MYOC_RAT
ID MYOC_RAT Reviewed; 502 AA.
AC Q9R1J4; Q9Z2Y4;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Myocilin;
DE AltName: Full=Trabecular meshwork-induced glucocorticoid response protein;
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; Synonyms=Tigr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Eye;
RX PubMed=10833334; DOI=10.1006/mgme.2000.2986;
RA Taguchi M., Kanno H., Kubota R., Miwa S., Shishiba Y., Ozawa Y.;
RT "Molecular cloning and expression profile of rat myocilin.";
RL Mol. Genet. Metab. 70:75-80(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar Kyoto; TISSUE=Eye;
RA Yaoeda K., Yamamoto T., Funaki H., Koyama Y., Nihei K., Tani T., Yaoita E.,
RA Kawasaki K., Abe H., Kihara I.;
RT "Molecular cloning of myocilin gene from rat eye.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INDUCTION.
RX PubMed=23629661; DOI=10.1074/jbc.m112.422972;
RA Kwon H.S., Johnson T.V., Tomarev S.I.;
RT "Myocilin stimulates osteogenic differentiation of mesenchymal stem cells
RT through mitogen-activated protein kinase signaling.";
RL J. Biol. Chem. 288:16882-16894(2013).
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; activates
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: Highly expressed in skeletal muscle and retina.
CC Also detected at lower levels in thyroid gland but not in other
CC endocrine glands such as the adrenal or pituitary glands.
CC {ECO:0000269|PubMed:10833334}.
CC -!- INDUCTION: Up-regulated by dexamethasone.
CC {ECO:0000269|PubMed:23629661}.
CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}.
CC -!- PTM: Undergoes a calcium-dependent proteolytic cleavage at Gln-225 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}.
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DR EMBL; AF093567; AAD46401.1; -; mRNA.
DR EMBL; AB019393; BAA34199.1; -; mRNA.
DR RefSeq; NP_110492.1; NM_030865.1.
DR AlphaFoldDB; Q9R1J4; -.
DR SMR; Q9R1J4; -.
DR BioGRID; 249520; 1.
DR IntAct; Q9R1J4; 1.
DR STRING; 10116.ENSRNOP00000004386; -.
DR GlyGen; Q9R1J4; 1 site.
DR iPTMnet; Q9R1J4; -.
DR PhosphoSitePlus; Q9R1J4; -.
DR PaxDb; Q9R1J4; -.
DR PRIDE; Q9R1J4; -.
DR GeneID; 81523; -.
DR KEGG; rno:81523; -.
DR UCSC; RGD:620430; rat.
DR CTD; 4653; -.
DR RGD; 620430; Myoc.
DR eggNOG; KOG3545; Eukaryota.
DR InParanoid; Q9R1J4; -.
DR OrthoDB; 421994at2759; -.
DR PhylomeDB; Q9R1J4; -.
DR PRO; PR:Q9R1J4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
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:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0097453; C:mesaxon; IDA:RGD.
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:0035748; C:myelin sheath abaxonal region; IDA:RGD.
DR GO; GO:0033268; C:node of Ranvier; ISS:UniProtKB.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0043220; C:Schmidt-Lanterman incisure; IDA:RGD.
DR GO; GO:0001968; F:fibronectin binding; ISO:RGD.
DR GO; GO:0005109; F:frizzled binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032027; F:myosin light chain binding; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IEP:RGD.
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:0021675; P:nerve development; IEP:RGD.
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:0007165; P:signal transduction; IBA:GO_Central.
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..31
FT /evidence="ECO:0000250"
FT CHAIN 32..502
FT /note="Myocilin"
FT /id="PRO_0000020088"
FT CHAIN 32..225
FT /note="Myocilin, N-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428747"
FT CHAIN 226..502
FT /note="Myocilin, C-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428748"
FT DOMAIN 242..501
FT /note="Olfactomedin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT REGION 166..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 82..183
FT /evidence="ECO:0000255"
FT BINDING 378
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 427
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 475
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 476
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT SITE 225..226
FT /note="Cleavage; by CAPN2"
FT /evidence="ECO:0000250"
FT CARBOHYD 229
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 243..431
FT /evidence="ECO:0000250|UniProtKB:Q99972,
FT ECO:0000255|PROSITE-ProRule:PRU00446"
FT CONFLICT 6
FT /note="Y -> R (in Ref. 1; BAA34199)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="S -> A (in Ref. 1; BAA34199)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 502 AA; 56442 MW; 2FE8FBE53CF48BBA CRC64;
MPSCAYCCSC GPKMPALQLL FLACLVWGMG ARTAQFRKAN DRSGRCQYTF TVASPSESSC
PREDQAMSAI QDLQRDSSIQ HADLESTKAR VRSLESLLHQ MTSGGVTGTQ EVQEGLQGQL
GALRRERDQL ETQTRDLEVA YNNLLRDKSA LEEEKRQLEQ ENKDLARRLE GSSQEVARLR
RGQCPSTHHP SQDMLPGSRE VSQWNLDTLA FQELKSELTE VPASQILKNQ SGHPRSKEGD
KGCGVLMWVG EPVTLRTAET ITGKYGVWMR DPKPTHPYTQ ETTWRIDTVG TGIRQVFEYS
QISQFEQGYP SKVHVLPQAL ESTGAVVYSG SLYFQGAESR TVLRYELNTE TVKAEKEIPG
AGYHGQFPYA WGGYTDIDLA VDESGLWVIY STEETRGAIV LSKLNPENLE LESTWETNIR
KQSVANAFVI CGILYTVSSY SSVHATINFA YDTNTGISKT LTIPFKNRYK YSSMVDYNPL
ERKLFAWDNF NMVTYDIKLS EM
