UniProt functional annotation for P50281



	UniProt functional annotation for P50281

UniProt code: P50281.

Organism: Homo sapiens (Human).

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

Function: Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (PubMed:22330140). {ECO:0000250|UniProtKB:P53690, ECO:0000269|PubMed:12714657, ECO:0000269|PubMed:20837484, ECO:0000269|PubMed:22065321, ECO:0000269|PubMed:22330140}.

Catalytic activity: Reaction=Endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at 37-Asn-|-Leu-38. Other bonds hydrolyzed include 35-Gly-|-Ile-36 in the propeptide of collagenase 3, and 341-Asn-|- Phe-342, 441-Asp-|-Leu-442 and 354-Gln-|-Thr-355 in the aggrecan interglobular domain.; EC=3.4.24.80;

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};

Subunit: Interacts (via C-terminal cytoplasmic tail) with BST2. Interacts with DLL1; inhibits DLL1-induced Notch signaling (PubMed:21572390). {ECO:0000269|PubMed:21572390, ECO:0000269|PubMed:22065321, ECO:0000269|PubMed:9724659}.

Subcellular location: Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Melanosome. Cytoplasm. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Forms a complex with BST2 and localizes to the cytoplasm.

Tissue specificity: Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors. {ECO:0000269|PubMed:18223680}.

Induction: Up-regulated by NANOS1. {ECO:0000269|PubMed:18223680}.

Domain: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation- peptide release activates the enzyme.

Ptm: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.

Ptm: Tyrosine phosphorylated by PKDCC/VLK. {ECO:0000269|PubMed:25171405}.

Disease: Winchester syndrome (WNCHRS) [MIM:277950]: A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. {ECO:0000269|PubMed:22922033}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase M10A 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:		Endopeptidase that degrades various components of the extracellular matrix such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (PubMed:22330140). {ECO:0000250\|UniProtKB:P53690, ECO:0000269\|PubMed:12714657, ECO:0000269\|PubMed:20837484, ECO:0000269\|PubMed:22065321, ECO:0000269\|PubMed:22330140}.


Catalytic activity:		Reaction=Endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at 37-Asn-\|-Leu-38. Other bonds hydrolyzed include 35-Gly-\|-Ile-36 in the propeptide of collagenase 3, and 341-Asn-\|- Phe-342, 441-Asp-\|-Leu-442 and 354-Gln-\|-Thr-355 in the aggrecan interglobular domain.; EC=3.4.24.80;
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
Subunit:		Interacts (via C-terminal cytoplasmic tail) with BST2. Interacts with DLL1; inhibits DLL1-induced Notch signaling (PubMed:21572390). {ECO:0000269\|PubMed:21572390, ECO:0000269\|PubMed:22065321, ECO:0000269\|PubMed:9724659}.
Subcellular location:		Membrane {ECO:0000305}; Single-pass type I membrane protein {ECO:0000305}. Melanosome. Cytoplasm. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Forms a complex with BST2 and localizes to the cytoplasm.
Tissue specificity:		Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors. {ECO:0000269\|PubMed:18223680}.
Induction:		Up-regulated by NANOS1. {ECO:0000269\|PubMed:18223680}.
Domain:		The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation- peptide release activates the enzyme.
Ptm:		The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
Ptm:		Tyrosine phosphorylated by PKDCC/VLK. {ECO:0000269\|PubMed:25171405}.
Disease:		Winchester syndrome (WNCHRS) [MIM:277950]: A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes. {ECO:0000269\|PubMed:22922033}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase M10A family. {ECO:0000305}.