IFI16 interferon gamma inducible protein 16 [Homo sapiens (human)] - Gene

Summary

Official Symbol: IFI16provided by HGNC
Official Full Name: interferon gamma inducible protein 16provided by HGNC
Primary source: HGNC:HGNC:5395
See related: Ensembl:ENSG00000163565 MIM:147586
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PYHIN2; IFNGIP1
Summary: This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]
Expression: Ubiquitous expression in lymph node (RPKM 45.3), appendix (RPKM 41.3) and 24 other tissues See more
Orthologs: all

Genomic context

Location:: 1q23.1

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	1	NC_000001.11 (158999976..159055151)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (158979682..159024945)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Upon infection with herpes simplex virus 1 (HSV-1) in human fibroblasts, we characterize the contribution of IFI16 oligomerization to downstream protein interactions and antiviral functions, including cytokine induction and suppression of HSV-1 replication.
Title: Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA.
The authors show that IFI16 is in complex with the H3K9 methyltransferase SUV39H1 and GLP and recruits them to the human herpesvirus 8 genome during de novo infection and latency. The resulting depositions of H3K9me2/me3 serve as a docking site for the heterochromatin-inducing HP1alpha protein leading into the IFI16-dependent epigenetic modifications and silencing of the virus lytic genes.
Title: IFI16, a nuclear innate immune DNA sensor, mediates epigenetic silencing of herpesvirus genomes by its association with H3K9 methyltransferases SUV39H1 and GLP.
Motif siRNA specifically interrupts IFI16.
Title: siRNA containing a unique 5-nucleotide motif acts as a quencher of IFI16-mediated innate immune response.
The aim of the present study is to determine the expression levels of PYHIN (IFI16 and AIM2) and APOBEC3 (A3A, A3B, A3C, A3D, A3F, A3G, and A3H) gene family members in a cohort of patients with head and neck squamous cell carcinoma (HNSCC) and assess their potential correlation with human papillomavirus (HPV) infection status, clinical characteristics, and survival.
Title: PYHIN genes as potential biomarkers for prognosis of human papillomavirus-positive or -negative head and neck squamous cell carcinomas.
The authors show that IFI16 restricts HIV-1 independently of immune sensing by binding and inhibiting the host transcription factor Sp1 that drives viral gene expression.
Title: IFI16 Targets the Transcription Factor Sp1 to Suppress HIV-1 Transcription and Latency Reactivation.
The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus.
Title: The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes.
these results showed that HSV-1 infection can enhance the expression of IFI16 in the human term placenta
Title: Enhanced expression of IFI16 and RIG-I in human third-trimester placentas following HSV-1 infection.
Enforced expression of IFI16-b inhibits the activation of AIM2 inflammasome, whereas knockdown of IFI16-b augments interleukin-1b secretion triggered by dsDNA but not dsRNA Thus, cytoplasm-localized IFI16-b is functionally equivalent to mouse p202 that exerts an inhibitory effect on AIM2 inflammasome.
Title: Inhibition of AIM2 inflammasome activation by a novel transcript isoform of IFI16.
data suggest a critical role for IFI16 during HTLV-1 infection by interacting with HTLV-1 RTI ssDNA90 and restricting HTLV-1 replication
Title: IFI16 regulates HTLV-1 replication through promoting HTLV-1 RTI-induced innate immune responses.
The authors propose that IFI16 filaments with associated restriction factors that form in replication compartments constitute a "restrictosome" structure that signals in cis and trans to silence the progeny viral DNA throughout the herpes simplex virus 1-infected cell nucleus.
Title: Role for a Filamentous Nuclear Assembly of IFI16, DNA, and Host Factors in Restriction of Herpesviral Infection.

Submit: New GeneRIF Correction See all GeneRIFs (115)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
GWAS of blood cell traits identifies novel associated loci and epistatic interactions in Caucasian and African-American children. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Nef may antagonize restriction activity of IFI16 against production of infectious wild-type HIV-1	PubMed
Pr55(Gag)	gag	HIV-1 Gag interacts with IfI16 as demonstrated by proximity dependent biotinylation proteomics	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat upregulates the interferon-responsive gene expression of many proteins, including IFI16, in immature dendritic cells, an effect that likely facilitates the expansion of HIV-1 infection	PubMed
Vpr	vpr	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpr may antagonize restriction activity of IFI16 against production of infectious wild-type HIV-1	PubMed
Vpu	vpu	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of IFI16 against production of infectious wild-type HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G60217 (e-PCR)
- UniSTS:137474

