The saposin domains refers to two evolutionally-conserved

protein domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...

s found in

saposin Prosaposin, also known as PSAP, is a protein which in humans is encoded by the ''PSAP'' gene. This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator Pr ...

and related proteins (SAPLIP). Saposins are small lysosomal proteins that serve as activators of various lysosomal lipid-degrading enzymes. They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble

degradative enzyme A degradative enzyme is an enzyme (in a broader sense a protein) which degrades biological molecules. Some examples of degradative enzymes: *Lipase, which digests lipids, *Carbohydrases, which digest carbohydrates (e.g., sugars), *Proteases, which d ...

s. All mammalian saposins are synthesized as a single precursor molecule (

prosaposin Prosaposin, also known as PSAP, is a protein which in humans is encoded by the ''PSAP'' gene. This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator Pr ...

) which contains four ''Saposin-B domains'', yielding the active saposins after proteolytic cleavage, and two ''Saposin-A domains'' that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, most of them playing a role in interacting with membranes.

Classification

The saposin (SapB1-SapB2) domains are found in a wide range of proteins. Each half-domain encodes two alpha helices in the SapB domain for a total of four. The mamallian

(domain organization below) is a prototypic family member. It also includes the N- and

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...

SapA domains, both of which are proteolyticly cleaved as the

proprotein A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule ...

matures. Four connected pairs of SapB1-SapB2 domains are released, sequentially named Saposin-A through D. Some closely related proteins, such as PSAPL1 and SFTPB, share the architecture and the cleaving mechanism in whole or in part. While Prosaposin and PSAPL1 act in lysosomal lipid degradation, SFTPB is released into the

pulmonary surfactant Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells. The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic In chemistry, hydrophobicity is t ...

, playing a role in rearranging lipids. However, proteins like GNLY and AOAH do not carry a SapA domain. While GNLY is essentially a SapB with N-terminal extensions specialized for lysing pathogen cell membranes, the ADAH protein uses the uncleaved SapB domain for targeting the correct intracellular compartment. The

plant-specific insert The plant-specific insert (PSI) or plant-specific sequence (PSS) is an independent domain, exclusively found in plants, consisting of approximately 100 residues, found on the C-terminal lobe on some aspartic proteases (AP) called phytepsins. The ...

is an unusual variation on the SapB domains. It features a

circular permutation In mathematics, and in particular in group theory, a cyclic permutation (or cycle) is a permutation of the elements of some set ''X'' which maps the elements of some subset ''S'' of ''X'' to each other in a cyclic fashion, while fixing (that is, ma ...

compared to the usual topology: instead of featuring a SapB1-SapB2 unit, it is made up of a SapB2-linker-SapB1 unit seemingly derived by taking a half of each of two SapB units.

Human proteins containing this domain

AOAH Acyloxyacyl hydrolase, also known as AOAH, is a protein which in humans is encoded by the ''AOAH'' gene. Function Acyloxyacyl hydrolase (AOAH) is a lipase that selectively releases the secondary (acyloxyacyl-linked) fatty acyl chains from the he ...

GNLY Granulysin (GNLY) is a protein expressed in most mammals which functions as an antimicrobial peptide Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fun ...

Prosaposin Prosaposin, also known as PSAP, is a protein which in humans is encoded by the ''PSAP'' gene. This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator Pr ...

PSAPL1 Proactivator polypeptide-like 1 is a protein in humans that is encoded by the PSAPL1 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation ...

SFTPB Surfactant protein B is an essential lipid-associated protein found in pulmonary surfactant. Without it, the lung would not be able to inflate after a deep breath out. It rearranges lipid molecules in the fluid lining the lung so that tiny air sa ...

References

External links

Saposin B-type domain
in

PROSITE PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformati ...

{{InterPro content, IPR008138 Protein domains Protein families Peripheral membrane proteins

Classification

Human proteins containing this domain

References

Further reading

External links