UniProt functional annotation for Q99LM3



	UniProt functional annotation for Q99LM3

UniProt code: Q99LM3.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-301 reduces this inhibitory activity. {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.

Subunit: Interacts with PPP1R12A. {ECO:0000269|PubMed:20634291}.

Subcellular location: Cytoplasm, myofibril, sarcomere, I band. Cytoplasm, myofibril, sarcomere, M line. Nucleus. Note=Colocalizes with MYH2. In its unphosphorylated state, localizes to the cytoplasm. Phosphorylation at Ser-301 promotes translocation to the nucleus.

Tissue specificity: Widely expressed, with highest expression in skeletal muscles (at protein level). Within striated muscles, significantly more expressed in soleus muscle compared with plantaris muscle or white vastus (at protein level). 30-40% lower expression in females than in males (at protein level). Expressed in type 2a fibers, but not detected in fast twitch type 2b muscle white vastus nor in oxidative type I/b heart muscle (at protein level). Expressed within myometrial cells of the uterus, as well as in the endometrial layer. In the aorta, confined to smooth muscle cells. Not detected in endothelial cells. {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.

Developmental stage: Not detected in somites which give rise to skeletal muscle at 10.5 dpc (at protein level). Expressed in skeletal muscle of the tongue, diaphragm and axial muscles from 14.5 through 17.5 dpc (at protein level). Not detected in limb buds (at protein level). Overall increase by up to 10-12-fold in vascular and uterine smooth muscle during pregnancy (at protein level). At day 13 of pregnancy, expression increases in striated muscle by 2.5-fold compared with non-pregnant mice, and by about 2-fold over levels expressed in males (at protein level). At the same time, dramatically increased in myometrial cells of the uterus, in the endometrial layer and in aortal smooth muscle. Steadily declines through parturition and the onset of lactation (at protein level). {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.

Induction: Significantly reduced by exercise in smooth and in skeletal muscles. {ECO:0000269|PubMed:18310078}.

Ptm: Maximal phosphorylation of Ser-301 correlates with maximal relaxation of aorta in response to acetylcholine. {ECO:0000269|PubMed:15327999, ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.

Disruption phenotype: Male mutant mice perform better than wild type in exercise stress test after endurance training. Females do not differ significantly during these tests. Even in the absence of endurance exercise, mutant mice exhibit muscle fiber adaptation, i.e. more type 2a fibers and lower levels of type 1b fibers. Endothelium-dependent vasorelaxation of the aorta is enhanced and responses to beta- adrenergic constriction are reduced. Expression of PPP1R12A is 30-40- fold higher in mutant mice than in wild-type littermates and exhibits a steady decline as the animals become sexually mature (at protein level). During pregnancy, by day 13, PPP1R12A expression is dramatically increased to 6-14 times over the levels observed in pregnant wild-type littermates (at protein level). PPP1R12B expression levels are unaffected. In vascular smooth muscle, force development in response to phenylephrine is reduced and both the rate and extent of relaxation in response to acetylcholine are promoted. Myosin dephosphorylation is promoted in mutant animals. {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.

Similarity: Belongs to the smoothelin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Plays a role in the regulation of contractile properties of both striated and smooth muscles. When unphosphorylated, may inhibit myosin dephosphorylation. Phosphorylation at Ser-301 reduces this inhibitory activity. {ECO:0000269\|PubMed:18310078, ECO:0000269\|PubMed:20634291}.


Subunit:		Interacts with PPP1R12A. {ECO:0000269\|PubMed:20634291}.
Subcellular location:		Cytoplasm, myofibril, sarcomere, I band. Cytoplasm, myofibril, sarcomere, M line. Nucleus. Note=Colocalizes with MYH2. In its unphosphorylated state, localizes to the cytoplasm. Phosphorylation at Ser-301 promotes translocation to the nucleus.
Tissue specificity:		Widely expressed, with highest expression in skeletal muscles (at protein level). Within striated muscles, significantly more expressed in soleus muscle compared with plantaris muscle or white vastus (at protein level). 30-40% lower expression in females than in males (at protein level). Expressed in type 2a fibers, but not detected in fast twitch type 2b muscle white vastus nor in oxidative type I/b heart muscle (at protein level). Expressed within myometrial cells of the uterus, as well as in the endometrial layer. In the aorta, confined to smooth muscle cells. Not detected in endothelial cells. {ECO:0000269\|PubMed:18310078, ECO:0000269\|PubMed:20634291}.
Developmental stage:		Not detected in somites which give rise to skeletal muscle at 10.5 dpc (at protein level). Expressed in skeletal muscle of the tongue, diaphragm and axial muscles from 14.5 through 17.5 dpc (at protein level). Not detected in limb buds (at protein level). Overall increase by up to 10-12-fold in vascular and uterine smooth muscle during pregnancy (at protein level). At day 13 of pregnancy, expression increases in striated muscle by 2.5-fold compared with non-pregnant mice, and by about 2-fold over levels expressed in males (at protein level). At the same time, dramatically increased in myometrial cells of the uterus, in the endometrial layer and in aortal smooth muscle. Steadily declines through parturition and the onset of lactation (at protein level). {ECO:0000269\|PubMed:18310078, ECO:0000269\|PubMed:20634291}.
Induction:		Significantly reduced by exercise in smooth and in skeletal muscles. {ECO:0000269\|PubMed:18310078}.
Ptm:		Maximal phosphorylation of Ser-301 correlates with maximal relaxation of aorta in response to acetylcholine. {ECO:0000269\|PubMed:15327999, ECO:0000269\|PubMed:18310078, ECO:0000269\|PubMed:20634291}.
Disruption phenotype:		Male mutant mice perform better than wild type in exercise stress test after endurance training. Females do not differ significantly during these tests. Even in the absence of endurance exercise, mutant mice exhibit muscle fiber adaptation, i.e. more type 2a fibers and lower levels of type 1b fibers. Endothelium-dependent vasorelaxation of the aorta is enhanced and responses to beta- adrenergic constriction are reduced. Expression of PPP1R12A is 30-40- fold higher in mutant mice than in wild-type littermates and exhibits a steady decline as the animals become sexually mature (at protein level). During pregnancy, by day 13, PPP1R12A expression is dramatically increased to 6-14 times over the levels observed in pregnant wild-type littermates (at protein level). PPP1R12B expression levels are unaffected. In vascular smooth muscle, force development in response to phenylephrine is reduced and both the rate and extent of relaxation in response to acetylcholine are promoted. Myosin dephosphorylation is promoted in mutant animals. {ECO:0000269\|PubMed:18310078, ECO:0000269\|PubMed:20634291}.
Similarity:		Belongs to the smoothelin family. {ECO:0000305}.