ID MYOC_HUMAN Reviewed; 504 AA. AC Q99972; B2RD84; O00620; Q7Z6Q9; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 2. DT 27-MAR-2024, entry version 206. DE RecName: Full=Myocilin {ECO:0000303|PubMed:9169133}; DE AltName: Full=Myocilin 55 kDa subunit; DE AltName: Full=Trabecular meshwork-induced glucocorticoid response protein {ECO:0000303|PubMed:9497363}; DE Contains: DE RecName: Full=Myocilin, N-terminal fragment; DE AltName: Full=Myocilin 20 kDa N-terminal fragment; DE Contains: DE RecName: Full=Myocilin, C-terminal fragment; DE AltName: Full=Myocilin 35 kDa N-terminal fragment; DE Flags: Precursor; GN Name=MYOC; Synonyms=GLC1A, TIGR {ECO:0000303|PubMed:9280311}; 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 [MRNA]. RX PubMed=9280311; DOI=10.1016/s0014-5793(97)00934-4; RA Ortego J., Escribano J., Coca-Prados M.; RT "Cloning and characterization of subtracted cDNAs from a human ciliary body RT library encoding TIGR, a protein involved in juvenile open angle glaucoma RT with homology to myosin and olfactomedin."; RL FEBS Lett. 413:349-353(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RC TISSUE=Retina; RX PubMed=9169133; DOI=10.1006/geno.1997.4682; RA Kubota R., Noda S., Wang Y., Minoshima S., Asakawa S., Kudoh J., RA Mashima Y., Oguchi Y., Shimizu N.; RT "A novel myosin-like protein (myocilin) expressed in the connecting cilium RT of the photoreceptor: molecular cloning, tissue expression, and chromosomal RT mapping."; RL Genomics 41:360-369(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLC1A ARG-246; LEU-370; RP SER-477; LYS-480 AND PHE-499. RC TISSUE=Leukocyte; RX PubMed=9328473; DOI=10.1093/hmg/6.12.2091; RA Adam M.F., Belmouden A., Binisti P., Brezin A.P., Valtot F., RA Bechetoille A., Dascotte J.-C., Copin B., Gomez L., Chaventre A., RA Bach J.-F., Garchon H.-J.; RT "Recurrent mutations in a single exon encoding the evolutionarily conserved RT olfactomedin-homology domain of TIGR in familial open-angle glaucoma."; RL Hum. Mol. Genet. 6:2091-2097(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS GLC1A VAL-364 AND RP HIS-437. RX PubMed=9005853; DOI=10.1126/science.275.5300.668; RA Stone E.M., Fingert J.H., Alward W.L.M., Nguyen T.D., Polansky J.R., RA Sunden S.L.F., Nishimura D., Clark A.F., Nystuen A., Nichols B.E., RA Mackey D.A., Ritch R., Kalenak J.W., Craven E.R., Sheffield V.C.; RT "Identification of a gene that causes primary open angle glaucoma."; RL Science 275:668-670(1997). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9446806; DOI=10.1006/bbrc.1997.7972; RA Kubota R., Kudoh J., Mashima Y., Asakawa S., Minoshima S., Hejtmancik J.F., RA Oguchi Y., Shimizu N.; RT "Genomic organization of the human myocilin gene (MYOC) responsible for RT primary open angle glaucoma (GLC1A)."; RL Biochem. Biophys. Res. Commun. 242:396-400(1998). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9548973; DOI=10.1101/gr.8.4.377; RA Fingert J.H., Ying L., Swiderski R.E., Nystuen A.M., Arbour N.C., RA Alward W.L.M., Sheffield V.C., Stone E.M.; RT "Characterization and comparison of the human and mouse GLC1A glaucoma RT genes."; RL Genome Res. 8:377-384(1998). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [11] RP PROTEIN SEQUENCE OF 1-6 (PRECURSOR PROTEIN), PROTEIN SEQUENCE OF 33-37, RP SEQUENCE REVISION, OLIGOMERIZATION, SUBUNIT, SUBCELLULAR LOCATION, AND RP INDUCTION BY GLUCOCORTICOIDS. RX PubMed=9497363; DOI=10.1074/jbc.273.11.6341; RA Nguyen T.D., Chen P., Huang W.D., Chen H., Johnson D., Polansky J.R.; RT "Gene structure and properties of TIGR, an olfactomedin-related RT glycoprotein cloned from glucocorticoid-induced trabecular meshwork RT cells."; RL J. Biol. Chem. 273:6341-6350(1998). RN [12] RP PROTEIN SEQUENCE OF 33-37, SUBCELLULAR LOCATION, AND GLYCOSYLATION. RX PubMed=19287508; RA Sohn S., Joe M.K., Kim T.E., Im J.E., Choi Y.R., Park H., Kee C.; RT "Dual localization of wild-type myocilin in the endoplasmic reticulum and RT extracellular compartment likely occurs due to its incomplete secretion."; RL Mol. Vis. 15:545-556(2009). RN [13] RP PROTEIN SEQUENCE OF 227-233, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP CHARACTERIZATION OF VARIANTS GLC1A LYS-323; LEU-370 AND GLY-380, AND RP PROTEOLYTIC PROCESSING. RX PubMed=15795224; DOI=10.1074/jbc.m501340200; RA Aroca-Aguilar J.D., Sanchez-Sanchez F., Ghosh S., Coca-Prados M., RA Escribano J.; RT "Myocilin mutations causing glaucoma inhibit the intracellular RT endoproteolytic cleavage of myocilin between amino acids Arg226 and RT Ile227."; RL J. Biol. Chem. 280:21043-21051(2005). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=11053284; RA O'Brien E.T., Ren X., Wang Y.; RT "Localization of myocilin to the golgi apparatus in Schlemm's canal RT cells."; RL Invest. Ophthalmol. Vis. Sci. 41:3842-3849(2000). RN [15] RP SUBCELLULAR LOCATION, INDUCTION BY GLUCOCORTICOIDS, GLYCOSYLATION, AND RP TISSUE SPECIFICITY. RX PubMed=11431441; RA Clark A.F., Steely H.T., Dickerson J.E. Jr., English-Wright S., Stropki K., RA McCartney M.D., Jacobson N., Shepard A.R., Clark J.I., Matsushima H., RA Peskind E.R., Leverenz J.B., Wilkinson C.W., Swiderski R.E., Fingert J.H., RA Sheffield V.C., Stone E.M.; RT "Glucocorticoid induction of the glaucoma gene MYOC in human and monkey RT trabecular meshwork cells and tissues."; RL Invest. Ophthalmol. Vis. Sci. 42:1769-1780(2001). RN [16] RP INTERACTION WITH OLFM3. RX PubMed=12019210; DOI=10.1093/hmg/11.11.1291; RA Torrado M., Trivedi R., Zinovieva R., Karavanova I., Tomarev S.I.; RT "Optimedin: a novel olfactomedin-related protein that interacts with RT myocilin."; RL Hum. Mol. Genet. 11:1291-1301(2002). RN [17] RP INTERACTION WITH FN1, AND SUBCELLULAR LOCATION. RX PubMed=11773026; RA Filla M.S., Liu X., Nguyen T.D., Polansky J.R., Brandt C.R., Kaufman P.L., RA Peters D.M.; RT "In vitro localization of TIGR/MYOC in trabecular meshwork extracellular RT matrix and binding to fibronectin."; RL Invest. Ophthalmol. Vis. Sci. 43:151-161(2002). RN [18] RP INTERACTION WITH MYL2. RX PubMed=11773029; RA Wentz-Hunter K., Ueda J., Yue B.Y.; RT "Protein interactions with myocilin."; RL Invest. Ophthalmol. Vis. Sci. 43:176-182(2002). RN [19] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11923248; RA Ueda J., Wentz-Hunter K., Yue B.Y.; RT "Distribution of myocilin and extracellular matrix components in the RT juxtacanalicular tissue of human eyes."; RL Invest. Ophthalmol. Vis. Sci. 43:1068-1076(2002). RN [20] RP DISULFIDE BOND AT 245-CYS--CYS-433. RX PubMed=12615070; DOI=10.1016/s0006-291x(03)00198-0; RA Nagy I., Trexler M., Patthy L.; RT "Expression and characterization of the olfactomedin domain of human RT myocilin."; RL Biochem. Biophys. Res. Commun. 302:554-561(2003). RN [21] RP CHARACTERIZATION OF VARIANT SER-57, GLYCOSYLATION, TISSUE SPECIFICITY, AND RP SUBCELLULAR LOCATION. RX PubMed=12697062; DOI=10.1186/1471-2156-4-5; RA Shepard A.R., Jacobson N., Sui R., Steely H.T., Lotery A.J., Stone E.M., RA Clark A.F.; RT "Characterization of rabbit myocilin: implications for human myocilin RT glycosylation and signal peptide usage."; RL BMC Genet. 