MYOC_RABIT
ID MYOC_RABIT Reviewed; 490 AA.
AC Q866N2;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 100.
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 {ECO:0000312|EMBL:AAO38666.1};
GN Synonyms=TIGR {ECO:0000250|UniProtKB:Q99972};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAO38666.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Eye {ECO:0000269|PubMed:12697062}, and
RC Heart {ECO:0000269|PubMed:12697062};
RX PubMed=12697062; DOI=10.1186/1471-2156-4-5;
RA Shepard A.R., Jacobson N., Sui R., Steely H.T., Lotery A.J., Stone E.M.,
RA Clark A.F.;
RT "Characterization of rabbit myocilin: implications for human myocilin
RT glycosylation and signal peptide usage.";
RL BMC Genet. 4:5-5(2003).
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:0000269|PubMed:12697062}. 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: Detected in eye aqueous humor (at protein level).
CC {ECO:0000269|PubMed:12697062}.
CC -!- PTM: Palmitoylated. {ECO:0000250|UniProtKB:Q2PT31}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:12697062}.
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}.
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DR EMBL; AY191317; AAO38666.1; -; mRNA.
DR RefSeq; NP_001075619.1; NM_001082150.2.
DR AlphaFoldDB; Q866N2; -.
DR SMR; Q866N2; -.
DR STRING; 9986.ENSOCUP00000013710; -.
DR PRIDE; Q866N2; -.
DR Ensembl; ENSOCUT00000015953; ENSOCUP00000013710; ENSOCUG00000015957.
DR GeneID; 100008897; -.
DR KEGG; ocu:100008897; -.
DR CTD; 4653; -.
DR eggNOG; KOG3545; Eukaryota.
DR GeneTree; ENSGT00940000158561; -.
DR HOGENOM; CLU_035236_4_0_1; -.
DR InParanoid; Q866N2; -.
DR OMA; FNMVTYD; -.
DR OrthoDB; 421994at2759; -.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000015957; Expressed in skeletal muscle tissue and 11 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; 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: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:0014734; P:skeletal muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; NAS: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..490
FT /note="Myocilin"
FT /evidence="ECO:0000255"
FT /id="PRO_0000020087"
FT CHAIN 19..212
FT /note="Myocilin, N-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428745"
FT CHAIN 213..490
FT /note="Myocilin, C-terminal fragment"
FT /evidence="ECO:0000250"
FT /id="PRO_0000428746"
FT DOMAIN 230..489
FT /note="Olfactomedin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00446"
FT REGION 168..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 55..170
FT /evidence="ECO:0000255"
FT MOTIF 488..490
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 172..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 366
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 414
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 415
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 463
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT BINDING 464
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q99972"
FT SITE 212..213
FT /note="Cleavage; by CAPN2"
FT /evidence="ECO:0000250"
FT DISULFID 231..419
FT /evidence="ECO:0000250|UniProtKB:Q99972,
FT ECO:0000255|PROSITE-ProRule:PRU00446"
SQ SEQUENCE 490 AA; 54885 MW; F975AC169461FD49 CRC64;
MPAVQLLLLA GLVWGAGART AQLRKANDRS GRCQYTFSVA SPSESSCPEQ GQTMSAIQDL
QRDSSTQRAD LESTKARLSS LESLLHRLTL AQTSGPQEIQ EELQKELGTL RRERDQLESQ
TRELEAAYSN LLRDKSALEE EKRRLMQENE DLARRLESSS QEVARLARGQ CPQARDTSQD
VPAGSREASQ WNLDTLAFQE LKSELTEVPA SRILKENPPV LPRGEEGDNG CGELVWVGQP
VTLRTAETIT GKYGVWMRDP KPTSPHTQET TWRIDTVGTD IRQVFEYDRI SQFVQGYPSK
VYVLPRSLES TGAVVYAGSL YFQGAGSRTV IRFELNTETV KAEKEIPGAG YRGQFPYSWG
GYTDIDLAVD ETGLWVIYST EEARGAIVLS KLNPENLELE KTWETNIRKQ SVANAFIICG
TLYTVSSYSS ADATVNFAYD TGTGISKPLA IPFKNRYKYS SMIDYNPLER KLFAWDSFNM
VTYDIKLSKI
