OPTN_HUMAN
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 03-AUG-2022, entry version 174.
DE RecName: Full=Optineurin;
DE AltName: Full=E3-14.7K-interacting protein;
DE AltName: Full=FIP-2;
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;
DE AltName: Full=Optic neuropathy-inducing protein;
DE AltName: Full=Transcription factor IIIA-interacting protein;
DE Short=TFIIIA-IntP;
GN Name=OPTN; Synonyms=FIP2, GLC1E, HIP7, HYPL, NRP;
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;
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, 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, 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.
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.
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 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 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 [19]
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 [20]
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 [21]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TBC1D17, INTERACTION WITH
RP RAB8A, AND 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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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. Plays a
CC neuroprotective role in the eye and optic nerve. May act by regulating
CC membrane trafficking and cellular morphogenesis via a complex that
CC contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8
CC with the probable GTPase-activating protein TBC1D17 during Rab8-
CC mediated endocytic trafficking, such as of transferrin receptor
CC (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the
CC endocytic recycling compartment. Autophagy receptor that interacts
CC directly with both the cargo to become degraded and an autophagy
CC modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria
CC (xenophagy), such as cytoplasmic Salmonella enterica, and appears to
CC function in the same pathway as SQSTM1 and CALCOCO2/NDP52.
CC {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15837803,
CC ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559,
CC ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040,
CC ECO:0000269|PubMed:27534431, ECO:0000269|PubMed:27538435}.
CC -!- FUNCTION: (Microbial infection) May constitute a cellular target for
CC adenovirus E3 14.7 and Bluetongue virus protein NS3 to inhibit innate
CC immune response. {ECO:0000269|PubMed:27538435,
CC ECO:0000269|PubMed:9488477}.
CC -!- SUBUNIT: Self-associates (PubMed:23669351). 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 (PubMed:24705354). Interacts with CYLD (PubMed:32185393).
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: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; 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; Q3SX64: ODF3L2; NbExp=3; IntAct=EBI-748974, EBI-6660184;
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; Q8IXS6: PALM2; NbExp=3; IntAct=EBI-748974, EBI-12871462;
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=6; 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=16; 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=19; 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; 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:27534431, ECO:0000269|PubMed:27538435}. Golgi
CC apparatus, trans-Golgi network. Cytoplasmic vesicle, autophagosome.
CC Cytoplasmic vesicle. Recycling endosome. 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). Highly expressed in trabecular meshwork. Expressed nonpigmented
CC ciliary epithelium, retina, brain, adrenal cortex, fetus, lymphocyte,
CC fibroblast, skeletal muscle, heart, liver, brain and placenta.
CC {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:9488477}.
CC -!- INDUCTION: Upon TNF and interferon treatments. Up-regulated in direct
CC response to viral infection. {ECO:0000269|PubMed:10807909,
CC ECO:0000269|PubMed:12379221, ECO:0000269|PubMed:12646749,
CC ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:9488477}.
CC -!- DOMAIN: Ubiquitin-binding motif (UBAN) is essential for its inhibitory
CC function, subcellular localization and interaction with TBK1.
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:22854040,
CC ECO:0000269|PubMed:23669351, ECO:0000269|PubMed:24752605}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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 -!- CAUTION: According to some authors (PubMed:12379221) its expression is
CC regulated by intraocular pressure, suggesting a protective role in case
CC of high pressure, while according to other authors (PubMed:12646749),
CC it is not up-regulated in response to pressure elevation.
CC {ECO:0000305|PubMed:12379221, ECO:0000305|PubMed:12646749}.
CC -!- CAUTION: Interaction of variant GLC1E LYS-50 with Rab8 is reported
CC conflictingly. Coimmunoprecipitation experiments with overexpressed
CC proteins suggested an increased interaction (PubMed:20085643) while
CC yeast-two-hybrid (PubMed:22854040) and protein complentation assays
CC with an equivalent mouse Optn construct (AC Q8K3K8) failed to show an
CC interaction. {ECO:0000305|PubMed:20085643,
CC ECO:0000305|PubMed:22854040}.
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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_001008212.1. [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 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 AlphaFoldDB; Q96CV9; -.
DR SMR; Q96CV9; -.
DR BioGRID; 115436; 420.
DR CORUM; Q96CV9; -.
DR DIP; DIP-42001N; -.
