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UniProt functional annotation for P03956 | ||
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| UniProt code: P03956. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:2557822, PubMed:2153297, PubMed:1645757). In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity (PubMed:16807369). {ECO:0000269|PubMed:1645757, ECO:0000269|PubMed:16807369, ECO:0000269|PubMed:2153297, ECO:0000269|PubMed:2557822}. |
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| Catalytic activity: | |
Reaction=Cleavage of the triple helix of collagen at about three- quarters of the length of the molecule from the N-terminus, at 775- Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1' is a hydrophobic residue.; EC=3.4.24.7; Evidence={ECO:0000269|PubMed:1645757, ECO:0000269|PubMed:16807369, ECO:0000269|PubMed:2153297, ECO:0000269|PubMed:2557822}; |
| Cofactor: | |
Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:7656013, ECO:0000269|PubMed:8031754, ECO:0000269|PubMed:8090713, ECO:0000269|PubMed:8278810, ECO:0000269|PubMed:9484219}; Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000269|PubMed:7656013, ECO:0000269|PubMed:8031754, ECO:0000269|PubMed:8090713, ECO:0000269|PubMed:8278810, ECO:0000269|PubMed:9484219}; |
| Cofactor: | |
Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:7656013, ECO:0000269|PubMed:8031754, ECO:0000269|PubMed:8090713, ECO:0000269|PubMed:8278810, ECO:0000269|PubMed:9484219}; Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:7656013, ECO:0000269|PubMed:8031754, ECO:0000269|PubMed:8090713, ECO:0000269|PubMed:8278810, ECO:0000269|PubMed:9484219}; |
| Activity regulation: | |
Can be activated without removal of the activation peptide. |
| Subunit: | |
(Microbial infection) Interacts with HIV-1 Tat. {ECO:0000269|PubMed:16807369}. |
| Subcellular location: | |
Secreted, extracellular space, extracellular matrix {ECO:0000305|PubMed:2167156}. |
| Domain: | |
There are two distinct domains in this protein; the catalytic N-terminal, and the C-terminal which is involved in substrate specificity and in binding TIMP (tissue inhibitor of metalloproteinases). |
| 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. {ECO:0000269|PubMed:15611040, ECO:0000269|PubMed:2153297}. |
| Ptm: | |
Undergoes autolytic cleavage to two major forms (22 kDa and 27 kDa). A minor form (25 kDa) is the glycosylated form of the 22 kDa form. The 27 kDa form has no activity while the 22/25 kDa form can act as activator for collagenase. {ECO:0000269|PubMed:10092871}. |
| Ptm: | |
Tyrosine phosphorylated in platelets by PKDCC/VLK. {ECO:0000269|PubMed:25171405}. |
| Similarity: | |
Belongs to the peptidase M10A family. {ECO:0000305}. |
Annotations taken from UniProtKB at the EBI.