ID MYOC_FELCA Reviewed; 490 AA. AC Q594P2; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2005, sequence version 1. DT 16-MAR-2016, entry version 62. DE RecName: Full=Myocilin; 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; OS Felis catus (Cat) (Felis silvestris catus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; OC Felinae; Felis. OX NCBI_TaxID=9685; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Fautsch M.P., Vrabel A.M., Johnson D.H.; RT "Characterization of the domestic cat myocilin cDNA."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Secreted glycoprotein regulating the activation of CC different signaling pathways in adjacent cells to control CC different processes including cell adhesion, cell-matrix adhesion, CC cytoskeleton organization and cell migration. Promotes substrate CC adhesion, spreading and formation of focal contacts. Negatively CC regulates cell-matrix adhesion and stress fiber assembly through CC Rho protein signal transduction. Modulates the organization of CC actin cytoskeleton by stimulating the formation of stress fibers CC through interactions with components of Wnt signaling pathways. CC Promotes cell migration through activation of PTK2 and the CC downstream phosphatidylinositol 3-kinase signaling. Plays a role CC in bone formation and promotes osteoblast differentiation in a CC dose-dependent manner through mitogen-activated protein kinase CC signaling. Mediates myelination in the peripheral nervous system CC through ERBB2/ERBB3 signaling. Plays a role as a regulator of CC muscle hypertrophy through the components of dystrophin-associated CC protein complex. Involved in positive regulation of mitochondrial CC depolarization. Plays a role in neurite outgrowth. May participate CC in the obstruction of fluid outflow in the trabecular meshwork. CC {ECO:0000250|UniProtKB:O70624, ECO:0000250|UniProtKB:Q99972}. CC -!- SUBUNIT: Homodimer (via N-terminus). Can also form higher CC oligomers. Interacts with OLFM3, FN1, NRCAM, GLDN and NFASC. CC Interacts (via N-terminus) with MYL2. Interacts with SFRP1, FRZB, CC FZD7, FZD10, FZD1 and WIF1; regulates Wnt signaling (By CC similarity). Interacts with SNTA1; regulates muscle hypertrophy. CC Interacts with ERBB2 and ERBB3; acivates ERBB2-ERBB3 signaling CC pathway. Interacts with SNCG; affects its secretion and its CC aggregation (By similarity). {ECO:0000250|UniProtKB:O70624, CC ECO:0000250|UniProtKB:Q99972}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q99972}. CC Golgi apparatus {ECO:0000250|UniProtKB:Q99972}. Cytoplasmic CC vesicle {ECO:0000250|UniProtKB:Q99972}. Secreted, extracellular CC space {ECO:0000250|UniProtKB:Q99972}. Secreted, extracellular CC space, extracellular matrix {ECO:0000250|UniProtKB:Q99972}. CC Secreted, exosome {ECO:0000250|UniProtKB:Q99972}. Mitochondrion CC {ECO:0000250|UniProtKB:Q99972}. Mitochondrion intermembrane space CC {ECO:0000250|UniProtKB:Q99972}. Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:Q99972}. Mitochondrion outer membrane CC {ECO:0000250|UniProtKB:Q99972}. Rough endoplasmic reticulum CC {ECO:0000250|UniProtKB:Q99972}. Cell projection CC {ECO:0000250|UniProtKB:Q99972}. Cell projection, cilium CC {ECO:0000250|UniProtKB:Q99972}. 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. It is CC only imported to mitochondria in the trabecular meshwork. CC Localizes to the Golgi apparatus in Schlemm's canal endothelial CC cells. Appears in the extracellular space of trabecular meshwork CC cells by an unconventional mechanism, likely associated with CC exosome-like vesicles. Localizes in trabecular meshwork CC extracellular matrix. {ECO:0000250|UniProtKB:Q99972}. CC -!- SUBCELLULAR LOCATION: Myocilin, C-terminal fragment: Secreted CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Myocilin, N-terminal fragment: Endoplasmic CC reticulum. Note=Remains retained in the endoplasmic reticulum. CC {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in optic nerve head, ciliary body CC and retina. CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}. CC -!