Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin. Midkine is a retinoic acid-responsive, heparin-binding growth factor expressed in various cell types during embryogenesis. It promotes angiogenesis, cell growth, and cell migration. Midkine is also expressed in several carcinomas, suggesting that it may play a role in tumorigenesis, perhaps through its effects on angiogenesis. Midkine binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase and the induction of cell proliferation. Midkine is involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development. Midkine exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Thus, it can be used as a breast carcinomas marker.

Signal Regulatory Protein α (SIRPα) is a monomeric approximately 90 kD type I transmembrane glycoprotein. The 504 amino acid human SIRPα contains two Ig-like C1-type domains and one Ig-like V-type domain. SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation.

Chondroitin sulfate proteoglycan 5 (CSPG-5), also known as neuroglycan C, has been previously associated to differentiation since it shapes neurite growth and synapse forming. CSPG-5 expression shifts in brain areas of the default mode network of suicide victims, which may reflect an impact in the pathogenesis of psychiatric diseases or support diagnostic power.

Ninjurin-1, also known as NINJ1, is a member of the Ninjurin family of transmembrane (TM) proteins. It is expressed in CD19(+) CD10(+) B-cell progenitor cells and higher levels in B-lineage acute lymphoblastic leukemia cells. Ninjurin-1 is expressed also in some other adult and embryonic tissues, predominantly in epithelial cells. Its expression is upregulated after axotomy in neurons and Schwann cells surrounding the distal nerve segment. Upregulated expression of ninjurin-1 has been identified as a marker of minimal residual disease in B-lineage acute lymphoblastic leukemia. It mediates homophilic adhesion and promotes neurite extension of dorsal root ganglion neurons in vitro. Ninjurin-1 has been found to show a high expression level in the liver tissue of patients with hepatocellular carcinoma, and this seems to be associated with cases of cirrhosis and chronic viral hepatitis. It has been reported that NINJURIN increases p21 expression and induces cellular senescence in human hepatoma cells.

Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes. Ligand for integrins alpha-8/beta-1, alpha-9/beta-1, alpha-V/beta-3 and alpha-V/beta-6. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells.

May play a role in cell differentiation, proliferation and apoptosis. Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. During early retinal development acts as a key regulator of disk morphogenesis. Involved in regulation of MAPK and Akt signaling pathways. In neuroblastoma cells suppresses cell differentiation such as neurite outgrowth in a RET-dependent manner. CD133/PROM1 Protein-VLP, Human, Recombinant (His) is expressed in HEK293 mammalian cells with C-10xHis tag. The predicted molecular weight is 96.7 kDa and the accession number is O43490.

Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation.

TALLA-1, also known as TSPAN7, is a member of the transmembrane 4 superfamily Most members of this family are cell-surface proteins that are characterized by the presence of four hydrophobic domains. TALLA-1 gene is associated with X-linked mental retardation and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. TALLA-1 is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. TM4SF2/TSPAN7 Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 14 kDa and the accession number is F6UX47.

Death-associated protein kinase 3, also known as DAP kinase 3, ZIP-kinase, DAPK3 and ZIPK, is a nucleus and cytoplasm protein which belongs to theprotein kinase superfamily, CAMK Ser/Thr protein kinase family and DAP kinase subfamily. DAPK3 / ZIPK contains oneprotein kinase domain. It is a serine/threonine kinase which acts as a positive regulator of apoptosis. It phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. DAPK3 / ZIPK is a homodimer or forms heterodimers with ATF4. Both interactions require an intact leucine zipper domain and oligomerization is required for full enzymatic activity. It also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. DAPK3 / ZIPK regulates myosin light chain phosphatase through phosphorylation of MYPT1 thereby regulating the assembly of the actin cytoskeleton, cell migration, invasiveness of tumor cells, smooth muscle contraction and neurite outgrowth. It is involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection.

Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans. Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth. Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection. Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase. Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3. Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases. Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta.

Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.

Serpin E2 is a secreted protein that belongs to the serpin family. Serpin E2 is a serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Serpin E2 expression is weak or absent in all normal pancreas and chronic pancreatitis tissue. In contrast, it was strongly over-expressed in the majority of pancreatic carcinoma as well as gastric and colorectal cancer samples. Serpin E2 promotes neurite extension by inhibiting thrombin. It also can bind heparin. It has been shown that Serpin E2 is a novel target of ERK signaling involved in human colorectal tumorigenesis. It plays an important role in controlling male fertility because its knockout male mice show a marked impairment in fertility from the onset of sexual maturity and its abnormal expression is found in the semen of men with seminal dysfunction.

