ID   OPTN_MOUSE              Reviewed;         584 AA.
AC   Q8K3K8; A2ASP3;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Optineurin;
GN   Name=Optn;
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 [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC   STRAIN=129;
RX   PubMed=15607428; DOI=10.1016/j.ygeno.2004.10.011;
RA   Rezaie T., Sarfarazi M.;
RT   "Molecular cloning, genomic structure, and protein characterization of
RT   mouse optineurin.";
RL   Genomics 85:131-138(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA   Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of mouse liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-187 AND SER-345, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, 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   [6]
RP   INTERACTION WITH RAB8, AND MUTAGENESIS OF GLU-50.
RX   PubMed=20388642; DOI=10.1093/hmg/ddq146;
RA   Chi Z.L., Akahori M., Obazawa M., Minami M., Noda T., Nakaya N.,
RA   Tomarev S., Kawase K., Yamamoto T., Noda S., Sasaoka M., Shimazaki A.,
RA   Takada Y., Iwata T.;
RT   "Overexpression of optineurin E50K disrupts Rab8 interaction and leads to a
RT   progressive retinal degeneration in mice.";
RL   Hum. Mol. Genet. 19:2606-2615(2010).
RN   [7]
RP   MUTAGENESIS OF GLU-50.
RX   PubMed=23669351; DOI=10.1093/hmg/ddt210;
RA   Minegishi Y., Iejima D., Kobayashi H., Chi Z.L., Kawase K., Yamamoto T.,
RA   Seki T., Yuasa S., Fukuda K., Iwata T.;
RT   "Enhanced optineurin E50K-TBK1 interaction evokes protein insolubility and
RT   initiates familial primary open-angle glaucoma.";
RL   Hum. Mol. Genet. 22:3559-3567(2013).
RN   [8]
RP   FUNCTION, AND MISCELLANEOUS.
RX   PubMed=26677802; DOI=10.1002/eji.201545863;
RA   Slowicka K., Vereecke L., Mc Guire C., Sze M., Maelfait J., Kolpe A.,
RA   Saelens X., Beyaert R., van Loo G.;
RT   "Optineurin deficiency in mice is associated with increased sensitivity to
RT   Salmonella but does not affect proinflammatory NF-kappaB signaling.";
RL   Eur. J. Immunol. 46:971-980(2016).
CC   -!- FUNCTION: Plays an important role in the maintenance of the Golgi
CC       complex, in membrane trafficking, in exocytosis, through its
CC       interaction with myosin VI and Rab8. Links myosin VI to the Golgi
CC       complex and plays an important role in Golgi ribbon formation. Plays a
CC       role in the activation of innate immune response during viral
CC       infection. Mechanistically, recruits TBK1 at the Golgi apparatus,
CC       promoting its trans-phosphorylation after RLR or TLR3 stimulation. In
CC       turn, activated TBK1 phosphorylates its downstream partner IRF3 to
CC       produce IFN-beta. Plays a neuroprotective role in the eye and optic
CC       nerve. May act by regulating membrane trafficking and cellular
CC       morphogenesis via a complex that contains Rab8 and hungtingtin (HD).
CC       Mediates the interaction of Rab8 with the probable GTPase-activating
CC       protein TBC1D17 during Rab8-mediated endocytic trafficking, such as
CC       that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to
CC       tubules emanating from the endocytic recycling compartment. Autophagy
CC       receptor that interacts directly with both the cargo to become degraded
CC       and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-
CC       coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica,
CC       and appears to function in the same pathway as SQSTM1 and
CC       CALCOCO2/NDP52. {ECO:0000250|UniProtKB:Q96CV9,
CC       ECO:0000269|PubMed:26677802}.
CC   -!- SUBUNIT: Self-associates (By similarity). Interacts with HD, GTF3A,
CC       TRAF3, TBK1 and MYO6. Interacts (via UBAN) with ubiquitinated TFRC.
CC       Interacts with active GTP-bound Rab8 (RAB8A and/or RAB8B). Interacts
CC       with TBC1D17. Binds to linear ubiquitin chains. Interacts with LC3
CC       family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2;
CC       OPTN phosphorylation increases the association (at least with
CC       MAP1LC3B). Interacts with RAB12; the interaction may be indirect.
CC       Interacts with TBK1; this interaction leads to the Golgi localization
CC       of TBK1 and its subsequent activation. Interacts with
CC       palmitoyltransferase ZDHHC17/HIP14; the interaction does not lead to
CC       palmitoylation of OPTN (By similarity). Interacts with CYLD (By
CC       similarity). Interacts with TOM1; the interaction is indirect and is
CC       mediated by MYO6, which acts as a bridge between TOM1 and OPTN (By
CC       similarity). {ECO:0000250|UniProtKB:Q96CV9,
CC       ECO:0000269|PubMed:20388642}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC       {ECO:0000269|PubMed:15607428}. Golgi apparatus
CC       {ECO:0000250|UniProtKB:Q96CV9}. Golgi apparatus, trans-Golgi network
CC       {ECO:0000250}. Cytoplasmic vesicle, autophagosome {ECO:0000250}.
