Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI2) is a single-pass type I membrane protein and contains two BPTI/Kunitz inhibitor domains. The first Kunitz domain is mainly responsible for the inhibitory activity against hepatocyte growth factor activator (HGFA). HAI2 is expressed in placenta, kidney, pancreas, prostate, testis, thymus and trachea. HAI2 serves as a inhibitor of HGF activator. It also inhibits plasmin, plasma and tissue kallikrein and factor XIa. Defects in HAI2 are the cause of diarrhea type 3 (DIAR3), also known as congenital sodium diarrhea (CSD).
Hydroxyacid Oxidase 1 (HAO1) is an enzyme that belongs to the FMN-Dependent α-Hydroxy Acid Dehydrogenase family. HAO1 contains 1 FMN Hydroxy Ccid Dehydrogenase domain. HAO1 is expressed primarily in the liver and pancreas. This protein has 2-Hydroxyacid Oxidase activity. Most HAO1 is active on the 2-Carbon substrate Glycolate; but it can also be active on 2-Hydroxy fatty acids; with higher activity towards 2-Hydroxy Palmitate and 2-Hydroxy Octanoate.
Hyaluronan (HA) is a high MW glycosaminoglycan significantly involved in the formation and stability of extracellular matrix via its association with specific HA-binding proteins. HAPLN1, also known as CRTL1 (Cartilage Link Protein 1, cLP ) and link protein, is a member of HA-binding protein (hyaladherins) family, and contains a common structural domain of about 100 amino acids that is termed a Link module with two α-helices and two antiparallel β-sheets. HAPLN1/CRTL1 stabilizes the interaction between hyaluronan (HA) and versican, two extracellular matrix components essential for cardiac development. Link module superfamily can be divided into three subgroups, and the HAPLN family are C domain-type proteins that have an extended structure with one N-terminal V-type Ig-like domain followed by two link modules. In cartilage, aggrecan forms - cLP stabilized aggregates with HA that provides the tissue with its load bearing properties. HAPLN1 is a component of follicular matrix, was shown to enhance cumulus-oocyte complex (COC) expansion in vitro. HAPLN1 may promote periovulatory granulosa cell survival, which would facilitate their differentiation into luteal cells.
Haptoglobin(HP) is a secreted protein which is a member of the peptidase S1 family of serine proteases. As a result of hemolysis; hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures; and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an Antimicrobial; Antioxidant has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidely cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway. Uncleaved haptoglogin; also known as zonulin; plays a role in intestinal permeability; allowing intercellular tight junction disassembly; and controlling the equilibrium between tolerance and immunity to non-self antigens.
Hemoglobin Subunit Zeta (HBZ) is a member of the Globin family. The zeta chain is an alpha-type chain of mammalian embryonic Hemoglobin that is synthesized primarily in the yolk sac of the early embryo, while alpha-globin is produced throughout fetal growth and adult life. The HBZ gene consists of five functional genes and two pseudogenes, the order of genes is 5-zeta-pseudozeta-mu-pseudoalpha-1-alpha-2-alpha-1-theta-1-3.
Heparin-binding EGF-like growth factor (HB-EGF) is a 12-16 kDa member of the epidermal growth factor (EGF) family. It possesses an EGF-like domain, and a heparin-binding motif. Mature HB-EGF is a soluble peptide that arises from proteolytic processing of the transmembrane form. Human HB-EGF shows 76% and 73% aa sequence identity with rat and mouse HB-EGF, respectively. It is required for normal cardiac valve formation and normal heart function, promotes smooth muscle cell proliferation. It may be involved in macrophage-mediated cellular proliferation; it is mitogenic for fibroblasts, but not endothelial cells. HB-EGF classified as a group 2 ErbB ligand based on its ability to activate both the EGF/ErbB1 and ErbB4 receptors. Activity associated with ErbB4 binding appears to be limited to non-mitogenic actions, while EGFR binding induces both mitogenic and non-mitogenic activity.
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