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Peptidase Inhibitor 16 (PI16) which a member of the CRISP family, is a putative serine protease inhibitor. PI16 interacts with PSP94/MSMB. PI16 is expressed in the prostate, testis, ovary and intestine. It also concentrates in prostate cancer patient's sera. PI16 may serve as a marker following prostatectomy for prostate cancer.

Von Hippel-Lindau disease is a dominant inherited syndrome characterized by the predisposition to develop various kinds of benign and malignant tumors, including clear cell renal carcinomas, pheochromocytomas and hemangioblastomas of the central nervous system and retina. VHL syndrome is caused by germline mutation in the VHL tumor suppressor, and VHL tumors are associated with loss or mutation of the remaining wild-type allele. VHL has two domains: a roughly 100-residue NH2-terminal domain rich in b sheet (b-domain) and a smaller a-helical domain (a-domain), held together by two linkers and a polar interface. VHL protein is also involved in the degradation of hypoxia-inducible factor (HIF).

Zinc Finger, CCHC Domain Containing 12 (ZCCHC12) which holds 1 CCHC-type zinc finger is a part of the ZCCHC12 family. ZCCHC12 takes part in the bone morphogenetic protein (BMP)-signaling pathway as a transcriptional coactivator. BMP signaling is positively modulated as a result of the interaction between ZCCHC12 with SMAD1 and the association with CBP in the transcription complex.

Interleukin-18 Binding Protein (IL18BP) serves as an inhibitor of the proinflammatory cytokine, IL18. IL18BP binds IL18, inhibits the binding of IL18 to its receptor, and consequently inhibits IL18-induced IFN-gamma production, resulting in reduced T-helper type 1 immune responses. The IL18BP protein is constitutively expressed and secreted in mononuclear cells. Elevated levels of IL18BP protein are detected in the intestinal tissues of patients with Crohn's disease.

Adiponectin is an adipocyte specific secreted protein that circulates in the plasma. It is induced during adipocyte differentiation and its secretion is stimulated by insulin. Mouse adiponectin shares about 83% amino acid identity with that human. Adiponectin plays a role in various physiological processes such as energy homeostasis and obesity. Adiponectin is reduced in obese humans, and decreased level is associated with insulin resistance and hyperinsulinemia.

Btc is a potent mitogen for retinal pigment epithelial cells and vascular smooth muscle cells. The effects of betacellulin are probably mediated by the egf receptor and other related receptors.

Connective Tissue Growth Factor belongs to the CCN family of proteins. The CCN family presently consists of six members in human also known as: Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), Nov (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). The CCN genes encode secreted proteins associated with the Extracellular Matrix (ECM) and cell membrane.
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: fibrosis, vascular ailments and tumorigenesis.
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 four 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. Module IV resembles the CT domain of several extracellular protein including, Von Willebrand's factor and mucins. Sequence similarities to heparin-binding motifs are also found within this domain.
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.

Neuronal Regeneration Related Protein (NREP) has roles in neural function. NREP promotes axonal regeneration. In addition, NREP has functions in cellular differentiation. NREP protein induces differentiation of fibroblast into myofibroblast and increases retinoic-acid regulation of lipid-droplet biogenesis. NREP down-regulates the expression of TGFB1 and TGFB2 but not of TGFB3. NREP has a role in the regulation of alveolar generation.

Endothelial cells express three different vascular endothelial growth factor (VEGF) receptors, belonging to the family of receptor tyrosine kinases (RTKs). They are named VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). Their expression is almost exclusively restricted to endothelial cells, but VEGFR-1 can also be found on monocytes. All VEGF-receptors have seven immunoglobulin-like extracellular domains, a single transmembrane region and an intracellular split tyrosine kinase domain. VEGFR-2 has a lower affinity for VEGF than the Flt-1 receptor, but a higher signalling activity. Mitogenic activity in endothelial cells is mainly mediated by VEGFR-2 leading to their proliferation. Differential splicing of the flt-1 gene leads to the formation of a secreted, soluble variant of VEGFR-1 (sVEGFR-1). No naturally occurring, secreted forms of VEGFR-2 have so far been reported. The binding of VEGF165 to VEGFR-2 is dependent on heparin.

