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 02-DEC-2020, entry version 78. 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; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; 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 different CC signaling pathways in adjacent cells to control different processes CC including cell adhesion, cell-matrix adhesion, cytoskeleton CC organization and cell migration. Promotes substrate adhesion, spreading CC and formation of focal contacts. Negatively regulates cell-matrix CC adhesion and stress fiber assembly through Rho protein signal CC transduction. Modulates the organization of actin cytoskeleton by CC stimulating the formation of stress fibers through interactions with CC components of Wnt signaling pathways. Promotes cell migration through CC activation of PTK2 and the downstream phosphatidylinositol 3-kinase CC signaling. Plays a role in bone formation and promotes osteoblast CC differentiation in a dose-dependent manner through mitogen-activated CC protein kinase signaling. Mediates myelination in the peripheral CC nervous system through ERBB2/ERBB3 signaling. Plays a role as a CC regulator of muscle hypertrophy through the components of dystrophin- CC associated protein complex. Involved in positive regulation of CC mitochondrial depolarization. Plays a role in neurite outgrowth. May CC participate in the obstruction of fluid outflow in the trabecular CC meshwork. {ECO:0000250|UniProtKB:O70624, ECO:0000250|UniProtKB:Q99972}. CC -!- SUBUNIT: Homodimer (via N-terminus). Can also form higher oligomers. CC Interacts with OLFM3, FN1, NRCAM, GLDN and NFASC. Interacts (via N- CC terminus) with MYL2. Interacts with SFRP1, FRZB, FZD7, FZD10, FZD1 and CC WIF1; regulates Wnt signaling (By similarity). Interacts with SNTA1; CC regulates muscle hypertrophy. Interacts with ERBB2 and ERBB3; acivates CC ERBB2-ERBB3 signaling pathway. Interacts with SNCG; affects its CC secretion and its aggregation (By similarity). CC {ECO:0000250|UniProtKB:O70624, ECO:0000250|UniProtKB:Q99972}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q99972}. Golgi CC apparatus {ECO:0000250|UniProtKB:Q99972}. Cytoplasmic vesicle CC {ECO:0000250|UniProtKB:Q99972}. Secreted, extracellular space CC {ECO:0000250|UniProtKB:Q99972}. Secreted, extracellular space, CC extracellular matrix {ECO:0000250|UniProtKB:Q99972}. Secreted, CC extracellular 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 only CC imported to mitochondria in the trabecular meshwork. Localizes to the CC Golgi apparatus in Schlemm's canal endothelial cells. Appears in the CC extracellular space of trabecular meshwork cells by an unconventional CC mechanism, likely associated with exosome-like vesicles. Localizes in CC trabecular meshwork extracellular matrix. CC {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 and CC retina. CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}. CC -!- PTM: Undergoes a calcium-dependent proteolytic cleavage at Arg-212 by CC CAPN2 in the endoplasmic reticulum. The result is the production of two CC fragments, one of 35 kDa containing the C-terminal olfactomedin-like CC domain, and another of 20 kDa containing the N-terminal leucine zipper- CC like domain (By similarity). {ECO:0000250}. CC -!- PTM: Glycosylated. {ECO:0000250|UniProtKB:Q99972}. 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 SMR; Q594P2; -. DR STRING; 9685.ENSFCAP00000012398; -. DR GeneID; 101087632; -. DR KEGG; fca:101087632; -. DR CTD; 4653; -. DR eggNOG; KOG3545; Eukaryota. DR InParanoid; Q594P2; -. DR OrthoDB; 421994at2759; -. DR TreeFam; TF315964; -. DR Proteomes; UP000011712; Unplaced. DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell. DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB. 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: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; Cytoplasmic vesicle; KW Disulfide bond; Endoplasmic reticulum; Extracellular matrix; Glycoprotein; KW Golgi apparatus; Lipoprotein; Membrane; Metal-binding; Mitochondrion; KW Mitochondrion inner membrane; Mitochondrion outer membrane; Palmitate; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..490 FT /note="Myocilin" FT /id="PRO_0000041830" FT CHAIN 19..212 FT /note="Myocilin, N-terminal fragment" FT /evidence="ECO:0000250" FT /id="PRO_0000428739" FT CHAIN 213..490 FT /note="Myocilin, C-terminal fragment" FT /evidence="ECO:0000250" FT /id="PRO_0000428740" FT DOMAIN 230..489 FT /note="Olfactomedin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446" FT COILED 52..169 FT /evidence="ECO:0000255" FT MOTIF 488..490 FT /note="Microbody targeting signal" FT /evidence="ECO:0000255" FT METAL 366 FT /note="Calcium" FT /evidence="ECO:0000250|UniProtKB:Q99972" FT METAL 414 FT /note="Calcium" FT /evidence="ECO:0000250|UniProtKB:Q99972" FT METAL 415 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q99972" FT METAL 463 FT /note="Calcium; via carbonyl oxygen" FT /evidence="ECO:0000250|UniProtKB:Q99972" FT METAL 464 FT /note="Calcium" FT /evidence="ECO:0000250|UniProtKB:Q99972" FT SITE 212..213 FT /note="Cleavage; by CAPN2" FT /evidence="ECO:0000250" FT CARBOHYD 43 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 231..419 FT /evidence="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 //