ID OPTN_HUMAN Reviewed; 577 AA. AC Q96CV9; B3KP00; D3DRS4; D3DRS8; Q5T672; Q5T673; Q5T674; Q5T675; Q7LDL9; AC Q8N562; Q9UET9; Q9UEV4; Q9Y218; DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 28-MAR-2018, sequence version 3. DT 10-JUN-2026, entry version 192. DE RecName: Full=Optineurin; DE AltName: Full=E3-14.7K-interacting protein {ECO:0000303|PubMed:9488477}; DE Short=FIP-2 {ECO:0000303|PubMed:9488477}; DE AltName: Full=Huntingtin yeast partner L; DE AltName: Full=Huntingtin-interacting protein 7; DE Short=HIP-7; DE AltName: Full=Huntingtin-interacting protein L; DE AltName: Full=NEMO-related protein {ECO:0000303|PubMed:10807909}; DE AltName: Full=Optic neuropathy-inducing protein; DE AltName: Full=Transcription factor IIIA-interacting protein; DE Short=TFIIIA-IntP; GN Name=OPTN; GN Synonyms=FIP2 {ECO:0000303|PubMed:9488477}, GLC1E, HIP7, HYPL, NRP GN {ECO:0000303|PubMed:10807909}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000312|Proteomes:UP000005640}; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 3), VARIANTS RP SER-201; HIS-213; ARG-216 AND PRO-357, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, INDUCTION BY TNF, AND INTERACTION WITH ADENOVIRUS E3. RC TISSUE=Cervix carcinoma; RX PubMed=9488477; DOI=10.1128/mcb.18.3.1601; RA Li Y., Kang J., Horwitz M.S.; RT "Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor RT necrosis factor alpha-inducible cellular protein containing leucine zipper RT domains."; RL Mol. Cell. Biol. 18:1601-1610(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, VARIANTS GLC1E LYS-50 AND GLN-545, AND VARIANTS LYS-98; RP SER-201; HIS-213; ARG-216 AND PRO-357. RC TISSUE=Trabecular meshwork; RX PubMed=11834836; DOI=10.1126/science.1066901; RA Rezaie T., Child A., Hitchings R., Brice G., Miller L., Coca-Prados M., RA Heon E., Krupin T., Ritch R., Kreutzer D., Crick R.P., Sarfarazi M.; RT "Adult-onset primary open-angle glaucoma caused by mutations in RT optineurin."; RL Science 295:1077-1079(2002). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-201; HIS-213; ARG-216 RP AND PRO-357. RA Li D., Roberts R.; RT "Human FIP-2: genomic structure and mutational analysis in ARVD patients."; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cervix, and Skin; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 412-555, AND INTERACTION WITH HD. RC TISSUE=Testis; RX PubMed=9700202; DOI=10.1093/hmg/7.9.1463; RA Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F., RA MacDonald M.E.; RT "Huntingtin interacts with a family of WW domain proteins."; RL Hum. Mol. Genet. 7:1463-1474(1998). RN [9] RP INTERACTION WITH HD AND RAB8. RX PubMed=11137014; DOI=10.1016/s0960-9822(00)00864-2; RA Hattula K., Peraenen J.; RT "FIP-2, a coiled-coil protein, links Huntingtin to Rab8 and modulates RT cellular morphogenesis."; RL Curr. Biol. 10:1603-1606(2000). RN [10] RP SUBCELLULAR LOCATION, INDUCTION BY IFNG, AND PHOSPHORYLATION. RX PubMed=10807909; DOI=10.1074/jbc.m001500200; RA Schwamborn K., Weil R., Courtois G., Whiteside S.T., Israeel A.; RT "Phorbol esters and cytokines regulate the expression of the NEMO-related RT protein, a molecule involved in a NF-kappa B-independent pathway."; RL J. Biol. Chem. 275:22780-22789(2000). RN [11] RP INTERACTION WITH GTF3A. RX PubMed=10756201; DOI=10.1093/nar/28.9.1986; RA Moreland R.J., Dresser M.E., Rodgers J.S., Roe B.A., Conaway J.W., RA Conaway R.C., Hanas J.S.; RT "Identification of a transcription factor IIIA-interacting protein."; RL Nucleic Acids Res. 28:1986-1993(2000). RN [12] RP INDUCTION BY INTRAOCULAR PRESSURE, AND TISSUE SPECIFICITY. RX PubMed=12379221; DOI=10.1016/s0006-291x(02)02395-1; RA Vittitow J., Borras T.; RT "Expression of optineurin, a glaucoma-linked gene, is influenced by RT elevated intraocular pressure."; RL Biochem. Biophys. Res. Commun. 298:67-74(2002). RN [13] RP INDUCTION BY INTRAOCULAR PRESSURE, AND TISSUE SPECIFICITY. RX PubMed=12646749; DOI=10.1159/000069133; RA Kamphuis W., Schneemann A.; RT "Optineurin gene expression level in human trabecular meshwork does not RT change in response to pressure elevation."; RL Ophthalmic Res. 35:93-96(2003). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MYO6 AND RAB8. RX PubMed=15837803; DOI=10.1083/jcb.200501162; RA Sahlender D.A., Roberts R.C., Arden S.D., Spudich G., Taylor M.J., RA Luzio J.P., Kendrick-Jones J., Buss F.; RT "Optineurin links myosin VI to the Golgi complex and is involved in Golgi RT organization and exocytosis."; RL J. Cell Biol. 169:285-295(2005). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TFRC; UBIQUITIN AND RAB8A, RP MUTAGENESIS OF GLU-50 AND ASP-474, AND CHARACTERIZATION OF VARIANT GLC1E RP LYS-50. RX PubMed=20085643; DOI=10.1186/1471-2121-11-4; RA Nagabhushana A., Chalasani M.L., Jain N., Radha V., Rangaraj N., RA Balasubramanian D., Swarup G.; RT "Regulation of endocytic trafficking of transferrin receptor by optineurin RT and its impairment by a glaucoma-associated mutant."; RL BMC Cell Biol. 11:4-4(2010). RN [18] RP CHARACTERIZATION OF VARIANT GLC1E LYS-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 [19] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, INTERACTION WITH TBK1 AND TRAF3, RP UBIQUITIN-BINDING MOTIF, AND MUTAGENESIS OF ASP-474. RX PubMed=20174559; DOI=10.1371/journal.ppat.1000778; RA Mankouri J., Fragkoudis R., Richards K.H., Wetherill L.F., Harris M., RA Kohl A., Elliott R.M., Macdonald A.; RT "Optineurin negatively regulates the induction of IFNbeta in response to RT RNA virus infection."; RL PLoS Pathog. 6:E1000778-E1000778(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB8A AND TBC1D17, AND RP CHARACTERIZATION OF VARIANT GLC1E LYS-50. RX PubMed=22854040; DOI=10.1242/jcs.102327; RA Vaibhava V., Nagabhushana A., Chalasani M.L., Sudhakar C., Kumari A., RA Swarup G.; RT "Optineurin mediates a negative regulation of Rab8 by the GTPase-activating RT protein TBC1D17."; RL J. Cell Sci. 125:5026-5039(2012). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [24] RP LIR MOTIF. RX PubMed=23908376; DOI=10.1242/jcs.126128; RA Birgisdottir A.B., Lamark T., Johansen T.; RT "The LIR motif - crucial for selective autophagy."; RL J. Cell Sci. 126:3237-3247(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177 AND SER-526, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP INTERACTION WITH ZDHHC17. RX PubMed=24705354; DOI=10.1093/hmg/ddu137; RA Butland S.L., Sanders S.S., Schmidt M.E., Riechers S.P., Lin D.T., RA Martin D.D., Vaid K., Graham R.K., Singaraja R.R., Wanker E.E., RA Conibear E., Hayden M.R.; RT "The palmitoyl acyltransferase HIP14 shares a high proportion of RT interactors with huntingtin: implications for a role in the pathogenesis of RT Huntington's disease."; RL Hum. Mol. Genet. 23:4142-4160(2014). