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Ataxin 3 is otherwise known as Machado-Joseph disease protein 1. Machado–Joseph disease is a hereditary autosomal dominant neurodegenerative disorder. ATXN3 contains trinucleotide CAG repeats in the coding region, and the expansion of these repeats from the normal 13-36 to 68-79 causes the Machado-Joseph disease. ATXN3 is a poly-ubiquitin-binding protein whose cellular turnover is regulated by its catalytic activity.
In addition, ATXN3 is a proteasome-associated factor which mediates the degradation of ubiquitinated proteins. ATXN3 folds reversibly using a single intermediate; partial destabilization of ATXN3 by chemical denaturation causes the formation of fibrillar aggregates by the non-pathological variant.
Ataxin-3 interacts with the major histone acetyltransferases cAMP-response-element binding protein (CREB)-binding protein, p300, and p300/CREB-binding protein-associated factor and hinders transcription by these coactivators.

Dickkopf-related protein 3 (DKK3) belongs to the DKK protein family including Dkk-1, 2, 3 and -4. DKK3 is a 350 amino acid secreted glycoprotein which is comprised of an N-terminal signal peptide and 2 conserved cysteine-rich domains that are separated by a 12 amino acid linker region. DKK3 is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK3 gene expression is decreased in a variety of cancer cell lines and it may act as a tumor suppressor gene.

Basic transcription factor 3 (BTF3), which is a member of the NAC-beta family, forms a stable complex with RNA polymerase II. The BTF3 protein is vital for the initiation of transcription.

Metallothionein 3 (MT3) contains 3 zinc and 3 copper atoms per polypeptide chain and a minor amount of cadmium. MT3 inhibits survival and neurite formation of cortical neurons in vitro. MT3 also binds heavy metals.

Tetratricopeptide repeat protein 33 (TTC33) is comprised of 3 TPR repeats.

Connective Tissue Growth Factor is a part of the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF, Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). CCN proteins are matricellular proteins which are involved in the regulation of various cellular functions including: proliferation, differentiation, survival, adhesion and migration. They are expressed in derivatives of the three embryonic sheets and are implicated in the development of kidney, nervous system, muscle, bone marrow, cartilage and bone. During adulthood, they are implicated in wound healing, bone fracture repair, and pathologies such as: tumorigenesis,fibrosis and vascular ailments. Full length secreted CCN proteins can show an antiproliferative activity, whereas truncated isoforms are likely to stimulate proliferation and behave as oncogenes.
The full length protein consists of 4 modules: Module I shares partial identity with the N-terminal part of the Insulin-like Growth Factor Binding Proteins (IGFBPs).
Module II includes a stretch of 70amino acid residues – which shares sequence identity with the Von Willebrand Factor Type C repeat (VWC).
Module III contains sequences sharing identity with the Thrombospondin type 1 repeat (TSP1) (WSXCSXXCG), which is thought to be implicated in the binding of sulfated glycoconjugates and to be important for cell adhesion.
Module IV, also designated CT, is encoded by exon5. It is the leasts conserved one of the four domains at the level of nucleotide sequence, but it appears to be critical for several of the biological functions attributed to the CCN proteins.
Proteolysis of the secreted full-length CCN proteins that has been reported in the case of CCN2 and CCN3 might result in the production of CCN-derived peptides with high affinity for ligands that full-length CNN proteins bind only poorly. Amino-truncated CCN2 isoforms were biologically active whereas no specific biological activity has been attributed to the truncated CCN3. Although the molecular processes underlying the production of these secreted isoforms is presently unknown, it is important to note that proteolysis occur at the same amino acid residues in both CCN2 and CCN3. An elevated expression of CCN2 has also been detected by Northern blotting in human invasive mammary ductal carcinomas, dermatofibromas, pyogenic granuloma, endothelial cells of angiolipomas and angioleiomyomas, and in pancreatic tumors. A study performed with chondrosarcomas representative of various histological grades established that CCN2 expression was closely correlated with increasing levels of malignancy.
In agreement with CCN2 playing a role in brain tumor angiogenesis, immunocytochemistry studies indicated that both glioblastoma tumor cells and proliferating endothelial cells stained positive for CCN2. In astrocytomas, CCN2 expression was particularly elevated in high grade tumors, with a marked effect of CCN2 on cell proliferation. Downregulation of CCN2 expression in these cells was associated with a growth arrest at the G1/S transition while over-expression of CCN2 induced a two-fold increase of the number of cells in the G1 phase. Gene profiling analysis allowed to identify a set of about 50 genes whose expression might account for the proliferative activity of CCN2 in these cells.
CCN2 was seen in a higher proportion of mononuclear cells of patients with acute lymphoblastic leukemia.

