UniProt functional annotation for P20807



	UniProt functional annotation for P20807

UniProt code: P20807.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at 'His-409'. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53 (PubMed:23357851, PubMed:27657329). {ECO:0000269|PubMed:23357851, ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:27657329}.

Catalytic activity: Reaction=Broad endopeptidase activity.; EC=3.4.22.54;

Activity regulation: Activated by micromolar concentrations of calcium and inhibited by calpastatin.

Subunit: Homodimer; via EF-hand domain 4 (PubMed:24846670). Interacts with TTN/titin (PubMed:14583192). Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis (PubMed:20634290). Interacts with SIMC1 (PubMed:23707407). Interacts with UTP25; the interaction is required for CAPN3 translocation to the nucleolus (PubMed:23357851, PubMed:27657329). {ECO:0000269|PubMed:14583192, ECO:0000269|PubMed:20634290, ECO:0000269|PubMed:23357851, ECO:0000269|PubMed:23707407, ECO:0000269|PubMed:24846670, ECO:0000269|PubMed:27657329}.

Subcellular location: Cytoplasm. Nucleus, nucleolus {ECO:0000269|PubMed:23357851, ECO:0000269|PubMed:27657329}.

Tissue specificity: Isoform I is skeletal muscle specific.

Disease: Muscular dystrophy, limb-girdle, autosomal recessive 1 (LGMDR1) [MIM:253600]: An autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset. {ECO:0000269|PubMed:27020652, ECO:0000269|PubMed:27234031, ECO:0000269|PubMed:7720071, ECO:0000269|PubMed:8624690, ECO:0000269|PubMed:9150160, ECO:0000269|PubMed:9266733, ECO:0000269|PubMed:9452114, ECO:0000269|PubMed:9655129, ECO:0000269|PubMed:9762961, ECO:0000269|PubMed:9771675}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Muscular dystrophy, limb-girdle, autosomal dominant 4 (LGMDD4) [MIM:618129]: A form of autosomal dominant limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDD4 is characterized by onset of proximal muscle weakness in young adulthood, gait difficulties, increased serum creatine kinase, myalgia, and back pain. Some patients may have upper limb involvement. Disease severity and expressivity are highly variable. {ECO:0000269|PubMed:27259757, ECO:0000269|PubMed:28881388}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase C2 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Calcium-regulated non-lysosomal thiol-protease. Proteolytically cleaves CTBP1 at 'His-409'. Mediates, with UTP25, the proteasome-independent degradation of p53/TP53 (PubMed:23357851, PubMed:27657329). {ECO:0000269\|PubMed:23357851, ECO:0000269\|PubMed:23707407, ECO:0000269\|PubMed:27657329}.


Catalytic activity:		Reaction=Broad endopeptidase activity.; EC=3.4.22.54;
Activity regulation:		Activated by micromolar concentrations of calcium and inhibited by calpastatin.
Subunit:		Homodimer; via EF-hand domain 4 (PubMed:24846670). Interacts with TTN/titin (PubMed:14583192). Interacts with CMYA5; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis (PubMed:20634290). Interacts with SIMC1 (PubMed:23707407). Interacts with UTP25; the interaction is required for CAPN3 translocation to the nucleolus (PubMed:23357851, PubMed:27657329). {ECO:0000269\|PubMed:14583192, ECO:0000269\|PubMed:20634290, ECO:0000269\|PubMed:23357851, ECO:0000269\|PubMed:23707407, ECO:0000269\|PubMed:24846670, ECO:0000269\|PubMed:27657329}.
Subcellular location:		Cytoplasm. Nucleus, nucleolus {ECO:0000269\|PubMed:23357851, ECO:0000269\|PubMed:27657329}.
Tissue specificity:		Isoform I is skeletal muscle specific.
Disease:		Muscular dystrophy, limb-girdle, autosomal recessive 1 (LGMDR1) [MIM:253600]: An autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset. {ECO:0000269\|PubMed:27020652, ECO:0000269\|PubMed:27234031, ECO:0000269\|PubMed:7720071, ECO:0000269\|PubMed:8624690, ECO:0000269\|PubMed:9150160, ECO:0000269\|PubMed:9266733, ECO:0000269\|PubMed:9452114, ECO:0000269\|PubMed:9655129, ECO:0000269\|PubMed:9762961, ECO:0000269\|PubMed:9771675}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Muscular dystrophy, limb-girdle, autosomal dominant 4 (LGMDD4) [MIM:618129]: A form of autosomal dominant limb-girdle muscular dystrophy, a myopathy characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. LGMDD4 is characterized by onset of proximal muscle weakness in young adulthood, gait difficulties, increased serum creatine kinase, myalgia, and back pain. Some patients may have upper limb involvement. Disease severity and expressivity are highly variable. {ECO:0000269\|PubMed:27259757, ECO:0000269\|PubMed:28881388}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase C2 family. {ECO:0000305}.