MYOC_CANLF
ID MYOC_CANLF Reviewed; 483 AA.
AC Q2PT31; Q3Y9M0;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 100.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, GLYCOSYLATION, AND
RP PALMITOYLATION.
RC STRAIN=Beagle; TISSUE=Trabecular meshwork;
RX PubMed=17149370;
RA Ricard C.S., Mukherjee A., Silver F.-L., Wagenknecht P.L.;
RT "Canine myocilin is associated with lipid modified by palmitic acid.";
RL Mol. Vis. 12:1427-1436(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Beagle; TISSUE=Trabecular meshwork;
RX PubMed=17973835; DOI=10.1111/j.1463-5224.2007.00530.x;
RA Kato K., Sasaki N., Matsunaga S., Nishimura R., Ogawa H.;
RT "Cloning of canine myocilin cDNA and molecular analysis of the myocilin
RT gene in Shiba Inu dogs.";
RL Vet. Ophthalmol. 10:53-62(2007).
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: Expressed in optic nerve head, ciliary body and
CC retina. {ECO:0000269|PubMed:17149370}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:17149370}.
CC -!- PTM: Palmitoylated. {ECO:0000269|PubMed:17149370}.
CC -!- PTM: Undergoes a calcium-dependent proteolytic cleavage at Arg-205 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}.
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DR EMBL; DQ149972; AAZ78213.1; -; mRNA.
DR EMBL; DQ303878; ABC17625.2; -; mRNA.
DR RefSeq; NP_001041495.2; NM_001048030.3.
DR AlphaFoldDB; Q2PT31; -.
DR SMR; Q2PT31; -.
DR STRING; 9615.ENSCAFP00000021988; -.
DR PaxDb; Q2PT31; -.
DR PRIDE; Q2PT31; -.
DR Ensembl; ENSCAFT00030001544; ENSCAFP00030001370; ENSCAFG00030000902.
DR Ensembl; ENSCAFT00845001747; ENSCAFP00845001380; ENSCAFG00845001014.
DR GeneID; 490344; -.
DR KEGG; cfa:490344; -.
DR CTD; 4653; -.
DR VEuPathDB; HostDB:ENSCAFG00845001014; -.
DR eggNOG; KOG3545; Eukaryota.
DR GeneTree; ENSGT00940000158561; -.
DR HOGENOM; CLU_035236_4_0_1; -.
DR InParanoid; Q2PT31; -.
DR OMA; FNMVTYD; -.
DR OrthoDB; 421994at2759; -.
DR TreeFam; TF315964; -.
DR Proteomes; UP000002254; Chromosome 7.
DR Bgee; ENSCAFG00000014924; Expressed in cartilage tissue and 37 other tissues.
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:0005615; C:extracellular space; IBA:GO_Central.
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:0001968; F:fibronectin binding; IEA:Ensembl.
DR GO; GO:0005109; F:frizzled binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0032027; F:myosin light chain binding; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
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: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 1: Evidence at protein 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..483
FT /note="Myocilin"
FT /id="PRO_0000232718"
FT CHAIN 19..205
FT /note="Myocilin, N-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428737"
FT CHAIN 206..483
FT /note="Myocilin, C-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428738"
FT DOMAIN 223..482
FT /note="Olfactomedin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT REGION 153..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 51..162
FT /evidence="ECO:0000255"
FT MOTIF 481..483
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 164..179
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 359
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 407
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 456
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 457
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT SITE 205..206
FT /note="Cleavage; by CAPN2"
FT /evidence="ECO:0000250"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 224..412
FT /evidence="ECO:0000250|UniProtKB:Q99972,
FT ECO:0000255|PROSITE-ProRule:PRU00446"
SQ SEQUENCE 483 AA; 54262 MW; DB8BA5467D4C6E6A CRC64;
MPTAQLLLLA CLLWGLEART AQLRKANDRS GRCQYIFSVA SPNESSCPEQ GQAMSAIQDL
QRDLESTKAR LSSLEGLLHQ LTLGQAAGPS ESQEGLHREL GTLRKEREQL ETQARELEVA
YSNLLRDKSA LEEEKRRLGE ENEDLAQRLE HSSQEVARLR RGQCPQAHSS SQDVPAGSRE
VSKWNVETVN FQELKSELTE VPASRILKES PSGHPRNEEG DSGCGELVWV GEPLTLRTAE
TITGKYGVWM RDPKPTYPHT RETTWRIDTV GTDIRQVFEY ELASQFLQGY PSKVHVLPRP
LESTGAVVYR GSLYFQGAGS GTVVRYELTA ETVKAEREIP GAGYHGQFPY SWGGYTDIDL
AVDETGLWVI YSTQEAKGAI VLSKLNPETL ELEQTWETNI RKQSVANAFV ICGHLYTISS
YSSPDATVNF AYDTGTGRSR VLSIPFKNRY KYSSMIDYNP LEKKLFAWDN FNMVTYDIRL
SKM