4:5-5(2003). RN [22] RP SUBCELLULAR LOCATION. RX PubMed=15944158; DOI=10.1074/jbc.m504803200; RA Hardy K.M., Hoffman E.A., Gonzalez P., McKay B.S., Stamer W.D.; RT "Extracellular trafficking of myocilin in human trabecular meshwork RT cells."; RL J. Biol. Chem. 280:28917-28926(2005). RN [23] RP CLEAVAGE BY CAPN2, SUBCELLULAR LOCATION, GLYCOSYLATION, AND MUTAGENESIS OF RP 226-ARG--GLU-230; ARG-226; ILE-227; LYS-229 AND GLU-230. RX PubMed=17650508; DOI=10.1074/jbc.m609608200; RA Sanchez-Sanchez F., Martinez-Redondo F., Aroca-Aguilar J.D., RA Coca-Prados M., Escribano J.; RT "Characterization of the intracellular proteolytic cleavage of myocilin and RT identification of calpain II as a myocilin-processing protease."; RL J. Biol. Chem. 282:27810-27824(2007). RN [24] RP FUNCTION IN MITOCHONDRIAL DEPOLARIZATION, AND SUBCELLULAR LOCATION. RX PubMed=17516541; DOI=10.1002/jcp.21147; RA Sakai H., Shen X., Koga T., Park B.C., Noskina Y., Tibudan M., Yue B.Y.; RT "Mitochondrial association of myocilin, product of a glaucoma gene, in RT human trabecular meshwork cells."; RL J. Cell. Physiol. 213:775-784(2007). RN [25] RP FUNCTION IN CELL-MATRIX ADHESION. RX PubMed=17984096; DOI=10.1074/jbc.m708250200; RA Shen X., Koga T., Park B.C., SundarRaj N., Yue B.Y.; RT "Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced RT alterations in cultured human trabecular meshwork cells."; RL J. Biol. Chem. 283:603-612(2008). RN [26] RP FUNCTION IN CELL ADHESION. RX PubMed=18855004; DOI=10.1007/s00418-008-0518-4; RA Goldwich A., Scholz M., Tamm E.R.; RT "Myocilin promotes substrate adhesion, spreading and formation of focal RT contacts in podocytes and mesangial cells."; RL Histochem. Cell Biol. 131:167-180(2009). RN [27] RP FUNCTION IN STRESS FIBER ASSEMBLY, INTERACTION WITH FRZB; FZD7; FZD10; FZD1 RP AND WIF1, AND CHARACTERIZATION OF VARIANT ASN-477. RX PubMed=19188438; DOI=10.1128/mcb.01274-08; RA Kwon H.S., Lee H.S., Ji Y., Rubin J.S., Tomarev S.I.; RT "Myocilin is a modulator of Wnt signaling."; RL Mol. Cell. Biol. 29:2139-2154(2009). RN [28] RP FUNCTION IN NEURITE OUTGROWTH. RX PubMed=19959812; DOI=10.2353/ajpath.2010.090194; RA Koga T., Shen X., Park J.S., Qiu Y., Park B.C., Shyam R., Yue B.Y.; RT "Differential effects of myocilin and optineurin, two glaucoma genes, on RT neurite outgrowth."; RL Am. J. Pathol. 176:343-352(2010). RN [29] RP FUNCTION IN CELL MIGRATION. RX PubMed=21656515; DOI=10.1002/jcp.22701; RA Kwon H.S., Tomarev S.I.; RT "Myocilin, a glaucoma-associated protein, promotes cell migration through RT activation of integrin-focal adhesion kinase-serine/threonine kinase RT signaling pathway."; RL J. Cell. Physiol. 226:3392-3402(2011). RN [30] RP FUNCTION IN OSTEOBLAST DIFFERENTIATION. RX PubMed=23629661; DOI=10.1074/jbc.m112.422972; RA Kwon H.S., Johnson T.V., Tomarev S.I.; RT "Myocilin stimulates osteogenic differentiation of mesenchymal stem cells RT through mitogen-activated protein kinase signaling."; RL J. Biol. Chem. 288:16882-16894(2013). RN [31] RP FUNCTION IN MYELINATION, AND INTERACTION WITH NFASC; GLDN AND NRCAM. RX PubMed=23897819; DOI=10.1074/jbc.m112.446138; RA Kwon H.S., Johnson T.V., Joe M.K., Abu-Asab M., Zhang J., Chan C.C., RA Tomarev S.I.; RT "Myocilin mediates myelination in the peripheral nervous system through RT ErbB2/3 signaling."; RL J. Biol. Chem. 288:26357-26371(2013). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 228-504 IN COMPLEX WITH CALCIUM, RP DISULFIDE BONDS, CHARACTERIZATION OF VARIANTS GLC1A LYS-293; ILE-353 AND RP VAL-445, AND CHARACTERIZATION OF VARIANTS MET-329; CYS-422; PRO-425 AND RP CYS-473. RX PubMed=25524706; DOI=10.1093/hmg/ddu730; RA Donegan R.K., Hill S.E., Freeman D.M., Nguyen E., Orwig S.D., Turnage K.C., RA Lieberman R.L.; RT "Structural basis for misfolding in myocilin-associated glaucoma."; RL Hum. Mol. Genet. 24:2111-2124(2015). RN [33] RP VARIANTS GLC1A ARG-367 AND LEU-370. RX PubMed=9345106; DOI=10.1086/301612; RA Suzuki Y., Shirato S., Taniguchi F., Ohara K., Nishimaki K., Ohta S.; RT "Mutations in the TIGR gene in familial primary open-angle glaucoma in RT Japan."; RL Am. J. Hum. Genet. 61:1202-1204(1997). RN [34] RP VARIANT GLC1A PRO-341. RX PubMed=9510647; DOI=10.3341/kjo.1997.11.2.75; RA Kee C., Ahn B.-H.; RT "TIGR gene in primary open-angle glaucoma and steroid-induced glaucoma."; RL Korean J. Ophthalmol. 11:75-78(1997). RN [35] RP VARIANT GLC1A ARG-337. RX PubMed=9361308; DOI=10.3109/13816819709057124; RA Stoilova D., Child A., Brice G., Crick R.P., Fleck B.W., Sarfarazi M.; RT "Identification of a new 'TIGR' mutation in a family with juvenile-onset RT primary open angle glaucoma."; RL Ophthalmic Genet. 18:109-118(1997). RN [36] RP VARIANTS GLC1A LYS-352; LEU-370; MET-377 AND HIS-437. RX PubMed=9792882; DOI=10.1086/302098; RA Wiggs J.L., Allingham R.R., Vollrath D., Jones K.H., De La Paz M., Kern J., RA Patterson K., Babb V.L., Del Bono E.A., Broomer B.W., Pericak-Vance M.A., RA Haines J.L.; RT "Prevalence of mutations in TIGR/Myocilin in patients with adult and RT juvenile primary open-angle glaucoma."; RL Am. J. Hum. Genet. 63:1549-1552(1998). RN [37] RP VARIANTS GLC1A ARG-367 AND LEU-370. RX PubMed=9490287; DOI=10.1007/s004390050661; RA Michels-Rautenstrauss K.G., Mardin C.Y., Budde W.M., Liehr T., RA Polansky J.R., Nguyen T., Timmerman V., van Broeckhoven C., Naumann G.O.H., RA Pfeiffer R.A., Rautenstrauss B.W.; RT "Juvenile open angle glaucoma: fine mapping of the TIGR gene to 1q24.3- RT q25.2 and mutation analysis."; RL Hum. Genet. 102:103-106(1998). RN [38] RP VARIANTS GLC1A ARG-367 AND PHE-426. RX PubMed=9521427; RX DOI=10.1002/(sici)1098-1004(1998)11:3<244::aid-humu10>3.0.co;2-z; RA Mansergh F.C., Kenna P.F., Ayuso C., Kiang A.-S., Humphries P., RA Farrar G.J.; RT "Novel mutations in the TIGR gene in early and late onset open angle RT glaucoma."; RL Hum. Mutat. 11:244-251(1998). RN [39] RP VARIANTS GLC1A LEU-370; ALA-380 AND PRO-502, AND VARIANT LYS-76. RX PubMed=9863594; DOI=10.1136/jmg.35.12.989; RA Stoilova D., Child A., Brice G., Desai T., Barsoum-Homsy M., Ozdemir N., RA Chevrette L., Adam M.F., Garchon H.-J., Pitts Crick R., Sarfarazi M.; RT "Novel TIGR/MYOC mutations in families with juvenile onset primary open RT angle glaucoma."; RL J. Med. Genet. 35:989-992(1998). RN [40] RP VARIANT GLC1A GLU-423. RX PubMed=9697688; DOI=10.1038/1203; RA Morissette J., Clepet C., Moisan S., Dubois S., Winstall E., Vermeeren D., RA Nguyen T.D., Polansky J.R., Cote G., Anctil J.-L., Amyot M., Plante M., RA Falardeau P., Raymond V.; RT "Homozygotes carrying an autosomal dominant TIGR mutation do not manifest RT glaucoma."; RL Nat. Genet. 