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177; SER-198 AND SER-342, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [28] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TBK1 AND BLUETONGUE RP VIRUS PROTEIN NS3. RX PubMed=27538435; DOI=10.1186/s12915-016-0292-z; RA Pourcelot M., Zemirli N., Silva Da Costa L., Loyant R., Garcin D., RA Vitour D., Munitic I., Vazquez A., Arnoult D.; RT "The Golgi apparatus acts as a platform for TBK1 activation after viral RNA RT sensing."; RL BMC Biol. 14:69-69(2016). RN [29] RP INTERACTION WITH USP12. RX PubMed=30266909; DOI=10.1038/s41467-018-05653-z; RA Aron R., Pellegrini P., Green E.W., Maddison D.C., Opoku-Nsiah K., RA Oliveira A.O., Wong J.S., Daub A.C., Giorgini F., Muchowski P., RA Finkbeiner S.; RT "Deubiquitinase Usp12 functions noncatalytically to induce autophagy and RT confer neuroprotection in models of Huntington's disease."; RL Nat. Commun. 9:3191-3191(2018). RN [30] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 170-181, STRUCTURE BY NMR OF RP 169-185, INTERACTION WITH MAP1LC3B, AND MUTAGENESIS OF MUTAGENESIS OF RP PHE-178. RX PubMed=23805866; DOI=10.1042/bj20121907; RA Rogov V.V., Suzuki H., Fiskin E., Wild P., Kniss A., Rozenknop A., Kato R., RA Kawasaki M., McEwan D.G., Lohr F., Guntert P., Dikic I., Wakatsuki S., RA Dotsch V.; RT "Structural basis for phosphorylation-triggered autophagic clearance of RT Salmonella."; RL Biochem. J. 454:459-466(2013). RN [31] RP VARIANT LYS-98. RX PubMed=14627677; DOI=10.1136/jmg.40.11.842; RA Melki R., Belmouden A., Akhayat O., Brezin A., Garchon H.-J.; RT "The M98K variant of the OPTINEURIN (OPTN) gene modifies initial RT intraocular pressure in patients with primary open angle glaucoma."; RL J. Med. Genet. 40:842-844(2003). RN [32] RP VARIANTS GLC1E ASP-103 AND ARG-486. RX PubMed=12939304; DOI=10.1167/iovs.02-0693; RA Leung Y.F., Fan B.J., Lam D.S.C., Lee W.S., Tam P.O.S., Chua J.K.H., RA Tham C.C.Y., Lai J.S.M., Fan D.S.P., Pang C.P.; RT "Different optineurin mutation pattern in primary open-angle glaucoma."; RL Invest. Ophthalmol. Vis. Sci. 44:3880-3884(2003). RN [33] RP VARIANT GLC1E GLN-545. RX PubMed=14597044; DOI=10.1016/s0002-9394(03)00577-4; RA Alward W.L.M., Kwon Y.H., Kawase K., Craig J.E., Hayreh S.S., Johnson A.T., RA Khanna C.L., Yamamoto T., Mackey D.A., Roos B.R., Affatigato L.M., RA Sheffield V.C., Stone E.M.; RT "Evaluation of optineurin sequence variations in 1,048 patients with open- RT angle glaucoma."; RL Am. J. Ophthalmol. 136:904-910(2003). RN [34] RP CHARACTERIZATION OF VARIANT LYS-98, AND INTERACTION WITH RAB12. RX PubMed=23357852; DOI=10.4161/auto.23458; RA Sirohi K., Chalasani M.L., Sudhakar C., Kumari A., Radha V., Swarup G.; RT "M98K-OPTN induces transferrin receptor degradation and RAB12-mediated RT autophagic death in retinal ganglion cells."; RL Autophagy 9:510-527(2013). RN [35] RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT GLC1E LYS-50, AND RP MUTAGENESIS OF GLU-50 AND ASP-474. RX PubMed=24752605; DOI=10.1371/journal.pone.0095758; RA Chalasani M.L., Kumari A., Radha V., Swarup G.; RT "E50K-OPTN-induced retinal cell death involves the Rab GTPase-activating RT protein, TBC1D17 mediated block in autophagy."; RL PLoS ONE 9:E95758-E95758(2014). RN [36] RP SELF-ASSOCIATION, SUBCELLULAR LOCATION, INTERACTION WITH TBK1, AND RP CHARACTERIZATION OF VARIANT GLC1E LYS-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 [37] RP VARIANT LYS-98. RX PubMed=15498064; DOI=10.1111/j.1442-9071.2004.00886.x; RA Baird P.N., Richardson A.J., Craig J.E., Mackey D.A., Rochtchina E., RA Mitchell P.; RT "Analysis of optineurin (OPTN) gene mutations in subjects with and without RT glaucoma: the blue mountains eye study."; RL Clin. Exp. Ophthalmol. 32:518-522(2004). RN [38] RP VARIANT GLC1E ARG-486. RX PubMed=15326130; DOI=10.1167/iovs.04-0107; RA Willoughby C.E., Chan L.L.Y., Herd S., Billingsley G., Noordeh N., RA Levin A.V., Buys Y., Trope G., Sarfarazi M., Heon E.; RT "Defining the pathogenicity of optineurin in juvenile open-angle RT glaucoma."; RL Invest. Ophthalmol. Vis. Sci. 45:3122-3130(2004). RN [39] RP VARIANTS GLC1E ASP-26 AND GLN-545, AND VARIANT LYS-98. RX PubMed=15557444; DOI=10.1167/iovs.03-1403; RA Funayama T., Ishikawa K., Ohtake Y., Tanino T., Kurosaka D., Kimura I., RA Suzuki K., Ideta H., Nakamoto K., Yasuda N., Fujimaki T., Murakami A., RA Asaoka R., Hotta Y., Tanihara H., Kanamoto T., Mishima H., Fukuchi T., RA Abe H., Iwata T., Shimada N., Kudoh J., Shimizu N., Mashima Y.; RT "Variants in optineurin gene and their association with tumor necrosis RT factor-alpha polymorphisms in Japanese patients with glaucoma."; RL Invest. Ophthalmol. Vis. Sci. 45:4359-4367(2004). RN [40] RP VARIANT GLC1E ASP-26. RX PubMed=15226658; DOI=10.1097/00061198-200408000-00007; RA Fuse N., Takahashi K., Akiyama H., Nakazawa T., Seimiya M., Kuwahara S., RA Tamai M.; RT "Molecular genetic analysis of optineurin gene for primary open-angle and RT normal tension glaucoma in the Japanese population."; RL J. Glaucoma 13:299-303(2004). RN [41] RP VARIANT NPG ASP-26. RX PubMed=15370540; DOI=10.1080/13816810490514298; RA Umeda T., Matsuo T., Nagayama M., Tamura N., Tanabe Y., Ohtsuki H.; RT "Clinical relevance of optineurin sequence alterations in Japanese glaucoma RT patients."; RL Ophthalmic Genet. 25:91-99(2004). RN [42] RP CHARACTERIZATION OF VARIANT GLC1E LYS-50. RX PubMed=17389490; DOI=10.1167/iovs.06-0834; RA Chalasani M.L., Radha V., Gupta V., Agarwal N., Balasubramanian D., RA Swarup G.; RT "A glaucoma-associated mutant of optineurin selectively induces death of RT retinal ganglion cells which is inhibited by antioxidants."; RL Invest. Ophthalmol. Vis. Sci. 48:1607-1614(2007). RN [43] RP VARIANT ALS12 GLY-478, AND SUBCELLULAR LOCATION. RX PubMed=20428114; DOI=10.1038/nature08971; RA Maruyama H., Morino H., Ito H., Izumi Y., Kato H., Watanabe Y., RA Kinoshita Y., Kamada M., Nodera H., Suzuki H., Komure O., Matsuura S., RA Kobatake K., Morimoto N., Abe K., Suzuki N., Aoki M., Kawata A., Hirai T., RA Kato T., Ogasawara K., Hirano A., Takumi T., Kusaka H., Hagiwara K., RA Kaji R., Kawakami H.; RT "Mutations of optineurin in amyotrophic lateral sclerosis."; RL Nature 465:223-226(2010). RN [44] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAP1LC3A; MAP1LC3B; RP GABARAP; GABARAPL1 AND GABARAPL2, PHOSPHORYLATION AT SER-177 BY TBK1, RP UBIQUITIN-BINDING, AND MUTAGENESIS OF PHE-178 AND 474-ASP-PHE-475. RX PubMed=21617041; DOI=10.1126/science.1205405; RA Wild P., Farhan H., McEwan D.G., Wagner S., Rogov V.V., Brady N.R., RA Richter B., Korac J., Waidmann O., Choudhary C., Dotsch V., Bumann D., RA Dikic I.; RT "Phosphorylation of the autophagy receptor optineurin restricts Salmonella RT growth."; RL Science 333:228-233(2011). RN [45] RP INTERACTION WITH TOM1 AND MYO6. RX PubMed=31371777; DOI=10.1038/s41467-019-11481-6; RA Hu S., Guo Y., Wang Y., Li Y., Fu T., Zhou Z., Wang Y., Liu J., Pan L.; RT "Structure of Myosin VI/Tom1 complex reveals a cargo recognition mode of RT Myosin VI for tethering."; RL Nat. Commun. 