Recombinant Human Semaphorin 4D Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-4196

Recombinant Human Semaphorin 4D Protein (His Tag)

Beta LifeScience SKU/CAT #: BLPSN-4196
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Product Overview

Tag His
Host Species Human
Accession Q92854
Synonym C9orf164, CD100, coll-4, M-sema-G, SEMAJ
Background Semaphorin 4D (SEMA4D or CD1) is a member of the semaphorin family of proteins and an important mediator of the movement and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. VEGF and SEMA4D had a positive correlation with the malignant degree of ovarian cancer, and SEMA4D can serve as an independent prognostic factor. SEMA4D was the first semaphorin described to have immune functions and serves important roles in T cell priming, antibody production, and cell-to-cell adhesion. Proteolytic cleavage of SEMA4D from the cell surface gives rise to a soluble fragment of SEMA4D (sSEMA4D). Similar to the transmembranal form, sSEMA4D is thought to have immunoregulatory properties.
Description A DNA sequence encoding the human SEMA4D isoform 1 (Q92854-1) extracellular domain (Met 1-Arg 734) was expressed, with a His tag at the C-terminus.
Source HEK293
Predicted N Terminal Met 22
AA Sequence Met 1-Arg 734
Molecular Weight The recombinant human SEMA4D consists of 725 a.a. and predictes a molecular mass of 80.7 kDa. In SDS-PAGE under reducing conditions, the apparent molecular mass of rhSEMA4D is approximately 110 kDa due to glycosylation.
Purity >92% as determined by SDS-PAGE
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity Measured by its binding ability in a functional ELISA. Immobilized human SEMA4D-His at 10 ug/ml (100 ul/well) can bind mouse PTPRC-Fc with a linear range of 0.625-5 ug/ml.
Formulation Lyophilized from sterile PBS, pH 7.4.
Stability The recombinant proteins are stable for up to 1 year from date of receipt at -70°C.
Usage For Research Use Only
Storage Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function Cell surface receptor for PLXNB1 and PLXNB2 that plays an important role in cell-cell signaling. Regulates GABAergic synapse development. Promotes the development of inhibitory synapses in a PLXNB1-dependent manner. Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA. Promotes the migration of cerebellar granule cells. Plays a role in the immune system; induces B-cells to aggregate and improves their viability (in vitro). Induces endothelial cell migration through the activation of PTK2B/PYK2, SRC, and the phosphatidylinositol 3-kinase-AKT pathway.
Subcellular Location Cell membrane; Single-pass type I membrane protein.
Protein Families Semaphorin family
Database References
Tissue Specificity Strongly expressed in skeletal muscle, peripheral blood lymphocytes, spleen, and thymus and also expressed at lower levels in testes, brain, kidney, small intestine, prostate, heart, placenta, lung and pancreas, but not in colon and liver.

