Homeobox B4 (HOXB4) is encoded by the HOXB4 gene which is a member of the the class I homeobox (HOX) gene family and encodes a nuclear protein with a homeobox DNA-binding domain. These genes are master control regulators of developmental programs including embryonic and adult hematopoiesis. Multiple HOX genes, including HOXB4, are highly expressed in the hematopoietic stem cells (HSC) compartment. HOXB4 gene can act in opposite ways when expressed by different cells, promoting the proliferation of stem cells whilst activating the apoptotic pathway in some embryonic structures. The protein HOXB4, as a homeodomain transcription factor, has been shown to be an important regulator of stem cell renewal and hematopoiesis. Incellular or ectopic expression of HOXB4 expands hematopoietic stem and progenitor cells in vivo and in vitro, making it a potential candidate for therapeutic stem cell expansion.
Hippocalcin-Like Protein 1 (HPCAL1) is a neuron-specific calcium-binding member of the recoverin family which found in the retina and brain. HPCAL1 contains four EF-hand domains and it is highly similar to human hippocalcin protein. HPCAL1 is involved in the calcium-dependent regulation of rhodopsin phosphorylation. In addition, it may be of relevance for neuronal signalling in the central nervous system.
4-Hydroxyphenylpyruvate Dioxygenase (4HPPD) belongs to the 4HPPD family. 4HPPD is a key enzyme in the degradation of tyrosine, which catalyzes the second reaction in the catabolism of tyrosine the conversation of 4-hydroxyphenylpyruvate to homogentisate. 4HPPD exists in homodimer forms, which uses zinc as a cofactor to catalyze the third step in the conversion of L-phenylalanine to fumarate and acetoacetic acid. When the active 4HPPD enzyme concentration is low in the human body, it results in high levels of tyrosine concentration in the blood, which can cause mild mental retardation at birth, and degradation in vision as a patient grows older.
Hematopoietic Prostaglandin D Synthase (HPGDS) belongs to the GST superfamily and Sigma family. HPGDS contains one GST C-terminal domain and one GST N-terminal domain. HPGDS is highly expressed in adipose tissue, macrophages, and placenta, and it exists in the form of homodimer in living body. HPGDS is a cytosolic enzyme that isomerizes PGH(2). HPGDS is a bifunctional enzyme that catalyzes both the conversion of PGH2 to PGD2 and also shows low glutathione-peroxidase activity towards cumenehydroperoxide.
Histidine-rich glycoprotein, also known as HRG and HPRG, is a glycoprotein located in plasma and platelets, and contains an unusually large amount of histidine and proline. In human, five distinct domains are recognized in the mature HPRG molecule. There are two N-terminal cystatin-like modules (aa 19 - 254) and one His-Pro-rich region (aa 350 - 497) that is flanked by two Pro-rich segments (aa 276 - 321 and 498 - 525). The His-Pro-rich region contains 10 tandem repeats with an HHPHG motif, and the N- and C-termini are linked by a disulfide bond. The specific functions of HRG remain unclear, but it is known that the protein binds heme, dyes and divalent metal ions. It inhibits rosette formation and interacts with heparin, thrombospondin and plasminogen. Two of the protein's effects, the inhibition of fibrinolysis and the reduction of inhibition of coagulation, indicate a potential prothrombotic effect. HPRG is evolutionarily, functionally and structurally related to cleaved high molecular weight kininogen (HKa), an anti-angiogenic polypeptide that stimulates apoptosis of proliferating endothelial cells through binding to cell-surface tropomyosin. The antiangiogenic activity of the multidomain plasma protein HPRG is localized to its histidine-proline-rich (H/P) domain and has recently been shown to be mediated, at least partially, through binding to cell-surface tropomyosin in fibroblast growth factor-2-activated endothelial cells.
HRas, also known as HRAS, belongs to the small GTPase superfamily, Ras family and is widely expressed. It functions in signal transduction pathways. HRas can bind GTP and GDP, and they have intrinsic GTPase activity. It undergoes a continuous cycle of de-and re-palmitoylation, which regulates its rapid exchange between the plasma membrane and the Golgi apparatus. Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS). FCSS is arare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities, tumor predisposition, skin and musculoskeletal abnormalities. Defects in HRAS also can cause congenital myopathy with excess of muscle spindles. HRAS deficiency may be a cause of susceptibility to Hurthle cell thyroid carcinoma. It has been shown that defects in HRAS can cause susceptibility to bladder cancer which is a malignancy
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