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SERPINA1 is secreted and is a serine protease inhibitor which its targets include elastase, plasmin, collagenase, leucocytic proteases, trypsin, chymotrypsin, and plasminogen activator. Defects in SERPINA1 gene can cause emphysema or liver disease. SERPINA1 is an endogenous inhibitor of serine proteases and inhibits the catalytic domain of human recombinant matriptase in vitro. Rise in SERPINA1 occurs as an acute phase response to tissue necrosis and inflammation. mutations in SERPINA1 and SLC11A1 genes change the balance between elastase produced by leukocytes during phagocytosis.

GADD45B is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45B reacts to environmental stresses by mediating activation of the p38/JNK pathway which is mediated through their protein binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45B is involved in the regulation of growth and apoptosis. GADD45b takes part during chondrocyte terminal differentiation and mediates MMP-13 gene expression. GADD45 in B cells is induced by CD40 via a mechanism that involves NF-kappa B and that induction suppresses Fas-mediated killing. GADD45b is down-regulated in most cases of hepatocellular carcinoma (HCC), and is a molecular marker in the diagnosis of HCC and as a possible therapeutic target.

PPP1R14A is a phosphorylation-dependent inhibitor of smooth muscle myosin phosphatase. Inhibition of PPP1R14A results to increased myosin phosphorylation and enhances smooth muscle contraction in the absence of increased intracellular Ca(2+) concentration. Myosin phosphatase can reverse MYL (myosin light chain) phosphorylation to induce a state of relaxation. However, during agonist-induced contraction at constant Ca2+ concurrent inhibition of myosin phosphatase leads to increases in MYL phosphorylation and tension. These calcium-independent increases in myosin phosphorylation and tension are termed calcium sensitization. Human pregnancy is characterized by the increases of PKN1 expression and CPI-17 phosphorylation in the myometrium. PPP1R14A is mapped to chromosome 19q13.13-q13.2. PPP1R14A binds directly to protein kinase C and casein kinase I. PPP1R14A siRNA decreased the level of merlin phosphorylation and consequently Ras and ERK activity in human tumor cell lines. PKC/CPI-17 medi

Purine-Rich Element Binding Protein B (PURB) is a single-stranded DNA-binding protein which takes part in the dendritic transport of a subset of mRNAs. PURB operates as repressor in myoblasts and fibroblasts in the control of vascular smooth muscle alpha-actin gene transcription. PURB binds preferentially to the single strand of the purine-rich element termed PUR, which is present at origins of replication and in gene flanking regions in various eukaryotes from yeasts through humans.

SRGN is identified as a hematopoietic cell granule proteoglycan. Proteoglycans stored in the secretory granules of various hematopoietic cells also hold a protease-resistant peptide core, and is vital for neutralizing hydrolytic enzymes. SRGN is related to the macromolecular complex of granzymes and perforin that acts as a intermediary of granule-mediated apoptosis.

Sonic Hedgehog is part of a small group of secreted proteins which are vital for development in both vertebrates and invertebrates. 3 mammalian hedgehog genes (sonic, desert, Indian) share about 60% homology. The Human Sonic Hedgehog is 99% homologous to the mouse gene. Sonic HedgeHog is a protein that is vital in guding the early embryo. It has been associated as the major inductive signal in patterning of the ventral neural tube, the anterior-posterior limb axis, and the ventral somites. Sonic HedgeHog binds to the patched receptor, which functions in association with smoothened, to activate the transcription of target genes. In the absence of sonic HedgeHog, patched receptor represses the constitutive signaling activity of smoothened. Sonic HedgeHog also regulates another factor, the gli oncogene. Sonic HedgeHog intercellular signal is essential for a various patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Sonic HedgeHog exhibits both floor plate- and motor neuron-inducing activity. Mutations in a long-range Sonic HedgeHog enhancer located in an intron of the limb region 1 gene result in preaxial polydactyly.

PRKAG1 is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer comprised of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is a vital energy-sensing enzyme which supervises cellular energy status. PRKAG1 is one of the gamma regulatory subunits of AMPK. Alternatively spliced transcript variants encoding dissimilar isoforms were found.

43 kDa receptor-associated protein of the synapse (RAPSN), is expressed in the postsynaptic membrane of skeletal muscle. RAPSN is essential for the clustering of nicotinic acetylcholine receptors (nAChR). In addition RAPSN self-associates via at least two of its seven tetra-tricopeptide repeats (TPRs). RAPSN interacts with the large intracellular domain of the nAChR a subunit all the way through the hydrophobic surface of the coiled-coil domain. RAPSN modifies trafficking of AChR within the cell. Overexpression inhibits agrin-induced AChR clustering pathway. RAPSN also plays a role in postsynaptic congenital myasthenic syndromes.

