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SNTA1 is a member of the syntrophin gene family. SNTA1 is a peripheral membrane protein found linked with dystrophin and dystrophin-related proteins. Dystrophin is a large, rod-like cytoskeletal protein located at the inner surface of muscle fibers. Dystrophin is absent in Duchenne Muscular Dystrophy patients, however it is present in reduced amounts in Becker Muscular Dystrophy patients. Syntrophins are cytoplasmic peripheral membrane scaffold proteins and components of the dystrophin-associated protein complex. The N-terminal PDZ domain of SNTA1 interacts with the C-terminus of the pore-forming alpha subunit (SCN5A) of the cardiac sodium channel Nav1.5. In addition, SNTA1 associates cardiac sodium channels with the nitric oxide synthase-PMCA4b (plasma membrane Ca-ATPase subtype 4b) complex in cardiomyocytes. The SNTA1 gene is a predisposition locus for Long-QT syndrome (LQT) - an inherited disorder associated with sudden cardiac death from arrhythmia - and sudden infant death syndrome (SIDS). SNTA1 also associates with dystrophin and dystrophin-related proteins at the neuromuscular junction and modifies intracellular calcium ion levels in muscle tissue.

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.

STE20-Related Kinase Adaptor Alpha (STRADA) is a part of the STE- 20 like kinase family which stimulates MAPK pathways by activating MAPKKK. STRADA is an upstream activator of LKB1 and also leads the sub-cellular localization of LKB1 by fixing it in the cytoplasm. The interaction between STRADA-LKB1 leads to phosphorylation of STRADA and enhanced autophosphorylation of LKB1.

VAMP8 also called endobrevin, is the main component of a SNARE complex involved in the docking and fusion of synaptic vesicles with the presynaptic membrane. VAMP8 protein is involved in the regulatation of enzyme secretion in pancreatic acinar cells and plays a part in the abscission of the midbody during cell division, which leads to completely separate daughter cells. VAMP8 is essential for dense-granule secretion in platelets. VAMP8 is related with the perinuclear vesicular structures of the early endocytic compartment. VAMP8 interacts particularly with the soluble NSF-attachment protein (alpha-SNAP), through an VAMP8-containing SNARE complex.

PQBP1 is a transcription repressor which is connected to polyglutamine tract-containing transcription regulators and connective genes for neurodegenerative disorders. PQBP1 is restricts to the nucleus and can be found in neurons all over the brain, with high levels in hippocampus, olfactory bulb and cerebellar cortex. PQBP1 holds a WWP/WW domain that binds proline-rich motifs and a C2 domain which is able to stimulate Ca2+-dependent phospholipid signaling.

Cysteine-rich PDZ-binding protein, also known as CRIPT, takes part in the cytoskeletal anchoring of DLG4 in excitatory synapses.

Transmembrane protein PRRT2 holds a proline-rich domain in its N-terminal half. PRRT2 is known to be primarily expressed in brain and spinal cord in embryonic and postnatal stages. Alterations in this gene are the cause for paroxysmal kinesigenic dyskinesia. PRRT2 mutations were found in nearly 30% of sporadic PKC patients.

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.

Serine peptidase inhibitor Kazal type 7 (SPINK7) which includes one Kazal-like domain is most likely serine protease inhibitor. Diseases linked with SPINK7 include esophageal cancer, and oral squamous cell carcinoma

VAMP3 is present in recycling endosomes and endosome-derived vesicles. VAMP3 has been implicated in recycling of transferrin receptors to the plasma membrane, secretion of alpha-granules in platelets, recycling of T-cell receptors to the immunological synapses, and membrane trafficking during cell migration. VAMP-3 is present in human platelets and necessary for granule secretion. Synaptobrevins are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP3 high homology to other VAMPs in its broad tissue distribution and subcellular localization is shown to be the human equivalent of the rodent cellubrevin. In platelets the protein resides on a compartment that is not mobilized to the plasma membrane on calcium or thrombin stimulation.

GNLY is part of the SAPLIP family and is located in the cytotoxic granules of T cells, which are discharged upon antigen stimulation. GNLY is localized in cytotoxic granules of cytotoxic T lymphocytes and natural killer cells, and it has antimicrobial activity against M. tuberculosis and other organisms. GNLY is an antimicrobial protein that kills intracellular pathogens. GNLY is active against a wide range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis.

Protein Kinase CAMP-Dependent Catalytic Beta (PRKACB) belongs to the Ser/Thr protein kinase family and is a catalytic subunit of cAMP-dependent protein kinase. cAMP is a signaling molecule imperative for various cellular functions. cAMP activates the cAMP-dependent protein kinase, which transduces the signal by way of phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of 2 regulatory and 2 catalytic subunits. cAMP triggers the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to 4 cAMP and 2 free monomeric catalytic subunits. PRKACB mediates cAMP-dependent signaling initiated by receptor binding to GPCRs. PKA activation regulates various cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, in addition to regulation of intracellular transport mechanisms and ion flux. PRKACB regulates the abundance of compartmentalized pools of its regulatory subunits via phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their consequent proteolysis.

