InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MYOC

Summary

InnateDB Protein

IDBP-104801.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

MYOC

Protein Name

myocilin, trabecular meshwork inducible glucocorticoid response

Synonyms

GLC1A; GPOA; JOAG; JOAG1; myocilin; TIGR;

Species

Homo sapiens

Ensembl Protein

ENSP00000037502

InnateDB Gene

IDBG-104799 (MYOC)

Protein Structure

UniProt Annotation

Function

Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling. Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling. Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling. Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex. Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork. {ECO:0000269PubMed:17516541, ECO:0000269PubMed:17984096, ECO:0000269PubMed:18855004, ECO:0000269PubMed:19188438, ECO:0000269PubMed:19959812, ECO:0000269PubMed:21656515, ECO:0000269PubMed:23629661, ECO:0000269PubMed:23897819}.

Subcellular Localization

Secreted. Golgi apparatus. Cytoplasmic vesicle. Secreted, extracellular space. Secreted, extracellular space, extracellular matrix. Secreted, exosome. Mitochondrion. Mitochondrion intermembrane space. Mitochondrion inner membrane. Mitochondrion outer membrane. Rough endoplasmic reticulum. Cell projection. Cell projection, cilium. Note=Located preferentially in the ciliary rootlet and basal body of the connecting cilium of photoreceptor cells, and in the rough endoplasmic reticulum. It is only imported to mitochondria in the trabecular meshwork. Localizes to the Golgi apparatus in Schlemm's canal endothelial cells. Appears in the extracellular space of trabecular meshwork cells by an unconventional mechanism, likely associated with exosome-like vesicles. Localizes in trabecular meshwork extracellular matrix.Myocilin, C-terminal fragment: Secreted.Myocilin, N-terminal fragment: Endoplasmic reticulum. Note=Remains retained in the endoplasmic reticulum.

Disease Associations

Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269PubMed:10196380, ECO:0000269PubMed:10330365, ECO:0000269PubMed:10340788, ECO:0000269PubMed:10644174, ECO:0000269PubMed:10798654, ECO:0000269PubMed:10819638, ECO:0000269PubMed:10873982, ECO:0000269PubMed:10916185, ECO:0000269PubMed:10980537, ECO:0000269PubMed:11004290, ECO:0000269PubMed:11774072, ECO:0000269PubMed:12189160, ECO:0000269PubMed:12356829, ECO:0000269PubMed:12362081, ECO:0000269PubMed:12442283, ECO:0000269PubMed:12860809, ECO:0000269PubMed:12872267, ECO:0000269PubMed:15025728, ECO:0000269PubMed:15255110, ECO:0000269PubMed:15534471, ECO:0000269PubMed:16401791, ECO:0000269PubMed:17210859, ECO:0000269PubMed:17499207, ECO:0000269PubMed:9005853, ECO:0000269PubMed:9328473, ECO:0000269PubMed:9345106, ECO:0000269PubMed:9361308, ECO:0000269PubMed:9490287, ECO:0000269PubMed:9510647, ECO:0000269PubMed:9521427, ECO:0000269PubMed:9535666, ECO:0000269PubMed:9697688, ECO:0000269PubMed:9792882, ECO:0000269PubMed:9863594}. Note=The disease is caused by mutations affecting the gene represented in this entry.Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269PubMed:15733270}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. MYOC mutations may contribute to GLC3A via digenic inheritance with CYP1B1 and/or another locus associated with the disease (PubMed:15733270). {ECO:0000269PubMed:15733270}.

Tissue Specificity

Expressed in large amounts in various types of muscle, ciliary body, papillary sphincter, skeletal muscle, heart, bone marrow-derived mesenchymal stem cells and other tissues. Expressed predominantly in the retina. In normal eyes, found in the inner uveal meshwork region and the anterior portion of the meshwork. In contrast, in many glaucomatous eyes, it is found in more regions of the meshwork and appeared more intensively than in normal eyes, regardless of the type or clinical severity of glaucoma. The myocilin 35 kDa fragment is detected in aqueous humor and at the less extend in iris and ciliary body. {ECO:0000269PubMed:15795224}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 44 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	44 [view]
Protein-Protein	43 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001968	fibronectin binding
GO:0005109	frizzled binding
GO:0005515	protein binding
GO:0030971	receptor tyrosine kinase binding
GO:0032027	myosin light chain binding

Biological Process

GO:0001649	osteoblast differentiation
GO:0001953	negative regulation of cell-matrix adhesion
GO:0014068	positive regulation of phosphatidylinositol 3-kinase signaling
GO:0014734	skeletal muscle hypertrophy
GO:0022011	myelination in peripheral nervous system
GO:0030335	positive regulation of cell migration
GO:0031175	neuron projection development
GO:0035024	negative regulation of Rho protein signal transduction
GO:0038031	non-canonical Wnt signaling pathway via JNK cascade
GO:0038133	ERBB2-ERBB3 signaling pathway
GO:0043408	regulation of MAPK cascade
GO:0045162	clustering of voltage-gated sodium channels
GO:0051496	positive regulation of stress fiber assembly
GO:0051497	negative regulation of stress fiber assembly
GO:0051894	positive regulation of focal adhesion assembly
GO:0051897	positive regulation of protein kinase B signaling
GO:0051901	positive regulation of mitochondrial depolarization
GO:0060348	bone development
GO:1900026	positive regulation of substrate adhesion-dependent cell spreading

Cellular Component

GO:0005578	proteinaceous extracellular matrix
GO:0005615	extracellular space
GO:0005741	mitochondrial outer membrane
GO:0005743	mitochondrial inner membrane
GO:0005758	mitochondrial intermembrane space
GO:0005783	endoplasmic reticulum
GO:0005791	rough endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005929	cilium
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0031012	extracellular matrix
GO:0031410	cytoplasmic vesicle
GO:0033268	node of Ranvier
GO:0070062	extracellular vesicular exosome