NMI_MOUSE
ID NMI_MOUSE Reviewed; 314 AA.
AC O35309; Q99M49;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=N-myc-interactor {ECO:0000250|UniProtKB:Q13287};
DE Short=Nmi {ECO:0000303|PubMed:23956435};
DE AltName: Full=N-myc and STAT interactor {ECO:0000303|PubMed:23956435};
GN Name=Nmi {ECO:0000312|MGI:MGI:1928368};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mehtani S., Zervos A.S.;
RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, INTERACTION WITH IRF7, INDUCTION BY SENDAI VIRUS, REGION, AND
RP MUTAGENESIS OF 1-MET--ILE-97 AND 201-SER--ILE-314.
RX PubMed=23956435; DOI=10.4049/jimmunol.1300740;
RA Wang J., Yang B., Hu Y., Zheng Y., Zhou H., Wang Y., Ma Y., Mao K.,
RA Yang L., Lin G., Ji Y., Wu X., Sun B.;
RT "Negative regulation of Nmi on virus-triggered type I IFN production by
RT targeting IRF7.";
RL J. Immunol. 191:3393-3399(2013).
RN [5]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29038465; DOI=10.1038/s41467-017-00930-9;
RA Xiahou Z., Wang X., Shen J., Zhu X., Xu F., Hu R., Guo D., Li H., Tian Y.,
RA Liu Y., Liang H.;
RT "NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and
RT injury.";
RL Nat. Commun. 8:950-950(2017).
CC -!- FUNCTION: Acts as a signaling pathway regulator involved in innate
CC immune system response (PubMed:23956435). In response to interleukin
CC 2/IL2 and interferon IFN-gamma/IFNG, interacts with signal transducer
CC and activator of transcription/STAT which activate the transcription of
CC downstream genes involved in a multitude of signals for development and
CC homeostasis (By similarity). Enhances the recruitment of CBP/p300
CC coactivators to STAT1 and STAT5, resulting in increased STAT1- and
CC STAT5-dependent transcription (By similarity). In response to
CC interferon IFN-alpha, associates in a complex with transcriptional
CC regulator IFI35 to regulate immune response; the complex formation
CC prevents proteasome-mediated degradation of IFI35 (By similarity). In
CC complex with IFI35, negatively regulates nuclear factor NF-kappa-B
CC signaling by inhibiting the nuclear translocation, activation and
CC transcription of NF-kappa-B subunit p65/RELA, resulting in the
CC inhibition of endothelial cell proliferation, migration and re-
CC endothelialization of injured arteries (By similarity). Negatively
CC regulates virus-triggered type I interferon/IFN production by inducing
CC proteosome-dependent degradation of IRF7, a transcriptional regulator
CC of type I IFN, thereby interfering with cellular antiviral responses
CC (PubMed:23956435). Beside its role as an intracellular signaling
CC pathway regulator, also functions extracellularly as damage-associated
CC molecular patterns (DAMPs) to promote inflammation, when actively
CC released by macrophage to the extracellular space during cell injury or
CC pathogen invasion (By similarity). Macrophage-secreted NMI activates
CC NF-kappa-B signaling in adjacent macrophages through Toll-like receptor
CC 4/TLR4 binding and activation, thereby inducing NF-kappa-B
CC translocation from the cytoplasm into the nucleus which promotes the
CC release of pro-inflammatory cytokines (By similarity).
CC {ECO:0000250|UniProtKB:Q13287, ECO:0000269|PubMed:23956435}.
CC -!- SUBUNIT: Interacts with MYCN and MYC, as well as with other
CC transcription factors with a Zip, HLH or a HLH-Zip motif. Interacts
CC with all STAT proteins except STAT2 (By similarity). Interacts with
CC IRF7, the interaction is direct and leads to the inhibition of IRF7-
CC mediated type I IFN production (PubMed:23956435). Interacts (via
CC coiled-coil domain) with TRIM21 (via the SPRY domain); the interaction
CC leads to 'Lys-63'-linked ubiquitination of NMI. Interacts with IFI35;
CC the interaction is direct and is facilitated by TRIM21. Interacts with
CC TLR4; the interaction is direct and leads to NF-kappa-B activation (By
CC similarity). {ECO:0000250|UniProtKB:Q13287,
CC ECO:0000269|PubMed:23956435}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13287}. Nucleus
CC {ECO:0000250|UniProtKB:Q13287}. Secreted
CC {ECO:0000250|UniProtKB:Q13287}. Note=Cytoplasmic NMI localizes in
CC punctate granular structures. Nuclear localization increased following
CC IFN-alpha treatment. Extracelullar following secretion by macrophage.
CC {ECO:0000250|UniProtKB:Q13287}.
CC -!- TISSUE SPECIFICITY: Expressed in macrophages.
CC {ECO:0000269|PubMed:29038465}.
CC -!- INDUCTION: Induced by Sendai virus. {ECO:0000269|PubMed:23956435}.
CC -!- DOMAIN: The coiled-coil domain may be necessary for interaction with
CC TRIM21 and for TRIM21-mediated ubiquitination of NMI.
CC {ECO:0000250|UniProtKB:Q13287}.
CC -!- DOMAIN: The NID domains are necessary for the interaction with IFI35
CC (By similarity). The NID domain 1 is necessary and IRF7
CC (PubMed:23956435). {ECO:0000250|UniProtKB:Q13287,
CC ECO:0000269|PubMed:23956435}.
CC -!- PTM: May be ubiquitinated. {ECO:0000250|UniProtKB:Q13287}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show decreased inflammatory
CC response when exposed to infection of injury, which can lead to lower
CC inflammation-induced mortality. Display normal development of the
CC immune system. {ECO:0000269|PubMed:29038465}.