Signal Regulatory Protein α (SIRPα) is a monomeric approximately 90 kD type I transmembrane glycoprotein. The 504 amino acid human SIRPα contains two Ig-like C1-type domains and one Ig-like V-type domain. SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation

SIRPα is a type I transmembrane glycoprotein.It contains two Ig-like C1-type domains and one Ig-like V-type domain. Mouse SIRP alpha ECD shares 61%, 75%, 62%, 61%, and 59% aa sequence identity with human, rat, equine, bovine, and porcine SIRP alpha, respectively.SIRPα can express in various tissues, mainly on brain and myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells. It also can detect in neurons, smooth muscle and endothelial cells. SIRPA is an immunoglobulin-like cell surface receptor for CD47. SIRPα acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. SIRPα shows adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. SIRPα engagement generally produces a negative regulatory signal; it may mediate negative regulation of phagocytosis, mast cell activation and dendritic cell activation.

TALLA-1, also known as TSPAN7, is a member of the transmembrane 4 superfamily Most members of this family are cell-surface proteins that are characterized by the presence of four hydrophobic domains. TALLA-1 gene is associated with X-linked mental retardation and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. TALLA-1 is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. TM4SF2/TSPAN7 Protein, Rat, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 13.9 kDa and the accession number is B3STU1.

Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro. ARTN triggers oncogenicity and metastasis by the activation of the AKT signaling pathway. Recent studies have reported that the expression of ARTN in hepatocellular carcinoma is associated with increased tumor size, quick relapse and shorter survival. Furthermore, ARTN promotes drug resistance such as antiestrogens, doxorubicin, fulvestrant, paclitaxel, tamoxifen and trastuzumab. Moreover, ARTN also stimulates the radio-therapeutic resistance. Hypoxia has been reported to regulate the cancer stem cell (CSC) population yet the underlying mechanism is poorly characterized. Artemin (ARTN) is a member of the glial cell derived neurotrophic factor family of ligands, is a hypoxia-responsive factor and is essential for hypoxia-induced CSC expansion in hepatocellular carcinoma (HCC). Clinically, elevated expression of ARTN in HCC was associated with larger tumor size, faster relapse and shorter survival. In vitro, HCC cells with forced expression of ARTN exhibited reduced apoptosis, increased proliferation, epithelial-mesenchymal transition (EMT) and enhanced motility. Additionally, ARTN dramatically increased xenograft tumor size and metastasis in vivo. Moreover, ARTN also enhanced tumorsphere formation and the tumor initiating capacity of HCC cells, consequent to expansion of the CD133+ CSC population. ARTN transcription was directly activated by hypoxia-induced factor-1α (HIF-1α) and hypoxia induced ARTN promoted EMT and increased the CSC population via AKT signaling.

CNPY2 is a novel MIR-interacting protein that enhances neurite outgrowth and increases myosin regulatory light chain. CNPY2 enhances migration of C6 glioma cells through phosphorylation of the myosin regulatory light chain. It is expressed in different tissues, including brain. Overexpression of CNPY2 enhanced the motility of glioma cells measured in matrigel invasion chambers and using a scratch assay. Downregulation of CNPY2 by RNA interference significantly decreased glioma cell migration and phosphorylation of MRLC. Inhibition of the corresponding MRLC kinase by ML-7 did not affect migration of CNPY2-overexpressing cells.

TALLA-1, also known as TSPAN7, is a member of the transmembrane 4 superfamily Most members of this family are cell-surface proteins that are characterized by the presence of four hydrophobic domains. TALLA-1 gene is associated with X-linked mental retardation and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. TALLA-1 is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. TM4SF2/TSPAN7 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 13 kDa and the accession number is AAH18036.1.

Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone. Stathmin-2 Protein, Rat, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 26.7 kDa and the accession number is P21818.

RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs. Plays a role in the regulation of mRNA stability, alternative splicing and translation. Binds to AU-rich element (ARE) sequences in the 3' untranslated region (UTR) of target mRNAs, including GAP43, VEGF, FOS, CDKN1A and ACHE mRNA. Many of the target mRNAs are coding for RNA-binding proteins, transcription factors and proteins involved in RNA processing and/or neuronal development and function. By binding to the mRNA 3'UTR, decreases mRNA deadenylation and thereby contributes to the stabilization of mRNA molecules and their protection from decay. Also binds to the polyadenylated (poly(A)) tail in the 3'UTR of mRNA, thereby increasing its affinity for mRNA binding. Mainly plays a role in neuron-specific RNA processing by stabilization of mRNAs such as GAP43, ACHE and mRNAs of other neuronal proteins, thereby contributing to the differentiation of neural progenitor cells, nervous system development, learning and memory mechanisms. Involved in the negative regulation of the proliferative activity of neuronal stem cells and in the positive regulation of neuronal differentiation of neural progenitor cells. Promotes neuronal differentiation of neural stem/progenitor cells in the adult subventricular zone of the hippocampus by binding to and stabilizing SATB1 mRNA. Binds and stabilizes MSI1 mRNA in neural stem cells. Exhibits increased binding to ACHE mRNA during neuronal differentiation, thereby stabilizing ACHE mRNA and enhancing its expression. Protects CDKN1A mRNA from decay by binding to its 3'-UTR. May bind to APP and BACE1 mRNAS and the BACE1AS lncRNA and enhance their stabilization. Plays a role in neurite outgrowth and in the establishment and maturation of dendritic arbors, thereby contributing to neocortical and hippocampal circuitry function. Stabilizes GAP43 mRNA and protects it from decay during postembryonic development in the brain. By promoting the stabilization of GAP43 mRNA, plays a role in NGF-mediated neurite outgrowth. Binds to BDNF long 3'UTR mRNA, thereby leading to its stabilization and increased dendritic translation after activation of PKC. By increasing translation of BDNF after nerve injury, may contribute to nerve regeneration. Acts as a stabilizing factor by binding to the 3'UTR of NOVA1 mRNA, thereby increasing its translation and enhancing its functional activity in neuron-specific splicing. Stimulates translation of mRNA in a poly(A)- and cap-dependent manner, possibly by associating with the EIF4F cap-binding complex. May also negatively regulate translation by binding to the 5'UTR of Ins2 mRNA, thereby repressing its translation. Upon glucose stimulation, Ins2 mRNA is released from ELAVL4 and translational inhibition is abolished. Also plays a role in the regulation of alternative splicing. May regulate alternative splicing of CALCA pre-mRNA into Calcitonin and Calcitonin gene-related peptide 1 (CGRP) by competing with splicing regulator TIAR for binding to U-rich intronic sequences of CALCA pre-mRNA.

Neuritin-like protein belongs to the neuritin family. Neuritin is a GPI-anchored protein that promotes neurite outgrowth and branching of neuritic processes in primary hippocampal and cortical cells. Neuritin expression also enhances the development of motor neuron axon arbors by promoting neuromuscular synaptogenesis and by stimulating the addition of new axon branches. Neuritin is induced by neuronal activity and by the neurotrophins, BDNF and NT3. NRN1L contains a consensus cleavage signal found in glycosylphoshatidylinositol (GPI)-anchored proteins.

Immunoglobulin Superfamily Member 8 (IGSF8) is a single-pass membrane protein. IGSF8 contains four Ig-like C2 type domains. The Ig-like C2-type domains 3 and 4 are required for interactions with CD81. IGSF8 may regulate proliferation and differentiation of keratinocytes. IGSF8 may participate in the regulation of neurite outgrowth and maintenance of the neural network in the adult brain. It also may play a role on integrin-dependent morphology and motility functions.

Kallikrein-8, also known as Neuropsin, Serine protease 19, Serine protease TADG-14, Tumor-associated differentially expressed gene 14 protein, and KLK8 is a secreted protein that belongs to the peptidase S1 family and Kallikrein subfamily. It is a serine protease that is capable of degrading some proteins such as casein, fibrinogen, kininogen, fibronectin, and collagen type IV. Kallikrein-8 / KLK8 plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway. It regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. It is involved in skin desquamation and keratinocyte proliferation and plays a role in the secondary phase of pathogenesis following spinal cord injury. It also cleaves L1CAM in response to increased neural activity. It induces neurite outgrowth and fasciculation of cultured hippocampal neurons. Kallikrein-8 / KLK8 is expressed at high levels in serum, ascites fluid, and tumor cytosol of advanced-stage ovarian cancer patients and may serve as a marker of ovarian cancer. Kallikrein-8 / KLK8 may have potential clinical value for disease diagnosis or prognosis and it may also be a useful therapeutic target.