CC       Cytoplasmic vesicle {ECO:0000250}. Recycling endosome {ECO:0000250}.
CC       Note=Found in the perinuclear region and associates with the Golgi
CC       apparatus. Colocalizes with MYO6 and RAB8 at the Golgi complex and in
CC       vesicular structures close to the plasma membrane. Localizes to LC3-
CC       positive cytoplasmic vesicles upon induction of autophagy (By
CC       similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q96CV9}.
CC   -!- TISSUE SPECIFICITY: In eye, it is expressed in anterior segment,
CC       retina, and optic nerve blood vessels (at protein level). Highly
CC       expressed in adult liver, heart and testis.
CC       {ECO:0000269|PubMed:15607428}.
CC   -!- DEVELOPMENTAL STAGE: Expressed from 7-day-old embryos.
CC       {ECO:0000269|PubMed:15607428}.
CC   -!- DOMAIN: Ubiquitin-binding motif (UBAN) is essential for its inhibitory
CC       function, subcellular localization and interaction with TBK1.
CC       {ECO:0000250}.
CC   -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC       with ATG8 family proteins. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by TBK1, leading to restrict bacterial
CC       proliferation in case of infection. {ECO:0000250}.
CC   -!- MISCELLANEOUS: OPTN E59K transgenic mice exhibit profound gliosis in
CC       the retina.
CC   -!- MISCELLANEOUS: OPTN-deficient cells display reduced TBK1 activation,
CC       IRF3 phosphorylation, and expression of type I IFNs in response to TLR3
CC       and TLR4 stimulation, indicating a role for OPTN in the innate immune
CC       response. {ECO:0000269|PubMed:26677802}.
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DR   EMBL; AY071834; AAL61853.1; -; mRNA.
DR   EMBL; AY340635; AAQ21118.1; -; Genomic_DNA.
DR   EMBL; AY340623; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340624; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340625; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340626; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340627; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340628; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340629; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340630; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340631; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340632; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340633; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AY340634; AAQ21118.1; JOINED; Genomic_DNA.
DR   EMBL; AL928662; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC061185; AAH61185.1; -; mRNA.
DR   CCDS; CCDS15663.1; -.
DR   RefSeq; NP_862896.1; NM_181848.4.
DR   RefSeq; XP_006497609.1; XM_006497546.1.
DR   RefSeq; XP_006497610.1; XM_006497547.3.
DR   RefSeq; XP_011237289.1; XM_011238987.2.
DR   PDB; 5WQ4; X-ray; 3.00 A; C/D/E/F=417-513.
DR   PDBsum; 5WQ4; -.
DR   AlphaFoldDB; Q8K3K8; -.
DR   SMR; Q8K3K8; -.
DR   BioGRID; 214832; 11.
DR   IntAct; Q8K3K8; 3.
DR   MINT; Q8K3K8; -.
DR   STRING; 10090.ENSMUSP00000110648; -.
DR   iPTMnet; Q8K3K8; -.
DR   PhosphoSitePlus; Q8K3K8; -.
DR   SwissPalm; Q8K3K8; -.
DR   EPD; Q8K3K8; -.
DR   jPOST; Q8K3K8; -.
DR   MaxQB; Q8K3K8; -.
DR   PaxDb; 10090-ENSMUSP00000027986; -.
DR   PeptideAtlas; Q8K3K8; -.
DR   ProteomicsDB; 293520; -.
DR   Pumba; Q8K3K8; -.
DR   Antibodypedia; 1010; 434 antibodies from 38 providers.
DR   DNASU; 71648; -.
DR   Ensembl; ENSMUST00000027986.5; ENSMUSP00000027986.5; ENSMUSG00000026672.12.
DR   Ensembl; ENSMUST00000114996.8; ENSMUSP00000110648.2; ENSMUSG00000026672.12.
DR   GeneID; 71648; -.
DR   KEGG; mmu:71648; -.
DR   UCSC; uc008ifm.1; mouse.
DR   AGR; MGI:1918898; -.
DR   CTD; 10133; -.
DR   MGI; MGI:1918898; Optn.
DR   VEuPathDB; HostDB:ENSMUSG00000026672; -.
DR   eggNOG; ENOG502QTG2; Eukaryota.
DR   GeneTree; ENSGT00530000063808; -.
DR   HOGENOM; CLU_034097_1_0_1; -.
DR   InParanoid; Q8K3K8; -.
DR   OMA; FVEIRMH; -.
DR   OrthoDB; 5406882at2759; -.
DR   PhylomeDB; Q8K3K8; -.
DR   TreeFam; TF326608; -.
DR   Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR   Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR   Reactome; R-MMU-5357956; TNFR1-induced NF-kappa-B signaling pathway.
DR   Reactome; R-MMU-8854214; TBC/RABGAPs.
DR   BioGRID-ORCS; 71648; 8 hits in 78 CRISPR screens.
DR   ChiTaRS; Optn; mouse.
DR   PRO; PR:Q8K3K8; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q8K3K8; Protein.
DR   Bgee; ENSMUSG00000026672; Expressed in retinal neural layer and 200 other cell types or tissues.