19:319-321(1998). RN [41] RP VARIANTS GLC1A, AND VARIANTS. RX PubMed=9535666; DOI=10.1056/nejm199804093381503; RA Alward W.L.M., Fingert J.H., Coote M.A., Johnson A.T., Lerner S.F., RA Junqua D., Durcan F.J., McCartney P.J., Mackey D.A., Sheffield V.C., RA Stone E.M.; RT "Clinical features associated with mutations in the chromosome 1 open-angle RT glaucoma gene."; RL N. Engl. J. Med. 338:1022-1027(1998). RN [42] RP VARIANT GLC1A ILE-353. RX PubMed=10330365; DOI=10.1086/302407; RA Yoon S.-J.K., Kim H.-S., Moon J.-I., Lim J.M., Joo C.-K.; RT "Mutations of the TIGR/MYOC gene in primary open-angle glaucoma in Korea."; RL Am. J. Hum. Genet. 64:1775-1778(1999). RN [43] RP VARIANTS GLC1A, AND VARIANTS. RX PubMed=10196380; DOI=10.1093/hmg/8.5.899; RA Fingert J.H., Heon E., Liebmann J.M., Yamamoto T., Craig J.E., Rait J., RA Kawase K., Hoh S.-T., Buys Y.M., Dickinson J., Hockey R.R., RA Williams-Lyn D., Trope G., Kitazawa Y., Ritch R., Mackey D.A., RA Alward W.L.M., Sheffield V.C., Stone E.M.; RT "Analysis of myocilin mutations in 1703 glaucoma patients from five RT different populations."; RL Hum. Mol. Genet. 8:899-905(1999). RN [44] RP VARIANT GLC1A PRO-448. RX PubMed=10340788; DOI=10.1016/s0021-5155(98)00077-x; RA Yokoyama A., Nao-i N., Date Y., Nakazato M., Chumann H., Chihara E., RA Sawada A., Matsukura S.; RT "Detection of a new TIGR gene mutation in a Japanese family with primary RT open angle glaucoma."; RL Jpn. J. Ophthalmol. 43:85-88(1999). RN [45] RP VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; MET-377; PHE-426; RP ASN-477 AND SER-499, VARIANTS ASP-57; LYS-76; MET-329 AND ARG-398, RP CHARACTERIZATION OF VARIANTS GLC1A ARG-252; GLY-272; LYS-323; LEU-370; RP MET-377; PHE-426; ASN-477 AND SER-499, AND CHARACTERIZATION OF VARIANTS RP ASP-57; LYS-76; MET-329 AND ARG-398. RX PubMed=11004290; DOI=10.1016/s0002-9394(00)00536-5; RA Shimizu S., Lichter P.R., Johnson A.T., Zhou Z., Higashi M., RA Gottfredsdottir M., Othman M., Moroi S.E., Rozsa F.W., Schertzer R.M., RA Clarke M.S., Schwartz A.L., Downs C.A., Vollrath D., Richards J.E.; RT "Age-dependent prevalence of mutations at the GLC1A locus in primary open- RT angle glaucoma."; RL Am. J. Ophthalmol. 130:165-177(2000). RN [46] RP VARIANT GLC1A ARG-252. RX PubMed=10873982; DOI=10.1136/bjo.84.7.722; RA Booth A.P., Anwar R., Chen H., Churchill A.J., Jay J., Polansky J., RA Nguyen T., Markham A.F.; RT "Genetic screening in a large family with juvenile onset primary open angle RT glaucoma."; RL Br. J. Ophthalmol. 84:722-726(2000). RN [47] RP VARIANT GLC1A ALA-53. RX PubMed=10644174; RX DOI=10.1002/(sici)1098-1004(200001)15:1<122::aid-humu38>3.0.co;2-o; RA Pang C.P., Leung Y.F., Chua J.K.H., Baum L., Fan D.S.P., Lam D.S.; RT "Novel TIGR sequence alteration Val53Ala."; RL Hum. Mutat. 15:122-122(2000). RN [48] RP VARIANTS GLC1A GLN-158; ASN-360 AND THR-363, AND VARIANTS HIS-19; LYS-76; RP GLU-208 AND HIS-470. RX PubMed=10980537; RX DOI=10.1002/1098-1004(200009)16:3<270::aid-humu13>3.0.co;2-m; RA Kubota R., Mashima Y., Ohtake Y., Tanino T., Kimura T., Hotta Y., Kanai A., RA Tokuoka S., Azuma I., Tanihara H., Inatani M., Inoue Y., Kudoh J., RA Oguchi Y., Shimizu N.; RT "Novel mutations in the myocilin gene in Japanese glaucoma patients."; RL Hum. Mutat. 16:270-270(2000). RN [49] RP VARIANTS GLC1A GLU-208 AND ILE-353, AND VARIANTS ARG-12 AND LYS-76. RX PubMed=10798654; RA Lam D.S.C., Leung Y.F., Chua J.K.H., Baum L., Fan D.S.P., Choy K.W., RA Pang C.P.; RT "Truncations in the TIGR gene in individuals with and without primary open- RT angle glaucoma."; RL Invest. Ophthalmol. Vis. Sci. 41:1386-1391(2000). RN [50] RP VARIANT GLC1A ARG-433. RX PubMed=10819638; DOI=10.1136/jmg.37.4.301; RA Vasconcellos J.P.C., Melo M.B., Tsukumo D.M.L., Basseres D.S., Bordin S., RA Saad S.T.O., Costa F.F.; RT "Novel mutation in the MYOC gene in primary open glaucoma patients."; RL J. Med. Genet. 37:301-303(2000). RN [51] RP VARIANTS GLC1A LYS-261 AND GLU-337, AND VARIANT ARG-398. RX PubMed=10916185; DOI=10.1076/1381-6810(200006)2121-8ft109; RA Vazquez C.M., Herrero O.M.V., Bastus B.M., Perez V.D.; RT "Mutations in the third exon of the MYOC gene in Spanish patients with RT primary open angle glaucoma."; RL Ophthalmic Genet. 21:109-115(2000). RN [52] RP VARIANTS GLC1A ARG-252; LYS-293; ARG-367; LEU-370; LYS-377; VAL-399 AND RP VAL-445, AND VARIANT ARG-398. RX PubMed=11774072; DOI=10.1086/338709; RA Vincent A.L., Billingsley G., Buys Y., Levin A.V., Priston M., Trope G., RA Williams-Lyn D., Heon E.; RT "Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier RT gene."; RL Am. J. Hum. Genet. 70:448-460(2002). RN [53] RP VARIANTS GLC1A TRP-126; LYS-293; LYS-352; ARG-367; GLU-423; THR-427; RP VAL-445 AND LEU-481, AND VARIANTS LYS-76; GLU-77 AND ARG-398. RX PubMed=12189160; DOI=10.1093/hmg/11.18.2077; RG The Quebec glaucoma network; RA Faucher M., Anctil J.-L., Rodrigue M.-A., Duchesne A., Bergeron D., RA Blondeau P., Cote G., Dubois S., Bergeron J., Arseneault R., Morissette J., RA Raymond V.; RT "Founder TIGR/myocilin mutations for glaucoma in the Quebec population."; RL Hum. Mol. Genet. 11:2077-2090(2002). RN [54] RP VARIANTS GLC1A ALA-251; MET-345; ARG-367; LEU-370; ASN-393; SER-434; RP ASP-450 AND CYS-470, AND VARIANT LYS-76. RX PubMed=12442283; DOI=10.1002/humu.9092; RA Michels-Rautenstrauss K., Mardin C., Wakili N., Juenemann A.M., RA Villalobos L., Mejia C., Soley G.C., Azofeifa J., Oezbey S., RA Naumann G.O.H., Reis A., Rautenstrauss B.; RT "Novel mutations in the MYOC/GLC1A gene in a large group of glaucoma RT patients."; RL Hum. Mutat. 20:479-480(2002). RN [55] RP VARIANTS GLC1A LYS-300 AND CYS-471, AND VARIANTS ARG-12; LEU-16; SER-17; RP LYS-76; PRO-95; GLU-208; PRO-215; ILE-353 AND LYS-414. RX PubMed=12356829; RA Pang C.P., Leung Y.F., Fan B., Baum L., Tong W.C., Lee W.S., Chua J.K.H., RA Fan D.S.P., Liu Y., Lam D.S.C.; RT "TIGR/MYOC gene sequence alterations in individuals with and without RT primary open-angle glaucoma."; RL Invest. Ophthalmol. Vis. Sci. 43:3231-3235(2002). RN [56] RP VARIANTS GLC1A LYS-342 AND ASN-380. RX PubMed=12362081; DOI=10.1097/00061198-200210000-00008; RA Challa P., Herndon L.W., Hauser M.A., Broomer B.W., Pericak-Vance M.A., RA Ababio-Danso B., Allingham R.R.; RT "Prevalence of myocilin mutations in adults with primary open-angle RT glaucoma in Ghana, West Africa."; RL J. Glaucoma 11:416-420(2002). RN [57] RP VARIANTS GLC1A ARG-25 AND GLU-423. RX PubMed=12860809; DOI=10.1001/archopht.121.7.1034; RA Bruttini M., Longo I., Frezzotti P., Ciappetta R., Randazzo A., RA Orzalesi N., Fumagalli E., Caporossi A., Frezzotti R., Renieri A.; RT "Mutations in the myocilin gene in families with primary open-angle RT glaucoma and juvenile open-angle glaucoma."; RL Arch. Ophthalmol. 121:1034-1038(2003). RN [58] RP VARIANTS GLC1A ARG-367; ILE-438; LYS-480 AND PHE-499, AND VARIANTS SER-57; RP LYS-76 AND ARG-398. RX PubMed=12872267; DOI=10.1002/humu.9165; RA Melki R., Belmouden A., Brezin A., Garchon H.-J.; RT "Myocilin analysis by DHPLC in French POAG patients: increased prevalence RT of Q368X mutation."; RL Hum. Mutat. 