10:3459-3459(2019). RN [46] RP INTERACTION WITH CYLD. RX PubMed=32185393; DOI=10.1093/brain/awaa039; RA Dobson-Stone C., Hallupp M., Shahheydari H., Ragagnin A.M.G., RA Chatterton Z., Carew-Jones F., Shepherd C.E., Stefen H., Paric E., Fath T., RA Thompson E.M., Blumbergs P., Short C.L., Field C.D., Panegyres P.K., RA Hecker J., Nicholson G., Shaw A.D., Fullerton J.M., Luty A.A., RA Schofield P.R., Brooks W.S., Rajan N., Bennett M.F., Bahlo M., RA Landers J.E., Piguet O., Hodges J.R., Halliday G.M., Topp S.D., Smith B.N., RA Shaw C.E., McCann E., Fifita J.A., Williams K.L., Atkin J.D., Blair I.P., RA Kwok J.B.; RT "CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral RT sclerosis."; RL Brain 143:783-799(2020). RN [47] RP VARIANT ALS12 PHE-295, CHARACTERIZATION OF VARIANT ALS12 PHE-295, FUNCTION, RP AND SUBCELLULAR LOCATION. RX PubMed=27534431; DOI=10.1080/21678421.2016.1218517; RA Fifita J.A., Williams K.L., Sundaramoorthy V., Mccann E.P., Nicholson G.A., RA Atkin J.D., Blair I.P.; RT "A novel amyotrophic lateral sclerosis mutation in OPTN induces ER stress RT and Golgi fragmentation in vitro."; RL Amyotroph. Lateral Scler. Frontotemporal Degener. 18:126-133(2017). 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 (PubMed:27534431). Links myosin VI CC to the Golgi complex and plays an important role in Golgi ribbon CC formation (PubMed:27534431). Plays a role in the activation of innate CC immune response during viral infection. Mechanistically, recruits TBK1 CC at the Golgi apparatus, promoting its trans-phosphorylation after RLR CC or TLR3 stimulation (PubMed:27538435). In turn, activated TBK1 CC phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. CC Plays a neuroprotective role in the eye and optic nerve. May act by CC regulating membrane trafficking and cellular morphogenesis via a CC complex that contains Rab8 and huntingtin (HD). Mediates the CC interaction of Rab8 with the probable GTPase-activating protein TBC1D17 CC during Rab8-mediated endocytic trafficking, such as that of transferrin CC receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating CC from the endocytic recycling compartment (PubMed:22854040). 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:0000269|PubMed:11834836, CC ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, CC ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, CC ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:27534431, CC ECO:0000269|PubMed:27538435}. CC -!- FUNCTION: (Microbial infection) May constitute a cellular target for CC various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to CC inhibit innate immune response (PubMed:27538435, PubMed:9488477). CC During RNA virus infection, such as that of Sendai virus, negatively CC regulates the induction of IFNB1 (PubMed:20174559). CC {ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:27538435, CC ECO:0000269|PubMed:9488477}. CC -!- SUBUNIT: Self-associates (PubMed:23669351). Interacts with HD CC (PubMed:11137014, PubMed:9700202). Interacts with GTF3A CC (PubMed:10756201). Interacts with MYO6 (PubMed:31371777). Interacts CC (via UBAN) with ubiquitinated TFRC (PubMed:20085643). Interacts with CC GTP-bound Rab8 (RAB8A and/or RAB8B) (PubMed:11137014, PubMed:20085643, CC PubMed:22854040). Interacts with TBC1D17 (PubMed:22854040). Interacts CC with TBK1 (PubMed:20174559, PubMed:23669351, PubMed:27538435). CC Interacts with TRAF3 (PubMed:20174559). Binds to linear ubiquitin CC chains (PubMed:20085643). Interacts with LC3 family members MAP1LC3A, CC MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN phosphorylation CC increases the association (at least with MAP1LC3B). Interacts with CC RAB12; the interaction may be indirect. Interacts with TBK1; this CC interaction leads to the Golgi localization of TBK1 and its subsequent CC activation. Interacts with palmitoyltransferase ZDHHC17/HIP14; the CC interaction does not lead to palmitoylation of OPTN (PubMed:24705354). CC Interacts with CYLD (PubMed:32185393). Interacts with TOM1; the CC interaction is indirect and is mediated by MYO6, which acts as a bridge CC between TOM1 and OPTN (PubMed:31371777). Interacts with USP12; the CC interaction is independent of USP12 deubiquitinase activity and may be CC involved in regulation of autophagic flux (PubMed:30266909). CC {ECO:0000269|PubMed:10756201, ECO:0000269|PubMed:11137014, CC ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, CC ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, CC ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:23357852, CC ECO:0000269|PubMed:23669351, ECO:0000269|PubMed:23805866, CC ECO:0000269|PubMed:24705354, ECO:0000269|PubMed:27538435, CC ECO:0000269|PubMed:30266909, ECO:0000269|PubMed:31371777, CC ECO:0000269|PubMed:32185393, ECO:0000269|PubMed:9700202}. CC -!- SUBUNIT: (Microbial infection) Interacts with E3 14.7 kDa protein of CC group C human adenovirus (PubMed:9488477). Interacts with Bluetongue CC virus protein NS3 (PubMed:27538435). {ECO:0000269|PubMed:27538435, CC ECO:0000269|PubMed:9488477}. CC -!- INTERACTION: CC Q96CV9; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-748974, EBI-22011868; CC Q96CV9; P24666-2: ACP1; NbExp=3; IntAct=EBI-748974, EBI-25910301; CC Q96CV9; Q9H6R3: ACSS3; NbExp=3; IntAct=EBI-748974, EBI-3921478; CC Q96CV9; Q8N302-2: AGGF1; NbExp=3; IntAct=EBI-748974, EBI-25838028; CC Q96CV9; Q12904-2: AIMP1; NbExp=6; IntAct=EBI-748974, EBI-12412735; CC Q96CV9; Q5TZF3-1: ANKRD45; NbExp=3; IntAct=EBI-748974, EBI-22011535; CC Q96CV9; P08758: ANXA5; NbExp=3; IntAct=EBI-748974, EBI-296601; CC Q96CV9; O00203: AP3B1; NbExp=3; IntAct=EBI-748974, EBI-1044383; CC Q96CV9; Q0P5N6: ARL16; NbExp=3; IntAct=EBI-748974, EBI-10186132; CC Q96CV9; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-748974, EBI-2875665; CC Q96CV9; Q9Y574-2: ASB4; NbExp=3; IntAct=EBI-748974, EBI-25911000; CC Q96CV9; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-748974, EBI-10254793; CC Q96CV9; O95671: ASMTL; NbExp=3; IntAct=EBI-748974, EBI-743231; CC Q96CV9; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-748974, EBI-2410266; CC Q96CV9; Q9BUH8: BEGAIN; NbExp=3; IntAct=EBI-748974, EBI-742722; CC Q96CV9; O15392: BIRC5; NbExp=3; IntAct=EBI-748974, EBI-518823; CC Q96CV9; Q9NSI6-4: BRWD1; NbExp=3; IntAct=EBI-748974, EBI-10693038; CC Q96CV9; Q96G97-4: BSCL2; NbExp=3; IntAct=EBI-748974, EBI-10178113; CC Q96CV9; P78410: BTN3A2; NbExp=3; IntAct=EBI-748974, EBI-17564670; CC Q96CV9; Q9UIR0-4: BTNL2; NbExp=3; IntAct=EBI-748974, EBI-25911105; CC Q96CV9; Q32M92-2: C15orf32; NbExp=3; IntAct=EBI-748974, EBI-25911375; CC Q96CV9; Q0P5P2: C17orf67; NbExp=3; IntAct=EBI-748974, EBI-10226540; CC Q96CV9; Q96LL4: C8orf48; NbExp=3; IntAct=EBI-748974, EBI-751596; CC Q96CV9; A2RRN7: CADPS; NbExp=3; IntAct=EBI-748974, EBI-10179719; CC Q96CV9; P07384: CAPN1; NbExp=3; IntAct=EBI-748974, EBI-1542113; CC Q96CV9; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-748974, EBI-10961312; CC Q96CV9; Q9UJX2: CDC23; NbExp=8; IntAct=EBI-748974, EBI-396137; CC Q96CV9; P49450: CENPA; NbExp=3; IntAct=EBI-748974, EBI-1751979; CC Q96CV9; Q9BV73: CEP250; NbExp=3; IntAct=EBI-748974, EBI-1053100; CC Q96CV9; Q9P209: CEP72; NbExp=3; IntAct=EBI-748974, EBI-739498; CC Q96CV9; P23528: CFL1; NbExp=3; IntAct=EBI-748974, EBI-352733; CC Q96CV9; Q3SX64: CIMAP1D; NbExp=3; IntAct=EBI-748974, EBI-6660184; CC Q96CV9; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-748974, EBI-12208021; CC Q96CV9; P15169: CPN1; NbExp=3; IntAct=EBI-748974, EBI-2116369; CC Q96CV9; Q14894: