NMI_BOVIN
ID NMI_BOVIN Reviewed; 309 AA.
AC Q3ZCL3;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 25-MAY-2022, entry version 76.
DE RecName: Full=N-myc-interactor {ECO:0000250|UniProtKB:Q13287};
DE Short=Nmi {ECO:0000250|UniProtKB:Q13287};
DE AltName: Full=N-myc and STAT interactor {ECO:0000250|UniProtKB:Q13287};
GN Name=NMI;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Acts as a signaling pathway regulator involved in innate
CC immune system response. In response to interleukin 2/IL2 and interferon
CC IFN-gamma/IFNG, interacts with signal transducer and activator of
CC transcription/STAT which activate the transcription of downstream genes
CC involved in a multitude of signals for development and homeostasis.
CC Enhances the recruitment of CBP/p300 coactivators to STAT1 and STAT5,
CC resulting in increased STAT1- and STAT5-dependent transcription. In
CC response to interferon IFN-alpha, associates in a complex with
CC signaling pathway regulator IFI35 to regulate immune response; the
CC complex formation prevents proteasome-mediated degradation of IFI35. In
CC complex with IFI35, inhibits virus-triggered type I IFN-beta production
CC when ubiquitinated by ubiquitin-protein ligase TRIM21. In complex with
CC IFI35, negatively regulates nuclear factor NF-kappa-B signaling by
CC inhibiting the nuclear translocation, activation and transcription of
CC NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial
CC cell proliferation, migration and re-endothelialization of injured
CC arteries (By similarity). Negatively regulates virus-triggered type I
CC interferon/IFN production by inducing proteosome-dependent degradation
CC of IRF7, a transcriptional regulator of type I IFN, thereby interfering
CC with cellular antiviral responses (By similarity). Beside its role as
CC an intracellular signaling pathway regulator, also functions
CC extracellularly as damage-associated molecular patterns (DAMPs) to
CC promote inflammation, when actively released by macrophage to the
CC extracellular space during cell injury or pathogen invasion.
CC Macrophage-secreted NMI activates NF-kappa-B signaling in adjacent
CC macrophages through Toll-like receptor 4/TLR4 binding and activation,
CC thereby inducing NF-kappa-B translocation from the cytoplasm into the
CC nucleus which promotes the release of pro-inflammatory cytokines (By
CC similarity). {ECO:0000250|UniProtKB:O35309,
CC ECO:0000250|UniProtKB:Q13287}.
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 (By similarity). Interacts (via coiled-
CC coil domain) with TRIM21 (via the SPRY domain); the interaction leads
CC to 'Lys-63'-linked ubiquitination of NMI. Interacts with IFI35; the
CC 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:O35309,
CC ECO:0000250|UniProtKB:Q13287}.
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 -!- DOMAIN: The coiled-coil domain is necessary for interaction with TRIM21
CC 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 The NID domain 1 is necessary and IRF7. {ECO:0000250|UniProtKB:O35309,
CC ECO:0000250|UniProtKB:Q13287}.
CC -!- PTM: Ubiquitinated. 'Lys-63'-linked ubiquitination by TRIM21 promotes
CC interaction with IFI35 and inhibits virus-triggered type I IFN-beta
CC production. {ECO:0000250|UniProtKB:Q13287}.
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}.
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DR EMBL; BC102054; AAI02055.1; -; mRNA.
DR RefSeq; NP_001030270.1; NM_001035098.2.
DR AlphaFoldDB; Q3ZCL3; -.
DR SMR; Q3ZCL3; -.
DR STRING; 9913.ENSBTAP00000021580; -.
DR PaxDb; Q3ZCL3; -.
DR PRIDE; Q3ZCL3; -.
DR GeneID; 511280; -.
DR KEGG; bta:511280; -.
DR CTD; 9111; -.
DR eggNOG; ENOG502QVH1; Eukaryota.
DR InParanoid; Q3ZCL3; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:InterPro.
DR Gene3D; 3.30.70.330; -; 1.
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 2: Evidence at transcript level;
KW Coiled coil; Cytoplasm; Immunity; Innate immunity; Isopeptide bond;
KW Nucleus; Reference proteome; Secreted; Ubl conjugation.
FT CHAIN 1..309
FT /note="N-myc-interactor"
FT /id="PRO_0000253475"
FT DOMAIN 104..193
FT /note="NID 1"
FT /evidence="ECO:0000255"
FT DOMAIN 202..294
FT /note="NID 2"
FT /evidence="ECO:0000255"
FT COILED 23..65
FT /evidence="ECO:0000255"
FT CROSSLNK 23
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13287"
SQ SEQUENCE 309 AA; 35395 MW; 8EEC6DD5EA3961E4 CRC64;
MSADEDNKEQ VLKECEQAEE IMKDKQNQKL ISEITKENIQ LKEEIKKLEA ELQETTRTSQ
INEDIPETKI KFTSVENPES DSEFSDISYS CQVSSKVPYE LQKGQALITF EKEEVAQNVI
RMEYHHVQVQ NENVMLTANP VSLNSGVKFQ VHVGVSKMKI NVTDIPDELP ESQMRDKLEL
SFSKSRNGGG EVEYVEYNKQ TRSALITFVE SGVADKILKM KDYPLYINQN CHRVTVYPYT
ETHLKKFQVF SGVSKRTVLL TGLKHLQTTD EEVVEDFISI HFQREKNGGG EVEVVKCSLG
QPHTAYFEE
