UniProt functional annotation for Q9CQM9



	UniProt functional annotation for Q9CQM9

UniProt code: Q9CQM9.

Organism: Mus musculus (Mouse).

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

Function: Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (By similarity). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (PubMed:16809552, PubMed:18258855, PubMed:18929570). Required for hemoglobin maturation. Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity (By similarity). {ECO:0000250|UniProtKB:O76003, ECO:0000269|PubMed:16809552, ECO:0000269|PubMed:18258855, ECO:0000269|PubMed:18929570}.

Subunit: Homodimer; the homodimer is independent of 2Fe-2S clusters. Heterotrimer; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters. Interacts (via N-terminus) with PRKCQ/PKC-theta (By similarity). Interacts (via C-terminus) with CSRP3 (PubMed:18258855). Interacts with CSRP2 (PubMed:18258855). {ECO:0000250|UniProtKB:O76003, ECO:0000269|PubMed:18258855}.

Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O76003}. Cytoplasm, cell cortex {ECO:0000269|PubMed:18258855}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269|PubMed:18258855}. Note=Under the plasma membrane (PubMed:18258855). After PMA stimulation, GLRX3 and PRKCQ/PKC-theta translocate to a more extended submembrane area (PubMed:18258855). In the Z line, found associated with CSRP3 (PubMed:18258855). {ECO:0000269|PubMed:18258855}.

Domain: The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity. {ECO:0000305}.

Disruption phenotype: Homozygous null mutants die in utero sometime between E12.5 and E14.5. E12.5 embryos have a smaller body size and hemorrhage in the head. Heterozygous mutants are fertile and show no abnormalities in growth and development, cardiomyocytes exhibit significantly reduced contractility. {ECO:0000269|PubMed:18929570}.

Miscellaneous: Transgenic mice with cardiac-specific Glrx3 overexpression show that it is a potent inhibitor of cardiac hypertrophy induced by pressure overload (transverse aortic constriction). In addition, overexpression dramatically increases the ventricular function and cardiomyocyte contractility. {ECO:0000269|PubMed:16809552, ECO:0000269|PubMed:18258855, ECO:0000269|PubMed:18929570}.

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:		Together with BOLA2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins (By similarity). Acts as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator (PubMed:16809552, PubMed:18258855, PubMed:18929570). Required for hemoglobin maturation. Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity (By similarity). {ECO:0000250\|UniProtKB:O76003, ECO:0000269\|PubMed:16809552, ECO:0000269\|PubMed:18258855, ECO:0000269\|PubMed:18929570}.


Subunit:		Homodimer; the homodimer is independent of 2Fe-2S clusters. Heterotrimer; forms a heterotrimeric complex composed by two BOLA2 molecules and one GLRX3 molecule; linked by [2Fe-2S] clusters. Interacts (via N-terminus) with PRKCQ/PKC-theta (By similarity). Interacts (via C-terminus) with CSRP3 (PubMed:18258855). Interacts with CSRP2 (PubMed:18258855). {ECO:0000250\|UniProtKB:O76003, ECO:0000269\|PubMed:18258855}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000250\|UniProtKB:O76003}. Cytoplasm, cell cortex {ECO:0000269\|PubMed:18258855}. Cytoplasm, myofibril, sarcomere, Z line {ECO:0000269\|PubMed:18258855}. Note=Under the plasma membrane (PubMed:18258855). After PMA stimulation, GLRX3 and PRKCQ/PKC-theta translocate to a more extended submembrane area (PubMed:18258855). In the Z line, found associated with CSRP3 (PubMed:18258855). {ECO:0000269\|PubMed:18258855}.
Domain:		The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity. {ECO:0000305}.
Disruption phenotype:		Homozygous null mutants die in utero sometime between E12.5 and E14.5. E12.5 embryos have a smaller body size and hemorrhage in the head. Heterozygous mutants are fertile and show no abnormalities in growth and development, cardiomyocytes exhibit significantly reduced contractility. {ECO:0000269\|PubMed:18929570}.
Miscellaneous:		Transgenic mice with cardiac-specific Glrx3 overexpression show that it is a potent inhibitor of cardiac hypertrophy induced by pressure overload (transverse aortic constriction). In addition, overexpression dramatically increases the ventricular function and cardiomyocyte contractility. {ECO:0000269\|PubMed:16809552, ECO:0000269\|PubMed:18258855, ECO:0000269\|PubMed:18929570}.