DR IntAct; Q96CV9; 238.
DR MINT; Q96CV9; -.
DR STRING; 9606.ENSP00000368022; -.
DR TCDB; 8.A.157.1.1; the optineurin (optn) family.
DR GlyGen; Q96CV9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96CV9; -.
DR MetOSite; Q96CV9; -.
DR PhosphoSitePlus; Q96CV9; -.
DR BioMuta; OPTN; -.
DR DMDM; 317373403; -.
DR EPD; Q96CV9; -.
DR jPOST; Q96CV9; -.
DR MassIVE; Q96CV9; -.
DR PaxDb; Q96CV9; -.
DR PeptideAtlas; Q96CV9; -.
DR PRIDE; Q96CV9; -.
DR ProteomicsDB; 76226; -. [Q96CV9-1]
DR ProteomicsDB; 76227; -. [Q96CV9-2]
DR ProteomicsDB; 76228; -. [Q96CV9-3]
DR ABCD; Q96CV9; 1 sequenced antibody.
DR Antibodypedia; 1010; 385 antibodies from 38 providers.
DR DNASU; 10133; -.
DR Ensembl; ENST00000263036.9; ENSP00000263036.3; ENSG00000123240.17. [Q96CV9-1]
DR Ensembl; ENST00000378747.8; ENSP00000368021.3; ENSG00000123240.17. [Q96CV9-1]
DR Ensembl; ENST00000378748.7; ENSP00000368022.3; ENSG00000123240.17. [Q96CV9-1]
DR Ensembl; ENST00000378752.7; ENSP00000368027.3; ENSG00000123240.17. [Q96CV9-2]
DR Ensembl; ENST00000378757.6; ENSP00000368032.2; ENSG00000123240.17. [Q96CV9-1]
DR Ensembl; ENST00000378764.6; ENSP00000368040.1; ENSG00000123240.17. [Q96CV9-2]
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 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 neXtProt; NX_Q96CV9; -.
DR OpenTargets; ENSG00000123240; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 353225; NON RARE IN EUROPE: Primary adult open-angle glaucoma.
DR PharmGKB; PA31948; -.
DR VEuPathDB; HostDB:ENSG00000123240; -.
DR eggNOG; ENOG502QTG2; Eukaryota.
DR GeneTree; ENSGT00530000063808; -.
DR HOGENOM; CLU_034097_1_0_1; -.
DR InParanoid; Q96CV9; -.
DR OMA; MAMSHEN; -.
DR OrthoDB; 745047at2759; -.
DR PhylomeDB; Q96CV9; -.
DR TreeFam; TF326608; -.
DR PathwayCommons; Q96CV9; -.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SignaLink; Q96CV9; -.
DR SIGNOR; Q96CV9; -.
DR BioGRID-ORCS; 10133; 16 hits in 1099 CRISPR screens.
DR ChiTaRS; OPTN; human.
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 207 other tissues.
DR ExpressionAtlas; Q96CV9; baseline and differential.
DR Genevisible; Q96CV9; HS.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0006914; P:autophagy; 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:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0001920; P:negative regulation of receptor recycling; IMP:UniProtKB.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
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 I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR IDEAL; IID00348; -.
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; 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 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 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..295
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 TBC1D17-
FT mediated inhibition of autophagy; altered interaction with
FT RAB8A; no effect on interaction with TBC1D17; increases
FT interaction with TFRC and impairs its endocytic recycling;
FT increases interactions with TBK1; decreases self-
FT association; disturbs transition from the ER to Golgi;
FT dbSNP:rs28939688)"
FT /evidence="ECO:0000269|PubMed:11834836,
FT ECO:0000269|PubMed:17389490, ECO:0000269|PubMed:20085643,
FT ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:23669351,
FT 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; unknown pathological 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: Reduces cell death, decreased interaction with
FT TFRC; when 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: Reduces cell death, decreased interaction with
FT TFRC; 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 and
FT interaction with TBK1. Inhibits localization to recycling
FT endosomes and disrupts interaction with TFRC. Loss of
FT ability to inhibit the activation of the IFNB promoter in
FT response to TLR3 or RIG-I signaling."
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 STRAND 177..180
FT /evidence="ECO:0007829|PDB:7CZM"
FT HELIX 447..497
FT /evidence="ECO:0007829|PDB:5B83"
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
