HP59 is a pathologic

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting ...

capillary endothelial marker

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

(7 or 12 transmembrane domains) which has been identified as the receptor for the Group B Streptococcal Toxin (GBS Toxin) molecule known as CM101, the etiologic agent for early-onset versus late-onset Group B Strep.

Expression

Fu, ''et al.'' coined the term "pathological angiogenesis" to distinguish between HP59-expressing, and non-HP59-expressing capillaries, however, other researchers have not used this terminology. Therefore it is not yet known whether HP59 is expressed in

vasculogenesis Vasculogenesis is the process of blood vessel formation, occurring by a '' de novo'' production of endothelial cells. It is sometimes paired with angiogenesis, as the first stage of the formation of the vascular network, closely followed by ang ...

arteriogenesis Arteriogenesis refers to an increase in the diameter of existing arterial vessels. Mechanical Stimulation Mechanically, arteriogenesis is linked to elevated pressure, which increases radial wall stress, and elevated flow, which increases endotheli ...

, sprouting angiogenesis or intussusceptive angiogenesis. However capillaries in all tumor tissues examined were positive for anti-HP59 antibodies and

Von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopen ...

(vWF) antibodies, while in normal tissues only vWF staining was observed. The target protein for GBStoxin/CM101 is expressed in vasculature of developing organs during their formation during embryogenesis. The lung is the last organ to develop so HP59 is present in the newborn lung for 5–10 days after birth, explaining the susceptibility to GBS induced "early onset" disease. HP59

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...

is expressed later in life only in pathologic angiogenesis, providing a receptor for CM101. The CM101-HP59 complex then activates

complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...

, and initiates an inflammatory

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

cascade which recruits

CD69 CD69 (Cluster of Differentiation 69) is a human transmembrane C-Type lectin protein encoded by the gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is ...

positive activated

granulocytes Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...

to destroy the capillaries and surrounding pathologic tissue. CM101 has been shown in a published Phase I, FDA-approved clinical trial under IND to have clinical safety and effectivity on select

stage IV cancer Cancer staging is the process of determining the extent to which a cancer has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that ha ...

patients, specifically targeting tumor vasculature HP59 is expressed in the adult in wound healing, and in tumor angiogenesis, as shown in mice. The gene for HP59 contains, entirely within its coding region, the

Sialin Sialin, also known as H(+)/nitrate cotransporter and H(+)/sialic acid cotransporter, is a protein which in humans is encoded by the ''SLC17A5'' gene. Clinical significance A deficiency of this protein causes Salla disease. and Infantile Siali ...

Gene SLC17A5 (Solute carrier family 17 (anion/sugar transporter). Member 5, also known asSLC17A5 or sialin is a lysosomal membrane

sialic acid Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...

transport protein which in humans is encoded by the SLC17A5 gene on Chromosome 6, and appears to be important in CNS myelination. HP59 has a transcription initiation site 300bp upstream of the initiation site for the Sialin Gene SLC17A5, and encodes 41 additional aminoacids at the Amino-terminal. Thus, using an upstream transcription initiation site, and thus a different

start codon The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and Archaea and a N-formylmethionine (fMet) in bacteria, mitochondria and plastids. The ...

, HP59, incorporating the Sialin gene product, becomes a pathologic angiogenesis capillary endothelial cell luminal membrane protein with unknown function, which the GBS Toxin CM101 specifically targets. Endothelial involvement is indicated by levels of Soluble E-

Selectin The selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus a ...

References

{{Reflist, 35em Proteins