22:179-179(2003). RN [59] RP VARIANT GLC1A HIS-48, AND VARIANT LYS-76. RX PubMed=15025728; DOI=10.1111/j.1399-0004.2004.00232.x; RA Sripriya S., Uthra S., Sangeetha R., George R.J., Hemamalini A., Paul P.G., RA Amali J., Vijaya L., Kumaramanickavel G.; RT "Low frequency of myocilin mutations in Indian primary open-angle glaucoma RT patients."; RL Clin. Genet. 65:333-337(2004). RN [60] RP VARIANTS GLC1A ASN-360; THR-363; LEU-369 AND PRO-448. RX PubMed=15534471; DOI=10.1097/0.ijg.0000138204.6d; RA Ishikawa K., Funayama T., Ohtake Y., Tanino T., Kurosaka D., Suzuki K., RA Ideta H., Fujimaki T., Tanihara H., Asaoka R., Naoi N., Yasuda N., RA Iwata T., Mashima Y.; RT "Novel MYOC gene mutation, Phe369Leu, in Japanese patients with primary RT open-angle glaucoma detected by denaturing high-performance liquid RT chromatography."; RL J. Glaucoma 13:466-471(2004). RN [61] RP VARIANT GLC1A ARG-274. RX PubMed=15255110; DOI=10.1076/opge.25.1.11.28995; RA Markandaya M., Ramesh T.K., Selvaraju V., Dorairaj S.K., Prakash R., RA Shetty J., Kumar A.; RT "Genetic analysis of an Indian family with members affected with juvenile- RT onset primary open-angle glaucoma."; RL Ophthalmic Genet. 25:11-23(2004). RN [62] RP VARIANT GLC3A HIS-48. RX PubMed=15733270; DOI=10.1111/j.1399-0004.2005.00411.x; RA Kaur K., Reddy A.B.M., Mukhopadhyay A., Mandal A.K., Hasnain S.E., Ray K., RA Thomas R., Balasubramanian D., Chakrabarti S.; RT "Myocilin gene implicated in primary congenital glaucoma."; RL Clin. Genet. 67:335-340(2005). RN [63] RP VARIANT GLC1A TYR-245, AND CHARACTERIZATION OF VARIANT GLC1A TYR-245. RX PubMed=16401791; DOI=10.1001/archopht.124.1.102; RA Fan B.J., Leung D.Y.L., Wang D.Y., Gobeil S., Raymond V., Tam P.O.S., RA Lam D.S.C., Pang C.P.; RT "Novel myocilin mutation in a Chinese family with juvenile-onset open-angle RT glaucoma."; RL Arch. Ophthalmol. 124:102-106(2006). RN [64] RP VARIANT GLC1A HIS-380. RX PubMed=17499207; DOI=10.1016/j.ajo.2007.03.037; RA Wirtz M.K., Samples J.R., Choi D., Gaudette N.D.; RT "Clinical features associated with an Asp380His Myocilin mutation in a US RT family with primary open-angle glaucoma."; RL Am. J. Ophthalmol. 144:75-80(2007). RN [65] RP VARIANTS GLC1A VAL-244 AND ARG-252. RX PubMed=17210859; DOI=10.1001/archopht.125.1.98; RA Hewitt A.W., Bennett S.L., Richards J.E., Dimasi D.P., Booth A.P., RA Inglehearn C., Anwar R., Yamamoto T., Fingert J.H., Heon E., Craig J.E., RA Mackey D.A.; RT "Myocilin Gly252Arg mutation and glaucoma of intermediate severity in RT Caucasian individuals."; RL Arch. Ophthalmol. 125:98-104(2007). CC -!- FUNCTION: Secreted glycoprotein regulating the activation of different CC signaling pathways in adjacent cells to control different processes CC including cell adhesion, cell-matrix adhesion, cytoskeleton CC organization and cell migration. Promotes substrate adhesion, spreading CC and formation of focal contacts. Negatively regulates cell-matrix CC adhesion and stress fiber assembly through Rho protein signal CC transduction. Modulates the organization of actin cytoskeleton by CC stimulating the formation of stress fibers through interactions with CC components of Wnt signaling pathways. Promotes cell migration through CC activation of PTK2 and the downstream phosphatidylinositol 3-kinase CC signaling. Plays a role in bone formation and promotes osteoblast CC differentiation in a dose-dependent manner through mitogen-activated CC protein kinase signaling. Mediates myelination in the peripheral CC nervous system through ERBB2/ERBB3 signaling. Plays a role as a CC regulator of muscle hypertrophy through the components of dystrophin- CC associated protein complex. Involved in positive regulation of CC mitochondrial depolarization. Plays a role in neurite outgrowth. May CC participate in the obstruction of fluid outflow in the trabecular CC meshwork. {ECO:0000250|UniProtKB:O70624, ECO:0000269|PubMed:17516541, CC ECO:0000269|PubMed:17984096, ECO:0000269|PubMed:18855004, CC ECO:0000269|PubMed:19188438, ECO:0000269|PubMed:19959812, CC ECO:0000269|PubMed:21656515, ECO:0000269|PubMed:23629661, CC ECO:0000269|PubMed:23897819}. CC -!- SUBUNIT: Homodimer (via N-terminus). Can also form higher oligomers CC (PubMed:9497363). Interacts with OLFM3, FN1, NRCAM, GLDN and NFASC CC (PubMed:12019210, PubMed:11773026, PubMed:23897819). Interacts (via N- CC terminus) with MYL2 (PubMed:11773029). Interacts with SFRP1, FRZB, CC FZD7, FZD10, FZD1 and WIF1; regulates Wnt signaling (PubMed:19188438). CC Interacts with SNTA1; regulates muscle hypertrophy. Interacts with CC ERBB2 and ERBB3; activates ERBB2-ERBB3 signaling pathway. Interacts CC with SNCG; affects its secretion and its aggregation (By similarity). CC {ECO:0000250|UniProtKB:O70624, ECO:0000269|PubMed:11773026, CC ECO:0000269|PubMed:11773029, ECO:0000269|PubMed:12019210, CC ECO:0000269|PubMed:19188438, ECO:0000269|PubMed:23897819, CC ECO:0000269|PubMed:9497363}. CC -!- INTERACTION: CC Q99972; P10916: MYL2; NbExp=7; IntAct=EBI-11692272, EBI-725770; CC Q99972; O43765: SGTA; NbExp=3; IntAct=EBI-11692272, EBI-347996; CC Q99972; P09486: SPARC; NbExp=3; IntAct=EBI-11692272, EBI-2800983; CC Q99972; Q14515: SPARCL1; NbExp=2; IntAct=EBI-11692272, EBI-2682673; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11431441, CC ECO:0000269|PubMed:12697062, ECO:0000269|PubMed:19287508, CC ECO:0000269|PubMed:9497363}. Golgi apparatus CC {ECO:0000269|PubMed:11053284}. Cytoplasmic vesicle CC {ECO:0000269|PubMed:11431441}. Secreted, extracellular space. Secreted, CC extracellular space, extracellular matrix {ECO:0000269|PubMed:11773026, CC ECO:0000305|PubMed:11431441}. Secreted, extracellular exosome CC {ECO:0000269|PubMed:15944158}. Mitochondrion CC {ECO:0000269|PubMed:17516541}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:17516541}. Mitochondrion inner membrane CC {ECO:0000269|PubMed:17516541}. Mitochondrion outer membrane CC {ECO:0000269|PubMed:17516541}. Rough endoplasmic reticulum CC {ECO:0000269|PubMed:19287508}. Cell projection. Cell projection, cilium CC {ECO:0000269|PubMed:9169133}. Note=Located preferentially in the CC ciliary rootlet and basal body of the connecting cilium of CC photoreceptor cells, and in the rough endoplasmic reticulum CC (PubMed:9169133). It is only imported to mitochondria in the trabecular CC meshwork (PubMed:17516541). Localizes to the Golgi apparatus in CC Schlemm's canal endothelial cells (PubMed:11053284). Appears in the CC extracellular space of trabecular meshwork cells by an unconventional CC mechanism, likely associated with exosome-like vesicles CC (PubMed:15944158). Localizes in trabecular meshwork extracellular CC matrix (PubMed:15944158). {ECO:0000269|PubMed:11053284, CC ECO:0000269|PubMed:15944158, ECO:0000269|PubMed:17516541, CC ECO:0000269|PubMed:9169133}. CC -!- SUBCELLULAR LOCATION: [Myocilin, C-terminal fragment]: Secreted. CC -!