UniProt functional annotation for Q15661



	UniProt functional annotation for Q15661

UniProt code: Q15661.

Organism: Homo sapiens (Human).

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

Function: Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. May play a role in innate immunity. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates (PubMed:18854315). {ECO:0000250, ECO:0000250|UniProtKB:P21845, ECO:0000269|PubMed:18854315}.

Catalytic activity: Reaction=Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa, but with more restricted specificity than trypsin.; EC=3.4.21.59;

Subunit: Homotetramer. The active tetramer is converted to inactive monomers at neutral and acidic pH in the absence of heparin. Low concentrations of inactive monomers become active monomers at pH 6.0 in the presence of heparin. When the concentration of active monomers is higher, they convert to active monomers and then to active tetramers. These monomers are active and functionally distinct from the tetrameric enzyme. In contrast to the hidden active sites in the tetrameric form, the active site of the monomeric form is accessible for macromolecular proteins and inhibitors eg: fibrinogen which is a substrate for the monomeric but not for the tetrameric form. The monomeric form forms a complex with SERPINB6. {ECO:0000269|PubMed:18039527}.

Subcellular location: Secreted. Note=Released from the secretory granules upon mast cell activation. {ECO:0000250}.

Tissue specificity: Isoform 1 and isoform 2 are expressed in lung, stomach, spleen, heart and skin; in these tissues, isoform 1 is predominant. Isoform 2 is expressed in aorta, spleen, and breast tumor, with highest levels in the endothelial cells of some blood vessels surrounding the aorta, as well as those surrounding the tumor and low levels, if any, in mast cells (at protein level). {ECO:0000269|PubMed:18854315}.

Polymorphism: There are two alleles alpha and beta-I. The sequence shown is that of allele beta-I. {ECO:0000269|PubMed:18854315, ECO:0000269|PubMed:2187193, ECO:0000269|PubMed:9920877}.

Disease: Note=Hereditary alpha tryptasemia is caused by an increase in the copy number (usually between two and three copies) of the alpha allele. Affected individuals have elevated basal serum tryptase levels that are associated with cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities. It is not clear if the associated multisystem complaints might be due to the coinheritance of a second functional genetic variant. {ECO:0000269|PubMed:27749843}.

Similarity: Belongs to the peptidase S1 family. Tryptase subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.

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:		Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type. May play a role in innate immunity. Isoform 2 cleaves large substrates, such as fibronectin, more efficiently than isoform 1, but seems less efficient toward small substrates (PubMed:18854315). {ECO:0000250, ECO:0000250\|UniProtKB:P21845, ECO:0000269\|PubMed:18854315}.


Catalytic activity:		Reaction=Preferential cleavage: Arg-\|-Xaa, Lys-\|-Xaa, but with more restricted specificity than trypsin.; EC=3.4.21.59;
Subunit:		Homotetramer. The active tetramer is converted to inactive monomers at neutral and acidic pH in the absence of heparin. Low concentrations of inactive monomers become active monomers at pH 6.0 in the presence of heparin. When the concentration of active monomers is higher, they convert to active monomers and then to active tetramers. These monomers are active and functionally distinct from the tetrameric enzyme. In contrast to the hidden active sites in the tetrameric form, the active site of the monomeric form is accessible for macromolecular proteins and inhibitors eg: fibrinogen which is a substrate for the monomeric but not for the tetrameric form. The monomeric form forms a complex with SERPINB6. {ECO:0000269\|PubMed:18039527}.
Subcellular location:		Secreted. Note=Released from the secretory granules upon mast cell activation. {ECO:0000250}.
Tissue specificity:		Isoform 1 and isoform 2 are expressed in lung, stomach, spleen, heart and skin; in these tissues, isoform 1 is predominant. Isoform 2 is expressed in aorta, spleen, and breast tumor, with highest levels in the endothelial cells of some blood vessels surrounding the aorta, as well as those surrounding the tumor and low levels, if any, in mast cells (at protein level). {ECO:0000269\|PubMed:18854315}.
Polymorphism:		There are two alleles alpha and beta-I. The sequence shown is that of allele beta-I. {ECO:0000269\|PubMed:18854315, ECO:0000269\|PubMed:2187193, ECO:0000269\|PubMed:9920877}.
Disease:		Note=Hereditary alpha tryptasemia is caused by an increase in the copy number (usually between two and three copies) of the alpha allele. Affected individuals have elevated basal serum tryptase levels that are associated with cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities. It is not clear if the associated multisystem complaints might be due to the coinheritance of a second functional genetic variant. {ECO:0000269\|PubMed:27749843}.
Similarity:		Belongs to the peptidase S1 family. Tryptase subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00274}.