UniProt functional annotation for O01761



	UniProt functional annotation for O01761

UniProt code: O01761.

Organism: Caenorhabditis elegans.

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.

Function: Structural component of the muscle M line which is involved in assembly and organization of sarcomere myofilaments (PubMed:15313609, PubMed:16453163, PubMed:18801371, PubMed:22621901, PubMed:23283987, PubMed:27009202). The large isoform a, isoform b, isoform d and isoform f play an essential role in maintaining the organization of sarcomeres but not myofilament alignment during body wall muscle development whereas the small isoform c and isoform d appear to have a minor role (PubMed:15313609, PubMed:16453163, PubMed:22768340). Isoform b and isoform f are required for the organization of unc-15/paramyosin into sarcomere thick filaments in body wall muscles (PubMed:27009202). By binding mel-26, a substrate adapter of the cul-3 E3 ubiquitin-protein ligase complex, regulates the organization of myosin thick filaments, likely by preventing the degradation of microtubule severing protein mei-1 (PubMed:22621901). Acts as guanine nucleotide exchange factor (GEF) for Rho GTPase rho-1 but not ced-10, mig-2 and cdc-42 (PubMed:18801371). The large isoforms regulate Ca(2+) signaling during muscle contraction by ensuring the correct localization of sarco-endoplamic reticulum Ca(2+) ATPase sca-1 and ryanodine receptor unc-68 (PubMed:22768340). By controlling the contraction and/or organization of pharyngeal muscles, plays a role in the formation of pharyngeal gland cell extension (PubMed:21868609). {ECO:0000269|PubMed:15313609, ECO:0000269|PubMed:16453163, ECO:0000269|PubMed:18801371, ECO:0000269|PubMed:21868609, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:22768340, ECO:0000269|PubMed:23283987, ECO:0000269|PubMed:27009202, ECO:0000269|PubMed:8603916}.

Subunit: May interact (via fibronectin type-III domain 1, Ig-like C2- type domain 48/49 and protein kinase domain 1 or C-terminus of the interkinase region) with lim-9 (via LIM zinc-binding domain) (PubMed:19244614). May interact (via fibronectin type-III domain 1, Ig- like C2-type domain 48/49 and kinase protein domain 1 or Ig-like C2- type domain 50, fibronectin type-III domain 2 and kinase protein domain 2) with scpl-1 isoforms a and b (via FCP1 homology domain); the interaction may act as a molecular bridge to bring two unc-89 molecules together or to stabilize a loop between the 2 kinase domains (PubMed:18337465, PubMed:19244614). May interact (via SH3 domain) with unc-15 (PubMed:27009202). May interact (via Ig-like C2-type domain 1-3) with cpna-1 (via VWFA domain) (PubMed:23283987). May interact (via Ig- like C2-type domain 2/3 and, Ig-like C2-type domain 50 and fibronectin type-III domain 2) with mel-26 (via MATH domain) (PubMed:22621901). May interact (via DH and PH domains) with rho-1, ced-10, mig-2 and cdc-42 (PubMed:18801371). {ECO:0000269|PubMed:18337465, ECO:0000269|PubMed:18801371, ECO:0000269|PubMed:19244614, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:23283987, ECO:0000269|PubMed:27009202}.

Subcellular location: Cytoplasm, myofibril, sarcomere, M line {ECO:0000269|PubMed:15313609, ECO:0000269|PubMed:18337465, ECO:0000269|PubMed:19244614, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:22768340, ECO:0000269|PubMed:23283987, ECO:0000269|PubMed:27009202, ECO:0000269|PubMed:8603916}. Note=Colocalizes with scpl-1 (isoform b) to the M line (PubMed:19244614). Colocalizes with cpna-1 to the M line (PubMed:23283987). Colocalizes with mel-26 to the M line (PubMed:22621901). Accumulates at the center of thick myofilaments in M line-like structures in myoepithelial sheath cells (PubMed:17326220). {ECO:0000269|PubMed:17326220, ECO:0000269|PubMed:19244614, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:23283987}.