- SUBCELLULAR LOCATION: [Myocilin, N-terminal fragment]: Endoplasmic CC reticulum. Note=Remains retained in the endoplasmic reticulum. CC -!- TISSUE SPECIFICITY: Detected in aqueous humor (PubMed:12697062). CC Detected in the eye (at protein level) (PubMed:11431441). Widely CC expressed. Highly expressed in various types of muscle, ciliary body, CC papillary sphincter, skeletal muscle, heart, and bone marrow-derived CC mesenchymal stem cells. Expressed predominantly in the retina. In CC normal eyes, found in the inner uveal meshwork region and the anterior CC portion of the meshwork. In contrast, in many glaucomatous eyes, it is CC found in more regions of the meshwork and seems to be expressed at CC higher levels than in normal eyes, regardless of the type or clinical CC severity of glaucoma. The myocilin 35 kDa fragment is detected in CC aqueous humor and to a lesser extent in iris and ciliary body. CC {ECO:0000269|PubMed:11431441, ECO:0000269|PubMed:12697062, CC ECO:0000269|PubMed:15795224}. CC -!- INDUCTION: Up-regulated by dexamethasone, a glucocorticoid. CC {ECO:0000269|PubMed:11431441, ECO:0000269|PubMed:9497363}. CC -!- PTM: Different isoforms may arise by post-translational modifications. CC {ECO:0000269|PubMed:9497363}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:11431441, CC ECO:0000269|PubMed:12697062, ECO:0000269|PubMed:17650508, CC ECO:0000269|PubMed:19287508}. CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}. CC -!- PTM: Undergoes a calcium-dependent proteolytic cleavage at Arg-226 by CC CAPN2 in the endoplasmic reticulum. The result is the production of two CC fragments, one of 35 kDa containing the C-terminal olfactomedin-like CC domain, and another of 20 kDa containing the N-terminal leucine zipper- CC like domain. {ECO:0000269|PubMed:15795224, CC ECO:0000269|PubMed:17650508}. CC -!- DISEASE: Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: 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:10196380, CC ECO:0000269|PubMed:10330365, ECO:0000269|PubMed:10340788, CC ECO:0000269|PubMed:10644174, ECO:0000269|PubMed:10798654, CC ECO:0000269|PubMed:10819638, ECO:0000269|PubMed:10873982, CC ECO:0000269|PubMed:10916185, ECO:0000269|PubMed:10980537, CC ECO:0000269|PubMed:11004290, ECO:0000269|PubMed:11774072, CC ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12356829, CC ECO:0000269|PubMed:12362081, ECO:0000269|PubMed:12442283, CC ECO:0000269|PubMed:12860809, ECO:0000269|PubMed:12872267, CC ECO:0000269|PubMed:15025728, ECO:0000269|PubMed:15255110, CC ECO:0000269|PubMed:15534471, ECO:0000269|PubMed:15795224, CC ECO:0000269|PubMed:16401791, ECO:0000269|PubMed:17210859, CC ECO:0000269|PubMed:17499207, ECO:0000269|PubMed:25524706, CC ECO:0000269|PubMed:9005853, ECO:0000269|PubMed:9328473, CC ECO:0000269|PubMed:9345106, ECO:0000269|PubMed:9361308, CC ECO:0000269|PubMed:9490287, ECO:0000269|PubMed:9510647, CC ECO:0000269|PubMed:9521427, ECO:0000269|PubMed:9535666, CC ECO:0000269|PubMed:9697688, ECO:0000269|PubMed:9792882, CC ECO:0000269|PubMed:9863594}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An CC autosomal recessive form of primary congenital glaucoma (PCG). PCG is CC characterized by marked increase of intraocular pressure at birth or CC early childhood, large ocular globes (buphthalmos) and corneal edema. CC It results from developmental defects of the trabecular meshwork and CC anterior chamber angle of the eye that prevent adequate drainage of CC aqueous humor. {ECO:0000269|PubMed:15733270}. Note=The disease is CC caused by variants affecting distinct genetic loci, including the gene CC represented in this entry. MYOC mutations may contribute to GLC3A via CC digenic inheritance with CYP1B1 and/or another locus associated with CC the disease (PubMed:15733270). {ECO:0000269|PubMed:15733270}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA24532.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; AF001620; AAC51725.1; -; mRNA. DR EMBL; D88214; BAA23531.1; -; mRNA. DR EMBL; Z97171; CAB09899.1; -; Genomic_DNA. DR EMBL; Z97177; CAB09899.1; JOINED; Genomic_DNA. DR EMBL; Z97174; CAB09899.1; JOINED; Genomic_DNA. DR EMBL; U85257; AAC52051.1; -; mRNA. DR EMBL; AB006688; BAA24532.1; ALT_INIT; Genomic_DNA. DR EMBL; AF049793; AAC14264.1; -; Genomic_DNA. DR EMBL; AF049791; AAC14264.1; JOINED; Genomic_DNA. DR EMBL; AF049792; AAC14264.1; JOINED; Genomic_DNA. DR EMBL; AK315443; BAG37831.1; -; mRNA. DR EMBL; Z98750; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW90903.1; -; Genomic_DNA. DR EMBL; BC029261; AAH29261.1; -; mRNA. DR CCDS; CCDS1297.1; -. DR PIR; JC5830; JC5830. DR RefSeq; NP_000252.1; NM_000261.1. DR PDB; 4WXQ; X-ray; 2.15 A; A=228-504. DR PDB; 4WXS; X-ray; 1.90 A; A=228-504. DR PDB; 4WXU; X-ray; 2.09 A; A=228-504. DR PDB; 6OU0; X-ray; 1.80 A; A=228-504. DR PDB; 6OU1; X-ray; 1.88 A; A/B=228-504. DR PDB; 6OU2; X-ray; 1.96 A; A=228-504. DR PDB; 6OU3; X-ray; 1.80 A; A=228-504. DR PDB; 6PKD; X-ray; 1.90 A; A/B=228-504. DR PDB; 6PKE; X-ray; 1.88 A; A/B=228-504. DR PDB; 6PKF; X-ray; 1.48 A; A=228-504. DR PDB; 7SIB; X-ray; 1.78 A; A=228-504. DR PDB; 7SIJ; X-ray; 1.54 A; A=228-504. DR PDB; 7SJT; X-ray; 1.54 A; A=228-504. DR PDB; 7SJU; X-ray; 1.39 A; A=228-504. DR PDB; 7SJV; X-ray; 1.39 A; A=228-504. DR PDB; 7SJW; X-ray; 1.38 A; A=228-504. DR PDB; 7SKD; X-ray; 1.71 A; A=228-504. DR PDB; 7SKE; X-ray; 1.24 A; A=228-504. DR PDB; 7SKF; X-ray; 1.28 A; A=228-504. DR PDB; 7SKG; X-ray; 1.33 A; A=228-504. DR PDB; 7T8D; X-ray; 1.38 A; A=228-504. DR PDBsum; 4WXQ; -. DR PDBsum; 4WXS; -. DR PDBsum; 4WXU; -. DR PDBsum; 6OU0; -. DR PDBsum; 6OU1; -. DR PDBsum; 6OU2; -. DR PDBsum; 6OU3; -. DR PDBsum; 6PKD; -. DR PDBsum; 6PKE; -. DR PDBsum; 6PKF; -. DR PDBsum; 7SIB; -. DR PDBsum; 7SIJ; -. DR PDBsum; 7SJT; -. DR PDBsum; 7SJU; -. DR PDBsum; 7SJV; -. DR PDBsum; 7SJW; -. DR PDBsum; 7SKD; -. DR PDBsum; 7SKE; -. DR PDBsum; 7SKF; -. DR PDBsum; 7SKG; -. DR PDBsum; 7T8D; -. DR AlphaFoldDB; Q99972; -. DR SMR; Q99972; -. DR BioGRID; 110736; 45. DR IntAct; Q99972; 4. DR STRING; 9606.ENSP00000037502; -. DR BindingDB; Q99972; -. DR ChEMBL; CHEMBL4105967; -. DR GlyCosmos; Q99972; 1 site, No reported glycans. DR GlyGen; Q99972; 1 site. DR iPTMnet; Q99972; -. DR PhosphoSitePlus; Q99972; -. DR BioMuta; MYOC; -. DR DMDM; 3024209; -. DR jPOST; Q99972; -. DR MassIVE; Q99972; -. DR PaxDb; 9606-ENSP00000037502; -. DR PeptideAtlas; Q99972; -. DR ProteomicsDB; 78558; -. DR Antibodypedia; 34380; 301 antibodies from 31 providers. DR DNASU; 4653; -. DR Ensembl; ENST00000037502.11; ENSP00000037502.5; ENSG00000034971.17. DR GeneID; 4653; -. DR KEGG; hsa:4653; -. DR MANE-Select; ENST00000037502.11; ENSP00000037502.5; NM_000261.2; NP_000252.1. DR UCSC; uc001ghu.4; human. DR AGR; HGNC:7610; -. DR CTD; 4653; -. DR DisGeNET; 4653; -. DR GeneCards; MYOC; -. DR HGNC; HGNC:7610; MYOC. DR HPA; ENSG00000034971; Tissue enhanced (tongue). DR MalaCards; MYOC; -. DR MIM; 137750; phenotype. DR MIM; 231300; phenotype. DR MIM; 601652; gene. DR neXtProt; NX_Q99972; -. DR OpenTargets; ENSG00000034971; -. DR Orphanet; 98976; Congenital glaucoma. DR Orphanet; 98977; Juvenile glaucoma. DR PharmGKB; PA31415; -. DR VEuPathDB; HostDB:ENSG00000034971; -. DR eggNOG; KOG3545; Eukaryota. DR GeneTree; ENSGT00940000158561; -. DR HOGENOM; CLU_035236_4_0_1; -. DR InParanoid; Q99972; -. DR OMA; REVSKWN; -. DR OrthoDB; 2876896at2759; -. DR PhylomeDB; Q99972; -. DR TreeFam; TF315964; -. DR PathwayCommons; Q99972; -. DR SignaLink; Q99972; -. DR BioGRID-ORCS; 4653; 17 hits in 1144 CRISPR screens. DR ChiTaRS; MYOC; human. DR GeneWiki; MYOC; -. DR GenomeRNAi; 4653; -. DR Pharos; Q99972; Tchem. DR PRO; PR:Q99972; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q99972; Protein. DR Bgee; ENSG00000034971; Expressed in calcaneal tendon and 135 other cell types or tissues. DR ExpressionAtlas; Q99972; baseline and differential. DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:MGI. