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Granulocyte/Macrophage Colony-Stimulating Factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. MCSF induces cells of the monocyte/macrophage lineage. MCSF plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Mago-Nashi Homolog B (MAGOHB) is a member of the mago nashi family. MAGOHB involved in mRNA splicing and in the nonsense-mediated decay (NMD) pathway. MAGOHB interacts with RBM8A and is a part of the exon junction complex (EJC) containing NCBP1, NCBP2, RNPS1, RBM8A, SRRM1, NXF1, UPF3B, UPF2 and ALYREF/THOC4.

MAO-B is a member of the flavin monoamine oxidase family. MAO-B (Monoamine oxidase B) is a flavin-containing mitochondrial enzyme that catalyzes the oxidative deamination of biogenic and xenobiotic monoamines. MAO-B controls the metabolic degradation of catecholamines and serotonin in neural and other target tissues. MAO-B is located in platelets and in DOPA-secreting neurons in the brain. MAOB and MAOA genes have an imperative function in DOPA degradation. Benzylamine and phenylethylamine are preferentially degraded by MAOB. The MAOB gene is linked to autistic traits, empathy and Asperger syndrome. Amplified levels of MAO B are identified in the brain of Alzheimer’s patients. High phenylethylamine levels in neonates as a result of low MAOB are consistent with phenylketonuria in newborns. Polymorphisms in MAO-B are connected to smoking behavior.

MMP28, which belongs to the matrix metalloproteinase (MMP) family, takes part in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction and tissue remodeling, and disease processes, like asthma and metastasis. MMP28 is a secreted enzyme which degrades casein. MMP28 participates in tissue homeostasis and in wound repair.

MMP-1 can break down a wide range of substrates including types I, II, III, VII, VIII, and X collagens as well as L-Selectin, pro-TNF, IL-1?, IGFBP-3, IGFBP-5, casein, gelatin, ?1 antitrypsin, myelin basic protein, pro-MMP2 and pro-MMP9. A significant function of MMP-1 is the degradation of fibrillar collagens in extracellular matrix remodeling. MMP-1 is expressed in fibroblasts, keratinocytes, endothelial cells, monocytes and macrophages. MMP1 can be divided into a number of distinct domains: a prodomain which is cleaved on activation, a catalytic domain containing the zinc binding site and a short hinge region with a carboxyl terminal domain. MMP1 is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Matrix metalloproteinase-2 (MMP-2) is involved in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. MMP-2 contains a number of distinct domains: a prodomain that is cleaved upon activation; a catalytic domain containing the zinc binding site; a fibronectin like domain believed to have a role in substrate targeting; and a carboxyl terminal (hemopexin like) domain containing 2 N-linked glycosylation. The MMP-2 can degrade an extensive array of substrates including type IV, V, VII and X collagens as well as gelatin type I. In addition, MMP-2 interacts with THBS2, TIMP2, Thrombospondin 1, CCL7 and TIMP4. MMP-2 autocatalytic cleavage in the C-terminal generates the anti-angiogenic peptide, PEX. This process seems to be made possible by binding integrinv/beta3. Defects in the MMP-2 are the cause of Torg-Winchester syndrome (TWS), aka multicentric osteolysis nodulosis and arthropathy (MONA).

Granulocyte/Macrophage Colony-Stimulating Factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.

Matrix metalloproteinases are a family of zinc and calcium-dependent endopeptidases that break down extracellular matrix proteins. The MMP9 is secreted as a 92kDa zymogen. Cleavage of ProMMP-9 results in the active enzyme, having a molecular weight of approximately 82kDa. MMP9 is composed of the following domains: a gelatin-binding domain consisting of three fibronectin type II units, a catalytic domain containing the zinc-binding site, a proline-rich type V collagen-homologous domain and a hemopexin-like domain. MMP9 is produced by the several cell types: monocytes, macrophages, neutrophils, keratinocytes, fibroblasts, osteoclasts and endothelial cells. MMP9 is involved in inflammatory responses, tissue remodeling, wound healing, tumor growth and metastasis. MMP9 may also play an important part in local proteolysis of the extracellular matrix and in leukocyte migration, as well as in bone osteoclastic resorption. MMP9 cleaves type IV and type V collagens into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. MMP9 can also degrade fibronectin but not laminin or Pz-peptide.
MMP9 defects may be a cause of susceptibility to intervertebral disc disease (IDD), also known as lumbar disk herniation (LDH).

Human immunodeficiency virus (HIV) is a retrovirusthat can lead to a condition in which the immune systembegins to fail, leading to opportunistic infections. HIV primarily infects vital cells in the humanimmune systemsuch as helper T cells(specifically CD4+ T cells), macrophagesand dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosisin infected cells; and thirdly, killing of infected CD4+ T cells by CD8 cytotoxic lymphocytesthat recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunityis lost, and the body becomes progressively more susceptible to opportunistic infections. HIV was classified as a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry of the target cell, the viral RNA genomeis converted to double-stranded DNAby a virally encoded reverse transcriptasethat is present in the virus particle. This viral DNA is then integrated into the cellular DNA by a virally encoded integraseso that the genome can be transcribed. Once the virus has infected the cell, two pathways are possible: either the virus becomes latentand the infected cell continues to function, or the virus becomes active and replicates, and a large number of virus particles are liberated that can then infect other cells.

Anti-Mullerian Hormone also known as AMH is a member of the TGF-beta family. AMH is a glycoprotein which is produced by the Sertoli cells of the testis, causes regression of the Muellerian duct. AMH inhibits the growth of tumors derived from tissues of Muellerian duct origin. Moreover, AMH participates in Leydig cell differentiation and function in addition to follicular development in adult females.

