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FHIT enzyme cleaves adenosine 5'' PPP 5'' A to yield AMP and ADP. FHIT gene includees the regular fragile site FRA3B on chromosome 3. Alterations and deletions of the FHIT gene are highly linked to the genesis and establishment of human tumors of the lung, cervix, breast, colon, stomach and pancreas. In normal cells, FHIT functions as a tumor suppressor and physically relates with ubiquitin conjugating enzyme 9.

FHIT is a member of the histidine triad gene family. FHIT gene encodes a diadenosine 5',5'''-P1,P3-triphosphate hydrolase involved in purine metabolism. FHIT gene includes the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and abnormal transcripts of this gene. The FHIT protein is a tumor suppressor with reduced or no expression in numerous types of cancer. FHIT may also act as a tumor suppressor in normal cells. Alterations and deletions of the FHIT (Fragile Histidine Triad) gene are strongly linked to the genesis and establishment of human tumors of the lung, cervix, breast, colon, stomach, and pancreas. The expression of FHIT is more often lost in cancers of individuals with familial mutations causing deficiency in DNA repair genes such as BRCA1, BRCA2 and MSH2. In vitro FHIT functions as a hydrolase that cleaves diadenosine triphosphate (Ap3A) to ADP and AMP. The FHIT -Ap3A enzyme-substrate complex seems to be the tumor suppressor signal. The restoration of FHIT expression in FHIT -deficient cancer cells leads to apoptosis, involving the intrinsic caspase pathway, in cancer-derived cells and in tumor xenografts.

HINT1, also known as Histidine triad nucleotide-binding protein 1 is part of the superfamily named for a near C-terminal HXHXHXX motif (H:Histidine, X:a hydrophobic amino acid) positioned at the ?-phosphate of nucleotide substrates. HINT1 hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2. Though it was initially considered to be a protein kinase C inhibitor and act as a haplod-insufficient tumor suppressor including spontaneous tumor formation in Hint+/- and Hint-/- , its actual physiologic function is not known.

Histidine triad nucleotide-binding protein 2 (HINT2) belongs to the triad proteins, which are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides. Hydrolase is most likely involved in steroid biosynthesis, furthermore it might play a role in apoptosis. HINT2 shows high expression in liver and pancreas. Expression is significantly down-regulated in hepatocellular carcinoma (HCC) patients.

Recombinant Fatty Acid Binding Protein is a newly introduced plasma marker of acute myocardial infarction (AMI). The plasma kinetics of FABP (15kD) closely resemble those of myoglobin in that elevated plasma concentrations are found within 2 hours after AMI and return to normal generally within 18 to 24 hours. But the concentration of FABP in the skeletal muscle is 20 times lower than in cardiac tissue (for myoglobin the same content for cardiac and skeletal tissue), that makes FABP to be more cardiac specific than myoglobin. This makes FABP a useful biochemical marker for the early assessment or exclusion of AMI. FABP also appears to be a useful plasma marker for the estimation of myocardial infarct size.

Fibroblast Growth Factors (FGFs) comprise a family of at least eighteen structurally realted proteins that are involved in a multitude of physiological and pathological cellular processes, including cell growth, differentation, angiogenesis, wound healing and tumorgenesis. The biological activities of the FGFs are mediated by a family if type I transmembrane tyrosine kinases which undergo dimerization and autophosphorylation after ligand binding. Four distinct genes encoding closely related FGF receptors, FGFR-1to -4 are known. Multiple forms of FGFR-1 to -3 are generated by alternative splicing of the mRNAs. A frequent splicing event involving FGFR-1 and -2 results in receptors containing all three Ig domains, referred to as the alpha isoform, or only IgII and IgIII, referred to as the ? isoform. Only the alpha isoform has been identified for FGFR-3 and FGFR-4. Additional splicing events for FGFR-1 to -3, involving the C-terminal half of the IgIII domain encoded by two mutually exclusive alternative exons, generate FGF receptors with alternative IgIII domains (IIIb and IIIc). A IIIa isoform which is a secreted FGF binding protein containing only the N-terminal half of the IgIII domain plus some intron sequences has also been reported for FGFR-1. Mutations in FGFR-1 to -3 have been found in patients with birth defects involving craniosynostosis.

APTX is a DNA-binding protein which participates in single-strand DNA break repair, double-strand DNA break repair and base excision repair. APTX determines abortive DNA ligation intermediates created each at base excision sites, or while DNA ligases attempt to restore non-ligatable breaks induced by reactive oxygen species. APTX catalyzes the release of adenylate groups covalently linked to 5''-phosphate termini, resulting in the production of 5''-phosphate termini that can be efficiently rejoined. APTX hydrolyzes adenosine 5''-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis.

The 14-3-3 family of proteins plays a key regulatory role in signal transduction, checkpoint control, apoptotic and nutrient-sensing pathways. 14-3-3 proteins are highly conserved and ubiquitously expressed. There are at least seven isoforms, β, γ, ε, σ, ζ, τ and η that have been identified in mammals. The 14-3-3 epsilon, a subtype of the 14-3-3 family of proteins, was thought to be brain and neuron-specific. It has been shown to interact with CDC25 phosphatases, RAF1 and IRS1 proteins, suggesting its role in diverse biochemical activities related to signal transduction, such as cell division and regulation of insulin sensitivity. It has also been implicated in the pathogenesis of small cell lung cancer.

Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis.

