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Chloride channels are various group of proteins that control fundamental cellular processes including stabilization of cell membrane potential, transepithelial transport, regulation of intracellular pH, and maintenance of cell volume. CLIC1 is part of the p64 family and is localized to the cell nucleus. CLIC1 displays both nuclear and plasma membrane chloride ion channel activity. CLIC1 inserts into membranes and forms chloride ion channels. CLIC1 channel activity depends on the pH. CLIC1 membrane insertion is redox-regulated and happens under oxydizing conditions.

Chloride intracellular channel 4 (CLIC4) belongs to the p64 family; CLIC4 is expressed in various tissues and exhibits an intracellular vesicular pattern in Panc-1 cells (pancreatic cancer cells). CLIC4 is a 253 amino acid single-pass membrane protein which localizes to both the nucleus and the cytoplasm and contains one GST C-terminal domain. CLIC4 acts as a monomer which is able to form selective ion channels in target proteins, thus facilitating the transport of chloride and other ions. CLIC4 is believed to have a role in apoptosis and is able to translocate to the nucleus under stress conditions.

Methylosome subunit pICln (CLNS1A), is a member of the pICln (TC 1.A.47) family. CLNS1A takes part in multiple regulatory pathways. CLNS1A interaction with Sm proteins, inhibits their compilation on U RNA and interferes with snRNP biogenesis. CLNS1A inhibits the binding of survival motor neuron protein (SMN) to Sm proteins. Methylosome subunit pICln is related with the plasma membrane where it functions as a chloride present regulator.

Chloride intracellular channel protein 2 (CLIC2) regulates cellular traffic of chloride ions, which is a critical component of all living cells. CLIC2 is involved in membrane potential stabilization, signal transduction, cell volume regulation and organic solute transport. CLIC2 is identified in the fetal liver and adult skeletal muscle tissue. CLIC2 is a likely candidate for one of the many diseases linked to Xq28.

Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. SCN3B is a part of the sodium channel beta subunit gene family whose members are responsible for the generation and propagation of action potentials in neurons and muscle. SCN3B influences the inactivation kinetics of the sodium channel.

Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. SCN3B is a part of the sodium channel beta subunit gene family whose members are responsible for the generation and propagation of action potentials in neurons and muscle. SCN3B influences the inactivation kinetics of the sodium channel.

The KCNMB3 belongs to a family of 4 auxiliary beta subunits found in the mammalian genome, which associate with Slo1 alpha subunits and regulate BK channel function. In humans, the KCNMB3 gene is comprised of 4 N-terminal alternative exons which produce 4 functionally distinct beta3 subunits, beta3a-d. Three variants, beta3a-c, display kinetically distinct inactivation behaviors.

KCNIP3 belongs to a family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the recoverin branch of the EF-hand superfamily. KCNIP family members are small calcium binding proteins containing EF-hand-like domains. KCNIP3 also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. Mutations in the presenilin genes are implicated in Alzheimer's disease.

KCTD15 protein is encoded in humans by the KCTD15 gene. KCTD15 is expressed at a high level in the brain and the hypothalamus. The potassium channel KCTD15 was identified as a genetic loci linked to higher than normal BMI in humans along with genes such as GNPDA2, MTCH2, FTO, and TMEM18. SNPs (Single nucleotide polymorphisms) in non-diabetic and diabetic patients showed that FTO was most strongly associated with obesity while MTCH2 and GNPDA2 were still notably associated with higher than normal BMI levels.

EDN3 interacts with endothelin receptor B, on the surface of cells. Throughout embryonic development, EDN3 takes part in neural crest cells that migrate from the developing spinal cord to specific regions in the embryo, where they give rise to many different types of cells. EDN3 and EDN3R are necessary for the formation of nerves in the large intestine (enteric nerves) and melanocytes (produce melanin). Mutations in the EDN3 gene is linked with Waardenburg syndrome, type IV that is characterized by changes in skin, hair, and eye coloring. Mutations in the EDN3 gene is linked with Hirschsprung disease that causes severe constipation or intestinal blockage.