TNFRSF17 is a receptor for tnfsf13b/blys/baff and tnfsf13/april. TNFRSF17 promotes b-cell survival and plays a role in the regulation of humoral immunity. TNFRSF17 activates nf-kappa-b and jnk. TNFRSF17 is a member of the TNF-receptor superfamily. TNFRSF17 is expressed in mature B lymphocytes, and is invloved in B cell development and autoimmune response. TNFRSF17 specifically binds to the tumor TNFSF13B/TALL-1/BAFF, which causes NF-kappaB and MAPK8/JNK activation. TNFRSF17 binds to a variety of TRAF family members, and therefore transduces signals for cell survival and proliferation. TNFRSF17 is a type III membrane protein having 1 extracellular cysteine rich domain. Within the TNFRSF, it shares the highest homology with TACI. BCMA and TACI have both been shown to bind to APRIL and BAFF, members of the TNF ligand superfamily. BCMA expression has been found in immune organs. TNFRSF17 appears to be localized to the Golgi compartment. The binding of BCMA to APRIL or BAFF has been shown to stimulate IgM production in peripheral blood B cells and increase the survival of cultured B cells.

Alpha 1-microglobulin (A1M) is a lipocalin superfamily member (kernal lipocalins). A1M is a low molecular weight protein component of plasma. A1M is distributed in plasma and extravascular compartments of all organs. Alpha-1 Microglobulin is found in mammals, birds, amphibians and fish. The primary sites of A1M synthesis are the liver and the kidney. Around the opening of the lipocalin pocket three lysyl residues are situated; those residues carry yellow-brown modification derived from the binding and degradation of heme and kynurenin (a tryptophan metabolite). A1-Microglobulin’s reductase and dehydrogenase have broad biological substrate specificity properties due to its’ free cysteine side-chain which is located in a flexible loop. Alpha-1-microglobulin is glycosylated by three separate carbohydrate chains: two complex carbohydrates which are N-linked to asparagines at residues 17 and 96, and the other simple carbohydrate which is O-linked to threonine at position 5. The carbohydrates comprise 22% of the total molecular mass of the protein. The glycosylation varies between species. A1M exists in two forms- a free form and complexed to other macromolecules: in humans- complexed to immunoglobulin A (IgA), in rat- complexed to alpha-1-inhibitor-3. Free A1M is exceptionally heterogeneous in charge (therefore also known as protein HC), and is found tightly linked to a chromophore. The free Alpha-1-microglobulin is a monomeric protein composed of one 188 residue polypeptide and contains three cysteines, two of which (residues 75 and 173) form a conserved intra-molecular disulphide link. The chromophoric group is covalently bound to the free cysteine residue at position 34. A1M binds retinol as a major ligand, but this is probably distinct from its covalent chromophore. Half of all human plasma A1M (approximately 0.03mg/ml) forms a 1:1 complex with about 5% of plasma immunoglobulin A. The resulting macromolecular complexes’ molecular weight is 200000, and a plasma concentration of 0.3mg/ml. The complex can exhibit both antibody activity and affect many of the biological actions of free Alpha-1-microglobulin. Alpha-1-microglobulin was first discovered in pathological human urine. It was suggested that A1M might be involved in tissue defense against reactive oxygen species, oxidation by heme and kynurenin. Evidence also suggests that A1M functions in the regulation of the immune system. Other functions include: inhibition of stimulation of cultured lymphocytes by protein antigens; induction of cell division of lymphocytes, a mitogenic effect that can either be enhanced or inhibited by the action of other plasma components; inhibition of neutrophil granulocyte migration in vitro; and inhibition of chemotaxis.
Other functions include inhibition of stimulation of cultured lymphocytes by protein antigens; induction of cell division of lymphocytes, a mitogenic effect that can either be enhanced or inhibited by the action of other plasma components; inhibition of neutrophil granulocyte migration in vitro; and inhibition of chemotaxis.