CRYM; NbExp=3; IntAct=EBI-748974, EBI-7107048; CC Q96CV9; Q15038: DAZAP2; NbExp=6; IntAct=EBI-748974, EBI-724310; CC Q96CV9; Q9UBT3: DKK4; NbExp=3; IntAct=EBI-748974, EBI-18030204; CC Q96CV9; Q86TI2-2: DPP9; NbExp=3; IntAct=EBI-748974, EBI-21529239; CC Q96CV9; Q96G46: DUS3L; NbExp=3; IntAct=EBI-748974, EBI-5458011; CC Q96CV9; Q9Y5L3: ENTPD2; NbExp=3; IntAct=EBI-748974, EBI-3913907; CC Q96CV9; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-748974, EBI-21567429; CC Q96CV9; Q3KNW7: FKSG83; NbExp=3; IntAct=EBI-748974, EBI-9087984; CC Q96CV9; P51116: FXR2; NbExp=3; IntAct=EBI-748974, EBI-740459; CC Q96CV9; Q8N1C3: GABRG1; NbExp=3; IntAct=EBI-748974, EBI-21747962; CC Q96CV9; Q49A26-4: GLYR1; NbExp=3; IntAct=EBI-748974, EBI-12143817; CC Q96CV9; O95872: GPANK1; NbExp=3; IntAct=EBI-748974, EBI-751540; CC Q96CV9; Q71DI3: H3C15; NbExp=3; IntAct=EBI-748974, EBI-750650; CC Q96CV9; Q8IYU2: HACE1; NbExp=15; IntAct=EBI-748974, EBI-308277; CC Q96CV9; P61296-2: HAND2; NbExp=3; IntAct=EBI-748974, EBI-13086076; CC Q96CV9; Q969S8: HDAC10; NbExp=3; IntAct=EBI-748974, EBI-301762; CC Q96CV9; A0A1C3PI11: HLA-DPB1; NbExp=3; IntAct=EBI-748974, EBI-25910418; CC Q96CV9; P04440: HLA-DPB1; NbExp=3; IntAct=EBI-748974, EBI-2802503; CC Q96CV9; O75031: HSF2BP; NbExp=3; IntAct=EBI-748974, EBI-7116203; CC Q96CV9; P28566: HTR1E; NbExp=3; IntAct=EBI-748974, EBI-1043151; CC Q96CV9; P42858: HTT; NbExp=13; IntAct=EBI-748974, EBI-466029; CC Q96CV9; Q13123: IK; NbExp=3; IntAct=EBI-748974, EBI-713456; CC Q96CV9; Q96RQ9: IL4I1; NbExp=3; IntAct=EBI-748974, EBI-20831744; CC Q96CV9; Q02556: IRF8; NbExp=3; IntAct=EBI-748974, EBI-2866563; CC Q96CV9; A1A4Y4: IRGM; NbExp=3; IntAct=EBI-748974, EBI-20844678; CC Q96CV9; Q6IE81-3: JADE1; NbExp=3; IntAct=EBI-748974, EBI-12120084; CC Q96CV9; Q8IV33: KIAA0825; NbExp=3; IntAct=EBI-748974, EBI-17702098; CC Q96CV9; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-748974, EBI-1044640; CC Q96CV9; Q14847-2: LASP1; NbExp=3; IntAct=EBI-748974, EBI-9088686; CC Q96CV9; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-748974, EBI-1108377; CC Q96CV9; Q99732: LITAF; NbExp=3; IntAct=EBI-748974, EBI-725647; CC Q96CV9; Q8N448: LNX2; NbExp=3; IntAct=EBI-748974, EBI-2340947; CC Q96CV9; A2RU56: LOC401296; NbExp=3; IntAct=EBI-748974, EBI-9088215; CC Q96CV9; O60711: LPXN; NbExp=3; IntAct=EBI-748974, EBI-744222; CC Q96CV9; P51608: MECP2; NbExp=3; IntAct=EBI-748974, EBI-1189067; CC Q96CV9; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-748974, EBI-4397720; CC Q96CV9; Q9UQ53: MGAT4B; NbExp=3; IntAct=EBI-748974, EBI-725713; CC Q96CV9; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-748974, EBI-21250407; CC Q96CV9; Q9BUB5: MKNK1; NbExp=3; IntAct=EBI-748974, EBI-73837; CC Q96CV9; Q96EY8: MMAB; NbExp=3; IntAct=EBI-748974, EBI-7825413; CC Q96CV9; Q00013: MPP1; NbExp=2; IntAct=EBI-748974, EBI-711788; CC Q96CV9; Q9UDX5: MTFP1; NbExp=3; IntAct=EBI-748974, EBI-1042890; CC Q96CV9; Q96EZ4: MYEOV; NbExp=3; IntAct=EBI-748974, EBI-12260130; CC Q96CV9; Q9Y6Q9-5: NCOA3; NbExp=3; IntAct=EBI-748974, EBI-11057583; CC Q96CV9; Q9Y221: NIP7; NbExp=3; IntAct=EBI-748974, EBI-749003; CC Q96CV9; Q9HBL8: NMRAL1; NbExp=3; IntAct=EBI-748974, EBI-2862643; CC Q96CV9; P54845-1: NRL; NbExp=6; IntAct=EBI-748974, EBI-9819090; CC Q96CV9; Q8WVJ2: NUDCD2; NbExp=3; IntAct=EBI-748974, EBI-1052153; CC Q96CV9; Q8IZS5: OFCC1; NbExp=3; IntAct=EBI-748974, EBI-8477661; CC Q96CV9; Q96CV9: OPTN; NbExp=16; IntAct=EBI-748974, EBI-748974; CC Q96CV9; P51582: P2RY4; NbExp=3; IntAct=EBI-748974, EBI-4392513; CC Q96CV9; Q8IVL6-2: P3H3; NbExp=3; IntAct=EBI-748974, EBI-12149899; CC Q96CV9; Q9Y2D5: PALM2AKAP2; NbExp=3; IntAct=EBI-748974, EBI-1754555; CC Q96CV9; O95340: PAPSS2; NbExp=3; IntAct=EBI-748974, EBI-1053912; CC Q96CV9; Q9BUH6: PAXX; NbExp=3; IntAct=EBI-748974, EBI-2839993; CC Q96CV9; Q08499-8: PDE4D; NbExp=3; IntAct=EBI-748974, EBI-9090666; CC Q96CV9; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-748974, EBI-716063; CC Q96CV9; Q9Y5Y5: PEX16; NbExp=3; IntAct=EBI-748974, EBI-981985; CC Q96CV9; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-748974, EBI-79165; CC Q96CV9; P55058-2: PLTP; NbExp=3; IntAct=EBI-748974, EBI-12701312; CC Q96CV9; P78424: POU6F2; NbExp=3; IntAct=EBI-748974, EBI-12029004; CC Q96CV9; O60927: PPP1R11; NbExp=3; IntAct=EBI-748974, EBI-1048104; CC Q96CV9; P07225: PROS1; NbExp=3; IntAct=EBI-748974, EBI-2803380; CC Q96CV9; P35998: PSMC2; NbExp=3; IntAct=EBI-748974, EBI-359710; CC Q96CV9; Q96PU8: QKI; NbExp=3; IntAct=EBI-748974, EBI-945792; CC Q96CV9; P61026: RAB10; NbExp=3; IntAct=EBI-748974, EBI-726075; CC Q96CV9; P61006: RAB8A; NbExp=4; IntAct=EBI-748974, EBI-722293; CC Q96CV9; P52306-4: RAP1GDS1; NbExp=3; IntAct=EBI-748974, EBI-25910540; CC Q96CV9; Q13702-2: RAPSN; NbExp=3; IntAct=EBI-748974, EBI-22012855; CC Q96CV9; P10276-2: RARA; NbExp=3; IntAct=EBI-748974, EBI-10197061; CC Q96CV9; P50749: RASSF2; NbExp=3; IntAct=EBI-748974, EBI-960081; CC Q96CV9; Q9NTZ6: RBM12; NbExp=7; IntAct=EBI-748974, EBI-310707; CC Q96CV9; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-748974, EBI-10192441; CC Q96CV9; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-748974, EBI-21535400; CC Q96CV9; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-748974, EBI-25829984; CC Q96CV9; Q9NWF9: RNF216; NbExp=3; IntAct=EBI-748974, EBI-723313; CC Q96CV9; Q9BWG1: RNF220; NbExp=3; IntAct=EBI-748974, EBI-10300482; CC Q96CV9; Q99942: RNF5; NbExp=3; IntAct=EBI-748974, EBI-348482; CC Q96CV9; Q9BUL9: RPP25; NbExp=3; IntAct=EBI-748974, EBI-366570; CC Q96CV9; P23297: S100A1; NbExp=3; IntAct=EBI-748974, EBI-743686; CC Q96CV9; O00560: SDCBP; NbExp=3; IntAct=EBI-748974, EBI-727004; CC Q96CV9; Q2NKQ1-4: SGSM1; NbExp=3; IntAct=EBI-748974, EBI-10182463; CC Q96CV9; Q96QE2: SLC2A13; NbExp=3; IntAct=EBI-748974, EBI-18082698; CC Q96CV9; Q9NY26: SLC39A1; NbExp=3; IntAct=EBI-748974, EBI-726491; CC Q96CV9; Q15797: SMAD1; NbExp=3; IntAct=EBI-748974, EBI-1567153; CC Q96CV9; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-748974, EBI-358489; CC Q96CV9; Q53HV7-2: SMUG1; NbExp=3; IntAct=EBI-748974, EBI-12275818; CC Q96CV9; Q13573: SNW1; NbExp=3; IntAct=EBI-748974, EBI-632715; CC Q96CV9; Q496A3: SPATS1; NbExp=3; IntAct=EBI-748974, EBI-3923692; CC Q96CV9; Q9NRA0: SPHK2; NbExp=3; IntAct=EBI-748974, EBI-985324; CC Q96CV9; Q13501: SQSTM1; NbExp=7; IntAct=EBI-748974, EBI-307104; CC Q96CV9; Q92185: ST8SIA1; NbExp=3; IntAct=EBI-748974, EBI-21541735; CC Q96CV9; Q13586: STIM1; NbExp=3; IntAct=EBI-748974, EBI-448878; CC Q96CV9; Q9P2R7: SUCLA2; NbExp=3; IntAct=EBI-748974, EBI-2269898; CC Q96CV9; Q8N205-2: SYNE4; NbExp=3; IntAct=EBI-748974, EBI-12099160; CC Q96CV9; P26639: TARS1; NbExp=3; IntAct=EBI-748974, EBI-1042683; CC Q96CV9; Q8TC07: TBC1D15; NbExp=9; IntAct=EBI-748974, EBI-1048247; CC Q96CV9; Q9HA65: TBC1D17; NbExp=7; IntAct=EBI-748974, EBI-714625; CC Q96CV9; Q9UHD2: TBK1; NbExp=17; IntAct=EBI-748974, EBI-356402; CC Q96CV9; P28347-2: TEAD1; NbExp=3; IntAct=EBI-748974, EBI-12151837; CC Q96CV9; P54274-2: TERF1; NbExp=3; IntAct=EBI-748974, EBI-711018; CC Q96CV9; Q6YHU6: THADA; NbExp=3; IntAct=EBI-748974, EBI-2824523; CC Q96CV9; Q8TBB0: