TMPRSS6
Domain
Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s).
Function
Membrane-bound serine protease (PubMed:18976966, PubMed:20518742, PubMed:25156943, PubMed:25588876). Through the cleavage of cell surface HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis (PubMed:18408718, PubMed:18976966, PubMed:25156943).
Involvement in disease
Iron-refractory iron deficiency anemia
IRIDA
Key features include congenital hypochromic microcytic anemia, very low mean corpuscular erythrocyte volume, low transferrin saturation, abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron, and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron.
None
The disease is caused by variants affecting the gene represented in this entry. Mutations leading to abrogation of TMPRSS6 activity are associated with IRIDA due to elevated levels of hepcidin, a negative regulator of plasma iron pool (PubMed:20232450).
Post-translational modifications
The single-chain zymogen undergoes autoproteolytic processing (PubMed:18976966, PubMed:20518742, PubMed:25156943). This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly (PubMed:18976966, PubMed:20518742, PubMed:25156943). The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization (PubMed:20518742, PubMed:25156943).
Sequence Similarities
Belongs to the peptidase S1 family.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- The processed, activated two-chains form is released in the extracellular space.
Alternative names
UNQ354/PRO618, TMPRSS6, Transmembrane protease serine 6, Matriptase-2