Milk fat globule-EGF factor 8 protein (Mfge8) is pleiotropic secreted glycoprotein which promotes mammary gland morphogenesis, angiogenesis, and tumor progression. Mfge8 has also an imperative role in tissue homeostasis and the prevention of inflammation. Mfge8 functions as a bridge between phosphatidylserine on apoptotic cells and Integrin alpha V beta 3 on phagocytes, leading to the clearance of apoptotic debris.

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.

Adipocyte plasma membrane-associated protein, also known as APMAP, is a member of the strictosidine synthase family. APMAP exhibits strong arylesterase activity with beta-naphthyl acetate in addition to phenyl acetate and takes part in adipocyte differentiation.

JUN N-terminal Kinase 2is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase targets specific transcription factors, and thus mediates immediate-early gene expression in response to various cell stimuli. It is most closely related to MAPK8, both of which are involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway. This gene and MAPK8 are also known as c-Jun N-terminal kinases. This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells. Studies of this gene's mouse counterpart suggest a key role in T-cell differentiation. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

MAP1LC3B is a member of the MAP1 LC3 family. MAP1LC3B is a subunit of neuronal microtubule-associated MAP1A and MAP1B proteins, that are involved in microtubule assembly and important for neurogenesis. In addition, MAP1LC3B takes part in formation of autophagosomal vacuoles and is expressed mainly in heart, testis, brain and skeletal muscle.

ME2 catalyzes the oxidative decarboxylation of malate to pyruvate, malat + NAD(P)+? pyruvate + CO2 + NAD(P)H+, and is found both in eukaryotic and prokaryotic cells. Three different isoforms of ME are known to be in mammalian tissues: a strictly cytosolic NADP+-dependent enzyme, an NADP+-dependent mitochondriail isoform, and a mitochondrial isoenzyme that is able to use both NAD+ and NADP+ but is more effective with NAD+. The mammalian isoforms size is about 62-64 kDa. A native size of 240,000 Da proposes a tetrameric structure for the active enzyme.
Mitochondrial NAD+-dependent ME 2 activity is seen in tissues that experience many cell divisions, like spleen, thymus, and the basal cells of the small intestinal mucosa. ME2 is also expressed all through the rapid cleavage stages of early Xenopus development. Activity for this isoform is low or nonexistent in brain, muscle, and normal and regenerating liver tissue from rat but was observed in rat adrenal cortex, pigeon and human skeletal muscle, and in heart muscle of some species. In addition, it is expressed in mitochondria of all tumor cells inspected to detain ascites tumors, hepatoma cells, and a variety of other tumors and transformed cell lines.

USE1 Belongs to the USE1 family, this protein is a vesicle transport protein. USE1 is a component of a SNAREcomplex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B. In addition USE1 interacts directly with STX18. SNARE maybe involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER. Diseases associated with USE1 comprise dysentery and hemolytic-uremic syndrome. Among its related super-pathways are Nicotine Pathway (Dopaminergic Neuron) and Pharmacodynamics. GO annotations related to this gene include protein binding.

Melanoma-associated antigen D1 (MAGED1) belongs to the melanoma antigen gene (MAGE) family and expressed in virtually all normal adult tissues. MAGED1 is involved in the p75 neurotrophin receptor mediated programmed cell death pathway. MAGED1 is involved in Prader-Willi syndrome including hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. MAGED1 is involved in the apoptotic response following NGF (nerve growth factor) binding in neuronal cells. MAGED1 hinders cell cycle progression, and facilitates NGFR-mediated apoptosis. MAGED1 functions as a regulator of the function of DLX family members. MAGED1 has a role in the circadian rythm regulation.

Mitogen-Activated Protein Kinase 6 (MAP2K6) is a part of the dual specificity protein kinase family. MAP2K6 phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. MAP2K6 is a vital component of the MAP kinase signal transduction pathway. MAP2K6 takes part in various cellular processes such as stress induced cell cycle arrest and apoptosis.

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.

PBLD is member of the phenazine biosynthesis-like protein (PhzF) family. PBLD which is expressed in most tissues is the only representative of the PhzF family in the human genome. PBLD participates in the MAPK signaling pathway. PBLD is involved in multiple basic cellular functions, its expression is elevated in several disease processes, including folate deficiency and hypotension.

MANF is a 20kDa protein which belongs to the ARMET family. MANF was originally known as an arginine-rich region protein which was extremely mutated in a large number of tumors. MANF Expression is induced during ER stress, signifying that MANF takes part in protein quality control during ER stress.

Matrix metalloproteinase-7 (MMP-7) also known as matrilysin and PUMP (EC 3.4.24.23) cleaves a number of substrates including collagen types IV and X, elastin, fibronectin, gelatin, laminin and proteoglycans. MMP-7 is closely related to the stromelysin family members but is encoded by a different gene. MMP-7 is the smallest of all the MMPs consisting of a pro-peptide domain and a catalytic domain. It lacks the hemopexin-like domain common to other members of the MMPs. MMP-7 is secreted as a 28 kDa proenzyme and can be activated in vitro by organomercurials and trypsin and in vivo by MMP-3 to a 18 kDa active MMP-7 enzyme. Once activated, MMP-7 can activate pro-MMP-1 and pro-MMP-9 but not pro-MMP-2. MMP-7 is widely expressed having been reported in elevated levels in cycling endometrium as well as in colorectal cancers and adenomas, hepatocellular carcinomas, rectal carcinomas, and approximately 50% of gliomas.