Novel serine protease
It is disclosed that a novel polypeptide useful for screening for an agent for specific diseases to which gastrointestinal hormones are related, particularly irritable bowel syndrome, a polynucleotide encoding the polypeptide, a vector comprising the polynucleotide, and a transfected cell by the vector. It is disclosed that the polypeptide is a novel type II transmembrane serine protease related to the regulation of hormones produced in gastrointestinal tract or a precursor thereof. Additionally, a screening method of an agent for gastrointestinal diseases using the polypeptide and a method for producing a pharmaceutical composition for the treatment of gastrointestinal diseases, comprising a substance obtained by the screening method as the active ingredient are disclosed.
1 . A polypeptide which comprises the 237th to 531st amino acid sequence in the amino acid sequence represented by SEQ ID NO:2 and is an enzyme which shows a protease activity.
2 . A polypeptide consisting of the 237th to 531st amino acid sequence in the amino acid sequence represented by SEQ ID NO:2.
3 . A polypeptide which comprises the 51st to 531st amino acid sequence in the amino acid sequence represented by SEQ ID NO:2 and is a precursor of an enzyme which shows a protease activity.
4 . A polypeptide which comprises an amino acid sequence in which the 51st to 531st amino acid sequence in the amino acid sequence represented by SEQ ID NO:2 is conjugated to the C-terminus side of
an amino acid sequence consisting of the 1st to 50th amino acid sequence in the amino acid sequence represented by SEQ ID NO:2, or
an amino acid sequence comprising the 1st to 50th amino acid sequence in the amino acid sequence represented by SEQ ID NO:2 in which 1 to 10 amino acids are deleted, substituted and/or inserted,
and is a precursor of an enzyme which shows a protease activity.
5 . A polypeptide consisting of an amino acid sequence represented by SEQ ID NO:2, or
a polypeptide consisting of the 51st to 531st amino acid sequence in the amino acid sequence represented by SEQ ID NO:2.
6 . A polynucleotide encoding a polypeptide according to any one of claims 1 to 5 .
7 . An expression vector comprising a polynucleotide according to claim 6 .
8 . A cell transformed with an expression vector according to claim 7 .
9 . A method for screening an agent for treating gastrointestinal diseases, which comprises
a step of allowing i) a polypeptide according to claim 1 or claim 2 to contact with ii) a substrate cleavable with said polypeptide and iii) a test substance,
a step of analyzing the cleavage of the substrate and
a step of selecting a substance inhibiting the activity for cleaving the substrate.
10 . A method for producing a pharmaceutical composition for treating gastrointestinal diseases, which comprises
a screening step using the screening method according to claim 9 and
a formulation step using a substance obtainable by the screening.