Neuritin 1 (NRN1) is a member of the neuritin family. Neuritin is a glycosylphosphatidylinositol-anchored protein induced by neural activity. It is expressed in postmitotic-differentiating neurons of the developing nervous system and a population of small-diameter neurons in the dorsal root ganglia and was anterogradely and retrogradely transported. Neuritin message is induced by neuronal activity and by the activity-regulated neurotrophins BDNF, nerve growth factor (NGF), and NT-3. Purified recombinant neuritin promotes neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures. Thus, neuritin is considered as a downstream effector of activity-induced neurite outgrowth. In clinical, neuritin levels in diabetes were reduced in both dorsal root ganglia and sciatic nerve of rats, and these deficits were reversed in vivo by treatment with NGF. This manipulation of neuritin levels in diabetes may provide a potential target for therapeutic intervention in the management of neuropathy.

SLITRK6 belongs to the SLITRK family. Members of this family share two conserved leucine-rich repeat domains in the extracellular domain. SLITRK6 contains 11 LRR (leucine-rich) repeats, 2 LRRCT domains and 2 LRRNT domains. Expression of SlITRK proteins is highly restricted to neural and brain tumor tissues, but varies within the protein family. SLITRK6 is highly expressed in putamen with no expression in cerebral cortex. It also can be detected in adult and fetal lung and fetal liver. It can suppress neurite outgrowth. In adult brain, SLITRK6 has a critical role in the development of the inner ear neural circuit.

Reticulon-4, also known as Foocen, Neurite outgrowth inhibitor, Nogo protein, Neuroendocrine-specific protein, Neuroendocrine-specific protein C homolog, RTN-x, Reticulon-5 and RTN4, is a multi-pass membrane protein that contains one reticulon domain. Isoform 1 of RTN4 is specifically expressed in brain and testis and weakly in heart and skeletal muscle. Isoform 2 of RTN4 is widely expressed except for the liver. Isoform 3 of RTN4 is expressed in brain, skeletal muscle and adipocytes. Isoform 4 of RTN4 is testis-specific. Reticulon-4 / RTN4 is a developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Reticulon-4 / RTN4 regulates neurite fasciculation, branching and extension in the developing nervous system. Reticulon-4 / RTN4 is involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. It regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex. Isoform 2 of RTN4 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 of RTN4 inhibit BACE1 activity and amyloid precursor protein processing.

Neuromodulin, also known as Axonal membrane protein GAP-43, Growth-associated protein 43, Neural phosphoprotein B-5, pp46 and GAP43, is a cell membrane protein which belongs to theneuromodulin family. Neuromodulin / GAP43 contains oneIQ domain. Neuromodulin / GAP43 is associated with nerve growth. It is a major component of the motile growth cones that form the tips of elongating axons. Neuromodulin / GAP43 is involved in neurite outgrowth, a crucial process for the differentiation of neurons. The sudden infant death syndrome (SIDS) is the main cause of postneonatal infant death and its cause is still unknown. Neuromodulin / GAP43 is a marker of synaptic plasticity and is critical for normal development of the serotonergic innervation. Neuromodulin / GAP43 is a major cortical cytoskeleton-associated and calmodulin binding protein that is widely and abundantly expressed during development, maintained in selected brain structures in the adult, and reinduced during nerve regeneration. CAP23 and GAP43 are functionally related intrinsic determinants of anatomical plasticity. These proteins function by locally promoting subplasmalemmal actin cytoskeleton accumulation.

Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale microdeletions or microduplications in the 3p26.3 region are often the cause of neurodevelopmental disorders, including intellectual disability and developmental delay. Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. The deletion or duplication of the CNTN6 gene is associated with a wide spectrum of neurodevelopmental behavioral disorders. The protein encoded by CNTN6 is a member of the immunoglobulin superfamily and functions as a cell adhesion molecule that is involved in the formation of axon connections in the developing nervous system.