Tissue specificity: Expressed in body-wall, pharyngeal muscles and a few muscle cells of the tail (at protein level) (PubMed:8603916, PubMed:18337465, PubMed:19244614, PubMed:22621901, PubMed:22768340, PubMed:23283987, PubMed:27009202). Expressed in gonadal myoepithelial sheath cells (at protein level) (PubMed:17326220). Isoform c: Expressed in body wall and vulval muscles but not in pharyngeal muscles (PubMed:15313609). Isoform d: Specifically expressed in vulval, intestinal, anal depressor and anal sphincter muscles (PubMed:15313609). {ECO:0000269|PubMed:15313609, ECO:0000269|PubMed:17326220, ECO:0000269|PubMed:18337465, ECO:0000269|PubMed:19244614, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:22768340, ECO:0000269|PubMed:23283987, ECO:0000269|PubMed:27009202, ECO:0000269|PubMed:8603916}.

Developmental stage: Expressed in embryos (PubMed:23283987). Isoform a: Expressed in embryo, throughout larval development and in adults (PubMed:15313609). Isoform b: Expressed in embryo, throughout larval development and in adults and is one of the most abundant (PubMed:15313609). Isoform c: Expressed in embryo, throughout larval development and in adults and is one of the most abundant (PubMed:15313609). Isoform d: Expressed in embryo, throughout larval development and in adults (PubMed:15313609). {ECO:0000269|PubMed:15313609, ECO:0000269|PubMed:23283987}.

Domain: Protein kinase domains 1 and 2 are predicted to be catalytically inactive (PubMed:16453163). The two kinase domains are required for the organization of thick filament component myosin heavy chain myo-3 but not of myosin heavy chain unc-54 and unc-15/paramyosin (PubMed:27009202). {ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000269|PubMed:27009202, ECO:0000303|PubMed:16453163}.

Domain: The SH3 domain is required for the organization of thick filament components myosin heavy chain unc-54 and myo-3 and unc- 15/paramyosin. {ECO:0000269|PubMed:27009202}.

Domain: The PH domain does not bind inositol 1,4,5-trisphosphate. The PH domain has an unusual closed conformation of the lipid binding site which is lined by negative charged amino acids which probably prevents binding to membrane lipids. {ECO:0000269|PubMed:11080629}.

Disruption phenotype: Mutants lacking isoform a, isoform b, isoform e and isoform f have an abnormal organization of the myofilament lattice of body wall and pharyngeal muscles (PubMed:16453163, PubMed:18801371, PubMed:22621901, PubMed:27009202). In body wall muscles, unc- 15/paramyosin accumulates in large foci outside thick filaments and myosin heavy chains unc-54 and myo-3 fail to assemble into parallel myofibrils (PubMed:27009202). In addition, myosin thick filaments are disorganized with the formation of abnormal myosin heavy chain myo-3 aggregates and V-shaped crossing of A bands (PubMed:18801371, PubMed:22621901). In mutants lacking isoform b, isoform c, isoform d and isoform f, myo-3 fails to assemble into parallel myofibrils whereas unc-54 and unc-15 localization is normal (PubMed:27009202). Mutants lacking isoform b, isoform c, isoform d and isoform f have defects only in body wall muscle structure (PubMed:16453163). RNAi-mediated knockdown of isoform a or isoform b, isoform c and isoform d causes similar defects in the organization although RNAi-mediated knockdown of isoform c causes a less severe defect in myofilament organization (PubMed:15313609). In mutants lacking isoform a, isoform b, isoform e and isoform f, mei-1 protein levels are decreased by 20 percent (PubMed:22621901). RNAi-mediated knockdown of isoform a, isoform b, isoform e and isoform f but not of isoforms c and d disrupts sca-1 localization to linear punctate structures along in the M line in body wall muscles (PubMed:22768340). RNAi-mediated knockdown has no effect on ovulation (PubMed:17326220). {ECO:0000269|PubMed:15313609, ECO:0000269|PubMed:16453163, ECO:0000269|PubMed:17326220, ECO:0000269|PubMed:18801371, ECO:0000269|PubMed:22621901, ECO:0000269|PubMed:22768340, ECO:0000269|PubMed:27009202}.

Similarity: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Caenorhabditis elegans.
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.