ARP3 Actin-Related Protein 3, also known as ACTR3, belongs to the actin family. The specific function of ACTR3 has not been established yet. On the other hand, ACTR3 is identified as being a major constituent of the ARP2/3 complex. In addition, this complex is located at the cell surface and vital to cell shape & motility through lamellipodial actin assembly and protrusion. 3 transcript variants encoding 2 different isoforms have been discovered for ACTR3.

SEMA3C, also known as Semaphorin 3C, is a member of the semaphorin family 3 that are grouped into 8 major classes based on phylogenetic tree analyses and structure. Class 3 have an important function after traumatic central nervous system injuries. SEMA3C regulates neuronal and non-neuronal cells associated with the traumatic injury due to their presence in the scar tissue. SEMA3C is expressed in all somatic motor neurons, in cardiac neural crest cells during development and in lung buds. The SEMA3C functions are mediated through binding to the Plexin-D1 and Neuropilin 1 or Neuropilin 2 coreceptor complex. SEMA3C activates integrins in certain cells, so besides its repulsive activities, it also acts as a chemoattractant.

Eukaryotic translation initiation factor 3 subunit J (EIF3J) is a member of the EIF-3 subunit J family. EIF3 has a crucial role in binding of initiator methionyl-tRNA and mRNA to the 40S ribosomal subunit to produce the 40S initiation complex. EIF3J binds to the aminoacyl (A) site and mRNA access channel of the 40S subunit, setting EIF3J directly in the ribosomal decoding center. In addition, EIF3J interacts with eIF1A and reduces 40S subunit affinity for mRNA. An elevated affinity for mRNA is restored upon enlistment of initiator tRNA, despite the fact EIF3J remains in the mRNA-binding cleft in the presence of tRNA.

Lysosomal-Associated Membrane Protein 3, also known as LAMP3 is part of the lysosome-associated membrane protein family. LAMP3 and CD68 share an extremely similar predicted structure. LAMP3 performs in dendritic cell function and in adaptive immunity as well. Furthermore, LAMP3 overexpression is actively involved in tumor invasion via increased migration into lymph-vascular spaces.

GNAI3 is a member of the G-alpha family and G (i/o/t/z) subfamily which act as modulators or transducers in several transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K+ channels. The active GTP-bound form inhibits the connotation of RGS14 with centrosomes and is essential for the translocation of RGS14 from the cytoplasm to the plasma membrane. GNAI3 takes part in cell division and is known to cooperate with RIC8A, S1PR1, RGS5, RGS10, RGS12, RGS14, RGS16, RGS18, and RGS19.

MAGE belongs to the MAGE gene family, that comprises 12 known genes, of which 6 are expressed in tumors. The Melanoma-associated antigen 3 genes were originally isolated from different kinds of tumors, and based on their virtually limited tumor-specific expression in adult tissues, they were used as targets for cancer immunotherapy. MAGEA3 is a tumor-specific antigen extensively expressed in solid and hematologic malignancies, but not in normal tissues, with the exclusion of testis and placenta. Consequently, MAGEA3 is an outstanding candidate tumor antigen.

VRK3 is a member of the protein kinase superfamily. The VRK3 gene has replacements at a number of residues within the ATP binding motifs which in other kinases were proved to be required for catalysis in both human and mouse. In vitro assays show that VRK3 has no phosphorylation activity but probably holds its substrate binding capability. VRK3 is universally expressed in human tissues and its protein is restricts to the nucleus.

IGFBP3 is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

PDCL3 belongs to the phosducin-like protein family which its members are known to bind to the beta-gamma subunits of G proteins. PDCL3 is a potential regulator of heterotrimeric G proteins and has a large amino acid sequence homology with phosducin.