TALLA-1, also known as TSPAN7, is a member of the transmembrane 4 superfamily Most members of this family are cell-surface proteins that are characterized by the presence of four hydrophobic domains. TALLA-1 gene is associated with X-linked mental retardation and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. TALLA-1 is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. TM4SF2/TSPAN7 Protein, Cynomolgus, Recombinant (mFc) is expressed in HEK293 mammalian cells with mFc tag. The predicted molecular weight is 38.2 kDa and the accession number is Q4R5A3.

Has mitogenic activity, and neurite extension activity for PC12 cells. Midkine Protein, Chicken, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 20.9 kDa and the accession number is P24052.

May play a role in cell differentiation, proliferation and apoptosis. Binds cholesterol in cholesterol-containing plasma membrane microdomains and may play a role in the organization of the apical plasma membrane in epithelial cells. During early retinal development acts as a key regulator of disk morphogenesis. Involved in regulation of MAPK and Akt signaling pathways. In neuroblastoma cells suppresses cell differentiation such as neurite outgrowth in a RET-dependent manner.

Growth Arrest-Specific Protein 7 (GAS7) is expressed primarily in terminalaly differentiated brain cells and predominantly in mature cerebellar Purkinje neurons. GAS7 may play a role in neuronal development by promoting maturation and morphological differentiation of cerebellar neurons. Inhibition of GAS7 production in terminally differentiating cultures of embryonic murine cerebullum impedes neurite outgrowth. The hyper-expression of GAS7 may play an major role in the initiation and development of huaman osteosarcoma.

EphA8, also known as Hek3 and Eek, is a 120 kDa glycosylated member of the Eph family of transmembrane receptor tyrosine kinases. The A and B classes of Eph proteins are distinguished by Ephrin ligand binding preference but have a common structural organization. Eph-Ephrin interactions are widely involved in the regulation of cell migration, tissue morphogenesis, and cancer progression. Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.

Amyloid precursor protein (APP) is a type I membrane protein with several isoforms due to alternative splicing, performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Of the three major splice isoforms of APP (APP695, APP751, and APP770) APP695 is the predominant neuronal form from which Amyloid beta peptide and transcriptionally-active cleaved intracellular domain of APP (AICD) are preferentially generated by selective processing through the amyloidogenic pathway. Human APP695 consists of a 17 amino acid (aa) signal sequence, a 607 aa extracellular domain (ECD), a 24 aa transmembrane domain, and a 47 aa cytoplasmic domain. Within the ECD, human APP695 shares 97% aa sequence identity with mouse and rat APP695. Amyloid beta is a major molecule implicated in pathogenesis of Alzheimer's disease (AD) and related dementias. AICD regulates expression by direct promoter binding of multiple genes, including APP itself, the beta-secretase, BACE-1 and the Amyloid beta-degrading enzyme, Neprilysin. As such, APP695 plays an important role in brain development, learning and memory, synaptic plasticity, and neurodegeneration including AD.

Calcium/Calmodulin-Dependent Protein Kinase Type 1 (CAMK1) belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family, and CaMK subfamily. CAMK1 contains one protein kinase domain and widely expressed. CAMK1 is phosphorylated by CaMKK1 and CaMKK2 on Thr-177. CAMK1 regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization, and neurite outgrowth. CAMK1 plays a role in K+ and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex.

Leucine-rich repeat transmembrane protein FLRT3, also known as Fibronectin-like domain-containing leucine-rich transmembrane protein 3, and FLRT3, is a single-pass type I membrane protein which belongs to the fibronectin leucine rich transmembrane protein (FLRT) family. FLRT3 contains one fibronectin type-III domain and ten LRR (leucine-rich) repeats and is expressed in kidney, brain, pancreas, skeletal muscle, lung, liver, placenta, and heart. It has a provocative expression pattern during somite development being expressed in regions of the somite where muscle precursor cells migrate from the dermomyotome and move into the myotome, and later in myotomal precursors destined to migrate towards their final destination. FLRT1, FLRT2 and FLRT3 are members of the FLRT family. The FLRT family of leucine-rich repeat (LRR) proteins is implicated in fibroblast growth factor (FGF) signalling, early embryonic development and neurite outgrowth. FLRT3 shares 55% amino acid sequence identity with FLRT1 and 44% identity with FLRT2. Two alternatively spliced transcript variants encoding the same protein have been described. The expression of FLRT3 is controlled by fibroblast growth factors (FGFs). FLRT3 has been implicated in neurite outgrowth after nerve damage, as a positive regulator of FGF signalling and in homotypic cell adhesion. FLRT3 may have a crucial role in regulating cellular adhesion between the epithelial apical ridge and the underlying mesenchyme and in establishing the dorso-ventral position of the ridge.