PDRG1 is a 133 amino acid protein that localizes to the cytoplasm and belongs to the prefoldin subunit beta family. PDRG1 is expressed primarily in normal testicular tissue, it is functionally induced by ultraviolet light and is thought to have a role in chaperone-mediated protein folding, possibly having a role in cellular degradation. PDRG1 is linked to Creutzfeldt-Jakob disease, amyotrophic lateral sclerosis, spinal muscular atrophy, ring chromosome 20 epilepsy syndrome and Alagille syndrome.

SAR1A is a member of the small GTPase superfamily. SAR1A is a vital component of COPII vesicle coats involved in export of cargo from the ER (Endoplasmic Reticulum). The GTPase activity of SAR1A serves as a molecular switch to control protein-protein and protein-lipid interactions which dictate vesicle budding from the ER. SAR1A, while GDP-bound interacts with the membrane-bound exchange factor Sec12 and trades its bound GDP for GTP. SAR1A is also involved in the transport from the ER to the Golgi apparatus. SAR1A is required to maintain SEC16A localization at distinct locations on the ER membrane possibly by preventing its dissociation. SAR1A-GTP-dependent compilation of SEC16A on the ER membrane creates a structured scaffold defining endoplasmic reticulum exit sites.

ADP-ribosylation factor-like 14 (ARL14) is a developmentally regulated member of the ADP-ribosylation factor/ARF-like protein (ARF/ARL) family of Ras-related GTPases. ARL14 is GTPase which recruits MYO1E to MHC class II-containing vesicles via the effector protein C11orf46/ARF7EP and thus controls the movement of these vesicles along the actin cytoskeleton in dendritic cells. MHC-II transport was controlled by the GTPase ARL14/ARF7, which recruits the motor myosin 1E via an effector protein ARF7EP.

IHH belongs to the hedgehog family of secreted signaling molecules. Hedgehog proteins are vital regulators of various developmental processes including growth, patterning and morphogenesis. The vertebrate homologues of Hh comprise several proteins including sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). IHH has a specific role in bone growth and differentiation. In addition, IHH is involved in yolk sac vasculogenesis, having a central role in differentiation of epiblast cells into endothelial and red blood cells. IHH mRNA expression is detected in fetal lung, gut, stomach, liver, kidney, pancreas and strongly in cartilage in growth regions of the developing bone. IHH gene mutations cause the brachydactyly type A1 which is characterized by shortening or malformation of the phalanges and also the acrocapitofemoral dysplasia.

Zinc Finger Protein 689 (ZNF689) is a member of the krueppel C2H2-type zinc-finger protein family. The ZNF689 protein contains 12 C2H2-type zinc fingers and 1 KRAB domain. ZNF689 may be involved in transcriptional regulation.

MECP2 is the key modificator of eukaryotic genomes and has a crucial part in mammalian development.
Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 form a family of nuclear proteins linked by the existence in each of a methyl-CpG binding domain (MBD). Each one of these proteins, with the exception of MBD3, can bind specifically to methylated DNA. In addition, MECP2, MBD1 and MBD2 can inhibit transcription from methylated gene promoters. Unlike other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is expendable in stem cells, but is vital for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common reasons of mental retardation in females.

The protein encoded by this gene is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. This particular family member plays an important role in the onset of endochondral bone formation in humans, and a reduction in expression has been associated with a variety of bone diseases, including the heritable disorder Fibrodysplasia Ossificans Progressiva. Alternative splicing in the 5' untranslated region of this gene has been described and three variants are described, all encoding an identical protein.

Transferrin receptor protein 1 (TFRC) is required for iron delivery from transferring to cells. The TFRC protein is a transmembrane glycoprotein comprised of 2 disulfide-linked monomers joined by 2 disulfide bonds. Each monomer will bind one holo-transferrin molecule producing an iron-Tf-TfR complex which enters the cell by endocytosis.

