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Cytokeratin 8 (KRT8) belongs to the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. KRT8 typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. KRT8 has a role in retaining cellular structural integrity and also functions in signal transduction and cellular differentiation. KRT8 gene mutations cause cryptogenic cirrhosis.

TREM1 is a transmembrane receptor protein that is involved in monocytic activation and in the inflammatory response. TREM1 is expressed on the surface of neutrophils, mature monocytes and macrophages. TREM1 stimulates neutrophil and monocyte-mediated inflammatory responses. TREM1 also triggers the release of pro-inflammatory chemokines and cytokines, as well as increased surface expression of cell activation markers. Furthermore, TREM1 is an amplifier of inflammatory responses that are triggered by bacterial and fungal infections and is a fundamental mediator of septic shock. The expression of the soluble form of TREM1 increases during sepsis and can consequently be used as a biological marker for septic shock. TREM1 is strongly expressed in acute inflammatory lesions caused by bacteria and fungi. Increased TREM1 expression on monocytes is related to both infectious and noninfectious inflammatory processes.
TREM1 is vastly expressed in adult liver, lung and spleen than in corresponding fetal tissue. TREM1 is also expressed in the lymph node, placenta, spinal cord and heart tissues. TREM1 expression is more elevated in peripheral blood leukocytes than in the bone marrow and in normal cells than malignant cells. TREM1 is expressed at low levels in the early development of the hematopoietic system and in the promonocytic stage and at high levels in mature monocytes.

Eosinophil lysophospholipase (CLC) acts on biological membranes to regulate the multifunctional lysophospholipids. CLC is a lysophospholipase expressed in eosinophils and basophils. CLC hydrolyzes lysophosphatidylcholine to glycerophosphocholine and a free fatty acid. The CLC protein may possess carbohydrate or IgE-binding activities. CLC is both structurally and functionally related to the galectin family of beta-galactoside binding proteins. CLC may be linked with inflammation and some myeloid leukemias.

CIB2 is a member of the calcium and integrin-binding family.CIB2 is possibly a Ca2+-binding regulatory protein which interacts with DNA-dependent protein kinase catalytic subunit (DNA-PKcs). In the skeletal muscle, CIB2 co-localizes with the integrin alpha7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. CIB2 is closely related to CIB1.

GSTP1 is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are believed to function in xenobiotic metabolism and have a part in susceptibility to cancer, and other diseases. GSTP1 is a glutathione S-transferase belonging to the pi class. GST family enzymes play a significant role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based upon the biochemical, immunologic and structural properties of the soluble GSTs they are grouped into 4 main classes: alpha, mu, pi, and theta. The GSTP1 enzyme acts by catalyzing the reaction of glutathione with an acceptor molecule to form a Sulfur-substituted glutathione. The reactions employing glutathione contribute the transformation of a broad range of electrophiles, including reactive products of lipid, protein, carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress.
The GSTP1 inactivation through CpG hypermethylation is frequent in pituitary adenomas and may be a factor in aggressive pituitary tumor behavior. GSTP1 is may be a transcriptional target of the p53 tumor suppressor gene. Single-nucleotide polymorphism in GSTP1 is linked to modified protein binding, which influence GSTP1's contribution to carcinogen and drug metabolism, and possibly disease pathogenesis and/or drug response. GST-pi might have central roles in proliferation of androgen-independent human prostate cancer cells.

VAPA is involved in vesicle traficking. VAPA is a type IV membrane protein. It is localized in the plasma membrane and intracellular vesicles. VAPA is related with the cytoskeleton. VAPA functions membrane fusion, protein complex assembly and cell motility. VAPA is an essential regulator both of the subcellular localization of protrudin and of its ability to stimulate neurite outgrowth.

Prefoldin subunit 3 (VBP1) is a member of the prefoldin subunit alpha family. VBP1 interacts with the Von Hippel-Lindau protein in order to create an intracellular complex. Since VBP1 serves as a chaperone protein, it is assumed to have a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm. VBP1 binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. VBP1 also binds to nascent polypeptide chain and stimulates folding in an environment in which there are numerous competing pathways for nonnative proteins.

