLTPVRL CCCHHHHHHCCCCCC	24.10	27251275
311	Phosphorylation	TWLDSLLTPVRLPSI HHHHHHCCCCCCCCC	25.65	27251275
317	Phosphorylation	LTPVRLPSIQAIPCA CCCCCCCCCCEEECC	31.74	27251275

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
180	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
184	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
215	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
219	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
221	S	Phosphorylation	Kinase	IKBKE	Q14164	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:20947504
-	K	Ubiquitination	E3 ubiquitin ligase	MDM2	Q00987	PMID:23134341
-	K	Ubiquitination	E3 ubiquitin ligase	BIRC3	Q13489	PMID:24464131

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of IRF1_HUMAN !!

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 IRF1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KAT2B_HUMAN	KAT2B	physical	10022868
KAT2A_HUMAN	KAT2A	physical	10022868
STAT1_HUMAN	STAT1	physical	16512786
IRF9_HUMAN	IRF9	physical	20211142
EP300_HUMAN	EP300	physical	14662860
TAT_HV1H2	tat	physical	12021315
CHIP_HUMAN	STUB1	physical	20947504
TRAF3_HUMAN	TRAF3	physical	21903422
HCFC1_HUMAN	HCFC1	physical	21903422
KEAP1_HUMAN	KEAP1	physical	21903422
SEC63_HUMAN	SEC63	physical	21903422
TRM2A_HUMAN	TRMT2A	physical	21903422
NPM_HUMAN	NPM1	physical	21245151
YBOX1_HUMAN	YBX1	physical	21245151
TIF1B_HUMAN	TRIM28	physical	21245151
SP2_HUMAN	SP2	physical	19482358
MDM2_HUMAN	MDM2	physical	23134341
IRF8_HUMAN	IRF8	physical	11483597
HS90A_HUMAN	HSP90AA1	physical	23729439
CHIP_HUMAN	STUB1	physical	23729439
CBL_HUMAN	CBL	physical	21740303
H31_HUMAN	HIST1H3A	physical	21740303
SYQ_HUMAN	QARS	physical	21988832
BIRC3_HUMAN	BIRC3	physical	24464131
EP300_HUMAN	EP300	physical	23670564
KAT2B_HUMAN	KAT2B	physical	23670564
IRF2_HUMAN	IRF2	physical	16982896
EP300_HUMAN	EP300	physical	10438822
MDM2_HUMAN	MDM2	physical	27795392
TAT_HV1H2	tat	physical	27795392

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
613659	Gastric cancer (GASC)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of IRF1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Interferon regulatory factor 1 transactivates the expression of humanDNA polymerase eta in response to the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine."; Qi H., Zhu H., Lou M., Fan Y., Liu H., Shen J., Li Z., Lv X., Shan J.,Zhu L., Chin Y.E., Shao J.; J. Biol. Chem. 287:12622-12633(2012). Cited for: FUNCTION, ACETYLATION AT LYS-78, AND MUTAGENESIS OF LYS-78.	22367195 [Abstract]
Sumoylation
Reference	PubMed
"Elevated level of SUMOylated IRF-1 in tumor cells interferes withIRF-1-mediated apoptosis."; Park J., Kim K., Lee E.-J., Seo Y.-J., Lim S.-N., Park K., Rho S.B.,Lee S.-H., Lee J.-H.; Proc. Natl. Acad. Sci. U.S.A. 104:17028-17033(2007). Cited for: SUMOYLATION AT LYS-275 AND LYS-299, UBIQUITINATION AT LYS-275 ANDLYS-299, FUNCTION, AND MUTAGENESIS OF LYS-275 AND LYS-299.	17942705 [Abstract]