FKBP3 is part of a family of immunosuppressant receptors which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. FKBP3 accelerates the folding of proteins. FKBP3 is part of the immunophilin protein family, which participates in immunoregulation and fundamental cellular processes concerning protein folding and trafficking. FKBP3 is a cis-trans prolyl isomerase enzyme that binds the immunosuppressants FK506 and rapamycin, as well as histone deacetylases, the transcription factor YY1, casein kinase II, and nucleolin. It has a greater affinity for rapamycin than for FK506 and therefore is a significant protein for immunosuppression by rapamycin.

KLF3 belongs to the Sp1-like/KLF family. KLFs is a family of evolutionarily conserved zinc finger-having transcription factors with various regulatory purposes in cell growth, embryogenesis, proliferation and differentiation. KLF3 is Kruppel-like zinc finger which contain transcription factors and take part in hematopoiesis.

GNB3 belongs to the WD repeat G protein beta family. GNB3 is an important regulator of alpha subunit, as well as of certain signal transduction receptor and effector. A single-nucleotide polymorphism (C825T) in GNB3 is linked with essential hypertension and obesity. In addition, this polymorphism is also linked with the occurrence of the splice variant GNB3-s, which seems to have increased activity. GNB3-s is an example of alternative splicing caused by a nucleotide change outside of the splice donor and acceptor sites. Further splice variants may exist for GNB3, however they have not been fully described. Among the diseases associated with GNB3 are syncope, and aortic coarctation.

Chemokine (C-X-C motif) ligand 3 (CXCL3) is a small cytokine belonging to the CXC chemokine family that is also known as GRO3 oncogene (GRO3), GRO protein gamma (GROg) and macrophage inflammatory protein-2-beta (MIP2b). CXCL3 controls migration and adhesion of monocytes and mediates it effects on its target cell by interacting with a cell surface chemokine receptor called CXCR2. The gene for CXCL3 is located on chromosome 4 in a cluster of other CXC chemokines.

Chemokine (C-X-C motif) ligand 3 (CXCL3) is a small cytokine belonging to the CXC chemokine family that is also known as GRO3 oncogene (GRO3), GRO protein gamma (GROg) and macrophage inflammatory protein-2-beta (MIP2b). CXCL3 controls migration and adhesion of monocytes and mediates it effects on its target cell by interacting with a cell surface chemokine receptor called CXCR2. The gene for CXCL3 is located on chromosome 4 in a cluster of other CXC chemokines.

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 that have been identified in mammals. The 14-3-3gamma, 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 RAF1 and protein kinase C, proteins involved in various signal transduction pathways.

Cystatins are a superfamily of cysteine proteinase inhibitors found in both plants and animals. They comprise a group of proteinase inhibitors, widely distributed in tissues and body fluids, and form tight complexes with cysteine proteases such as cathepsin B, H, L and S. Cystatin C, a secreted molecule of this family, is of interest from biochemical, medicine and evolutionary points of view. Cystatin C, with molecular weight of 13260 Da, is composed of 120 amino acids, lacks carbohydrate and has two disulfide bridges located near the carboxyl terminus. Cystatin C is increased in patients with malignant diseases, and is related to the insufficiency of renal function and appears to be a better marker than creatinine. On the other hand, low levels of cystatin C involve cause the breakdown of the elastic laminae and, subsequently, the atherosclerosis and abdominal aortic aneurysm.

Ectonucleoside Triphosphate Diphosphohydrolase 3, also known as ENTPD3, which owns a threefold preference for the hydrolysis of ATP over ADP is similar to E-type nucleotidases (NTPases). ENTPD3 is a protein coding gene which contains four apyrase-conserved areas which is characteristic of NTPases.

Kallikrein-3 (KLK3) belongs to the kallikrein-related peptidase family. Kallikreins are a subgroup of serine proteases having various physiological functions. Numerous kallikreins are involved in carcinogenesis and some may be prospective cancer and other disease biomarkers. Kallikrein-3 is 1 of the 15 kallikrein subfamily members located in a cluster on chromosome 19 and is a protease present in seminal plasma. KLK3 hydrolyzes semenogelin-1 consequently leading to the liquefaction of the seminal coagulum. KLK3 is assumed to act normally in the liquefaction of seminal coagulum, probably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of the KLK3 protein, called PSA in the clinical setting, is beneficial in the diagnosis and monitoring of prostatic carcinoma.