CPLX1 is part of the SNARE family complex binding proteins that are catalysts or inhibitors of vesicle exocytosis. CPLX1 shows reduced Ca2+-triggered fast neurotransmitter release at hippocampal glutamatergic synapses, indicating that CPLX1 is a positive regulator of transmitter release. In contrast, CPLX1 inhibits SNARE-mediated liposome and cell fusions in vitro, that result in hypothesis thus acts as a fusion clamp of synaptic exocytosis. CPLX1 regulates a late step in synaptic vesicle exocytosis.

Recoverin is a member of the recoverin family of neuronal calcium sensors. Recoverin is a heterogeneously acylated calcium-binding and intracellular signal transduction 23kDa protein in the photoreceptor cells of retina. Recoverin contains four EF-hands, of which two bind Ca. Ca-induced extrusion of the acyl group from a hydrophobic cleft in the protein drives the translocation of recoverin from solution to the disc membrane. Recoverin may prolong the termination of the phototransduction cascade in the retina by blocking the phosphorylation of photo-activated rhodopsin. Recoverin plays a key role in the inhibition of rhodopsin kinase, a molecule that regulates the phosphorylation of rhodopsin. This in due course controls the ability of the eye to adapt to, and recover from, exposure to the presence of light. Recoverin is a detectable serologic protein that is expressed in patients with cancer-associated retinopathy, a paraneoplastic syndrome.

RELM-beta (Resistin-Like Molecule-beta) is a member of a recently identified family of secreted proteins containing a conserved cystein-rich C-terminus. The RELM family consists of resistin (also called FIZZ3), RELM-alfa (FIZZ1), RELM-beta (FIZZ2) and RELM-gamma. Only resisistin and RELM-beta were found in humans whereas all four RELM family members were identified in rodents.
RELM-beta appears to be produced as a homodimer exclusively by intestinal goblet cells and can be found in high quantities in stool. Remarkably, stool of germ-free mice displaying sterile intestinal tract does not contain RELM-beta until bacterial colonization takes place after pathogen-free mice entered natural environment. Some, but not all, colon carcinoma cell lines secrete RELM-beta into the cell culture supernatant.
The physiological function of RELM-beta is not known. High doses of recombinant RELM-beta showed hyperglycemic effects including lowered glucose disposal and increased hepatic glucose production in mice.

RELM-gamma is a novel member of the resistin-like molecule/found in inflammatory zone (RELM/FIZZ) family in mice and rats. Microarray and real-time RT-PCR experiments revealed a repression of RELMgamma mRNA in nasal respiratory epithelium of cigarette smoke-exposed versus untreated rats. The analysis of the physiological tissue-specific expression revealed highest expression in hematopoietic tissues, suggesting a cytokine-like role for RELM-gamma. RELM-gamma-mRNA is detectable in bone marrow, spleen, and lung as well as in peripheral blood granulocytes. Promyelocytic HL60 cells transfected with a RELM-gamma expression plasmid have an increased proliferation rate compared to mock-transfected cells and display an altered response to retinoic acid-induced granulocytic differentiation. Taken together, these data provide the first experimental evidence that RELM-gamma is a secreted molecule with a restricted expression pattern that may play a role in promyelocytic differentiation.

NME2 takes an important part in the synthesis of nucleoside triphosphates other than ATP. NME2 negatively controls Rho activity by interacting with AKAP13/LBC. NME2 acts as a transcriptional activator of the MYC gene. NME2 binds DNA non-specifically. NME2 is a heterodimeric enzyme functioning as a nucleoside diphosphate kinase. NME1 and NME2 contain 152 amino acids, A and B polypeptide chains of the NM23 enzyme, respectively. NME2 is identical to the beta subunit of human erythrocyte NDP kinase. NDP kinases participate in the synthesis of nucleoside triphosphates, and NM23 is involved in the regulation of signal transduction by complexing with G proteins, causing activation/inactivation of developmental pathways.