Function:		Structural component of the muscle M line which is involved in assembly and organization of sarcomere myofilaments (PubMed:15313609, PubMed:16453163, PubMed:18801371, PubMed:22621901, PubMed:23283987, PubMed:27009202). The large isoform a, isoform b, isoform d and isoform f play an essential role in maintaining the organization of sarcomeres but not myofilament alignment during body wall muscle development whereas the small isoform c and isoform d appear to have a minor role (PubMed:15313609, PubMed:16453163, PubMed:22768340). Isoform b and isoform f are required for the organization of unc-15/paramyosin into sarcomere thick filaments in body wall muscles (PubMed:27009202). By binding mel-26, a substrate adapter of the cul-3 E3 ubiquitin-protein ligase complex, regulates the organization of myosin thick filaments, likely by preventing the degradation of microtubule severing protein mei-1 (PubMed:22621901). Acts as guanine nucleotide exchange factor (GEF) for Rho GTPase rho-1 but not ced-10, mig-2 and cdc-42 (PubMed:18801371). The large isoforms regulate Ca(2+) signaling during muscle contraction by ensuring the correct localization of sarco-endoplamic reticulum Ca(2+) ATPase sca-1 and ryanodine receptor unc-68 (PubMed:22768340). By controlling the contraction and/or organization of pharyngeal muscles, plays a role in the formation of pharyngeal gland cell extension (PubMed:21868609). {ECO:0000269\|PubMed:15313609, ECO:0000269\|PubMed:16453163, ECO:0000269\|PubMed:18801371, ECO:0000269\|PubMed:21868609, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:22768340, ECO:0000269\|PubMed:23283987, ECO:0000269\|PubMed:27009202, ECO:0000269\|PubMed:8603916}.