KLRC3 belongs to the NKG2 group that can be found mostly in natural killer (NK) cells and encodes a family of transmembrane proteins known for their C-type lectin domain and their type II membrane orientation (extracellular C terminus). The NKG2 gene family is situated inside the NK complex, a region which has quite a few C-type lectin genes mostly expressed on NK cells.

SLC3A2, also known as Solute Carrier Family 3 Member 2, is a single-pass type II membrane protein which is part of the SLC3A transporter family. SLC3A2 is expressed ubiquitously in all tissues tested with the highest levels detected in kidney, placenta and testis and lowest level in thymus. SLC3A2 is essential for the function of light chain amino-acid transporters and also takes part in sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan. SLC3A2 participates in guiding and targeting of LAT1 and LAT2 to the plasma membrane.

Decorin (DCN) is a small cellular or pericellular matrix proteoglycan which is closely related in structure to biglycan protein. Decorin is a secreted protein which binds to collagen and fibronectin in extracellular matrix. Decorin appears in different glycoforms, substituted with chondroitin sulfate or dermatan sulfate consistent with the original tissue. DCN contains one attached glycosaminoglycan chain. Decorin influences the rate of fibril formation. Decorin is capable of suppressing the growth of various tumor cell lines. DCN gene defects cause corneal dystrophy. The DCN gene is a candidate gene for Marfan syndrome.

KCTD4 also known as Potassium Channel Tetramerisation Domain Containing 4 has an N-terminal homodimerization domain which contains multiple copies of kelch repeats and C2H2-type zinc fingers. Proteins which include BTB domains are consider being involved in transcriptional regulation through control of chromatin structure and function. In addition, KCTD4 is a 259 amino acid protein which contains one BTB domain, a possible role as a transcriptional regulator may be suggested.

Mouse MIP-1 gamma is 75% identical in its amino acid compostion as compared to the rat specie. MIP-1 gamma is a CC chemokine localized in murine blood and a widespread range of murine tissues, without having an identified human homolog. MIP-1 gamma signals through the CCR1 receptor. MIP-1 gamma chemoattracts neutrophils and also inhibits colony formation of bone marrow myeloid immature progenitors. MIP-1 gamma has six cysteines including the four highly conserved cysteine residues present in CC chemokines.

Decorin (DCN) is a small cellular or pericellular matrix proteoglycan which is closely related in structure to biglycan protein. Decorin is a secreted protein which binds to collagen and fibronectin in extracellular matrix. Decorin appears in different glycoforms, substituted with chondroitin sulfate or dermatan sulfate consistent with the original tissue. DCN contains one attached glycosaminoglycan chain. Decorin influences the rate of fibril formation. Decorin is capable of suppressing the growth of various tumor cell lines. DCN gene defects cause corneal dystrophy. The DCN gene is a candidate gene for Marfan syndrome.

Chemokine (C-C motif) ligand 7 (CCL7) is a small cytokine known as a chemokine that was previously called monocyte-specific chemokine 3 (MCP3). Due to CCL7 possessing two adjacent N-terminal cysteine residues in its mature protein, it is classified among the subfamily of chemokines known as CC chemokines. CCL7 specifically attracts monocytes, and regulates macrophage function. It is produced by certain tumor cell lines and by macrophages. This chemokine is located on chromosome 17 in humans, in a large cluster containing many other CC chemokines and is most closely related to CCL2(previously called MCP1).