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0033268; C:node of Ranvier; ISS:UniProtKB. DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0001968; F:fibronectin binding; IPI:UniProtKB. DR GO; GO:0005109; F:frizzled binding; IPI:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0032027; F:myosin light chain binding; IPI:UniProtKB. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl. DR GO; GO:0060348; P:bone development; ISS:UniProtKB. DR GO; GO:0045162; P:clustering of voltage-gated sodium channels; ISS:UniProtKB. DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; ISS:UniProtKB. DR GO; GO:0022011; P:myelination in peripheral nervous system; ISS:UniProtKB. DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; IDA:UniProtKB. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IDA:UniProtKB. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:UniProtKB. DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:UniProtKB. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IDA:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0014734; P:skeletal muscle hypertrophy; ISS:UniProtKB. DR Gene3D; 1.10.287.1490; -; 1. DR InterPro; IPR003112; Olfac-like_dom. DR PANTHER; PTHR23192:SF33; MYOCILIN; 1. DR PANTHER; PTHR23192; OLFACTOMEDIN-RELATED; 1. DR Pfam; PF02191; OLF; 1. DR SMART; SM00284; OLF; 1. DR PROSITE; PS51132; OLF; 1. DR Genevisible; Q99972; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cell projection; Cilium; Coiled coil; KW Cytoplasmic vesicle; Direct protein sequencing; Disease variant; KW Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Glaucoma; KW Glycoprotein; Golgi apparatus; Lipoprotein; Membrane; Metal-binding; KW Mitochondrion; Mitochondrion inner membrane; Mitochondrion outer membrane; KW Palmitate; Reference proteome; Secreted; Signal. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:19287508, FT ECO:0000269|PubMed:9497363" FT CHAIN 33..504 FT /note="Myocilin" FT /id="PRO_0000020084" FT CHAIN 33..226 FT /note="Myocilin, N-terminal fragment" FT /id="PRO_0000428749" FT CHAIN 227..504 FT /note="Myocilin, C-terminal fragment" FT /id="PRO_0000428750" FT DOMAIN 244..503 FT /note="Olfactomedin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446" FT REGION 106..131 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 170..200 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 74..184 FT /evidence="ECO:0000255" FT MOTIF 502..504 FT /note="Microbody targeting signal" FT /evidence="ECO:0000255" FT BINDING 380 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, FT ECO:0007744|PDB:4WXU" FT BINDING 428 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, FT ECO:0007744|PDB:4WXU" FT BINDING 429 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, FT ECO:0007744|PDB:4WXU" FT BINDING 477 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, FT ECO:0007744|PDB:4WXU" FT BINDING 478 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, FT ECO:0007744|PDB:4WXU" FT SITE 226..227 FT /note="Cleavage; by CAPN2" FT CARBOHYD 57 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305|PubMed:17650508" FT DISULFID 245..433 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446, FT ECO:0000269|PubMed:12615070, ECO:0007744|PDB:4WXQ, FT ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU" FT VARIANT 4 FT /note="F -> S" FT /id="VAR_009665" FT VARIANT 9 FT /note="C -> S" FT /id="VAR_009666" FT VARIANT 12 FT /note="G -> R (in dbSNP:rs199752860)" FT /evidence="ECO:0000269|PubMed:10798654, FT ECO:0000269|PubMed:12356829" FT /id="VAR_009667" FT VARIANT 16 FT /note="P -> L (in dbSNP:rs745439002)" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054269" FT VARIANT 17 FT /note="A -> S" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054270" FT VARIANT 19 FT /note="Q -> H (in dbSNP:rs2234925)" FT /evidence="ECO:0000269|PubMed:10980537" FT /id="VAR_009668" FT VARIANT 25 FT /note="C -> R (in GLC1A; dbSNP:rs755246983)" FT /evidence="ECO:0000269|PubMed:12860809" FT /id="VAR_054271" FT VARIANT 48 FT /note="Q -> H (in GLC1A and GLC3A; the GLC3A patient also FT carries mutation H-368 in CYP1B1 suggesting digenic FT inheritance; dbSNP:rs74315339)" FT /evidence="ECO:0000269|PubMed:15025728, FT ECO:0000269|PubMed:15733270" FT /id="VAR_054272" FT VARIANT 53 FT /note="V -> A (in GLC1A; dbSNP:rs200208925)" FT /evidence="ECO:0000269|PubMed:10644174" FT /id="VAR_008969" FT VARIANT 57 FT /note="N -> D" FT /evidence="ECO:0000269|PubMed:11004290" FT /id="VAR_054273" FT VARIANT 57 FT /note="N -> S (loss of higher molecular weight isoform; FT dbSNP:rs561439247)" FT /evidence="ECO:0000269|PubMed:12697062, FT ECO:0000269|PubMed:12872267" FT /id="VAR_054274" FT VARIANT 73 FT /note="N -> S" FT /id="VAR_009669" FT VARIANT 76 FT /note="R -> K (in dbSNP:rs2234926)" FT /evidence="ECO:0000269|PubMed:10798654, FT ECO:0000269|PubMed:10980537, ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12356829, FT ECO:0000269|PubMed:12442283, ECO:0000269|PubMed:12872267, FT ECO:0000269|PubMed:15025728, ECO:0000269|PubMed:9863594" FT /id="VAR_009670" FT VARIANT 77 FT /note="D -> E" FT /evidence="ECO:0000269|PubMed:12189160" FT /id="VAR_054275" FT VARIANT 82 FT /note="R -> C (in GLC1A; dbSNP:rs764005392)" FT /id="VAR_009671" FT VARIANT 82 FT /note="R -> H (in dbSNP:rs201552559)" FT /id="VAR_009672" FT VARIANT 95 FT /note="L -> P" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054276" FT VARIANT 126 FT /note="R -> W (in GLC1A; dbSNP:rs200120115)" FT /evidence="ECO:0000269|PubMed:12189160" FT /id="VAR_054277" FT VARIANT 158 FT /note="R -> Q (in GLC1A; dbSNP:rs199746824)" FT /evidence="ECO:0000269|PubMed:10980537" FT /id="VAR_054278" FT VARIANT 189 FT /note="R -> Q (in dbSNP:rs144579767)" FT /id="VAR_009673" FT VARIANT 203 FT /note="S -> F" FT /id="VAR_009674" FT VARIANT 208 FT /note="D -> E (in GLC1A; uncertain significance; FT dbSNP:rs2234927)" FT /evidence="ECO:0000269|PubMed:10798654, FT ECO:0000269|PubMed:10980537, ECO:0000269|PubMed:12356829" FT /id="VAR_014943" FT VARIANT 215 FT /note="L -> P (in dbSNP:rs531050114)" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054279" FT