Subunit:		May interact (via fibronectin type-III domain 1, Ig-like C2- type domain 48/49 and protein kinase domain 1 or C-terminus of the interkinase region) with lim-9 (via LIM zinc-binding domain) (PubMed:19244614). May interact (via fibronectin type-III domain 1, Ig- like C2-type domain 48/49 and kinase protein domain 1 or Ig-like C2- type domain 50, fibronectin type-III domain 2 and kinase protein domain 2) with scpl-1 isoforms a and b (via FCP1 homology domain); the interaction may act as a molecular bridge to bring two unc-89 molecules together or to stabilize a loop between the 2 kinase domains (PubMed:18337465, PubMed:19244614). May interact (via SH3 domain) with unc-15 (PubMed:27009202). May interact (via Ig-like C2-type domain 1-3) with cpna-1 (via VWFA domain) (PubMed:23283987). May interact (via Ig- like C2-type domain 2/3 and, Ig-like C2-type domain 50 and fibronectin type-III domain 2) with mel-26 (via MATH domain) (PubMed:22621901). May interact (via DH and PH domains) with rho-1, ced-10, mig-2 and cdc-42 (PubMed:18801371). {ECO:0000269\|PubMed:18337465, ECO:0000269\|PubMed:18801371, ECO:0000269\|PubMed:19244614, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:23283987, ECO:0000269\|PubMed:27009202}.
Subcellular location:		Cytoplasm, myofibril, sarcomere, M line {ECO:0000269\|PubMed:15313609, ECO:0000269\|PubMed:18337465, ECO:0000269\|PubMed:19244614, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:22768340, ECO:0000269\|PubMed:23283987, ECO:0000269\|PubMed:27009202, ECO:0000269\|PubMed:8603916}. Note=Colocalizes with scpl-1 (isoform b) to the M line (PubMed:19244614). Colocalizes with cpna-1 to the M line (PubMed:23283987). Colocalizes with mel-26 to the M line (PubMed:22621901). Accumulates at the center of thick myofilaments in M line-like structures in myoepithelial sheath cells (PubMed:17326220). {ECO:0000269\|PubMed:17326220, ECO:0000269\|PubMed:19244614, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:23283987}.
Tissue specificity:		Expressed in body-wall, pharyngeal muscles and a few muscle cells of the tail (at protein level) (PubMed:8603916, PubMed:18337465, PubMed:19244614, PubMed:22621901, PubMed:22768340, PubMed:23283987, PubMed:27009202). Expressed in gonadal myoepithelial sheath cells (at protein level) (PubMed:17326220). Isoform c: Expressed in body wall and vulval muscles but not in pharyngeal muscles (PubMed:15313609). Isoform d: Specifically expressed in vulval, intestinal, anal depressor and anal sphincter muscles (PubMed:15313609). {ECO:0000269\|PubMed:15313609, ECO:0000269\|PubMed:17326220, ECO:0000269\|PubMed:18337465, ECO:0000269\|PubMed:19244614, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:22768340, ECO:0000269\|PubMed:23283987, ECO:0000269\|PubMed:27009202, ECO:0000269\|PubMed:8603916}.
Developmental stage:		Expressed in embryos (PubMed:23283987). Isoform a: Expressed in embryo, throughout larval development and in adults (PubMed:15313609). Isoform b: Expressed in embryo, throughout larval development and in adults and is one of the most abundant (PubMed:15313609). Isoform c: Expressed in embryo, throughout larval development and in adults and is one of the most abundant (PubMed:15313609). Isoform d: Expressed in embryo, throughout larval development and in adults (PubMed:15313609). {ECO:0000269\|PubMed:15313609, ECO:0000269\|PubMed:23283987}.
Domain:		Protein kinase domains 1 and 2 are predicted to be catalytically inactive (PubMed:16453163). The two kinase domains are required for the organization of thick filament component myosin heavy chain myo-3 but not of myosin heavy chain unc-54 and unc-15/paramyosin (PubMed:27009202). {ECO:0000255\|PROSITE-ProRule:PRU00159, ECO:0000269\|PubMed:27009202, ECO:0000303\|PubMed:16453163}.
Domain:		The SH3 domain is required for the organization of thick filament components myosin heavy chain unc-54 and myo-3 and unc- 15/paramyosin. {ECO:0000269\|PubMed:27009202}.
Domain:		The PH domain does not bind inositol 1,4,5-trisphosphate. The PH domain has an unusual closed conformation of the lipid binding site which is lined by negative charged amino acids which probably prevents binding to membrane lipids. {ECO:0000269\|PubMed:11080629}.
Disruption phenotype:		Mutants lacking isoform a, isoform b, isoform e and isoform f have an abnormal organization of the myofilament lattice of body wall and pharyngeal muscles (PubMed:16453163, PubMed:18801371, PubMed:22621901, PubMed:27009202). In body wall muscles, unc- 15/paramyosin accumulates in large foci outside thick filaments and myosin heavy chains unc-54 and myo-3 fail to assemble into parallel myofibrils (PubMed:27009202). In addition, myosin thick filaments are disorganized with the formation of abnormal myosin heavy chain myo-3 aggregates and V-shaped crossing of A bands (PubMed:18801371, PubMed:22621901). In mutants lacking isoform b, isoform c, isoform d and isoform f, myo-3 fails to assemble into parallel myofibrils whereas unc-54 and unc-15 localization is normal (PubMed:27009202). Mutants lacking isoform b, isoform c, isoform d and isoform f have defects only in body wall muscle structure (PubMed:16453163). RNAi-mediated knockdown of isoform a or isoform b, isoform c and isoform d causes similar defects in the organization although RNAi-mediated knockdown of isoform c causes a less severe defect in myofilament organization (PubMed:15313609). In mutants lacking isoform a, isoform b, isoform e and isoform f, mei-1 protein levels are decreased by 20 percent (PubMed:22621901). RNAi-mediated knockdown of isoform a, isoform b, isoform e and isoform f but not of isoforms c and d disrupts sca-1 localization to linear punctate structures along in the M line in body wall muscles (PubMed:22768340). RNAi-mediated knockdown has no effect on ovulation (PubMed:17326220). {ECO:0000269\|PubMed:15313609, ECO:0000269\|PubMed:16453163, ECO:0000269\|PubMed:17326220, ECO:0000269\|PubMed:18801371, ECO:0000269\|PubMed:22621901, ECO:0000269\|PubMed:22768340, ECO:0000269\|PubMed:27009202}.
Similarity:		Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.