PDCD6IP is a Class E VPS protein which participates in concentration and sorting of cargo proteins of the multivesicular body or incorporation into intralumenal vesicles that are generated by invagination and scission from the limiting membrane of the endosome. PDCD6IP binds to the phospholipid lysobisphosphatidic acid which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. PDCD6IP is an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. PDCD6IP is mandatory for completion of cytokinesis. PDCD6IP takes part in HIV-1 virus budding. PDCD6IP replaces TSG101 in its function of supporting HIV-1 release. PDCD6IP takes part in the regulation of both apoptosis and cell proliferation. PDCD6IP is a cytoplasmic protein that cooperates with apoptosis-associated proteins (ALG-2 and PDCD6) and with the endocytosis-regulator CIN85. Overexpression of PDCD6IP and endophilin

ASRGL1 is a 308 amino acid protein which is a member of the Ntn-hydrolase family. ASRGL1 is an autoantigenic protein which is present in the mid-piece of sperm after obstruction of the male reproductive tract. ASRGL1 is expressed highly in the testis, but is also expressed in the brain, kidney and gastrointestinal tissues. High levels of ASRGL1 are also detected in ovarian, uterine and mammary tumors in comparison with normal tissues of the same origin.

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.

CARD18 belongs to the death-domain-fold superfamily which is induced by proinflammatory stimuli. CARD18 contains basically only a Caspase recruitment domain, inhibits generation of IL-1b by cooperating with caspase-1 and inhibiting connotation with RIP 2. The connotation of CARD18 to caspase-1 is enabled by the charge-charge interactions between the prodomain of caspase-1 and the surface charge of CARD18.

MAGEA4 is part of the MAGEA family, which directs the expression of tumor antigens that are identified on a human melanoma by autologous cytolytic T lymphocytes (CTL). MAGEA4 participates in embryonal development and tumor transformation or aspects of tumor progression. MAGEA4 is expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes and placenta.

DR1 is a phosphoprotein that inhibits both basal and activated levels of transcription. DR1 is phosphorylated in vivo which affects its interaction with TBP. DR1 has a histone fold motif at the amino terminus, a TBP-binding domain, and a glutamine- and alanine-rich region. By selectively repressing polymerases II and III, DR1 alters the physiological balance of transcriptional output in favor of polymerase I.

ENSA is an endogenous ligand for sulfonylurea receptor. ENSA reduces K(ATP) channel currents by inhibiting sulfonylurea from binding to the receptor and thus stimulates insulin secretion. Endosulfine Alpha is part of a conserved cAMP-regulated phosphoprotein (ARPP) family. Endosulfine Alpha is an endogenous ligand for the sulfonylurea receptor, ABCC8/SUR1. Endosulfine Alpha is an endogenous regulator of KATP channels. ENSA modulates insulin secretion through the interaction with KATP channel. ENSA is a candidate gene for type 2 diabetes. ENSA is expressed in a wide range of tissues including muscle, brain, and endocrine tissues.

Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance. CRMP2 was previously shown to mediate the repulsive effect of Sema3A on axons and to participate in axonal specification. The X-ray crystal structure of murine CRMP1 was determined at 2.1 resolution and demonstrates that CRMP1 is a bilobed ‘lung-shaped’ protein forming a tetrameric assembly.

Anaphase-promoting complex subunit 13 (ANAPC13) is a component of the anaphase promoting complex, which is a large ubiquitin-protein ligase that controls cell cycle progression by regulating the degradation of cell cycle regulators such as B-type cyclins. The ANAPC13 protein is evolutionarily conserved and is essential for the integrity and ubiquitin ligase activity of the anaphase promoting complex.

The human Lymphocyte Antigen 6 Complex Locus G6F (LY6G6F) protein is a type I transmembrane protein belonging to the immunoglobin (Ig) superfamily, which contains cell-surface proteins involved in the immune system and cellular recognition. The LY6G6F protein has a role in the downstream signal transduction pathways involving GRB2 and GRB7.

Mediator of ErbB2-driven cell motility 1 (MEMO1) is a member of the UPF0103 family. MEMO1 regulates cell migration by transmitting extracellular chemotactic signals to the microtubule cytoskeleton. Furthermore, MEMO1 controls the localization of APC and CLASP2 to the cell membrane, using the regulation of GSK3B activity. MEMO1 is essential for breast carcinoma cell migration, suggesting a key role in tumorigenesis. MEMO1 is also a mediator of ERBB2 signaling.

MNDA plays a role as a transcriptional activator/repressor in the myeloid lineage and in the granulocyte/monocyte cell-specific response. MNDA Stimulates the DNA binding of the transcriptional repressor protein YY1. MNDA is identified only in nuclei of cells of the granulocyte-monocyte lineage.

C17ORF49 is a component of chromatin complexes such as the MLL1/MLL and NURF complexes.