RANKL binds to tnfrsf11b/opg and to tnfrsf11a/rank. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive t-cell proliferation. May be an important regulator of interactions between t-cells and dendritic cells and may play a role in the regulation of the t-cell-dependent immune response. sRANKL may also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

Probable tRNA (His) guanylyltransferase (THG1L) is a member of the tRNA (His) gyanylytransferase family. THG1L which is localized to the cytoplasm also found adjacent to the nuclear membrane and expressed in various tissues, including liver and lung. THG1L is expressed in a cell cycle-dependent manner and may be involved in cell cycle progression and cell proliferation. THG1L adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage. This step is vital for accurate recognition of the tRNA and for the fidelity of protein synthesis. Upon DNA damage, THG1L is phosphorylated, presumably by ATM or ATR.

Fractalkine soluble form is chemotactic for t-cells and monocytes, but not for neutrophils. Fractalkine membrane-bound form promotes adhesion of those leukocytes to endothelial cells. Fractalkine regulates leukocyte adhesion and migration processes at the endothelium and binds to CX3CR1. Natural Human Fractalkine is produced as a long protein (373-amino acid) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the cell surface. Fractalkine gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.

Histidyl-tRNA synthetase (HARS) functions to catalyze the aminoacylation of tRNAs by their corresponding amino acids. HARS is a member of the class II family of aminoacyl-tRNA synthetases. HARS is responsible for the synthesis of histidyl-transfer RNA, which is vital for the incorporation of histidine into proteins. HARS is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis.

Zinc Finger HIT-Type Containing 3 (ZNHIT3) which contains one HIT-type zinc finger, requires the presence of thyroid hormone for its interaction. Thyroid receptor interacting proteins particularly interact with the ligand binding domain of the thyroid receptor (TR).

Fractalkine soluble form is chemotactic for t-cells and monocytes, but not for neutrophils. Fractalkine membrane-bound form promotes adhesion of those leukocytes to endothelial cells. Fractalkine regulates leukocyte adhesion and migration processes at the endothelium and binds to CX3CR1. Natural Human Fractalkine is produced as a long protein (373-amino acid) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the cell surface. Fractalkine gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.

HMGB3 is a member of the high mobility group (HMG) protein superfamily. HMGB3 holds DNA-binding HMG box domains, as do HMG1 and HMG2, and like the rest of the HMG protein superfamily members has a vital part in DNA replication, transcription and nucleosome assembly.

Chromgranin-A is part of the neuroendocrine secretory protein family. CHGA is located in secretory vesicles of neurons and endocrine cells. Chromgranin-A is a precursor to three biologically active peptides; vasostatin, pancreastatin, and parastatin. These peptides act as autocrine or paracrine negative modulators of the neuroendocrine system. Other peptides, including chromostatin, beta-granin, WE-14 and GE-25, are also derived from the full-length protein. Chromgranin-A has numerous biological activities on some tissues and organs and exerts a large spectrum of homeostatic actions, including antifungal and antimicrobial effect, modulation of cell adhesion, and inhibition of parathyroid hormone secretion.

STIP1 is an adaptor protein that mediates the functions of HSP70 & HSP90 in protein folding. STIP1 supports the transfer of proteins from HSP70 to HSP90 by binding together HSP90 and substrate-bound HSP70. STIP1 stimulates the ATPase activity of HSP70 and inhibits the ATPase activity of HSP90, suggesting that it regulates both the conformations and ATPase cycles of these chaperones. STIP1 genetic variations are involved in regulating corticosteroid response in asthmatic subjects with reduced lung function.

HSPB8 is part of the superfamily of small heat-shock proteins containing a conservative alpha-crystallin domain at the C-terminal part of the molecule. HSPB8 is induced by estrogen in estrogen receptor-positive breast cancer cells. HSPB8 protein functions as a chaperone in association with BAG3, a stimulator of macroautophagy. HSPB8 participates in the regulation of cell proliferation, apoptosis, and carcinogenesis. Mutations in HSPB8 gene have been related with different neuromuscular diseases, including Charcot-Marie-Tooth disease.

AKR1C3 is part of the aldo/keto reductase superfamily, which has at least 40 identified proteins. AKR1C3 catalyzes the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. AKR1C3 displays overlapping but distinct substrate specificity. AKR1C3 catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. AKR1C3 is involved in the pathogenesis of allergic diseases such as asthma. AKR1C3 controls cell growth and/or differentiation. AKR1C3 takes part in adrenal testosterone production. AKR1C3 expression is affected by metabolic disease, and its levels are considerably reduced in response to diet-induced weight loss and correlate with leptin levels.

OTOR proteins is also known as fibrocyte-derived protein (Fdp) and Melanoma inhibitory activity-like (MIAL). Otoraplin is a member of the melanoma-inhibiting activity gene family. Otoraplin is a secreted 16 kDa globular protein that is expressed in the inner ear by periotic mesenchyme and developing and mature fibrocytes. OTOR is highly homologous to MIA/cartilage-derived retinoic acid-sensitive protein (CD-RAP), which is a cartilage-specific protein that is also expressed in malignant melanoma cells. The 111 amino acid mature human otoraplin contains 1 SH3 domain (46 – 107 amino acids) and a Tyr at position 50 that is reportedly sulfated. Otoraplin takes pasrt in the initiation of periotic mesenchyme chondrogenesis.
Otoraplin is secreted through the Golgi apparatus and plays a role in cartilage development and maintenance. A frequent polymorphism in the translation start codon of OTOR can abolish translation and may be associated with forms of deafness.

Fractalkine soluble form is chemotactic for t-cells and monocytes, but not for neutrophils. Fractalkine membrane-bound form promotes adhesion of those leukocytes to endothelial cells. Fractalkine regulates leukocyte adhesion and migration processes at the endothelium and binds to CX3CR1. Fractalkine gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.