THAP6; NbExp=3; IntAct=EBI-748974, EBI-3925505; CC Q96CV9; P52888: THOP1; NbExp=3; IntAct=EBI-748974, EBI-372399; CC Q96CV9; Q15025: TNIP1; NbExp=23; IntAct=EBI-748974, EBI-357849; CC Q96CV9; I6L9D0: TTLL7; NbExp=3; IntAct=EBI-748974, EBI-9092141; CC Q96CV9; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-748974, EBI-9088812; CC Q96CV9; P49459: UBE2A; NbExp=3; IntAct=EBI-748974, EBI-2339348; CC Q96CV9; O75604: USP2; NbExp=3; IntAct=EBI-748974, EBI-743272; CC Q96CV9; P18206-2: VCL; NbExp=3; IntAct=EBI-748974, EBI-11027067; CC Q96CV9; O15195-2: VILL; NbExp=3; IntAct=EBI-748974, EBI-21845957; CC Q96CV9; Q9Y3C0: WASHC3; NbExp=17; IntAct=EBI-748974, EBI-712969; CC Q96CV9; Q8IZQ1-2: WDFY3; NbExp=3; IntAct=EBI-748974, EBI-10264625; CC Q96CV9; Q6ZS81-2: WDFY4; NbExp=3; IntAct=EBI-748974, EBI-25911158; CC Q96CV9; O43829: ZBTB14; NbExp=3; IntAct=EBI-748974, EBI-10176632; CC Q96CV9; P10074: ZBTB48; NbExp=3; IntAct=EBI-748974, EBI-744864; CC Q96CV9; Q8N5A5-2: ZGPAT; NbExp=3; IntAct=EBI-748974, EBI-10183064; CC Q96CV9; Q96EF9: ZHX1-C8orf76; NbExp=3; IntAct=EBI-748974, EBI-25830993; CC Q96CV9; P17029: ZKSCAN1; NbExp=3; IntAct=EBI-748974, EBI-10199654; CC Q96CV9; Q96NC0: ZMAT2; NbExp=4; IntAct=EBI-748974, EBI-2682299; CC Q96CV9; Q5VZL5-4: ZMYM4; NbExp=3; IntAct=EBI-748974, EBI-10984536; CC Q96CV9; O95789: ZMYM6; NbExp=2; IntAct=EBI-748974, EBI-2514645; CC Q96CV9; P17021: ZNF17; NbExp=3; IntAct=EBI-748974, EBI-1105334; CC Q96CV9; Q9Y2X9: ZNF281; NbExp=3; IntAct=EBI-748974, EBI-396200; CC Q96CV9; Q9NR11-2: ZNF302; NbExp=3; IntAct=EBI-748974, EBI-12988373; CC Q96CV9; Q86UD4: ZNF329; NbExp=3; IntAct=EBI-748974, EBI-7233259; CC Q96CV9; Q8TD17: ZNF398; NbExp=3; IntAct=EBI-748974, EBI-8643207; CC Q96CV9; Q96HQ0: ZNF419; NbExp=3; IntAct=EBI-748974, EBI-10288482; CC Q96CV9; Q9BUY5: ZNF426; NbExp=4; IntAct=EBI-748974, EBI-743265; CC Q96CV9; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-748974, EBI-12010736; CC Q96CV9; Q9NWS9-2: ZNF446; NbExp=3; IntAct=EBI-748974, EBI-740232; CC Q96CV9; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-748974, EBI-25831733; CC Q96CV9; Q96LX8: ZNF597; NbExp=3; IntAct=EBI-748974, EBI-9091553; CC Q96CV9; Q9BS34: ZNF670; NbExp=6; IntAct=EBI-748974, EBI-745276; CC Q96CV9; Q9C0D3: ZYG11B; NbExp=3; IntAct=EBI-748974, EBI-1811414; CC Q96CV9; Q8N1Y9; NbExp=3; IntAct=EBI-748974, EBI-25911564; CC Q96CV9; Q29122: MYO6; Xeno; NbExp=3; IntAct=EBI-748974, EBI-15804516; CC Q96CV9; PRO_0000045599 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-748974, EBI-6858501; CC Q96CV9-2; Q92870-2: APBB2; NbExp=3; IntAct=EBI-9091423, EBI-21535880; CC Q96CV9-2; P50570-2: DNM2; NbExp=3; IntAct=EBI-9091423, EBI-10968534; CC Q96CV9-2; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-9091423, EBI-11110431; CC Q96CV9-2; P42858: HTT; NbExp=18; IntAct=EBI-9091423, EBI-466029; CC Q96CV9-2; Q99732: LITAF; NbExp=3; IntAct=EBI-9091423, EBI-725647; CC Q96CV9-2; P49821: NDUFV1; NbExp=3; IntAct=EBI-9091423, EBI-748312; CC Q96CV9-2; O14656-2: TOR1A; NbExp=3; IntAct=EBI-9091423, EBI-25847109; CC Q96CV9-2; O76024: WFS1; NbExp=3; IntAct=EBI-9091423, EBI-720609; CC Q96CV9-2; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-9091423, EBI-524753; CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Golgi apparatus CC {ECO:0000269|PubMed:10807909, ECO:0000269|PubMed:20085643, CC ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:27534431, CC ECO:0000269|PubMed:27538435}. Golgi apparatus, trans-Golgi network. CC Cytoplasmic vesicle, autophagosome. Cytoplasmic vesicle. Recycling CC endosome {ECO:0000269|PubMed:20085643}. Note=Found in the perinuclear CC region and associates with the Golgi apparatus (PubMed:27534431). CC Colocalizes with MYO6 and RAB8 at the Golgi complex and in vesicular CC structures close to the plasma membrane. Localizes to LC3-positive CC cytoplasmic vesicles upon induction of autophagy. CC {ECO:0000269|PubMed:27534431}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96CV9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96CV9-2; Sequence=VSP_013262; CC Name=3; CC IsoId=Q96CV9-3; Sequence=VSP_013261; CC -!- TISSUE SPECIFICITY: Present in aqueous humor of the eye (at protein CC level). Expressed in the trabecular meshwork (at protein level) CC (PubMed:11834836, PubMed:12379221, PubMed:12646749). Expressed in CC nonpigmented ciliary epithelium (at protein level) (PubMed:11834836). CC Expressed at high levels in skeletal muscle, also detected in heart, CC brain, pancreas, kidney, placenta and liver (PubMed:9488477). Expressed CC in dermal fibroblasts (at protein level) (PubMed:11834836). CC {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:12379221, CC ECO:0000269|PubMed:12646749, ECO:0000269|PubMed:9488477}. CC -!- INDUCTION: Up-regulated by TNF (PubMed:10807909, PubMed:12379221, CC PubMed:9488477). Up-regulated by IFNG. TNF and IFNG act synergistically CC to stimulate OPTN expression (PubMed:10807909). Induced by CC glucocorticoids, such as dexamethasone (PubMed:12379221). In an in CC vitro experimental setting, in which donor eyes are subjected to CC increased perfusion pressure (10 to 30 mm Hg) in the anterior chamber, CC there is no up-regulation in the trabecular meshwork at the transcript CC level for periods ranging between 1 and 24 hours (PubMed:12646749). CC However, exposure to continuous elevated pressure for several days CC shows an induction of OPTN expression, with a 56% increase after 7 days CC (PubMed:12379221). {ECO:0000269|PubMed:10807909, CC ECO:0000269|PubMed:12379221, ECO:0000269|PubMed:12646749, CC ECO:0000269|PubMed:9488477}. CC -!- INDUCTION: (Microbial infection) Up-regulated in response to Sendai CC virus infection or double stranded RNA treatment (at protein level); CC the up-regulation is direct and not mediated through a response to type CC I interferons; this may negatively regulate the interferon response to CC RNA-activated antiviral signaling pathways. CC {ECO:0000269|PubMed:20174559}. CC -!- DOMAIN: Ubiquitin-binding motif (UBAN), also called UBD, is essential CC for subcellular localization to recycling endosomes and for proper CC trafficking of transferrin to the juxtanuclear region. It is involved CC in interaction with ubiquitinated TFRC. {ECO:0000269|PubMed:20085643}. CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction CC with ATG8 family proteins. {ECO:0000269|PubMed:23908376}. CC -!- PTM: Phosphorylated by TBK1, leading to restrict bacterial CC proliferation in case of infection. Phosphorylation is induced by CC phorbol esters and decreases its half-time. CC {ECO:0000269|PubMed:10807909, ECO:0000269|PubMed:21617041}. CC -!