Editing Reelin (section)

== Structure ==
[[File:2e26.png|thumb|left|250px|The structure of two [[mouse|murine]] ''reelin repeats'' as revealed by [[X-ray crystallography]].<ref name="pmid17548821" />]]
Reelin is composed of 3461 amino acids with a relative molecular mass of 388 [[Atomic mass unit|kDa]]. It also has [[serine protease]] activity.<ref name="pmid11689558" /> Murine RELN gene consists of 65 [[exon]]s spanning approximately 450 [[base pair|kb]].<ref name="pmid9417911" /> One exon, coding for only two amino acids near the protein's [[C-terminus]], undergoes [[alternative splicing]], but the exact functional impact of this is unknown.<ref name="Reelin_book_2008" /> Two transcription initiation sites and two polyadenylation sites are identified in the gene structure.<ref name="pmid9417911" />

The reelin protein starts with a signaling peptide 27 amino acids in length, followed by a region bearing similarity to [[spondin 1|F-spondin]] (the [[reeler domain]]), marked as "SP" on the scheme, and by a region unique to reelin, marked as "H". Next comes 8 repeats of 300–350 amino acids. These are called ''reelin repeats'' and have an [[epidermal growth factor]] motif at their center, dividing each repeat into two subrepeats, ''A'' (the [[BNR/Asp-box repeat]]) and ''B'' (the [[EGF-like domain]]). Despite this interruption, the two subdomains make direct contact, resulting in a compact overall structure.<ref name="reelinstructure2006japan" />

The final reelin domain contains a highly basic and short C-terminal region (CTR, marked "+") with a length of 32 amino acids. This region is highly conserved, being 100% identical in all investigated mammals. It was thought that CTR is necessary for reelin secretion, because the Orleans [[reeler]] mutation, which lacks a part of 8th repeat and the whole CTR, is unable to secrete the misshaped protein, leading to its concentration in cytoplasm. However, other studies have shown that the CTR is not essential for secretion itself, but mutants lacking the CTR were much less efficient in activating downstream signaling events.<ref name="Nakano_2007_CTR_1" />

Reelin is cleaved ''in vivo'' at two sites located after domains 2 and 6 – approximately between repeats 2 and 3 and between repeats 6 and 7, resulting in the production of three fragments.<ref name="cleave" /> This splitting does not decrease the protein's activity, as constructs made of the predicted central fragments (repeats 3–6) bind to lipoprotein receptors, trigger [[DAB1|Dab1]] [[phosphorylation]] and mimic functions of reelin during [[cortical plate]] development.<ref name="centralfragment" /> Moreover, the processing of reelin by embryonic neurons may be necessary for proper corticogenesis.<ref name="pmid17442808" />