| IED ID | IndEnz0002015521 |
| Enzyme Type ID | protease015521 |
| Protein Name |
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 |
| Gene Name | MYOC GLC1A TIGR |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRFFCARCCSFGPEMPAVQLLLLACLVWDVGARTAQLRKANDQSGRCQYTFSVASPNESSCPEQSQAMSVIHNLQRDSSTQRLDLEATKARLSSLESLLHQLTLDQAARPQETQEGLQRELGTLRRERDQLETQTRELETAYSNLLRDKSVLEEEKKRLRQENENLARRLESSSQEVARLRRGQCPQTRDTARAVPPGSREVSTWNLDTLAFQELKSELTEVPASRILKESPSGYLRSGEGDTGCGELVWVGEPLTLRTAETITGKYGVWMRDPKPTYPYTQETTWRIDTVGTDVRQVFEYDLISQFMQGYPSKVHILPRPLESTGAVVYSGSLYFQGAESRTVIRYELNTETVKAEKEIPGAGYHGQFPYSWGGYTDIDLAVDEAGLWVIYSTDEAKGAIVLSKLNPENLELEQTWETNIRKQSVANAFIICGTLYTVSSYTSADATVNFAYDTGTGISKTLTIPFKNRYKYSSMIDYNPLEKKLFAWDNLNMVTYDIKLSKM |
| Enzyme Length | 504 |
| Uniprot Accession Number | Q99972 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | 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:0000250|UniProtKB:O70624, ECO:0000269|PubMed:17516541, ECO:0000269|PubMed:17984096, ECO:0000269|PubMed:18855004, ECO:0000269|PubMed:19188438, ECO:0000269|PubMed:19959812, ECO:0000269|PubMed:21656515, ECO:0000269|PubMed:23629661, ECO:0000269|PubMed:23897819}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (24); Chain (3); Coiled coil (1); Disulfide bond (1); Domain (1); Erroneous initiation (1); Glycosylation (1); Helix (2); Metal binding (5); Motif (1); Mutagenesis (6); Natural variant (90); Region (2); Signal peptide (1); Site (1); Turn (7) |
| Keywords | 3D-structure;Calcium;Cell projection;Cilium;Coiled coil;Cytoplasmic vesicle;Direct protein sequencing;Disease variant;Disulfide bond;Endoplasmic reticulum;Extracellular matrix;Glaucoma;Glycoprotein;Golgi apparatus;Lipoprotein;Membrane;Metal-binding;Mitochondrion;Mitochondrion inner membrane;Mitochondrion outer membrane;Palmitate;Reference proteome;Secreted;Signal |
| Interact With | P10916; O43765; P09486; Q14515 |
| Induction | INDUCTION: Up-regulated by dexamethasone, a glucocorticoid. {ECO:0000269|PubMed:11431441, ECO:0000269|PubMed:9497363}. |
| Subcellular Location | 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. |
| Modified Residue | |
| Post Translational Modification | PTM: Different isoforms may arise by post-translational modifications. {ECO:0000269|PubMed:9497363}.; PTM: Glycosylated. {ECO:0000269|PubMed:11431441, ECO:0000269|PubMed:12697062, ECO:0000269|PubMed:17650508, ECO:0000269|PubMed:19287508}.; PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}.; PTM: Undergoes a calcium-dependent proteolytic cleavage at Arg-226 by CAPN2 in the endoplasmic reticulum. The result is the production of two fragments, one of 35 kDa containing the C-terminal olfactomedin-like domain, and another of 20 kDa containing the N-terminal leucine zipper-like domain. {ECO:0000269|PubMed:15795224, ECO:0000269|PubMed:17650508}. |
| Signal Peptide | SIGNAL 1..32; /evidence="ECO:0000269|PubMed:19287508, ECO:0000269|PubMed:9497363" |
| Structure 3D | X-ray crystallography (10) |
| Cross Reference PDB | 4WXQ; 4WXS; 4WXU; 6OU0; 6OU1; 6OU2; 6OU3; 6PKD; 6PKE; 6PKF; |
| Mapped Pubmed ID | 11133859; 11595024; 11738824; 11853639; 11910561; 11979979; 11992263; 12060848; 12126543; 12190780; 12215093; 12411077; 12447164; 12470758; 12504739; 12522550; 12671462; 12671463; 12782842; 12789574; 12817590; 12851728; 12868033; 12912696; 14680806; 14688426; 14740993; 14767915; 15137056; 15161538; 15194423; 15338275; 15342693; 15354075; 15483649; 15646469; 15652337; 15723004; 15851979; 15953455; 16148883; 16198165; 16226543; 16280977; 16316624; 16358725; 16374045; 16392033; 16431959; 16458712; 16636654; 16681888; 16688110; 16902400; 17122126; 17197538; 17224759; 17304254; 17317787; 17417609; 17417611; 17438518; 17562996; 17563717; 17605937; 17615537; 17663725; 17679945; 17867509; 17893664; 17893668; 17960117; 17966125; 18195223; 18303389; 18334962; 18385784; 18427622; 18436825; 18449353; 18537981; 18591929; 18728751; 18776955; 18841557; 18852424; 18952665; 19023451; 19096718; 19145250; 19148291; 19180258; 19234343; 19260140; 19407846; 19662433; 19668597; 19688280; 19784393; 20021252; 20107173; 20198978; 20447966; 20664688; 20668460; 20801516; 20806035; 21031026; 21168818; 21174523; 21203411; 21426841; 21552496; 21655360; 21677793; 22194650; 22197377; 22247475; 22463803; 22550394; 22615763; 22736945; 22809227; 22876119; 22879734; 22933836; 22942166; 23028769; 23029558; 23035116; 23129764; 23218701; 23304066; 23453510; 23517641; 23566828; 23764838; 23886590; 24333014; 24406458; 24417561; 24563482; 24732711; 24741044; 24766640; 24768183; 24883016; 24940937; 25027323; 25197353; 25268471; 25330346; 25450062; 25582056; 25711070; 25777973; 26095806; 26237198; 26313302; 26396484; 26550974; 27355837; 27485216; 27779752; 27900994; 27993484; 28038983; 28153738; 28564705; 28575017; 29056483; 29475084; 29630620; 30267046; 30389787; 30395621; 30484747; 30557320; 30612094; 30802039; 30816137; 30816940; 31270212; 31302906; 31478904; 32300215; 32410836; 32421983; 32818018; 32937162; 32945492; 33539326; 33713785; 33793440; 34497454; |
| Motif | MOTIF 502..504; /note=Microbody targeting signal; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 56,972 |
| Kinetics | |
| Metal Binding | METAL 380; /note="Calcium"; /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU"; METAL 428; /note="Calcium"; /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU"; METAL 429; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU"; METAL 477; /note="Calcium; via carbonyl oxygen"; /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU"; METAL 478; /note="Calcium"; /evidence="ECO:0007744|PDB:4WXQ, ECO:0007744|PDB:4WXS, ECO:0007744|PDB:4WXU" |
| Rhea ID | |
| Cross Reference Brenda |