- DISEASE: Glaucoma 1, open angle, E (GLC1E) [MIM:137760]: A form of CC primary open angle glaucoma (POAG). POAG is characterized by a specific CC pattern of optic nerve and visual field defects. The angle of the CC anterior chamber of the eye is open, and usually the intraocular CC pressure is increased. However, glaucoma can occur at any intraocular CC pressure. The disease is generally asymptomatic until the late stages, CC by which time significant and irreversible optic nerve damage has CC already taken place. {ECO:0000269|PubMed:11834836, CC ECO:0000269|PubMed:12939304, ECO:0000269|PubMed:14597044, CC ECO:0000269|PubMed:15226658, ECO:0000269|PubMed:15326130, CC ECO:0000269|PubMed:15557444, ECO:0000269|PubMed:17389490, CC ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20388642, CC ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:23669351, CC ECO:0000269|PubMed:24752605}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Glaucoma, normal pressure (NPG) [MIM:606657]: A primary CC glaucoma characterized by intraocular pression consistently within the CC statistically normal population range. {ECO:0000269|PubMed:15370540}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Amyotrophic lateral sclerosis 12 with or without CC frontotemporal dementia (ALS12) [MIM:613435]: A form of amyotrophic CC lateral sclerosis, a neurodegenerative disorder affecting upper motor CC neurons in the brain and lower motor neurons in the brain stem and CC spinal cord, resulting in fatal paralysis. Sensory abnormalities are CC absent. The pathologic hallmarks of the disease include pallor of the CC corticospinal tract due to loss of motor neurons, presence of CC ubiquitin-positive inclusions within surviving motor neurons, and CC deposition of pathologic aggregates. The etiology of amyotrophic CC lateral sclerosis is likely to be multifactorial, involving both CC genetic and environmental factors. The disease is inherited in 5-10% of CC the cases. ALS12 inheritance can be autosomal dominant or autosomal CC recessive. There is also sporadic occurrence. ALS12 patients may CC develop frontotemporal dementia. {ECO:0000269|PubMed:20428114, CC ECO:0000269|PubMed:27534431}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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; AF061034; AAC16046.1; -; mRNA. DR EMBL; AF061034; AAC16047.1; -; mRNA. DR EMBL; AF420371; AAL76327.1; -; mRNA. DR EMBL; AF420372; AAL76328.1; -; mRNA. DR EMBL; AF420373; AAL76329.1; -; mRNA. DR EMBL; AF283527; AAG00497.1; -; Genomic_DNA. DR EMBL; AF283520; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283521; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283522; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283523; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283524; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283525; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AF283526; AAG00497.1; JOINED; Genomic_DNA. DR EMBL; AK055403; BAG51512.1; -; mRNA. DR EMBL; AL355355; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471072; EAW86301.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86302.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86303.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86304.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86306.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86308.1; -; Genomic_DNA. DR EMBL; CH471072; EAW86309.1; -; Genomic_DNA. DR EMBL; BC013876; AAH13876.1; -; mRNA. DR EMBL; BC032762; AAH32762.1; -; mRNA. DR EMBL; AF049614; AAC26850.1; -; mRNA. DR CCDS; CCDS7094.1; -. [Q96CV9-1] DR RefSeq; NP_001008212.1; NM_001008211.1. [Q96CV9-1] DR RefSeq; NP_001008213.1; NM_001008212.2. [Q96CV9-1] DR RefSeq; NP_001008214.1; NM_001008213.1. [Q96CV9-1] DR RefSeq; NP_068815.2; NM_021980.4. [Q96CV9-1] DR PDB; 2LO4; NMR; -; A=550-577. DR PDB; 2LUE; NMR; -; B=169-185. DR PDB; 3VTV; X-ray; 1.70 A; A=170-181. DR PDB; 3VTW; X-ray; 2.52 A; A/B/C=170-181. DR PDB; 5AAZ; NMR; -; A=548-577. DR PDB; 5B83; X-ray; 2.69 A; B/C/E/F=416-510. DR PDB; 5EOA; X-ray; 2.50 A; A/B=26-103. DR PDB; 5EOF; X-ray; 2.05 A; A/B=26-103. DR PDB; 7CZM; X-ray; 2.00 A; C/D=173-185. DR PDB; 9B0B; X-ray; 1.70 A; A/B/C/D=419-512. DR PDB; 9B0Z; X-ray; 2.41 A; A/B=419-512. DR PDB; 9B12; X-ray; 1.81 A; C/D/E/F=419-512. DR PDB; 9IKQ; X-ray; 1.93 A; C/D=133-170. DR PDB; 9M0O; X-ray; 1.83 A; A=138-170. DR PDBsum; 2LO4; -. DR PDBsum; 2LUE; -. DR PDBsum; 3VTV; -. DR PDBsum; 3VTW; -. DR PDBsum; 5AAZ; -. DR PDBsum; 5B83; -. DR PDBsum; 5EOA; -. DR PDBsum; 5EOF; -. DR PDBsum; 7CZM; -. DR PDBsum; 9B0B; -. DR PDBsum; 9B0Z; -. DR PDBsum; 9B12; -. DR PDBsum; 9IKQ; -. DR PDBsum; 9M0O; -. DR AlphaFoldDB; Q96CV9; -. DR SMR; Q96CV9; -. DR BioGRID; 115436; 448. DR CORUM; Q96CV9; -. DR DIP; DIP-42001N; -. DR FunCoup; Q96CV9; 1536. DR IntAct; Q96CV9; 278. DR MINT; Q96CV9; -. DR NDEx; IQUERY-CP-OPTN; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000368022; -. DR TCDB; 8.A.157.1.1; the optineurin (optn) family. DR GlyCosmos; Q96CV9; 1 site, 1 glycan. DR GlyGen; Q96CV9; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q96CV9; -. DR MetOSite; Q96CV9; -. DR PhosphoSitePlus; Q96CV9; -. DR BioMuta; OPTN; -. DR DMDM; 317373403; -. DR jPOST; Q96CV9; -. DR MassIVE; Q96CV9; -. DR PaxDb; 9606-ENSP00000368022; -. DR PeptideAtlas; Q96CV9; -. DR ProteomicsDB; 76226; -. [Q96CV9-1] DR ProteomicsDB; 76227; -. [Q96CV9-2] DR ProteomicsDB; 76228; -. [Q96CV9-3] DR Pumba; Q96CV9; -. DR ABCD; Q96CV9; 1 sequenced antibody. DR Antibodypedia; 1010; 394 antibodies from 39 providers. DR DNASU; 10133; -. DR Ensembl; ENST00000263036.9; ENSP00000263036.3; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000378747.8; ENSP00000368021.3; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000378748.7; ENSP00000368022.3; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000378752.7; ENSP00000368027.3; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000378757.6; ENSP00000368032.2; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000378764.6; ENSP00000368040.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867523.1; ENSP00000537582.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867524.1; ENSP00000537583.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867525.1; ENSP00000537584.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867526.1; ENSP00000537585.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867527.1; ENSP00000537586.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867528.1; ENSP00000537587.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867530.1; ENSP00000537589.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867531.1; ENSP00000537590.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867533.1; ENSP00000537592.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867534.1; ENSP00000537593.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867535.1; ENSP00000537594.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867536.1; ENSP00000537595.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867537.1; ENSP00000537596.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867538.1; ENSP00000537597.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867539.1; ENSP00000537598.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867543.1; ENSP00000537602.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867545.1; ENSP00000537604.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867546.1; ENSP00000537605.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867547.1; ENSP00000537606.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867548.1; ENSP00000537607.