MYOC_HUMAN
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 03-AUG-2022, entry version 197.
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};
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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 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 AlphaFoldDB; Q99972; -.
DR SMR; Q99972; -.
DR BioGRID; 110736; 45.
DR IntAct; Q99972; 4.
DR STRING; 9606.ENSP00000037502; -.
DR BindingDB; Q99972; -.
DR ChEMBL; CHEMBL4105967; -.
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; Q99972; -.
DR PeptideAtlas; Q99972; -.
DR PRIDE; Q99972; -.
DR ProteomicsDB; 78558; -.
DR Antibodypedia; 34380; 263 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 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; FNMVTYD; -.
DR OrthoDB; 421994at2759; -.
DR PhylomeDB; Q99972; -.
DR TreeFam; TF315964; -.
DR PathwayCommons; Q99972; -.
DR SignaLink; Q99972; -.
DR BioGRID-ORCS; 4653; 17 hits in 1066 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 tissues.
DR ExpressionAtlas; Q99972; baseline and differential.
DR Genevisible; Q99972; HS.
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:0038031; P:non-canonical Wnt signaling pathway via JNK cascade; 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:0051901; P:positive regulation of mitochondrial depolarization; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; 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 InterPro; IPR031213; Myocilin.
DR InterPro; IPR003112; Olfac-like_dom.
DR PANTHER; PTHR23192:SF33; PTHR23192:SF33; 1.
DR Pfam; PF02191; OLF; 1.
DR SMART; SM00284; OLF; 1.
DR PROSITE; PS51132; OLF; 1.
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; unknown pathological 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; unknown pathological 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 wild-
FT 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; unknown pathological
FT 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; unknown pathological 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; unknown pathological 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; unknown pathological significance;
FT no 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; unknown pathological 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 C-
FT terminal fragment with similar electrophoretic mobility to
FT 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:6PKF"
FT HELIX 259..264
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 297..302
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:6OU3"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 341..348
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 349..352
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 353..359
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 375..378
FT /evidence="ECO:0007829|PDB:4WXU"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 387..392
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 395..399
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 413..422
FT /evidence="ECO:0007829|PDB:6PKF"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 426..432
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 435..445
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 447..454
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 455..457
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 460..467
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 470..473
FT /evidence="ECO:0007829|PDB:6OU3"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:6PKF"
FT TURN 481..484
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 485..489
FT /evidence="ECO:0007829|PDB:6PKF"
FT STRAND 494..501
FT /evidence="ECO:0007829|PDB:6PKF"
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
