Protein: Myocilin (Myocilin 55 kDa subunit) (Trabecular meshwork-induced glucocorticoid response protein) [Cleaved into: Myocilin, N-terminal fragment (Myocilin 20 kDa N-terminal fragment); Myocilin, C-terminal fragment (Myocilin 35 kDa N-terminal fragment)] (Q99972)
Organism: Homo sapiens (Human)
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.
Subcellular location: Secreted {ECO:0000269|PubMed:11431441, ECO:0000269|PubMed:12697062, ECO:0000269|PubMed:19287508, ECO:0000269|PubMed:9497363}. Golgi apparatus {ECO:0000269|PubMed:11053284}. Cytoplasmic vesicle {ECO:0000269|PubMed:11431441}. Secreted, extracellular space. Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:11773026, ECO:0000305|PubMed:11431441}. Secreted, extracellular exosome {ECO:0000269|PubMed:15944158}. Mitochondrion {ECO:0000269|PubMed:17516541}. Mitochondrion intermembrane space {ECO:0000269|PubMed:17516541}. Mitochondrion inner membrane {ECO:0000269|PubMed:17516541}. Mitochondrion outer membrane {ECO:0000269|PubMed:17516541}. Rough endoplasmic reticulum {ECO:0000269|PubMed:19287508}. Cell projection. Cell projection, cilium {ECO:0000269|PubMed:9169133}. Note=Located preferentially in the ciliary rootlet and basal body of the connecting cilium of photoreceptor cells, and in the rough endoplasmic reticulum (PubMed:9169133). It is only imported to mitochondria in the trabecular meshwork (PubMed:17516541). Localizes to the Golgi apparatus in Schlemm's canal endothelial cells (PubMed:11053284). Appears in the extracellular space of trabecular meshwork cells by an unconventional mechanism, likely associated with exosome-like vesicles (PubMed:15944158). Localizes in trabecular meshwork extracellular matrix (PubMed:15944158). {ECO:0000269|PubMed:11053284, ECO:0000269|PubMed:15944158, ECO:0000269|PubMed:17516541, ECO:0000269|PubMed:9169133}.; SUBCELLULAR LOCATION: [Myocilin, C-terminal fragment]: Secreted.; SUBCELLULAR LOCATION: [Myocilin, N-terminal fragment]: Endoplasmic reticulum. Note=Remains retained in the endoplasmic reticulum.
Interaction partners:
- WD repeat-containing protein 36
- Noelin-3
- Optineurin
- Cytochrome P450 1B1
- Fibrillin-1
- Flotillin-1
- Ankyrin repeat and SOCS box protein 10
- SPARC-like protein 1
- Fibronectin
- Peroxisomal targeting signal 1 receptor
Sequence:
MRFFCARCCSFGPEMPAVQLLLLACLVWDVGARTAQLRKANDQSGRCQYTFSVASPNESSCPEQSQAMSVIHNLQRDSSTQRLDLEATKARLSSLESLLHQLTLDQAARPQETQEGLQRELGTLRRERDQLETQTRELETAYSNLLRDKSVLEEEKKRLRQENENLARRLESSSQEVARLRRGQCPQTRDTARAVPPGSREVSTWNLDTLAFQELKSELTEVPASRILKESPSGYLRSGEGDTGCGELVWVGEPLTLRTAETITGKYGVWMRDPKPTYPYTQETTWRIDTVGTDVRQVFEYDLISQFMQGYPSKVHILPRPLESTGAVVYSGSLYFQGAESRTVIRYELNTETVKAEKEIPGAGYHGQFPYSWGGYTDIDLAVDEAGLWVIYSTDEAKGAIVLSKLNPENLELEQTWETNIRKQSVANAFIICGTLYTVSSYTSADATVNFAYDTGTGISKTLTIPFKNRYKYSSMIDYNPLEKKLFAWDNLNMVTYDIKLSKM