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867550.1; ENSP00000537609.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867551.1; ENSP00000537610.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867554.1; ENSP00000537613.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867555.1; ENSP00000537614.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867557.1; ENSP00000537616.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867558.1; ENSP00000537617.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000867559.1; ENSP00000537618.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000867560.1; ENSP00000537619.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000921482.1; ENSP00000591541.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942671.1; ENSP00000612730.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942672.1; ENSP00000612731.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942673.1; ENSP00000612732.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942678.1; ENSP00000612737.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942679.1; ENSP00000612738.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942680.1; ENSP00000612739.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942685.1; ENSP00000612744.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942686.1; ENSP00000612745.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942687.1; ENSP00000612746.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942688.1; ENSP00000612747.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942689.1; ENSP00000612748.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942690.1; ENSP00000612749.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942692.1; ENSP00000612751.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942693.1; ENSP00000612752.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942697.1; ENSP00000612756.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942701.1; ENSP00000612760.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942702.1; ENSP00000612761.1; ENSG00000123240.18. [Q96CV9-2] DR Ensembl; ENST00000942704.1; ENSP00000612763.1; ENSG00000123240.18. [Q96CV9-1] DR Ensembl; ENST00000942711.1; ENSP00000612770.1; ENSG00000123240.18. [Q96CV9-1] DR GeneID; 10133; -. DR KEGG; hsa:10133; -. DR MANE-Select; ENST00000378747.8; ENSP00000368021.3; NM_001008212.2; NP_001008213.1. DR UCSC; uc001ilv.2; human. [Q96CV9-1] DR AGR; HGNC:17142; -. DR ClinPGx; PA31948; -. DR CTD; 10133; -. DR DisGeNET; 10133; -. DR GeneCards; OPTN; -. DR HGNC; HGNC:17142; OPTN. DR HPA; ENSG00000123240; Group enriched (skeletal muscle, tongue). DR MalaCards; OPTN; -. DR MIM; 137760; phenotype. DR MIM; 602432; gene. DR MIM; 606657; phenotype. DR MIM; 613435; phenotype. DR OpenTargets; ENSG00000123240; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR VEuPathDB; HostDB:ENSG00000123240; -. DR eggNOG; ENOG502QTG2; Eukaryota. DR GeneTree; ENSGT00530000063808; -. DR HOGENOM; CLU_034097_1_0_1; -. DR InParanoid; Q96CV9; -. DR OMA; NETICAR; -. DR OrthoDB; 6343844at2759; -. DR PAN-GO; Q96CV9; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q96CV9; -. DR PathwayCommons; Q96CV9; -. DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition. DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-HSA-5357786; TNFR1-induced proapoptotic signaling. DR Reactome; R-HSA-5357905; Regulation of TNFR1 signaling. DR Reactome; R-HSA-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-HSA-8854214; TBC/RABGAPs. DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7. DR Reactome; R-HSA-936964; Activation of IRF3, IRF7 mediated by TBK1, IKKEpsilon (IKBKE). DR Reactome; R-HSA-9824878; Regulation of TBK1, IKKEpsilon (IKBKE)-mediated activation of IRF3, IRF7. DR Reactome; R-HSA-9828211; Regulation of TBK1, IKKEpsilon-mediated activation of IRF3, IRF7 upon TLR3 ligation. DR SignaLink; Q96CV9; -. DR SIGNOR; Q96CV9; -. DR Agora; ENSG00000123240; -. DR BioGRID-ORCS; 10133; 17 hits in 1177 CRISPR screens. DR ChiTaRS; OPTN; human. DR EvolutionaryTrace; Q96CV9; -. DR GeneWiki; Optineurin; -. DR GenomeRNAi; 10133; -. DR Pharos; Q96CV9; Tbio. DR PRO; PR:Q96CV9; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q96CV9; protein. DR Bgee; ENSG00000123240; Expressed in amniotic fluid and 209 other cell types or tissues. DR ExpressionAtlas; Q96CV9; baseline and differential. DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0055038; C:recycling endosome membrane; TAS:Reactome. DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central. DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:ParkinsonsUK-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0008219; P:cell death; TAS:ProtInc. DR GO; GO:0034620; P:cellular response to unfolded protein; IMP:UniProtKB. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB. DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB. DR GO; GO:0090161; P:Golgi ribbon formation; IDA:UniProtKB. DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IMP:UniProtKB. DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW. DR GO; GO:0001920; P:negative regulation of receptor recycling; IMP:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:GO_Central. DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0034067; P:protein localization to Golgi apparatus; IMP:UniProtKB. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0061734; P:type 2 mitophagy; IMP:ParkinsonsUK-UCL. DR CDD; cd09803; UBAN; 1. DR DisProt; DP03201; -. DR FunFam; 1.20.5.390:FF:000004; Optineurin; 1. DR FunFam; 1.20.5.390:FF:000007; Optineurin; 1. DR FunFam; 1.20.5.990:FF:000002; Optineurin; 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 IDEAL; IID00348; -. DR InterPro; IPR032419; CC2-LZ_dom. DR InterPro; IPR021063; NEMO_N. DR InterPro; IPR034735; NEMO_ZF. DR InterPro; IPR051301; Optineurin/NFkB_EssMod. 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. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis; KW Autophagy; Coiled coil; Cytoplasm; Cytoplasmic vesicle; Disease variant; KW Endosome; Glaucoma; Golgi apparatus; Host-virus interaction; Immunity; KW Innate immunity; Metal-binding; Neurodegeneration; Phosphoprotein; KW Proteomics identification; Reference proteome; Zinc; Zinc-finger. FT CHAIN 1..577 FT /note="Optineurin" FT /id="PRO_0000058066" FT ZN_FING 547..577 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..209 FT /note="Interaction with Rab8" FT REGION 101..143 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 186..209 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 261..297 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 411..577 FT /note="Interaction with HD" FT REGION 412..520 FT /note="Interaction with MYO6" FT /evidence="ECO:0000269|PubMed:15837803" FT COILED 38..170 FT /evidence="ECO:0000255" FT COILED 239..508 FT /evidence="ECO:0000255" FT MOTIF 176..181 FT /note="LIR" FT MOTIF 474..479 FT /note="UBAN" FT COMPBIAS 186..197 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 261..274 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 281..292 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 555 