Relaxin-3 (RLN3) belongs to the relaxin family. Relaxins are endocrine and autocrine/paracrine hormones. Relaxin, which is produced by the ovary, targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. Unlike human Relaxins 1 and 2, Relaxin 3 does not seem to have a role in reproduction; however it is involved in stress response in the brain stem. RLN3 is the only known ligand for the G-protein-coupled receptor GPCR135, titled RXFP3. In addition, RLN3 binds the LGR7 (RXFP1) receptor, however with lower affinity than Relaxin-2. Even though binding of RLN3 to LGR7 increases intracellular cAMP, binding to GPCR135 suppresses cAMP accumulation, indicating coupling to Gi, Go, or Gz by this receptor.

E3 ubiquitin-protein ligase RNF181 (RNF181) accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the thioester form and subsequently directly transfers the ubiquitin to targeted substrates. RNF181 is widely expressed, with the highest levels in the liver and heart and the lowest levels in the brain and skeletal muscle. RNF181 is also expressed in platelets (at protein level).

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.

Growth Differentiation Factor-7 (GDF-7) belongs to the BMP family of TGF-b superfamily proteins. GDF7 elicits its bioactivity via a heterodimeric receptor complex comprised of a type 1 (BMPR-IB) and a type II (BMPR-II or Activin RII) serine/threonine kinase receptor. GDF7 signaling results in the phosphorylation and activation of Smad proteins. GDF-7 is also involved in tendon and ligament formation and repair. In addition, GDF7 regulates bone formation, mesenchymal stem cell differentiation, neuronal differentiation, and axon guidance.

GMFB is part of the GMF subfamily of the larger actin-binding protein ADF family. GMFB is phosphorylated after phorbol ester stimulation, and is crucial for the nervous system. GMFB causes brain cell differentiation, stimulates neural regeneration and inhibits tumor cell proliferation. GMFB overexpression in astrocytes results in the increase of BDNF production. GMFB expression is increased by exercise, thus BDNF is important for exercise-induction of BDNF.

UPK3A is a member of the uroplakin-3 family. Uroplakins (UP) which are transmembrane proteins are important components of the urothelium that pass the lipid bilayer once (UPII, UPIIIa, and UPIIIb) or four times (UPIa and UPIb; both members of the "tetraspanin" family). All hold great luminal/extracellular domains, but only UPIIIa and UPIIIb have significant cytoplasmic shares in their C-termini. UPK3A is an extremely specific and moderately sensitive immunohistochemical marker for primary and metastatic urothelial carcinomas. Alterations in this gene are related to renal adysplasia.

SEMA7A (semaphorin-7A isoform 1), is a membrane-bound semaphorin which is linked with cell surfaces via a glycosylphosphatidylinositol (GPI) linkage. SEMA7A encourages formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK3 & MAPK1. SEMA7A takes a vital part in integrin-mediated signaling and functions in regulating cell migration as well as immune responses. In addition, SEMA7A promotes the production of proinflammatory cytokines by macrophages & monocytes.

SERTA domain-containing protein (SERTAD1) functions with E2F-responsive promoters to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. SERTAD1 stimulates E2F-1/DP-1 transcriptional activity. SERTAD1 reduces the activity of cyclin D1/CDK4 resistant to the inhibitory effects of p16(INK4a). In addition, SERTAD1 interacts with the PHD-bromodomain of TIF1, TRIM28/TIF1B and p300/CBP. Furthermore, SERTAD1 binds to DP1 and interacts with CDK4.

Non-Metastatic Cells 4 or NME4, is a nucleoside diphosphate kinase located in the mitochondria, and is part of the NDK family of proteins. NME4 ais a very common enzyme that enhances transfer of gamma-phosphates, through a phosphohistidine as a intermediate, between dioxynucleoside tri- and diphosphates. NME4 is originated from the nm23 gene. NME4 has a crucial part in the creation of nucleoside triphosphates that are not ATP.