Gene Functions References

  1. Combined detection of tumor-associated macrophages markers, CD68 and Sema4D, in gastric carcinoma tissue shows potential to predict the trend of gastric carcinoma progression. PMID: 29434448
  2. SEMA4D coordinates with VEGF during angiogenesis via plexin-B1 in epithelial ovarian cancer. PMID: 29308068
  3. knockdown of Sema4D in Head and neck squamous cell carcinomas (HNSCCs)cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion. PMID: 28656278
  4. The results obtained make significant adjustments in understanding of Seam4D effects in lymphoid cells. PMID: 28508207
  5. describe the transfection, purification, and visualization of Fc-tagged SEMA4D (semaphorin 4D) recombinant protein PMID: 27787840
  6. describe the application of in vitro migration and tubulogenesis assays and the directed in vivo angiogenesis assay (DIVAA) in the measurement of the angiogenic potential of cell-derived and soluble SEMA4D PMID: 27787869
  7. The positive expression of both Sema4D and PlexinB1 was found to be an independent risk factor for a worse survival in colorectal cancer. PMID: 27456345
  8. Serum levels of soluble SEMA4D were elevated in patients with ANCA-associated vasculitis. Cell-surface expression of SEMA4D was downregulated, a consequence of proteolytic cleavage of membrane SEMA4D. Soluble SEMA4D exerted pro-inflammatory effects on endothelial cells. Membranous SEMA4D on neutrophils bound to plexin B2 on endothelial cells, and this interaction decreased NET formation. PMID: 28416516
  9. We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415). A novel variant in SEMA4D was significantly associated with body mass index. Carriers of the C allele were 4.6 BMI units heavier than carriers of the T allele. PMID: 28296344
  10. A critical pathogenic engagement of Semaphorin 4D produced by gamma delta T cells in the development of medication-related osteonecrosis of the jaw PMID: 27720716
  11. Our results identified FGL2, GAL, SEMA4D, SEMA7A, and IDO1 as new candidate genes that could be involved in MSCs-mediated immunomodulation. FGL2, GAL, SEMA4D, SEMA7A, and IDO1 genes appeared to be differentially transcribed in the different MSC populations. Moreover, these genes were not similarly modulated following MSCs-exposure to inflammatory signals PMID: 28336906
  12. Interferon-alpha-induced CD100 expression on naive CD8(+) T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction. PMID: 28222623
  13. In this review, we summarized the current findings on neuroimmune Sema4A and Sema4D molecules in chronic inflammation underlying many diseases and discussed their positive or negative impacts on the implicated molecular and cellular processes PMID: 27554682
  14. we have identified a novel reverse signaling pathway acting through Tiam1 and Rac that promotes aggressive behavior in OSCC expressing S4D and PB1. PMID: 28038319
  15. sema 4D was the direct target of miR-214 and was negatively regulated by miR-214 in ovarian cancer cells PMID: 26718213
  16. Tax and semaphorin 4D released from lymphocytes infected with human lymphotropic virus type 1 and inhibit neurite growth in a neuron cell line. PMID: 26389656
  17. This assay specifically and reproducibly measured cSEMA4D saturation and expression levels. Evaluation of the SEMA4D-specific PD markers were critical in determining the clinical saturation threshold of cSEMA4D by VX15/2503 PMID: 26566052
  18. Serum sSema4D levels are increased in patients with atrial fibrillation and are independently associated with atrial remodeling PMID: 26417899
  19. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. PMID: 26910109
  20. this study describes a novel immunosuppressive role for Sema4D in head and neck squamous cell carcinoma through induction of myeloid derived suppressor cells PMID: 26740106
  21. Plexin-B1 induces cutaneous squamous cell carcinoma cell proliferation, migration, and invasion by interacting with Sema4D. Plexin-B1 might serve as a useful biomarker and/or as a novel therapeutic target for cSCC. PMID: 26051877
  22. Results show that decreased expression of Sema4D, plexin-B1 and -B2 was associated with local recurrence and poor prognosis of breast neoplasm. PMID: 26035216
  23. Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. PMID: 26275342
  24. Suggest that HIF-1alpha and Sema4D expression correlates with histological tumor type, TNM stage, and lymphatic metastasis in colorectal carcinoma. PMID: 25717256
  25. A positive feedback loop involving sSema4D/IL-6 and TNFalpha/ADAMTS-4 may contribute to the pathogenesis of rheumatoid arthritis. PMID: 25707877
  26. Sema4D contributes to enhanced invasion and tumor progression through increased motility of cervical cancer and VEGF-C/-D-mediated lymphangiogenesis. PMID: 24603190
  27. SEMA4D might possibly serve as a reliable tool for early and accurate prediction of EOC poor prognosis. PMID: 24289594
  28. results suggest that the contribution of Sema4D in platelets applies to ITAM-containing receptors as a class PMID: 24131822
  29. Sema4D could play an important role in promoting tumor proliferation, migration and metastasis in the NSCLC, by influencing the Akt protein phosphorylation. Inhibition of Sema4D may be a useful approach for the treatment of NSCLC. PMID: 25135716
  30. Data suggest that CD100 seems to be involved in hepatitis C virus (HCV) clearance by natural killer (NK) cells. PMID: 25108441
  31. The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4. PMID: 24114199
  32. Elevated plasma soluble Sema4D/CD100 levels are associated with disease severity in patients of hemorrhagic fever with renal syndrome. PMID: 24040126
  33. CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas. PMID: 24098722
  34. There was an increased level of plasma soluble Sema4 in the Sema4D(high) population of T-cells suggesting a potential role of these T-cells in heart failure. PMID: 23741311
  35. The membrane-proximal cytoplasmic domain of Sema4D contains a binding site for calmodulin within the polybasic region Arg762-Lys779, that regulates Sema4D exodomain shedding in platelets. PMID: 23564909
  36. copy number loss of the Sema4D gene region may play a role in the etiology of acetabular dysplasia PMID: 23335257
  37. Lycorine hydrochloride suppressed the expression of several key angiogenic genes, including VE-cadherin and Sema4D, and reduced Akt phosphorylation in Hey1B cells. PMID: 23376478
  38. CD72 mRNA expression level correlates with Sema4D expression in peripheral blood mononuclear cells in immune thrombocytopenia. PMID: 22111667
  39. CD100 protein levels were highly dysregulated around 10 weeks of gestation in first and second miscarriage placentas. The CD100 soluble form was produced and immediately shed from placental tissue in all samples. PMID: 22606231
  40. The expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). PMID: 22652457
  41. Sema4D, the ligand for Plexin B1, suppresses c-Met activation and migration and promotes melanocyte survival and growth. PMID: 22189792
  42. Sema4D potentiates the invasiveness of pancreatic cancer cells. The binding of Sema4D to plexinB1 induced small GTPase Ras homolog gene family, member A activation and resulted in the phosphorylation of MAPK and Akt. PMID: 21812859
  43. From the data obtained in this study, SEMA4D may have a role in more aggressive and potentially metastatic breast tumours. PMID: 21925246
  44. Rho-mediated activation of PI(4)P5K and lipid second messengers is necessary for promotion of angiogenesis by Semaphorin 4D. PMID: 21538148
  45. dysregulations in CD100 expression and release could play a role in SSc development and/or maintenance. PMID: 21244334
  46. crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto) PMID: 20877282
  47. CD100-CD72 interaction can be the mechanism by which NK cell communicate with B cells. PMID: 17786190
  48. Leukemic & normal CD5+ B cells express CD100; upon interaction between CD100 & Plexin-B1, both increase their proliferative activity & life span. CD100/Plexin-B1 crosstalk is not malignancy related but reproduces a mechanism used by normal CD5+ B cells. PMID: 12406905
  49. Soluble CD100 induces a progressive decrease in process extension of oligodendrocytes, followed by their death and the death of multipotent neural precursors. PMID: 14707103
  50. up-modulation of the survival receptor CD100 is restricted to proliferating B-cell leukemia cells PMID: 15613544


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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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