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142" FT BINDING 558 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142" FT BINDING 571 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142" FT BINDING 575 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142" FT MOD_RES 177 FT /note="Phosphoserine; by TBK1" FT /evidence="ECO:0000269|PubMed:21617041, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 198 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 342 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 526 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..57 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:9488477" FT /id="VSP_013261" FT VAR_SEQ 210..215 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013262" FT VARIANT 26 FT /note="H -> D (in GLC1E; dbSNP:rs200710076)" FT /evidence="ECO:0000269|PubMed:15226658, FT ECO:0000269|PubMed:15370540, ECO:0000269|PubMed:15557444" FT /id="VAR_021537" FT VARIANT 50 FT /note="E -> K (in GLC1E; selectively promotes cell death of FT retinal ganglion cells probably by inducing FT TBC1D17-mediated inhibition of autophagy; affects FT Rab8-mediated endocytic trafficking; no effect on FT interaction with TBC1D17; increases colocalization with FT TBC1D17 and Rab8; increases interaction with TFRC and FT impairs its endocytic recycling; increases interactions FT with TBK1; decreases self-association; disturbs transition FT from the ER to Golgi; no effect on ubiquitin-binding; FT increases interaction with RAB8A as shown by FT immunoprecipitation in transfected HeLa cells, although FT other assays in yeast and mice show loss of direct FT interaction, it has been proposed that the variant might FT abolish direct interaction with Rab8 and enhance indirect FT interaction, hence altering the functional positioning of FT the molecules in the complex in such a way that it leads to FT constitutive or increased inactivation of Rab8 by TBC1D17; FT dbSNP:rs28939688)" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:17389490, ECO:0000269|PubMed:20085643, FT ECO:0000269|PubMed:20388642, ECO:0000269|PubMed:22854040, FT ECO:0000269|PubMed:23669351, ECO:0000269|PubMed:24752605" FT /id="VAR_021538" FT VARIANT 98 FT /note="M -> K (may modify intraocular pressure and increase FT risk of GLC1E and NPG; induces TFRC degradation leading to FT autophagic death in retinal ganglion cells; FT dbSNP:rs11258194)" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:14627677, ECO:0000269|PubMed:15498064, FT ECO:0000269|PubMed:15557444, ECO:0000269|PubMed:23357852" FT /id="VAR_021539" FT VARIANT 103 FT /note="E -> D (in GLC1E; dbSNP:rs1346865805)" FT /evidence="ECO:0000269|PubMed:12939304" FT /id="VAR_021540" FT VARIANT 201 FT /note="P -> S" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:9488477, ECO:0000269|Ref.3" FT /id="VAR_021541" FT VARIANT 213 FT /note="K -> H (requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:9488477, ECO:0000269|Ref.3" FT /id="VAR_021542" FT VARIANT 216 FT /note="S -> R (in dbSNP:rs750088207)" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:9488477, ECO:0000269|Ref.3" FT /id="VAR_021543" FT VARIANT 295 FT /note="V -> F (in ALS12; no effect on Golgi subcellular FT location; no effect on protein expression level; increased FT Golgi fragmentation; decreased Golgi ribbon formation; FT increased susceptibility to endoplasmic reticulum (ER) FT stress; dbSNP:rs761558354)" FT /evidence="ECO:0000269|PubMed:27534431" FT /id="VAR_078108" FT VARIANT 308 FT /note="S -> P (in dbSNP:rs7068431)" FT /id="VAR_030769" FT VARIANT 322 FT /note="E -> K (in dbSNP:rs523747)" FT /id="VAR_021544" FT VARIANT 357 FT /note="T -> P" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:9488477, ECO:0000269|Ref.3" FT /id="VAR_021545" FT VARIANT 478 FT /note="E -> G (in ALS12; dbSNP:rs267606929)" FT /evidence="ECO:0000269|PubMed:20428114" FT /id="VAR_063597" FT VARIANT 486 FT /note="H -> R (in GLC1E; juvenile onset; FT dbSNP:rs373425395)" FT /evidence="ECO:0000269|PubMed:12939304, FT ECO:0000269|PubMed:15326130" FT /id="VAR_021546" FT VARIANT 545 FT /note="R -> Q (in GLC1E; uncertain significance; FT dbSNP:rs75654767)" FT /evidence="ECO:0000269|PubMed:11834836, FT ECO:0000269|PubMed:14597044, ECO:0000269|PubMed:15557444" FT /id="VAR_021547" FT MUTAGEN 50 FT /note="E->K: No effect on retinal ganglion cell death, FT decreased interaction with TFRC, loss of localization to FT recycling endosomes, loss of ubiquitin-binding; when FT associated with N-474." FT /evidence="ECO:0000269|PubMed:20085643, FT ECO:0000269|PubMed:24752605" FT MUTAGEN 178 FT /note="F->A: Abolishes interaction with MAP1LC3A and FT GABARAPL1, no effect on binding to linear ubiquitin." FT /evidence="ECO:0000269|PubMed:21617041, FT ECO:0000269|PubMed:23805866" FT MUTAGEN 178 FT /note="F->W: Increases interaction with MAP1LC3B." FT /evidence="ECO:0000269|PubMed:21617041, FT ECO:0000269|PubMed:23805866" FT MUTAGEN 474..475 FT /note="DF->NA: Abolishes colocalization with cytosolic FT Salmonella." FT /evidence="ECO:0000269|PubMed:21617041" FT MUTAGEN 474 FT /note="D->N: No effect on retinal ganglion cell death, FT drastically decreased interaction with TFRC, loss of FT localization to recycling endosomes, loss of FT ubiquitin-binding; when associated with K-50." FT /evidence="ECO:0000269|PubMed:20085643, FT ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:24752605" FT MUTAGEN 474 FT /note="D->N: Significant reduction in ubiquitin binding, FT decreased interaction with TBK1, loss of localization to FT recycling endosomes, disruption of interaction with TFRC, FT loss of inhibition of IFNB activation in response to TLR3 FT or RIG-I signaling, no effect on retinal ganglion cell FT death." FT /evidence="ECO:0000269|PubMed:20085643, FT ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:24752605" FT CONFLICT 436 FT /note="A -> V (in Ref. 8; AAC26850)" FT /evidence="ECO:0000305" FT TURN 30..33 FT /evidence="ECO:0007829|PDB:5EOF" FT HELIX 37..98 FT /evidence="ECO:0007829|PDB:5EOF" FT HELIX 136..139 FT /evidence="ECO:0007829|PDB:9IKQ" FT HELIX 140..168 FT /evidence="ECO:0007829|PDB:9IKQ" FT STRAND 177..180 FT /evidence="ECO:0007829|PDB:7CZM" FT HELIX 421..468 FT /evidence="ECO:0007829|PDB:9B0B" FT HELIX 470..502 FT /evidence="ECO:0007829|PDB:9B0B" FT TURN 556..560 FT /evidence="ECO:0007829|PDB:2LO4" FT STRAND 561..564 FT /evidence="ECO:0007829|PDB:5AAZ" FT HELIX 566..574 FT /evidence="ECO:0007829|PDB:2LO4" SQ SEQUENCE 577 AA; 65922 MW; 2BAF841BA515AAE2 CRC64; MSHQPLSCLT EKEDSPSEST GNGPPHLAHP NLDTFTPEEL LQQMKELLTE NHQLKEAMKL NNQAMKGRFE ELSAWTEKQK EERQFFEIQS KEAKERLMAL SHENEKLKEE LGKLKGKSER SSEDPTDDSR LPRAEAEQEK DQLRTQVVRL QAEKADLLGI VSELQLKLNS SGSSEDSFVE IRMAEGEAEG SVKEIKHSPG PTRTVSTGTA LSKYRSRSAD GAKNYFEHEE LTVSQLLLCL REGNQKVERL EVALKEAKER VSDFEKKTSN RSEIETQTEG STEKENDEEK GPETVGSEVE ALNLQVTSLF KELQEAHTKL SEAELMKKRL QEKCQALERK NSAIPSELNE KQELVYTNKK LELQVESMLS EIKMEQAKTE DEKSKLTVLQ MTHNKLLQEH NNALKTIEEL TRKESEKVDR AVLKELSEKL ELAEKALASK QLQMDEMKQT IAKQEEDLET MTILRAQMEV YCSDFHAERA AREKIHEEKE QLALQLAVLL KENDAFEDGG RQSLMEMQSR HGARTSDSDQ QAYLVQRGAE DRDWRQQRNI PIHSCPKCGE VLPDIDTLQI HVMDCII //