VARIANT 244 FT /note="G -> V (in GLC1A; uncertain significance; FT dbSNP:rs757769997)" FT /evidence="ECO:0000269|PubMed:17210859" FT /id="VAR_054280" FT VARIANT 245 FT /note="C -> Y (in GLC1A; forms homomultimeric complexes FT that migrate at molecular weights larger than their FT wild-type counterparts; these mutant complexes remain FT sequestered intracellularly; dbSNP:rs74315340)" FT /evidence="ECO:0000269|PubMed:16401791" FT /id="VAR_054281" FT VARIANT 246 FT /note="G -> R (in GLC1A)" FT /evidence="ECO:0000269|PubMed:9328473" FT /id="VAR_005468" FT VARIANT 251 FT /note="V -> A (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_054282" FT VARIANT 252 FT /note="G -> R (in GLC1A; dbSNP:rs74315341)" FT /evidence="ECO:0000269|PubMed:10873982, FT ECO:0000269|PubMed:11004290, ECO:0000269|PubMed:11774072, FT ECO:0000269|PubMed:17210859" FT /id="VAR_054283" FT VARIANT 261 FT /note="E -> K (in GLC1A; dbSNP:rs982896610)" FT /evidence="ECO:0000269|PubMed:10916185" FT /id="VAR_054284" FT VARIANT 272 FT /note="R -> G (in GLC1A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:11004290" FT /id="VAR_054285" FT VARIANT 274 FT /note="P -> R (in GLC1A)" FT /evidence="ECO:0000269|PubMed:15255110" FT /id="VAR_054286" FT VARIANT 286 FT /note="W -> R (in GLC1A; dbSNP:rs1351328951)" FT /id="VAR_009675" FT VARIANT 293 FT /note="T -> K (in GLC1A; no effect on protein stability; FT dbSNP:rs139122673)" FT /evidence="ECO:0000269|PubMed:11774072, FT ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:25524706" FT /id="VAR_009676" FT VARIANT 300 FT /note="E -> K (in GLC1A; uncertain significance; FT dbSNP:rs748621461)" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054287" FT VARIANT 323 FT /note="E -> K (in GLC1A; inhibits endoproteolytic FT processing; mainly accumulates as insoluble aggregates FT inside the endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:15795224" FT /id="VAR_054288" FT VARIANT 329 FT /note="V -> M (slightly decreased protein stability; FT dbSNP:rs146391864)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:25524706" FT /id="VAR_009677" FT VARIANT 337 FT /note="Q -> E (in GLC1A)" FT /evidence="ECO:0000269|PubMed:10916185" FT /id="VAR_054289" FT VARIANT 337 FT /note="Q -> R (in GLC1A; dbSNP:rs74315335)" FT /evidence="ECO:0000269|PubMed:9361308" FT /id="VAR_005469" FT VARIANT 341 FT /note="S -> P (in GLC1A; dbSNP:rs1572210748)" FT /evidence="ECO:0000269|PubMed:9510647" FT /id="VAR_054290" FT VARIANT 342 FT /note="R -> K (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12362081" FT /id="VAR_054291" FT VARIANT 345 FT /note="I -> M (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_054292" FT VARIANT 352 FT /note="E -> K (in GLC1A; uncertain significance; FT dbSNP:rs61745146)" FT /evidence="ECO:0000269|PubMed:12189160, FT ECO:0000269|PubMed:9792882" FT /id="VAR_009678" FT VARIANT 353 FT /note="T -> I (in GLC1A; uncertain significance; no FT significant effect on protein stability; FT dbSNP:rs137853277)" FT /evidence="ECO:0000269|PubMed:10330365, FT ECO:0000269|PubMed:10798654, ECO:0000269|PubMed:12356829, FT ECO:0000269|PubMed:25524706" FT /id="VAR_009679" FT VARIANT 360 FT /note="I -> N (in GLC1A)" FT /evidence="ECO:0000269|PubMed:10980537, FT ECO:0000269|PubMed:15534471" FT /id="VAR_054293" FT VARIANT 361 FT /note="P -> S (in GLC1A; dbSNP:rs1344039930)" FT /id="VAR_009680" FT VARIANT 363 FT /note="A -> T (in GLC1A)" FT /evidence="ECO:0000269|PubMed:10980537, FT ECO:0000269|PubMed:15534471" FT /id="VAR_054294" FT VARIANT 364 FT /note="G -> V (in GLC1A; dbSNP:rs121909193)" FT /evidence="ECO:0000269|PubMed:9005853" FT /id="VAR_005470" FT VARIANT 367 FT /note="G -> R (in GLC1A; dbSNP:rs74315334)" FT /evidence="ECO:0000269|PubMed:11774072, FT ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12442283, FT ECO:0000269|PubMed:12872267, ECO:0000269|PubMed:9345106, FT ECO:0000269|PubMed:9490287, ECO:0000269|PubMed:9521427" FT /id="VAR_005471" FT VARIANT 369 FT /note="F -> L (in GLC1A)" FT /evidence="ECO:0000269|PubMed:15534471" FT /id="VAR_054295" FT VARIANT 370 FT /note="P -> L (in GLC1A; severe form; inhibits FT endoproteolytic processing; produced the highest inhibition FT of the endoproteolytic processing; mainly accumulates as FT insoluble aggregates inside the endoplasmic reticulum; FT inhibits neurite outgrowth; dbSNP:rs74315330)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:12442283, FT ECO:0000269|PubMed:15795224, ECO:0000269|PubMed:9328473, FT ECO:0000269|PubMed:9345106, ECO:0000269|PubMed:9490287, FT ECO:0000269|PubMed:9792882, ECO:0000269|PubMed:9863594" FT /id="VAR_005472" FT VARIANT 377 FT /note="T -> K (in GLC1A)" FT /evidence="ECO:0000269|PubMed:11774072" FT /id="VAR_054296" FT VARIANT 377 FT /note="T -> M (in GLC1A; dbSNP:rs566289099)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:9792882" FT /id="VAR_009681" FT VARIANT 380 FT /note="D -> A (in GLC1A; incomplete penetrance; inhibits FT endoproteolytic processing; mainly accumulates as insoluble FT aggregates inside the endoplasmic reticulum)" FT /evidence="ECO:0000269|PubMed:9863594" FT /id="VAR_009682" FT VARIANT 380 FT /note="D -> G (in GLC1A)" FT /evidence="ECO:0000269|PubMed:15795224" FT /id="VAR_009683" FT VARIANT 380 FT /note="D -> H (in GLC1A; dbSNP:rs121909194)" FT /evidence="ECO:0000269|PubMed:17499207" FT /id="VAR_054297" FT VARIANT 380 FT /note="D -> N (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12362081" FT /id="VAR_054298" FT VARIANT 393 FT /note="S -> N (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_054299" FT VARIANT 393 FT /note="S -> R (in GLC1A; dbSNP:rs998968146)" FT /id="VAR_009684" FT VARIANT 398 FT /note="K -> R (in dbSNP:rs56314834)" FT /evidence="ECO:0000269|PubMed:10916185, FT ECO:0000269|PubMed:11004290, ECO:0000269|PubMed:11774072, FT ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:12872267" FT /id="VAR_009685" FT VARIANT 399 FT /note="G -> V (in GLC1A; dbSNP:rs28936694)" FT /evidence="ECO:0000269|PubMed:11774072" FT /id="VAR_054300" FT VARIANT 402 FT /note="V -> I" FT /id="VAR_009686" FT VARIANT 414 FT /note="E -> K (in dbSNP:rs1351097164)" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054301" FT VARIANT 422 FT /note="R -> C (no effect on protein stability; FT dbSNP:rs751113505)" FT /evidence="ECO:0000269|PubMed:25524706" FT /id="VAR_009687" FT VARIANT 422 FT /note="R -> H (in GLC1A; dbSNP:rs201573718)" FT /id="VAR_009688" FT VARIANT 423 FT /note="K -> E (in GLC1A; heterozygote specific phenotype; FT dbSNP:rs74315336)" FT /evidence="ECO:0000269|PubMed:12189160, FT ECO:0000269|PubMed:12860809, ECO:0000269|PubMed:9697688" FT /id="VAR_009689" FT VARIANT 425 FT /note="S -> P (decreases protein stability)" FT /evidence="ECO:0000269|PubMed:25524706" FT /id="VAR_009690" FT VARIANT 426 FT /note="V -> F (in GLC1A)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:9521427" FT /id="VAR_005473" FT VARIANT 427 FT /note="A -> T (in GLC1A; dbSNP:rs754237376)" FT /evidence="ECO:0000269|PubMed:12189160" FT /id="VAR_054302" FT VARIANT 433 FT /note="C -> R (in GLC1A; severe form; dbSNP:rs74315338)" FT /evidence="ECO:0000269|PubMed:10819638" FT /id="VAR_008970" FT VARIANT 434 FT /note="G -> S (in GLC1A; dbSNP:rs1200513428)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_054303" FT VARIANT 437 FT /note="Y -> H (in GLC1A; dbSNP:rs74315328)" FT /evidence="ECO:0000269|PubMed:9005853, FT ECO:0000269|PubMed:9792882" FT /id="VAR_005474" FT VARIANT 438 FT /note="T -> I (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12872267" FT /id="VAR_054304" FT VARIANT 445 FT /note="A -> V (in GLC1A; no effect on protein stability; FT dbSNP:rs140967767)" FT /evidence="ECO:0000269|PubMed:11774072, FT ECO:0000269|PubMed:12189160, ECO:0000269|PubMed:25524706" FT /id="VAR_009691" FT VARIANT 448 FT /note="T -> P (in GLC1A)" FT /evidence="ECO:0000269|PubMed:10340788, FT ECO:0000269|PubMed:15534471" FT /id="VAR_054305" FT VARIANT 450 FT /note="N -> D (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_054306" FT VARIANT 465 FT /note="I -> M (in GLC1A)" FT /id="VAR_009692" FT VARIANT 470 FT /note="R -> C (in GLC1A; dbSNP:rs771122834)" FT /evidence="ECO:0000269|PubMed:12442283" FT /id="VAR_009693" FT VARIANT 470 FT /note="R -> H (in dbSNP:rs750791099)" FT /evidence="ECO:0000269|PubMed:10980537" FT /id="VAR_054307" FT VARIANT 471 FT /note="Y -> C (in GLC1A; uncertain significance; FT dbSNP:rs554235897)" FT /evidence="ECO:0000269|PubMed:12356829" FT /id="VAR_054308" FT VARIANT 473 FT /note="Y -> C (no effect on protein stability)" FT /evidence="ECO:0000269|PubMed:25524706" FT /id="VAR_009694" FT VARIANT 477 FT /note="I -> N (in GLC1A; induces stress fiber formation in FT only 5% of cells; dbSNP:rs74315331)" FT /evidence="ECO:0000269|PubMed:11004290, FT ECO:0000269|PubMed:19188438" FT /id="VAR_009695" FT VARIANT 477 FT /note="I -> S (in GLC1A; dbSNP:rs74315331)" FT /evidence="ECO:0000269|PubMed:9328473" FT /id="VAR_005475" FT VARIANT 480 FT /note="N -> K (in GLC1A; dbSNP:rs74315332)" FT /evidence="ECO:0000269|PubMed:12872267, FT ECO:0000269|PubMed:9328473" FT /id="VAR_005476" FT VARIANT 481 FT /note="P -> L (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12189160" FT /id="VAR_009696" FT VARIANT 481 FT /note="P -> T (in GLC1A)" FT /id="VAR_009697" FT VARIANT 495 FT /note="V -> I" FT /id="VAR_009698" FT VARIANT 499 FT /note="I -> F (in GLC1A)" FT /evidence="ECO:0000269|PubMed:12872267, FT ECO:0000269|PubMed:9328473" FT /id="VAR_005477" FT VARIANT 499 FT /note="I -> S (in GLC1A)" FT /evidence="ECO:0000269|PubMed:11004290" FT /id="VAR_054309" FT VARIANT 500 FT /note="K -> R (in dbSNP:rs145977437)" FT /id="VAR_009699" FT VARIANT 502 FT /note="S -> P (in GLC1A)" FT /evidence="ECO:0000269|PubMed:9863594" FT /id="VAR_009700" FT MUTAGEN 226..230 FT /note="Missing: Impairs endoproteolytic processing." FT /evidence="ECO:0000269|PubMed:17650508" FT MUTAGEN 226 FT /note="R->A: Reduced processing. Impairs endoproteolytic FT processing; when associated with A-229 or A-230. Completely FT processed after 6 days of expression, and releases a FT C-terminal fragment with similar electrophoretic mobility FT to that obtained by processing wild-type myocilin; when FT associated with A-229 or A-230." FT /evidence="ECO:0000269|PubMed:17650508" FT MUTAGEN 226 FT /note="R->Q: Slightly increases endoproteolytic FT processing." FT /evidence="ECO:0000269|PubMed:17650508" FT MUTAGEN 227 FT /note="I->G: Reduced processing." FT /evidence="ECO:0000269|PubMed:17650508" FT MUTAGEN 229 FT /note="K->A: Completely blocks endoproteolytic processing; FT when associated with A-226. Completely processed after 6 FT days of expression, and releases a C-terminal fragment with FT similar electrophoretic mobility to that obtained by FT processing wild-type myocilin; when associated with A-226." FT /evidence="ECO:0000269|PubMed:17650508" FT MUTAGEN 230 FT /note="E->A: Impairs endoproteolytic processing; when FT associated with A-226. Completely processed after 6 days of FT expression, and released a C-terminal fragment with similar FT electrophoretic mobility to that obtained by processing FT wild-type myocilin; when associated with A-226." FT /evidence="ECO:0000269|PubMed:17650508" FT STRAND 248..251 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:7SKE" FT HELIX 263..265 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 266..271 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 285..289 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 292..294 FT /evidence="ECO:0007829|PDB:6PKF" FT STRAND 297..303 FT /evidence="ECO:0007829|PDB:7SKE" FT HELIX 304..309 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 313..317 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 322..325 FT /evidence="ECO:0007829|PDB:6PKF" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 333..338 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 341..348 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 349..352 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 353..359 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 366..369 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 375..378 FT /evidence="ECO:0007829|PDB:4WXU" FT STRAND 380..384 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 387..392 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 395..399 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 400..406 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 408..410 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 413..422 FT /evidence="ECO:0007829|PDB:7SKE" FT HELIX 423..425 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 426..432 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 435..440 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 442..445 FT /evidence="ECO:0007829|PDB:6OU3" FT STRAND 447..454 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 455..457 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 460..467 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 470..473 FT /evidence="ECO:0007829|PDB:6OU3" FT STRAND 474..480 FT /evidence="ECO:0007829|PDB:7SKE" FT TURN 481..484 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 485..490 FT /evidence="ECO:0007829|PDB:7SKE" FT STRAND 493..501 FT /evidence="ECO:0007829|PDB:7SKE" SQ SEQUENCE 504 AA; 56972 MW; 9588C04F1D227623 CRC64; MRFFCARCCS FGPEMPAVQL LLLACLVWDV GARTAQLRKA NDQSGRCQYT FSVASPNESS CPEQSQAMSV IHNLQRDSST QRLDLEATKA RLSSLESLLH QLTLDQAARP QETQEGLQRE LGTLRRERDQ LETQTRELET AYSNLLRDKS VLEEEKKRLR QENENLARRL ESSSQEVARL RRGQCPQTRD TARAVPPGSR EVSTWNLDTL AFQELKSELT EVPASRILKE SPSGYLRSGE GDTGCGELVW VGEPLTLRTA ETITGKYGVW MRDPKPTYPY TQETTWRIDT VGTDVRQVFE YDLISQFMQG YPSKVHILPR PLESTGAVVY SGSLYFQGAE SRTVIRYELN TETVKAEKEI PGAGYHGQFP YSWGGYTDID LAVDEAGLWV IYSTDEAKGA IVLSKLNPEN LELEQTWETN IRKQSVANAF IICGTLYTVS SYTSADATVN FAYDTGTGIS KTLTIPFKNR YKYSSMIDYN PLEKKLFAWD NLNMVTYDIK LSKM //