CC -!- SIMILARITY: Belongs to the NMI family. {ECO:0000305}.
CC -!- CAUTION: The TRIM21-mediated ubiquitinated residue is not conserved in
CC mice, therefore it remains unclear whether the physiological role of
CC NMI ubiquitination is preserved throughout mammals.
CC {ECO:0000250|UniProtKB:Q13287}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF019249; AAB70819.1; -; mRNA.
DR EMBL; BC002019; AAH02019.1; -; mRNA.
DR CCDS; CCDS16031.1; -.
DR RefSeq; NP_001135420.1; NM_001141948.1.
DR RefSeq; NP_001135421.1; NM_001141949.1.
DR RefSeq; NP_062274.1; NM_019401.2.
DR RefSeq; XP_006498281.1; XM_006498218.3.
DR AlphaFoldDB; O35309; -.
DR BioGRID; 211098; 2.
DR CORUM; O35309; -.
DR IntAct; O35309; 2.
DR STRING; 10090.ENSMUSP00000120647; -.
DR iPTMnet; O35309; -.
DR PhosphoSitePlus; O35309; -.
DR REPRODUCTION-2DPAGE; O35309; -.
DR EPD; O35309; -.
DR PaxDb; O35309; -.
DR PeptideAtlas; O35309; -.
DR PRIDE; O35309; -.
DR ProteomicsDB; 252913; -.
DR Antibodypedia; 1783; 272 antibodies from 28 providers.
DR DNASU; 64685; -.
DR Ensembl; ENSMUST00000028314; ENSMUSP00000028314; ENSMUSG00000026946.
DR Ensembl; ENSMUST00000112705; ENSMUSP00000108325; ENSMUSG00000026946.
DR Ensembl; ENSMUST00000145481; ENSMUSP00000120647; ENSMUSG00000026946.
DR GeneID; 64685; -.
DR KEGG; mmu:64685; -.
DR UCSC; uc008jqm.2; mouse.
DR CTD; 9111; -.
DR MGI; MGI:1928368; Nmi.
DR VEuPathDB; HostDB:ENSMUSG00000026946; -.
DR eggNOG; ENOG502QVH1; Eukaryota.
DR GeneTree; ENSGT00530000063686; -.
DR HOGENOM; CLU_047262_0_0_1; -.
DR InParanoid; O35309; -.
DR OMA; KYQVFSG; -.
DR OrthoDB; 1133123at2759; -.
DR PhylomeDB; O35309; -.
DR TreeFam; TF332752; -.
DR BioGRID-ORCS; 64685; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Nmi; mouse.
DR PRO; PR:O35309; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O35309; protein.
DR Bgee; ENSMUSG00000026946; Expressed in small intestine Peyer's patch and 202 other tissues.
DR ExpressionAtlas; O35309; baseline and differential.
DR Genevisible; O35309; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0003712; F:transcription coregulator activity; IEA:InterPro.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; IEA:InterPro.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IDA:MGI.
DR GO; GO:0032687; P:negative regulation of interferon-alpha production; IMP:MGI.
DR GO; GO:0032688; P:negative regulation of interferon-beta production; IMP:MGI.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0032480; P:negative regulation of type I interferon production; IGI:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; IDA:MGI.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:MGI.
DR GO; GO:0009615; P:response to virus; IMP:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:InterPro.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR033527; NMI.
DR InterPro; IPR009909; Nmi/IFP35_dom.
DR InterPro; IPR009938; Nmi/IFP35_N.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR PANTHER; PTHR15225:SF4; PTHR15225:SF4; 1.
DR Pfam; PF07334; IFP_35_N; 1.
DR Pfam; PF07292; NID; 2.
PE 1: Evidence at protein level;
KW Coiled coil; Cytoplasm; Immunity; Innate immunity; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Secreted; Ubl conjugation.
FT CHAIN 1..314
FT /note="N-myc-interactor"
FT /id="PRO_0000159703"
FT DOMAIN 104..193
FT /note="NID 1"
FT /evidence="ECO:0000303|PubMed:23956435"
FT DOMAIN 202..293
FT /note="NID 2"
FT /evidence="ECO:0000250|UniProtKB:Q13287"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 31..65
FT /evidence="ECO:0000255"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13287"
FT CONFLICT 79
FT /note="K -> E (in Ref. 2; AAH02019)"
FT /evidence="ECO:0000305"
FT CONFLICT 103
FT /note="E -> K (in Ref. 2; AAH02019)"
FT /evidence="ECO:0000305"
FT CONFLICT 243
FT /note="C -> R (in Ref. 2; AAH02019)"
FT /evidence="ECO:0000305"
FT CONFLICT 267
FT /note="P -> R (in Ref. 2; AAH02019)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 35236 MW; CC97E0853C296DA3 CRC64;
MDADKDNIKQ ACDERSAEMD DMRGEQSMGL VHEIMSENKE LDEEIKKLEA ELQSDAREFQ
IKENVPEKKL KLTSVESPKD GCHFSNSSCS FQVSSQILYE LQEGQALITF EKEEVAQNVI
SMGNHVVQME GTPVKVSAHP VPLNTGVRFQ VHVDISKMKI NVTGIPDELS EEQTRDKLEL
SFCKSRNGGG EVESVDYDRK SRSAVITFVE TGVVDKILKK KTYPLYMNQK CHSVAVSPCI
ERCLEKYQVF SAVSKKTVLL TGLEGIPVDE ETGEDLLNIH FQRKNNGGGE VEVVKCSLDQ
SFAAYFKEEA RETI
