Rat a1-Microglobulin (alpha1-m/A1M; also protein HC) is a secreted, 25-26kD glycoprotein member of the lipocalin family, calycin superfamily of molecules. It is expressed by hepatocytes, keratinocytes, and endodermal derivatives in the embryo. A1M appears to act as a heme scavenger, protecting cells and collagen against oxidative damage. It also acts as an immunosuppressant, inhibiting polyclonal lymphocyte activation and dampening granulocyte migration in response to chemokines. A1M circulates either as a monomer, or bound to IgA, albumin or prothrombin. Rat A1M is generated through cleavage of a precursor molecule termed AMBP. This AMBP should not be confused with AMBP-1, a 120-140kD adrenomedullinbinding protein that is also known as Complement Factor H. The AMBP precursor contains a 19aa signal sequence, an N-terminal 183aa A1M protein (aa20-202), and a C-terminal serine protease inhibitor termed bikunin (aa205-349). A1M possesses one lipocalin domain (aa41-186). Although cleavage of AMBP in the Golgi apparatus typically generates a 25kD A1M and 28kD bikunin molecule, the 55-65kD AMBP precursor can also be released intact. In human, A1M will undergo extracellular processing, generating an isoform that is missing the Cterminal four aa. There are four potential isoform variants. One utilizes an alternative start site at Met181, a second contains an Asn substitution for aa112-228, a third possesses an 11aa substitution for aa1-141, and a fourth shows a 17aa substitution for aa201-349. Over aa20-202, rat A1M shares 76% and aa86% sequence identity with human and mouse A1M, respectively.
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