UniProt functional annotation for P43235



	UniProt functional annotation for P43235

UniProt code: P43235.

Organism: Homo sapiens (Human).

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

Function: Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:11082042). {ECO:0000269|PubMed:11082042}.

Catalytic activity: Reaction=Broad proteolytic activity. With small-molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.; EC=3.4.22.38;

Subcellular location: Lysosome {ECO:0000269|PubMed:11082042}. Secreted {ECO:0000269|PubMed:11082042}. Apical cell membrane {ECO:0000269|PubMed:11082042}; Peripheral membrane protein {ECO:0000269|PubMed:11082042}; Extracellular side {ECO:0000269|PubMed:11082042}. Note=Localizes to the lumen of thyroid follicles and to the apical membrane of thyroid epithelial cells. {ECO:0000269|PubMed:11082042}.

Tissue specificity: Predominantly expressed in osteoclasts (bones) (PubMed:7805878). Expressed in thyroid epithelial cells (PubMed:11082042). {ECO:0000269|PubMed:11082042, ECO:0000269|PubMed:7805878}.

Disease: Pycnodysostosis (PKND) [MIM:265800]: A rare autosomal recessive bone disorder characterized by deformity of the skull, maxilla and phalanges, osteosclerosis, and fragility of bone. {ECO:0000269|PubMed:10491211, ECO:0000269|PubMed:10878663, ECO:0000269|PubMed:22822386, ECO:0000269|PubMed:25731711, ECO:0000269|PubMed:8703060, ECO:0000269|PubMed:9529353}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE- ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}.

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:		Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:11082042). {ECO:0000269\|PubMed:11082042}.


Catalytic activity:		Reaction=Broad proteolytic activity. With small-molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.; EC=3.4.22.38;
Subcellular location:		Lysosome {ECO:0000269\|PubMed:11082042}. Secreted {ECO:0000269\|PubMed:11082042}. Apical cell membrane {ECO:0000269\|PubMed:11082042}; Peripheral membrane protein {ECO:0000269\|PubMed:11082042}; Extracellular side {ECO:0000269\|PubMed:11082042}. Note=Localizes to the lumen of thyroid follicles and to the apical membrane of thyroid epithelial cells. {ECO:0000269\|PubMed:11082042}.
Tissue specificity:		Predominantly expressed in osteoclasts (bones) (PubMed:7805878). Expressed in thyroid epithelial cells (PubMed:11082042). {ECO:0000269\|PubMed:11082042, ECO:0000269\|PubMed:7805878}.
Disease:		Pycnodysostosis (PKND) [MIM:265800]: A rare autosomal recessive bone disorder characterized by deformity of the skull, maxilla and phalanges, osteosclerosis, and fragility of bone. {ECO:0000269\|PubMed:10491211, ECO:0000269\|PubMed:10878663, ECO:0000269\|PubMed:22822386, ECO:0000269\|PubMed:25731711, ECO:0000269\|PubMed:8703060, ECO:0000269\|PubMed:9529353}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase C1 family. {ECO:0000255\|PROSITE- ProRule:PRU10088, ECO:0000255\|PROSITE-ProRule:PRU10089, ECO:0000255\|PROSITE-ProRule:PRU10090}.