GPMDB0032526OtherDiner BA, et al.InstrumentNot AvailableNot availableHomo_sapiens_viruses, Humanicristea@princeton.edu25665578Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princetonhttp://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018438http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018427http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018437http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018429http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018439http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018428http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018441http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018440http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018432http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018443http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018442http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018431http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018445http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018434http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018433http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018444http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018447http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018436http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018446http://gpmdb.thegpm.org/~/dblist_gpmnum/gpmnum=GPM32310018435Not availableGPMDBThe human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identify over 300 PYHIN interactions reflective of diverse functions, including DNA damage response, transcription regulation, intracellular signaling, and antiviral response. In view of the IFIX interaction with antiviral factors, including nuclear PML bodies, we further characterize IFIX and demonstrate its function in restricting herpesvirus replication. We discover that IFIX detects viral DNA in both the nucleus and cytoplasm, binding foreign DNA via its HIN domain in a sequence-non-specific manner. Furthermore, IFIX contributes to the induction of interferon response. Our results highlight the value of integrative proteomics in deducing protein function and establish IFIX as an antiviral DNA sensor important for mounting immune responses.The functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.Diner Benjamin A BA,Li Tuo T,Greco Todd M TM,Crow Marni S MS,Fuesler John A JA,Wang Jennifer J,Cristea Ileana M IM,Diner Benjamin A BA, Li Tuo T, Greco Todd M TM, Crow Marni S MS, Fuesler John A JA, Wang Jennifer J, Cristea Ileana M IMsensory system organ, Viral DNA., organ of sensory organ system, AI447904, sensory organ system organ, IFIX, Ifix, sense organ system organ, Ifi209, organ of sensory system, sensillum, organ of sense organ system, sensory organ, 4930422C14, sensor, Sinnesorgantranscription, biological signaling, human being, nucleocytoplasm, A730048F03, Ifix, caspase-dependent programmed cell death, rHin-3, number, IFNGIP1, Gene, 4930422C14, Spectrum Analyses, Homo sapiense, apoptotic programmed cell death, type I programmed cell death, body system, presence, activation of apoptosis, Homo spaiens, Light Microscopy, Homo sapien, Viral DNA, Extrinsic Pathway Apoptoses, Homo sapians, IFIX, Cycle, Gene Products, Ifi209, Mass, system, transcription regulator activity, Ifi204, Analysis, Type I, Mass Spectroscopy, Mass Spectrum Analysis, protoplasm, Cell Division Cycles, Cycles, Homo sapients, anatomical systems, cellular DNA damage response, protoplast, Analyses, cell, Simple, Cell Division Cycle, cell-division cycle, ifi-205-B, proteins, Cell Division, Hand-Held Microscopy, defence response to virus, apoptosis activator activity, man, response to genotoxic stress, DNA-dependent, PYHIN3, Intrinsic Pathway Apoptosis, PYHIN2, Optical, Homo sapience, Homo sampiens, Hand-Held, signaling process, execution phase of apoptotic process, Cell Cycles, p204, programmed cell death by apoptosis, Home sapiens, PYHIN4, single organism signaling, Apoptosis, cellular suicide, data, cellular transcription, DNA damage response, defense response to viruses, cell suicide, DNA-dependent transcription, AI447904, Proteins, apoptotic cell death, Light, function, response to DNA damage stimulus, Optical Microscopy, Spectrum Analysis, Cell, Division Cycles, Spectroscopy, polypeptide, count in organism, signaling (initiator) caspase activity, induction of apoptosis, count, Homo sapian, Intrinsic Pathway, Programmed Cell Death, Extrinsic Pathway Apoptosis, Simple Microscopy, Protein, Homo sapeins, connected anatomical system, internal to cell, Mass Spectrum Analyses, apoptosis signaling, Mass Spectrum, Ifi205b, Ifi16, apoptosis, Division Cycle, Compound Microscopy, Spectrometry, Humo sapiens, Ifi210, Homo sapines, human, signalling, Hand Held Microscopy, Protein Gene Products, Intrinsic Pathway Apoptoses, organ system, Gene Proteins, Homo spiens, "human" EXACT