GDNF promotes the survival and differentiation of minergic neurons in culture, and is able to prevent apoptosis of motor neurons induced by axotomy. The encoded protein is processed to a mature secreted form that exists as a homodimer. The mature form of the protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. In addition to the transcript encoding GDNF, two additional alternative transcripts encoding distinct proteins, referred to as astrocyte-derived trophic factors, have also been described. Mutations in this gene may be associated with Hirschsprung disease.
GDNF enhances survival and morphological differentiation of minergic neurons and increases their high-affinity uptake.

VAMP5 is part of the vesicle-associated membrane protein (VAMP)/synaptobrevin family and the SNARE superfamily. VAMP5 is involved is vesicle trafficking events that are associated with myogenesis.

ACTN1 encodes a nonmuscle, cytoskeletal, alpha actinin isoform and maps to the same site as the structurally similar erythroid beta spectrin gene. Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments.

Podoplanin is a small mucin-like type-1 transmembrane protein, typically expressed in various specialized cell types throughout the body. Podoplanin is a type-I integral membrane glycoprotein with diverse distribution in human tissues. PDPN physiological function is related to its mucin-type character. The homologous protein in other species has been described as a differentiation antigen and influenza-virus receptor.
PDPN is expressed in lymphatic progenitor cells and afterwards during mouse development in lymphatic endothelial cells. Podoplanin is a specific marker for lymph vessel endothelial cells. Over-expression of podoplanin significantly elevates endothelial cell adhesion, migration, and tube formation. Inhibition of Podoplanin expression decreases cell adhesion in human dermal lymphatic endothelial cells. Podoplanin is used as a specific marker for lymphatic endothelium in histopathology.
Podoplanin expression is increased in nearly all human colon, rectum, and small intestine tumors. AGGRUS may serve as a diagnostic marker that distinguishes seminomas, the majority of which over express the protein, from embryonal carcinoma in testicular germ cell tumors.

Synaptotagmin-4 (SYT4) is a part of the synaptotagmin proteins family. Synaptotagmins are a large gene family of synaptic vesicle type III integral membrane proteins that operate as regulators of both exocytosis and endocytosis and are involved in neurotransmitter secretion from small secretory vesicles. SYT4 is expressed in neuronal tissues, and has the highest mRNA levels in the hippocampus. The proximity of the SYT4 gene to markers of several psychiatric disorders implies an involvement of SYT4 in human disease such as pheochromocytoma, and parkinson's disease.

CBFB beta subunit is a heterodimeric core-binding transcription factor that is part of the PEBP2/CBF transcription factor family which controls a host of genes particulary to hematopoiesis and osteogenesis. CBFB is a non-DNA binding regulatory subunit which increases DNA binding by alpha subunit.

Growth/differentiation factors (GDF1-GDF15) belong to the BMP family of TGF-beta superfamily proteins. These factors are produced as inactive preproproteins which are subsequently cleaved and assembled into active secreted homodimers. BMP13 is a growth factor which controls proliferation and cellular differentiation in the retina and bone formation. BMP13 has a central role in regulating apoptosis during retinal development. GDF proteins are vital during embryonic development, particularly in the skeletal, nervous, and muscular systems. BMP13 gene mutations result in colobomata, which are congenital abnormalities in ocular development, and in Klippel-Feil syndrome (KFS), which is a congenital disorder of spinal segmentation.

PEST proteolytic signal containing nuclear protein (PCNP) is a nuclear protein involved in cell cycle regulation and tumorigenesis. The PCNP protein is ubiquitinated post-translationally by NIRF (an ubiquitin ligase). The PCNP exists as 3 isoforms produced by alternative splicing events.

Gankyrin (proteasome 26S subunit) is a multicatalytic proteinase oncoprotein commonly overexpressed in most hepatocellular carcinomas. Proteasomes are found throughout eukaryotic cells at a high concentrations and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. Gankyrin interacts with S6 ATPase of the 19S regulatory particle of the 26S proteasome. Gankyrin is involved in theregulation of the phosphorylation of the retinoblastoma protein by CDK4, and to enhance the ubiquitinylation of p53 by MDM2. Gankyrin consists of 7 ankyrin repeats and is structurally similar to I kappa Bs. Gankyrin acts as a regulatory subunit of the 26s proteasome which is involved in the atp-dependent degradation of ubiquitinated proteins. Gankyrin is involved in progression of esophageal squamous cell carcinoma. gankyrin plays an oncogenic role especially in early stages of human epatocarcinogenesis. Gankyrin binds to NF-kappaB and suppresses its activity at the transcription level by modulating acetylation through SIRT1. Structural comparison between Gankyrin & p16(INK4A) identified numerous residues of gankyrin that are potentially important for CDK4 binding.

PDXK converts vitamin B6 to Pyridoxal-5-phosphate (PLP), which is a vital cofactor in the intermediate metabolism of amino acids and neurotransmitters. PDXK is cytoplasmic and probably acts as a homodimer. The biological validity of the alternatively spliced transcript variants has not been determined.

CDNF is a member of the ARMET family and acts as a trophic factor for dopamine neurons. CDNF inhibits the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When CDNF controlled after 6-OHDA-lesioning, it reestablishes the dopaminergic function and inhibits the degeneration of dopaminergic neurons in substantia nigra. CDNF is universally expressed in neuronal and non-neuronal tissues. The highest levels in the brain are found in the optic nerve and corpus callosum.