The three fibronectin leucine-rich repeat transmembrane (FLRT) proteins contain 10 leucine-rich repeats (LRR), a type III fibronectin (FN) domain, followed by the transmembrane region, and a short cytoplasmic tail. FLRT1 is expressed in kidney and brain, which is a target for tyrosine phosphorylation mediated by FGFR1 and implicates a non-receptor Src family kinase (SFK). All FLRTs can interact with FGFR1 and FLRTs can be induced by the activation of FGF signalling by FGF-2. The phosphorylation state of FLRT1, which is itself FGFR1 dependent, may play a critical role in the potentiation of FGFR1 signalling and may also depend on a SFK-dependent phosphorylation mechanism acting via the FGFR. This is consistent with an 'in vivo' role for FLRT1 regulation of FGF signalling via SFKs. Furthermore, the phosphorylation-dependent futile cycle mechanism controlling FGFR1 signalling is concurrently crucial for regulation of FLRT1-mediated neurite outgrowth. FLRT1, FLRT2 and FLRT3 are members of the fibronectin leucine rich transmembrane protein (FLRT) family. They may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. FLRT3 shares 55% amino acid sequence identity with FLRT1.

TALLA-1, also known as TSPAN7, is a member of the transmembrane 4 superfamily Most members of this family are cell-surface proteins that are characterized by the presence of four hydrophobic domains. TALLA-1 gene is associated with X-linked mental retardation and neuropsychiatric diseases such as Huntington's chorea, fragile X syndrome and myotonic dystrophy. TALLA-1 is a cell surface glycoprotein and may have a role in the control of neurite outgrowth. It is known to complex with integrins. TM4SF2/TSPAN7 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 13 kDa and the accession number is Q62283.

May play an important role in neural, kidney and vascular development. Promotes neurite elongation from olfactory bulb explants. Netrin-4/NTN4 Protein, Human, Recombinant (GST & His & Myc) is expressed in E. coli expression system with N-10xHis-GST and C-Myc tag. The predicted molecular weight is 58.9 kDa and the accession number is Q9HB63.

Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids with preference for phosphatidylcholines and phosphatidylglycerols over phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty acyls. Contributes to phospholipid remodeling of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing unsaturated fatty acids that regulate macrophage differentiation toward foam cells. Efficiently hydrolyzes and inactivates PAF, a potent lipid mediator present in oxidized LDL. May act in an autocrine and paracrine manner. Secreted by lung epithelium, targets membrane phospholipids of infiltrating eosinophils, releasing arachidonate and boosting eicosanoid and cysteinyl leukotriene synthesis involved in airway inflammatory response. Secreted by gut epithelium, hydrolyzes dietary and biliary phosphatidylcholines in the gastrointestinal lumen, thereby regulating adipogenesis and body weight. Plays a stem cell regulator role in colon epithelium. Within intracellular compartment, mediates Paneth-like cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates the Wnt signaling pathway in ISCs and tissue regeneration. May participate in hair follicle morphogenesis by regulating phosphatidylethanolamines metabolism at the outermost epithelial layer and facilitating melanin synthesis. By generating lysophosphatidylcholines (LPCs) at sperm acrosome controls sperm cell capacitation, acrosome reaction and overall fertility. May promote neurite outgrowth in neuron fibers involved in nociception. Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Cleaves sn-2 fatty acyl chains of phosphatidylglycerols and phosphatidylethanolamines, which are major components of membrane phospholipids in bacteria. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane. In pulmonary epithelium, may contribute to host defense response against adenoviral infection. Prevents adenovirus entry into host cells by hydrolyzing host cell plasma membrane, releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and viral infection. Likely prevents adenoviral entry into the endosomes of host cells. May play a role in maturation and activation of innate immune cells including macrophages, group 2 innate lymphoid cells and mast cells.