CCL23 (MIP-3) is a ligand for the CCR1chemokine receptor. CCL23 is one of several cytokine genes clustered on the q-arm of chromosome 17, in a locus containing several other CC chemokines. MIP-3 chemoattracts monocytes, resting T-lymphocytes and neutrophils, but not activated lymphocytes. Furthermore, it was shown that MIP-3 inhibits colony formation of bone marrow myeloid immature progenitors. MIP-3 is mainly expressed in lung and liver tissue, but can be also found in bone marrow and placenta, as well as in some cell lines of myeloid origin.
Alternative splicing of the CCL23 gene produces 2 mRNAs which encode a short (CK?8) and a long (CK?81) isoform of the MIP-3. CK?8 cDNA encodes a 120 amino acid residue precursor protein with a putative 21 a.a. residue signal peptide which is cleaved to generate a 99 a.a. residue mature CK?8 (a.a. 22-120). Further N-terminal processing of the 99 a.a. residue variant can produce a 75 a.a. residue CK?8 (a.a. 46-120) which is considerably more active than the 99 a.a. residue variant.
MIP-3 may be involved in the malignant progression of certain human cancer cells which overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. MIP-3 may also be involved in angiogenesis via upregulation of matrix metalloproteinase MMP-2 expression.

Potassium Channel Tetramerisation Domain Containing 11 (KCTD11) is a 232 amino acid regulator of neuronal differentiation which induces growth arrest, apoptosis and the expression of p27 (cyclin-dependent kinase inhibitor). KCTD11 is expressed most highly in cerebellum. KCTD11 functions as an antagonist of the Hedgehog pathway and activator of the caspase cascade and among its related super-pathways are Melatonin Signaling and Activation of cAMP-Dependent PKA.

The somatomedins, or insulin-like growth factors (IGFs), comprise a family of peptides that play important roles in mammalian growth and development. IGF1 mediates many of the growth-promoting effects of growth hormone (GH; MIM 139250). Early studies showed that growth hormone did not directly stimulate the incorporation of sulfate into cartilage, but rather acted through a serum factor, termed 'sulfation factor,' which later became known as 'somatomedin' (Daughaday et al., 1972). Three main somatomedins have been characterized: somatomedin C (IGF1), somatomedin A (IGF2; MIM 147470), and somatomedin B (MIM 193190) (Rotwein, 1986; Rosenfeld, 2003).

Chemokine (C-C motif) ligand 2 (CCL2) is a small cytokine belongs to the CC chemokine family which is also known as monocyte chemotactic protein-1 (MCP-1). MCP 1 is found at the site of tooth eruption and bone degradation. In the bone, CCL2 is expressed by mature osteoclasts. CCL2 recruits immune cells, such as monocytes, to sites of tissue injury and infection. MCP 1is produced as a protein precursor containing signal peptide of 23 amino acids and a mature peptide of 76 amino acids. As with many other CC chemokines, CCL2 is located on chromosome 17 in humans. The cell surface receptors that bind CCL2 are CCR2 and CCR5.

Chemokine (C-C motif) ligand 2 (CCL2) is a small cytokine belonging to the CC chemokine family that is also known as monocyte chemotactic protein-1 (MCP-1). It is found at the site of tooth eruption and bone degradation. In the bone, CCL2 is expressed by mature osteoclasts and osteoblasts and is under the control of nuclear factor ?B (NF?B).CCL2 recruits immune cells, such as monocytes, to sites of tissue injury and infection.This chemokine is produced as a protein precursor containing signal peptide of 23 amino acids and a mature peptide of 76 amino acids. It is a monomeric polypeptide, with a molecular weight of approximately 13kDa. As with many other CC chemokines, CCL2 is located on chromosome 17 in humans.The cell surface receptors that bind CCL2 are CCR2 and CCR5

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1a and MIP-1b that are now officially named CCL3 and CCL4 respectively. Both are major factors produced by macrophages after they are stimulated with bacterial endotoxins. They activate human granulocytes (neutrophils, eosinophils and basophils) which can lead to acute neutrophilic inflammation. They also induce the synthesis and release of other pro-inflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-a from fibroblasts and macrophages. The genes for CCL3 and CCL4 are both located on human chromosome 17.

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.