OPTN_MOUSE
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 03-AUG-2022, entry version 136.
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 of
CC transferrin receptor (TFRC/TfR); regulates Rab8 recruitnment to tubules
CC emanating from the endocytic recycling compartment. Autophagy receptor
CC that interacts directly with both the cargo to become degraded and an
CC autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated
CC bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and
CC appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52.
CC {ECO:0000250|UniProtKB:Q96CV9, ECO:0000269|PubMed:26677802}.
CC -!- SUBUNIT: Self-associates (By similarity). Interacts with HD, Rab8
CC (RAB8A and/or RAB8B) (active GTP-bound form), GTF3A, TRAF3, TBK1, MYO6
CC and TFRC. Binds to linear ubiquitin chains. Interacts with LC3 family
CC members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN
CC phosphorylation increases the association (at least with MAP1LC3B).
CC Interacts with RAB12; the interaction may be indirect. Interacts with
CC TBK1; this interaction leads to the Golgi localization of TBK1 and its
CC subsequent activation. Interacts with palmitoyltransferase
CC ZDHHC17/HIP14; the interaction does not lead to palmitoylation of OPTN
CC (By similarity). Interacts with CYLD (By similarity).
CC {ECO:0000250|UniProtKB:Q96CV9, 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.ENSMUSP00000027986; -.
DR iPTMnet; Q8K3K8; -.
DR PhosphoSitePlus; Q8K3K8; -.
DR EPD; Q8K3K8; -.
DR jPOST; Q8K3K8; -.
DR MaxQB; Q8K3K8; -.
DR PaxDb; Q8K3K8; -.
DR PeptideAtlas; Q8K3K8; -.
DR PRIDE; Q8K3K8; -.
DR ProteomicsDB; 293520; -.
DR Antibodypedia; 1010; 385 antibodies from 38 providers.
DR DNASU; 71648; -.
DR Ensembl; ENSMUST00000027986; ENSMUSP00000027986; ENSMUSG00000026672.
DR Ensembl; ENSMUST00000114996; ENSMUSP00000110648; ENSMUSG00000026672.
DR GeneID; 71648; -.
DR KEGG; mmu:71648; -.
DR UCSC; uc008ifm.1; mouse.
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; ELQLKMG; -.
DR OrthoDB; 745047at2759; -.
DR PhylomeDB; Q8K3K8; -.
DR TreeFam; TF326608; -.
DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-MMU-8854214; TBC/RABGAPs.
DR BioGRID-ORCS; 71648; 8 hits in 73 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 197 other tissues.
DR Genevisible; Q8K3K8; MM.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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; ISO:MGI.
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:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; 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:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP: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 I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR InterPro; IPR032419; CC2-LZ_dom.
DR InterPro; IPR021063; NEMO_N.
DR InterPro; IPR034735; NEMO_ZF.
DR InterPro; IPR032939; Optineurin.
DR PANTHER; PTHR31553:SF2; PTHR31553:SF2; 1.
DR Pfam; PF16516; CC2-LZ; 1.
DR Pfam; PF11577; NEMO; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
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"
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 interaction with Rab8; accumulation
FT in the retinal outer plexiform layer; loss of retinal
FT ganglion cells and connecting synapses, degeneration of
FT entire retina without elevation of 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
