UniProt Accession

 IF16_HUMAN; Q16666; B4DJT8; H3BLV7; Q59GX0; Q5T3W7; Q5T3W8; Q5T3X0; Q5T3X1; Q5T3X2; Q8N9E5; Q8NEQ7; Q96AJ5; Q9UH78 

Genbank Protein ID

 M63838; S75433; S75417; S75419; S75421; S75423; S75424; S75426; S75429; S75431; AF208043; AY138863; AK094968; AK296228; AB208989; AL359753; AL359753; AL359753; AL359753; AL359753; AL359753; BC017059 

Genbank Nucleotide ID

 AAA58683.1; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAB32519.2; AAF20997.1; AAM96005.1; BAC04462.1; BAG58950.1; BAD92226.1; CAI15081.1; CAI15082.1; CAI15083.1; CAI15084.1; CAI15085.1; CAI15086.1; AAH17059.1 

Protein Name

 Gamma-interferon-inducible protein 16 

Protein Synonyms/Alias

 Ifi-16; Interferon-inducible myeloid differentiation transcriptional activator 

Gene Name

 IFI16 

Gene Synonyms/Alias

 IFNGIP1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
26	DYHFRMVKSLLSNDL	ubiquitination	[1]
34	SLLSNDLKLNLKMRE	ubiquitination	[1]
55	IADLMEEKFRGDAGL	ubiquitination	[1]
64	RGDAGLGKLIKIFED	ubiquitination	[1, 2]
83	EDLAETLKKEKLKVK	ubiquitination	[1, 2, 3]
84	DLAETLKKEKLKVKG	ubiquitination	[1]
90	KKEKLKVKGPALSRK	ubiquitination	[1, 2]
99	PALSRKRKKEVDATS	ubiquitination	[1, 2]
100	ALSRKRKKEVDATSP	ubiquitination	[1, 2]
116	PSTSSTVKTEGAEAT	ubiquitination	[1, 2]
128	EATPGAQKRKKSTKE	ubiquitination	[1, 2, 3]
140	TKEKAGPKGSKVSEE	ubiquitination	[1, 2]
143	KAGPKGSKVSEEQTQ	ubiquitination	[1, 2]
190	ENPKTVAKCQVTPRR	ubiquitination	[1, 2]
202	PRRNVLQKRPVIVKV	ubiquitination	[1]
208	QKRPVIVKVLSTTKP	acetylation	[4]
214	VKVLSTTKPFEYETP	acetylation	[4]
214	VKVLSTTKPFEYETP	ubiquitination	[1]
226	ETPEMEKKIMFHATV	ubiquitination	[1]
250	KVLNTSLKEKFNGKK	ubiquitination	[1, 2, 3]
330	HKKTVNQKTTIYEIQ	ubiquitination	[1, 2]
361	IPCEEGDKLQLFCFR	ubiquitination	[1]
377	RKKNQMSKLISEMHS	ubiquitination	[1]
443	PSSSFFTKKSEDTIS	ubiquitination	[1, 2]
444	SSSFFTKKSEDTISK	ubiquitination	[1]
451	KSEDTISKMNDFMRM	ubiquitination	[1, 2]
557	SSFLTTLKPRLKTEP	ubiquitination	[1]
561	TTLKPRLKTEPEEVS	sumoylation	[5, 6]
561	TTLKPRLKTEPEEVS	ubiquitination	[1]
598	YEPKEQKKMFHATVA	ubiquitination	[2]
614	ENEVFRVKVFNIDLK	ubiquitination	[1, 2, 7]
621	KVFNIDLKEKFTPKK	ubiquitination	[1]
623	FNIDLKEKFTPKKII	ubiquitination	[1]
628	KEKFTPKKIIAIANY	ubiquitination	[2]
663	DRNMEIPKGLIRSAS	ubiquitination	[1]
674	RSASVTPKINQLCSQ	ubiquitination	[1, 2, 3]
683	NQLCSQTKGSFVNGV	ubiquitination	[1]
695	NGVFEVHKKNVRGEF	ubiquitination	[3]
732	INCEEGDKLKLTCFE	ubiquitination	[1, 2]
734	CEEGDKLKLTCFELA	ubiquitination	[1, 2]
743	TCFELAPKSGNTGEL	ubiquitination	[1, 2, 3]
759	SVIHSHIKVIKTRKN	ubiquitination	[1]
767	VIKTRKNKKDILNPD	ubiquitination	[1, 2]
768	IKTRKNKKDILNPDS	ubiquitination	[1, 2]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [5] In vivo identification of sumoylation sites by a signature tag and cysteine-targeted affinity purification.
 Blomster HA, Imanishi SY, Siimes J, Kastu J, Morrice NA, Eriksson JE, Sistonen L.
 J Biol Chem. 2010 Jun 18;285(25):19324-9. [PMID: 20388717]
 [6] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 