DR   GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0030424; C:axon; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR   GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISO:MGI.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR   GO; GO:0001155; F:TFIIIA-class transcription factor binding; ISO:MGI.
DR   GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0034620; P:cellular response to unfolded protein; ISS:UniProtKB.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR   GO; GO:0007030; P:Golgi organization; ISO:MGI.
DR   GO; GO:0090161; P:Golgi ribbon formation; ISS:UniProtKB.
DR   GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISO:MGI.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IMP:MGI.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR   GO; GO:0001920; P:negative regulation of receptor recycling; ISO:MGI.
DR   GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; ISO:MGI.
DR   GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISO:MGI.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR   GO; GO:1904417; P:positive regulation of xenophagy; ISO:MGI.
DR   GO; GO:0008104; P:protein localization; IMP:MGI.
DR   GO; GO:0034067; P:protein localization to Golgi apparatus; ISO:MGI.
DR   GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IBA:GO_Central.
DR   CDD; cd09803; UBAN; 1.
DR   Gene3D; 1.20.5.390; L1 transposable element, trimerization domain; 2.
DR   Gene3D; 1.20.5.990; Nemo cc2-lz domain - 1d5 darpin complex; 1.
DR   InterPro; IPR032419; CC2-LZ_dom.
DR   InterPro; IPR021063; NEMO_N.
DR   InterPro; IPR034735; NEMO_ZF.
DR   PANTHER; PTHR31553; NF-KAPPA-B ESSENTIAL MODULATOR; 1.
DR   PANTHER; PTHR31553:SF2; OPTINEURIN; 1.
DR   Pfam; PF16516; CC2-LZ; 1.
DR   Pfam; PF11577; NEMO; 1.
DR   Pfam; PF18414; zf_C2H2_10; 1.
DR   PROSITE; PS51801; ZF_CCHC_NOA; 1.
DR   Genevisible; Q8K3K8; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Autophagy; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW   Endosome; Golgi apparatus; Immunity; Innate immunity; Metal-binding;
KW   Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT   CHAIN           1..584
FT                   /note="Optineurin"
FT                   /id="PRO_0000058069"
FT   ZN_FING         554..584
FT                   /note="CCHC NOA-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   REGION          1..32
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          58..219
FT                   /note="Interaction with Rab8"
FT                   /evidence="ECO:0000250"
FT   REGION          267..302
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          414..584
FT                   /note="Interaction with HD"
FT                   /evidence="ECO:0000250"
FT   REGION          415..524
FT                   /note="Interaction with MYO6"
FT                   /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT   COILED          38..180
FT                   /evidence="ECO:0000255"
FT   COILED          243..278
FT                   /evidence="ECO:0000255"
FT   COILED          307..511
FT                   /evidence="ECO:0000255"
FT   MOTIF           186..191
FT                   /note="LIR"
FT   MOTIF           477..482
FT                   /note="UBAN"
FT   COMPBIAS        267..298
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         562
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         565
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         578
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   BINDING         582
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT   MOD_RES         187
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         345
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         530
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96CV9"
FT   MUTAGEN         50
FT                   /note="E->K: Disrupts direct interaction with Rab8;
FT                   accumulation in the retinal outer plexiform layer; loss of
FT                   retinal ganglion cells and connecting synapses,
FT                   degeneration of entire retina without elevation of
FT                   intraocular pressure."
FT                   /evidence="ECO:0000269|PubMed:20388642,
FT                   ECO:0000269|PubMed:23669351"
FT   HELIX           436..505
FT                   /evidence="ECO:0007829|PDB:5WQ4"
SQ   SEQUENCE   584 AA;  67018 MW;  4BCF3BD4F71921F0 CRC64;
     MSHQPLSCLT EKGDSPCETP GNGPSNMVHP SLDTFTPEEL LQQMKELLVE NHQLKEAMKL
     NNQAMKGRFE ELSAWTEKQK EERLLFEMQS KEVKERLKAL THENERLKEE LGKFKEKSEK
     PLEDLTGGYR YPRALEEEVE KLKTQVEQEV EHLKIQVMRL RAEKADLLGI VSELQLKLNS
     GGSSEDSFVE IRMTEGETEG AMKEMKNCPT PTRTDPISLS NCTEDARSCA EFEELTVSQL
     LLCLREGNQK VERLEVALRE AKERISDFEK KANGHSSTEK QTARRADREK EDKGQESVGS
     EVETLSIQVT SLFKELQEAH TKLSEAELMK KRLQEKCQAL ERKNSATPSE LNEKQELVYS
     NKKLELQVES MRSEIKMEQA KTEEEKSRLA TLQATHNKLL QEHNKALKTI EELTKQQAEK
     VDKMLLQELS EKLELAEQAL ASKQLQMDEM KQTLAKQEED LETMAVLRAQ MEVYCSDFHA
     ERAAREKIHE EKEQLALQLA ILLKENNDIE EGGSRQSLME MQCRHGARTS DSDQQTYLFQ
     RGAEDRSWQH GQQPRSIPIH SCPKCGEVLP DIDTLQIHVM DCII
//