Myocilin

Myocilin, trabecular meshwork inducible glucocorticoid response
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4WXQ​, 4WXS​, 4WXU​
Identifiers
Symbols	MYOC ; GLC1A; GPOA; JOAG; JOAG1; TIGR; myocilin
External IDs	OMIM: 601652 MGI: 1202864 HomoloGene: 220 GeneCards: MYOC Gene
Gene ontology Molecular function • fibronectin binding • frizzled binding • protein binding • receptor tyrosine kinase binding • myosin light chain binding Cellular component • proteinaceous extracellular matrix • extracellular space • mitochondrial outer membrane • mitochondrial inner membrane • mitochondrial intermembrane space • endoplasmic reticulum • rough endoplasmic reticulum • Golgi apparatus • cilium • cytoplasmic membrane-bounded vesicle • extracellular matrix • cytoplasmic vesicle • node of Ranvier • extracellular exosome Biological process • osteoblast differentiation • negative regulation of cell-matrix adhesion • positive regulation of phosphatidylinositol 3-kinase signaling • skeletal muscle hypertrophy • myelination in peripheral nervous system • positive regulation of cell migration • neuron projection development • negative regulation of Rho protein signal transduction • non-canonical Wnt signaling pathway via JNK cascade • ERBB2-ERBB3 signaling pathway • regulation of MAPK cascade • clustering of voltage-gated sodium channels • positive regulation of stress fiber assembly • negative regulation of stress fiber assembly • positive regulation of focal adhesion assembly • positive regulation of protein kinase B signaling • positive regulation of mitochondrial depolarization • bone development • positive regulation of substrate adhesion-dependent cell spreading Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4653	17926
Ensembl	ENSG00000034971	ENSMUSG00000026697
UniProt	Q99972	O70624
RefSeq (mRNA)	NM_000261	NM_010865
RefSeq (protein)	NP_000252	NP_034995
Location (UCSC)	Chr 1: 171.64 – 171.65 Mb	Chr 1: 162.64 – 162.65 Mb
PubMed search

Myocilin, trabecular meshwork inducible glucocorticoid response, also known as MYOC, is a protein which in humans is encoded by the MYOC gene.^[1][2] Mutations in MYOC are a major cause of glaucoma.

Function

MYOC encodes the protein myocilin. The precise function of myocilin is unknown, but it is normally secreted into the aqueous humor of the eye. MYOC mutations, which cause myocilin to accumulate in the cells of the trabecular meshwork are a common cause of glaucoma.

Myocilin is believed to have a role in cytoskeletal function. MYOC is expressed in many ocular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma.^[3]

Clinical significance

MYOC contains a signal sequence for secretion, and is secreted into the aqueous humor of the eye by the trabecular meshwork. Mutations in MYOC are found in 4% of adult-onset primary open-angle glaucoma and >10% of juvenile-onset primary open-angle glaucoma. Overexpression or underexpression of MYOC does not cause glaucoma. However, the MYOC gene also contains a signal sequence, which is normally not functional, that directs intracellular proteins to peroxisomes. Glaucoma-associated mutations activate that signal sequence and direct myocilin to peroxisomes, where they accumulate in the cell, instead of being secreted. Decreased secretion and increased accumulation appear to be the initial steps in myocilin-associated glaucoma.^[4]

Interactions

MYOC has been shown to interact with OLFM3.^[5]

References

1. Stone EM, Fingert JH, Alward WL, Nguyen TD, Polansky JR, Sunden SL, Nishimura D, Clark AF, Nystuen A, Nichols BE, Mackey DA, Ritch R, Kalenak JW, Craven ER, Sheffield VC (January 1997). "Identification of a gene that causes primary open angle glaucoma". Science 275 (5300): 668–70. doi:10.1126/science.275.5300.668. PMID 9005853.
2. Kubota R, Noda S, Wang Y, Minoshima S, Asakawa S, Kudoh J, Mashima Y, Oguchi Y, Shimizu N (May 1997). "A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping". Genomics 41 (3): 360–9. doi:10.1006/geno.1997.4682. PMID 9169133.
3. "Entrez Gene: MYOC myocilin, trabecular meshwork inducible glucocorticoid response".
4. Young H. Kwon, John H. Fingert, Markus H. Kuehn, Wallace L.M. Alward, Primary Open-Angle Glaucoma, N Engl J Med 2009;360:1113-24.
5. Torrado, Mario; Trivedi Ritu; Zinovieva Rina; Karavanova Irina; Tomarev Stanislav I (May 2002). "Optimedin: a novel olfactomedin-related protein that interacts with myocilin". Hum. Mol. Genet. (England) 11 (11): 1291–301. doi:10.1093/hmg/11.11.1291. ISSN 0964-6906. PMID 12019210.

Further reading

• Fingert JH, Stone EM, Sheffield VC, Alward WL (2003). "Myocilin glaucoma.". Survey of ophthalmology 47 (6): 547–61. doi:10.1016/S0039-6257(02)00353-3. PMID 12504739.
• Polansky JR (2004). "Current perspectives on the TIGR/MYOC gene (Myocilin) and glaucoma.". Ophthalmology clinics of North America 16 (4): 515–27, v–vi. doi:10.1016/S0896-1549(03)00068-3. PMID 14740993.
• Coca-Prados M, Escribano J (2007). "New perspectives in aqueous humor secretion and in glaucoma: the ciliary body as a multifunctional neuroendocrine gland". Progress in retinal and eye research 26 (3): 239–62. doi:10.1016/j.preteyeres.2007.01.002. PMID 17321191.