Functional Description

 Binds double-stranded DNA. Binds preferentially to supercoiled DNA and cruciform DNA structures. Seems to be involved in transcriptional regulation. May function as a transcriptional repressor. Could have a role in the regulation of hematopoietic differentiation through activation of unknown target genes. Controls cellular proliferation by modulating the functions of cell cycle regulatory factors including p53/TP53 and the retinoblastoma protein. May be involved in TP53-mediated transcriptional activation by enhancing TP53 sequence-specific DNA binding and modulating TP53 phosphorylation status. Seems to be involved in energy-level-dependent activation of the ATM/ AMPK/TP53 pathway coupled to regulation of autophagy. May be involved in regulation of TP53-mediated cell death also involving BRCA1. May be involved in the senescence of prostate epithelial cells. Involved in innate immune response by recognizing viral dsDNA in the cytosol and probably in the nucleus. After binding to viral DNA in the cytoplasm recruits TMEM173/STING and mediates the induction of IFN-beta. Has anti-inflammatory activity and inhibits the activation of the AIM2 inflammasome, probably via association with AIM2. Proposed to bind viral DNA in the nucleus, such as of Kaposi's sarcoma-associated herpesvirus, and to induce the formation of nuclear caspase-1-activating inflammasome formation via association with PYCARD. Inhibits replication of herpesviruses such as human cytomegalovirus (HCMV) probably by interfering with promoter recruitment of members of the Sp1 family of transcription factors. 

Sequence Annotation

 DOMAIN 1 88 DAPIN.
 DOMAIN 189 389 HIN-200 1.
 DOMAIN 562 761 HIN-200 2.
 REGION 192 393 Interaction with TP53 C-terminus.
 REGION 571 766 Interaction with TP53 core domain.
 MOTIF 96 100 Nuclear localization signal.
 MOTIF 128 131 Nuclear localization signal.
 MOTIF 134 136 Nuclear localization signal.
 MOTIF 140 143 Nuclear localization signal.
 MOD_RES 95 95 Phosphoserine.
 MOD_RES 99 99 N6-acetyllysine.
 MOD_RES 106 106 Phosphoserine.
 MOD_RES 153 153 Phosphoserine.
 MOD_RES 174 174 Phosphoserine.
 MOD_RES 214 214 N6-acetyllysine.
 MOD_RES 444 444 N6-acetyllysine.
 MOD_RES 451 451 N6-acetyllysine.
 MOD_RES 561 561 N6-acetyllysine; alternate.
 MOD_RES 575 575 Phosphoserine.
 MOD_RES 598 598 N6-acetyllysine.
 MOD_RES 614 614 N6-acetyllysine.
 MOD_RES 780 780 Phosphoserine.
 CROSSLNK 561 561 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Activator; Alternative splicing; Apoptosis; Autophagy; Complete proteome; Cytoplasm; DNA-binding; Immunity; Inflammatory response; Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 785 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0016607; C:nuclear speck; IDA:MGI.
 GO:0005730; C:nucleolus; IDA:HPA.
 GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
 GO:0008134; F:transcription factor binding; IDA:UniProtKB.
 GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0008283; P:cell proliferation; NAS:UniProtKB.
 GO:0042149; P:cellular response to glucose starvation; IDA:UniProtKB.
 GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB.
 GO:0051607; P:defense response to virus; IMP:UniProtKB.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:MGI.
 GO:0030224; P:monocyte differentiation; IDA:UniProtKB.
 GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IDA:UniProtKB.
 GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
 GO:0045824; P:negative regulation of innate immune response; IDA:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
 GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0010506; P:regulation of autophagy; IEP:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR004020; DAPIN.
 IPR011029; DEATH-like_dom.
 IPR004021; HIN200/IF120x.
 IPR012340; NA-bd_OB-fold. 

Pfam

 PF02760; HIN
 PF02758; PYRIN 

SMART

  

PROSITE

 PS50824; DAPIN
 PS50834; HIN_200 

PRINTS