SHGC-83418 (e-PCR)
- UniSTS:101918

D1S3285 (e-PCR)
- UniSTS:67710

RH48430 (e-PCR)
- UniSTS:27793

SHGC-35795 (e-PCR)
- UniSTS:20127

D1S1562 (e-PCR)
- UniSTS:43935

AL009415 (e-PCR)
- UniSTS:40878

SHGC-52731 (e-PCR)
- UniSTS:67281

RH103 (e-PCR)
- UniSTS:2007

AL009999 (e-PCR)
- UniSTS:5870

Homology

Homologs of the IFI16 gene: The IFI16 gene is conserved in chimpanzee, Rhesus monkey, mouse, and rat.
Orthologs from Annotation Pipeline: 43 organisms have orthologs with human gene IFI16
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
RNA binding	HDA more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
transcription factor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
activation of cysteine-type endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
activation of innate immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
activation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
autophagy	IEA Inferred from Electronic Annotation more info
cellular response to glucose starvation	IDA Inferred from Direct Assay more info	PubMed
cellular response to interferon-beta	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular response to ionizing radiation	IDA Inferred from Direct Assay more info	PubMed
defense response to virus	IDA Inferred from Direct Assay more info	PubMed
defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
inflammatory response	IEA Inferred from Electronic Annotation more info
innate immune response	IEA Inferred from Electronic Annotation more info
intrinsic apoptotic signaling pathway by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IDA Inferred from Direct Assay more info	PubMed
monocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
myeloid cell differentiation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of DNA binding	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
negative regulation of viral genome replication	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cytokine production	TAS Traceable Author Statement more info	PubMed
positive regulation of interleukin-1 beta production	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of interleukin-1 beta production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of type I interferon production	TAS Traceable Author Statement more info
regulation of autophagy	IEP Inferred from Expression Pattern more info	PubMed
regulation of gene expression, epigenetic	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytosol	IDA Inferred from Direct Assay more info
colocalizes_with cytosol	IPI Inferred from Physical Interaction more info	PubMed
cytosol	TAS Traceable Author Statement more info
membrane	HDA more info	PubMed
nuclear speck	IDA Inferred from Direct Assay more info	PubMed
nucleolus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: gamma-interferon-inducible protein 16

Names: IFI16 beta isoform; interferon-gamma induced protein IFI 16; interferon-inducible myeloid differentiation transcriptional activator

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029141.2 RefSeqGene

Range

14938..60182

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001206567.2 → NP_001193496.1 gamma-interferon-inducible protein 16 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) lacks an in-frame exon in the 5' coding region and has an additional in-frame exon in the 3' coding region, compared to variant 2. The additional exon is described as exon 7a in PMID:9718316. The resulting isoform (1) is of the same size but lacks a segment in the N-terminal region and has an additional segment in the C-terminal region, compared to isoform 2. Note the CDS was annotated to initiate translation from an in-frame downstream AUG, as it is flanked by a strong Kozak signal, and is better conserved than the upstream AUG located 4 codons upstream.

Source sequence(s)

AK296228, BM806453, DA945454, DB273519, M63838

Consensus CDS

CCDS58039.1

UniProtKB/Swiss-Prot

Q16666

Related

ENSP00000352740.3, ENST00000359709.7

Conserved Domains (3) summary

cd08305
Location:10 → 83

Pyrin; Pyrin: a protein-protein interaction domain

pfam02760
Location:145 → 313

HIN; HIN-200/IF120x domain

pfam06583
Location:343 → 545

Neogenin_C; Neogenin C-terminus
NM_001364867.2 → NP_001351796.1 gamma-interferon-inducible protein 16 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (3, also known as IFI 16A).

Source sequence(s)

AL359753

Conserved Domains (3) summary

cd08305
Location:10 → 83

Pyrin; Pyrin: a protein-protein interaction domain

pfam02760
Location:201 → 369

HIN; HIN-200/IF120x domain

cl25751
Location:100 → 215

DUF4045; Domain of unknown function (DUF4045)
NM_001376587.1 → NP_001363516.1 gamma-interferon-inducible protein 16 isoform 3

Status: REVIEWED

Source sequence(s)

AL359753

Related

ENSP00000295809.7, ENST00000295809.11
NM_001376588.1 → NP_001363517.1 gamma-interferon-inducible protein 16 isoform 2

Status: REVIEWED

Source sequence(s)

AL359753
NM_001376589.1 → NP_001363518.1 gamma-interferon-inducible protein 16 isoform 2

Status: REVIEWED

Source sequence(s)

AL359753
NM_001376591.1 → NP_001363520.1 gamma-interferon-inducible protein 16 isoform 4

Status: REVIEWED

Source sequence(s)

AL359753
NM_001376592.1 → NP_001363521.1 gamma-interferon-inducible protein 16 isoform 4

Status: REVIEWED

Source sequence(s)

AL359753

Related

ENSP00000404325.2, ENST00000448393.6
NM_005531.3 → NP_005522.2 gamma-interferon-inducible protein 16 isoform 2

See identical proteins and their annotated locations for NP_005522.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) consists of 11 exons and encodes isoform 2 (also known as isoform B, PMIDs:9718316 and 12588705). Note the CDS was annotated to initiate translation from an in-frame downstream AUG, as it is flanked by a strong Kozak signal, and is better conserved than the upstream AUG located 4 codons upstream.

Source sequence(s)

AL359753, BC017059, DA990524, M63838

Consensus CDS

CCDS1180.3

UniProtKB/Swiss-Prot

Q16666

Related

ENSP00000357113.4, ENST00000368131.8

Conserved Domains (2) summary

cd08305
Location:10 → 83

Pyrin; Pyrin: a protein-protein interaction domain

pfam02760
Location:201 → 369

HIN; HIN-200/IF120x domain