Streptavidin is a tetrameric protein secreted by Streptomyces avidinii which binds firmly to biotin. Streptavidin is widely used in molecular biology through its unique high affinity for the vitamin biotin. The dissociation constant (Kd) of the biotin-streptavidin complex is about ~10-15 mol/L. The strong affinity recognition of biotin and biotinylated molecules has made streptavidin one of the most important components in diagnostics and laboratory kits. The streptavidin/biotin system has one of the biggest free energies of association of yet observed for noncovalent binding of a protein and small ligand in aqueous solution (K_assoc = 10**14). The complexes are also extremely stable over a wide range of temperature and pH.

UMP-CMP kinase and deoxycytidylate kinase (CMPK1) is an enzyme which catalyzes the phosphoryl transfer from ATP to UMP, CMP and dCMP. This enzymatic reaction brings about the formation of ADP and the corresponding nucleoside diphosphate that are necessary for cellular nucleic acid synthesis. In addition, CMPK1 has a significant role in the activation of pyrimidine analogs, which are clinically useful anti-cancer and anti-viral drugs.

TRIM21 is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The 52 kDa Ro protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. Ro/SSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Ribonucleoprotein particle is composed of a single polypeptide and one of four small RNA molecules. The RoSSA is present in all mammalian cells studied but has no known function. At least 2 isoforms are present in nucleated and red blood cells, and tissue specific differences in Ro/SSA proteins were identified.

The adipose tissue exclusively expresses and secretes Adiponectin (Acrp30). Acrp30 is involved in various physiological processes such as energy homeostasis, insulin sensitivity, hormonal processes, fatty acid metabolism and obesity.
Adiponectin circulates in the plasma. Decreased levels of Adiponectin are associated with insulin resistance and hyperinsulinemia, as seen in people with obesity insulin resistance, and diabetes type 2, whose plasma levels of adiponectin are reduced.
The modular structure of Acrp30 is comprised of N-terminal collagenous domain followed by a C-terminal globular domain.
Acrp30 also acts as a significant negative regulator in hematopoiesis and immune systems; it may be involved in ending inflammatory responses through its inhibitory functions. Adiponectin inhibits endothelial NF-kappa-b signaling through a cAMP-dependent pathway, it also inhibits TNF-alpha- induced expression of endothelial adhesion molecules.

NCS1 is part of the neuronal calcium sensor gene family, which encode calcium-binding proteins expressed primarily in neurons. NCS1 regulates G protein-coupled receptor phosphorylation in a calcium-dependent manner and can substitute for calmodulin. NCS1 is related with secretory granules and modulates synaptic transmission and synaptic plasticity. NCS1 regulates GRK1 and substitutes for calmodulin. NCS1 stimulates PI4KB kinase activity and participates in long-term synaptic plasticity through its interaction with PICK1. NCS1 takes part in neuron differentiation through inhibition of the activity of N-type voltage-gated calcium channel.

DENR takes part in the translation of target mRNAs by scanning and recognizing the initiation codon. DENR protein is involved in the intonation of the translational profile of a subset of cancer-related mRNAs when engaged to the translational initiation complex by the oncogene MCTS1.

A natural cytotoxicity receptor (NCR) NKp46 has been shown to represent a novel NK cell-specific molecule involved in human NK cell activation. The natural cytotoxicity receptors (NCRs) are a recently characterized family of Ig-like activation receptors that appear to be major triggering receptors in tumor cell recognition. The three known NCRs include NKp46 and NKp30, which are expressed on circulating NKcells, and NKp44, which is expressed only on activating NK cells. NKp46 has been implicated in NK cell-mediated lysis of several autologous tumor cells, pathogen-infected cell lines and mononuclear phagocytes infected with an intracellular bacterium. The Lysis of tumor cells by NK-cells involves recognition by NKp46 of heparan sulfate moieties of membrane heparan sulfate proteoglycans. Furthermore, NKp46 is a surface receptor involved in NK-cell cell death by apoptosis. NKp46 has two extracellular Ig-like domains followed by a ~40 residue stalk region, a type I transmembrane domain, and a short cytoplasmic tail. The extracellular Ig-like domain of NKp46 (22-255aa) is purified by FPLC gel-filtration chromatography, after refolding of the isolated inclusion bodies in a redox buffer. In addition, engagement of the antigen with the monoclonal antibody stimulates intracellular calcium levels and the synthesis of cytokines. CD59 is an NKp46 coreceptor (by physical association) together they activate cytotoxicity of human NK-cells, their engagement results in tyrosine phosphorylation of CD3-zeta chains associated with NKp46. Reduced cell surface expression of NKp46 and other NK-cell receptors is linked to the impaired NK-cell cytolytic function in viremic HIV-1 infection.