- PTM: Undergoes a calcium-dependent proteolytic cleavage at Arg-212 CC by CAPN2 in the endoplasmic reticulum. The result is the CC production of two fragments, one of 35 kDa containing the C- CC terminal olfactomedin-like domain, and another of 20 kDa CC containing the N-terminal leucine zipper-like domain (By CC similarity). {ECO:0000250}. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q99972}. CC -!- SIMILARITY: Contains 1 olfactomedin-like domain. CC {ECO:0000255|PROSITE-ProRule:PRU00446}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY566569; AAS68633.1; -; mRNA. DR RefSeq; NP_001265779.1; NM_001278850.1. DR STRING; 9685.ENSFCAP00000012398; -. DR GeneID; 101087632; -. DR KEGG; fca:101087632; -. DR CTD; 4653; -. DR eggNOG; ENOG410INPA; Eukaryota. DR eggNOG; ENOG410YBJJ; LUCA. DR HOGENOM; HOG000059654; -. DR HOVERGEN; HBG105662; -. DR InParanoid; Q594P2; -. DR TreeFam; TF315964; -. DR Proteomes; UP000011712; Unplaced. DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB. DR GO; GO:0016023; C:cytoplasmic, membrane-bounded vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB. DR GO; GO:0005758; C:mitochondrial intermembrane space; ISS:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB. DR GO; GO:0033268; C:node of Ranvier; ISS:UniProtKB. DR GO; GO:0005578; C:proteinaceous extracellular matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. 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; ISS:UniProtKB. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:UniProtKB. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISS:UniProtKB. DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB. DR GO; GO:0038031; P:non-canonical Wnt signaling pathway via JNK cascade; ISS:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB. DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; ISS:UniProtKB. DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB. DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; ISS:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; ISS:UniProtKB. 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 2: Evidence at transcript level; KW Calcium; Cell projection; Cilium; Coiled coil; Complete proteome; KW Cytoplasmic vesicle; Disulfide bond; Endoplasmic reticulum; KW Extracellular matrix; Glycoprotein; Golgi apparatus; Lipoprotein; KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; KW Mitochondrion outer membrane; Palmitate; Reference proteome; Secreted; KW Signal. FT SIGNAL 1 18 {ECO:0000255}. FT CHAIN 19 490 Myocilin. FT /FTId=PRO_0000041830. FT CHAIN 19 212 Myocilin, N-terminal fragment. FT {ECO:0000250}. FT /FTId=PRO_0000428739. FT CHAIN 213 490 Myocilin, C-terminal fragment. FT {ECO:0000250}. FT /FTId=PRO_0000428740. FT DOMAIN 230 489 Olfactomedin-like. {ECO:0000255|PROSITE- FT ProRule:PRU00446}. FT COILED 52 169 {ECO:0000255}. FT MOTIF 488 490 Microbody targeting signal. FT {ECO:0000255}. FT METAL 366 366 Calcium. {ECO:0000250|UniProtKB:Q99972}. FT METAL 414 414 Calcium. {ECO:0000250|UniProtKB:Q99972}. FT METAL 415 415 Calcium; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:Q99972}. FT METAL 463 463 Calcium; via carbonyl oxygen. FT {ECO:0000250|UniProtKB:Q99972}. FT METAL 464 464 Calcium. {ECO:0000250|UniProtKB:Q99972}. FT SITE 212 213 Cleavage; by CAPN2. {ECO:0000250}. FT CARBOHYD 43 43 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 231 419 {ECO:0000250|UniProtKB:Q99972, FT ECO:0000255|PROSITE-ProRule:PRU00446}. SQ SEQUENCE 490 AA; 55306 MW; B7FC900365FF83A5 CRC64; MPATQLLLLA CLVWGLGART AQLRKANDRS GRCQYTFSVA SPNESSCPEQ GQAMSAIQDL QRDSSAQRAD LESTKARLRS LESLVHQLTL DEAAGPSATQ EGLQRELGAL RREREQLESQ NRELEASYSN LLRDKSALEE EKRRLREENE DLARRLDSSS QEVARLRRGQ CPQARGTPQD VPSGSREVSK WNVETVNFQE LKSELTEVPA SRILKESPSG HPRSEEGDPG CGELVWVGEP LTLRRAETIT GKYGVWMRDP KPAYPYTQET TWRIDTVGTD IRQVFEYDLS SQFLQGYPSK VHVLPRPLES TGAVVYWGSL YFQGAESRTV IRYELNTETV KAEKEIPGAG YHGQFPYSWG GYTDIDLAVD ETGLWVIYST QEAKGAIVLS KLNPESLELE RTWETNIRKQ SVANAFIICG RLYTVSSYSA PDATINFAYD TGTGRSRALT VPFKNRYKYS SMVDYNPLEK KLFAWDNFNM VTYDLRLSEM //