genbank_common_name [], induction of apoptosis by p53, signalling process, Compound, apoptotic program, Extrinsic Pathway, commitment to apoptosis, Microscopy, regulation, Gm1313, quantitative, antiviral response., Apoptoses, presence or absence in organismsensory system organ, Viral DNA., organ of sensory organ system, AI447904, sensory organ system organ, IFIX, Ifix, sense organ system organ, Ifi209, organ of sensory system, sensillum, organ of sense organ system, sensory organ, 4930422C14, sensor, Sinnesorgannucleocytoplasm, rHin-3, organ of sensory system, Homo sapiense, type I programmed cell death, Protoplasm, MYL, Trim19, Light Microscopy, Homo sapien, Viral DNA, Extrinsic Pathway Apoptoses, Homo sapians, responsivity, horsetail nucleus, Analysis, TRIM19, Mass Spectrum Analysis, Cell Division Cycles, neuronal nucleus, thymus nucleic acid, Homo sapients, Analyses, Simple, 1200009E24Rik, ifi-205-B, sensory organ, proteins, Hand-Held Microscopy, DNA-dependent, PYHIN3, Intrinsic Pathway Apoptosis, PYHIN2, Homo sapience, Hand-Held, signaling process, Cell Cycles, Double-Stranded DNA, deoxyribonucleic acids, DNAn, Home sapiens, PYHIN4, single organism signaling, cellular suicide, DNA-dependent transcription, AI447904, Cytoplasms, Light, response to DNA damage stimulus, Double-Stranded, Optical Microscopy, Spectrum Analysis, results, Division Cycles, Spectroscopy, (Deoxyribonucleotide)n+m, organ of sensory organ system, signaling (initiator) caspase activity, induction of apoptosis, count, Homo sapian, Intrinsic Pathway, Extrinsic Pathway Apoptosis, antiviral response, cell nucleus, internal to cell, desoxyribose nucleic acid, Division Cycle, Spectrometry, organ of sense organ system, Homo sapines, human, Hand Held Microscopy, Intrinsic Pathway Apoptoses, organ system, induction of apoptosis by p53, ds DNA, sense organ system organ, Extrinsic Pathway, Microscopy, Gm1313, DNA, Interferon, Apoptoses, transcription, biological signaling, human being, multinuclear leukocyte, A730048F03, DNS, (Deoxyribonucleotide)n, Ifix, caspase-dependent programmed cell death, number, IFNGIP1, Gene, 4930422C14, Spectrum Analyses, apoptotic programmed cell death, body system, presence, activation of apoptosis, Deoxyribonucleic acids, Homo spaiens, Deoxyribonucleic Acid, AI661194, IFIX, Cycle, Gene Products, Ifi209, Mass, system, transcription regulator activity, Ifi204, Type I, Mass Spectroscopy, protoplasm, Cycles, reactivity, anatomical systems, cellular DNA damage response, protoplast, cell, RNF71, nucleus of CNS, ligand, Cell Division Cycle, cell-division cycle, Double Stranded, Cell Division, defence response to virus, PP8675, apoptosis activator activity, man, response to genotoxic stress, Optical, nucleus, Homo sampiens, execution phase of apoptotic process, sensillum, p204, (Deoxyribonucleotide)m, programmed cell death by apoptosis, Apoptosis, cellular transcription, DNA damage response, defense response to viruses, cell suicide, DNAn+1, Proteins, apoptotic cell death, function, Cell, Sinnesorgan., polypeptide, sensory system organ, count in organism, nervous system nucleus, Programmed Cell Death, Simple Microscopy, Protein, sequence, Homo sapeins, connected anatomical system, ds-DNA, sensor, Mass Spectrum Analyses, apoptosis signaling, Mass Spectrum, Ifi205b, Ifi16, apoptosis, Compound Microscopy, sensory organ system organ, Humo sapiens, deoxyribonucleic acid, nucleus of neuraxis, Ifi210, neuraxis nucleus, primary structure of sequence macromolecule, signalling, Protein Gene Products, Gene Proteins, Homo spiens, "human" EXACT genbank_common_name [], signalling process, Compound, apoptotic program, PML, Protoplasms, Desoxyribonukleinsaeure, commitment to apoptosis, polymorphonuclear leucocyte, regulation, quantitative, response, presence or absence in 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archive~1varsite~00Resource Reanalysis0.00.00.009870450339296731.00.0falseThe functional interactome of PYHIN immune regulators reveals IFIX is a sensor of viral DNA.Data from ProteomeXchange, PXD ID: PXD001572. File: 2012_07_03_IFIXGFP_PD13.mzml. Published as part of . From the Abstract: {{i}} he human PYHIN proteins, AIM2, IFI16, IFIX, and MNDA, are critical regulators of immune response, transcription, apoptosis, and cell cycle. However, their protein interactions and underlying mechanisms remain largely uncharacterized. Here, we provide the interaction network for all PYHIN proteins and define a function in sensing of viral DNA for the previously uncharacterized IFIX protein. By designing a cell-based inducible system and integrating microscopy, immunoaffinity capture, quantitative mass spectrometry, and bioinformatics, we identify over 300 PYHIN interactions reflective of diverse functions, including DNA damage response, transcription regulation, intracellular signaling, and antiviral response ... {{/i}}2015-03-13GPM3231001844325665578PXD001572PXD001572