Recombinant Human Midkine Protein

Beta LifeScience SKU/CAT #: BLPSN-3366

Recombinant Human Midkine Protein

Beta LifeScience SKU/CAT #: BLPSN-3366
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Product Overview

Tag N/A
Host Species Human
Accession P21741
Synonym ARAP, MK, NEGF2
Background 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 breast carcinomas marker.
Description A DNA sequence encoding the human MDK (P21741) (Met 1-Asp 143) was expressed and purified.
Source Baculovirus-Insect Cells
Predicted N Terminal Val 21
AA Sequence Met 1-Asp 143
Molecular Weight The secreted recombinant human MDK consists of 123 a.a. and predicts a molecular mass of 13.4 kDa. It migrates as an approximately 18 kDa band in SDS-PAGE under reducing conditions.
Purity >95% 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 MDK at 10 ug/ml (100 ul/well) can bind mouse SDC4-Fc with a linear range of 0.16-1.25 ug/ml.
Formulation Lyophilized from sterile 50mM PBS, 1 M NaCl, pH 6.8.
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 Secreted protein that functions as cytokine and growth factor and mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors. Binds cell-surface proteoglycan receptors via their chondroitin sulfate (CS) groups. Thereby regulates many processes like inflammatory response, cell proliferation, cell adhesion, cell growth, cell survival, tissue regeneration, cell differentiation and cell migration. Participates in inflammatory processes by exerting two different activities. Firstly, mediates neutrophils and macrophages recruitment to the sites of inflammation both by direct action by cooperating namely with ITGB2 via LRP1 and by inducing chemokine expression. This inflammation can be accompanied by epithelial cell survival and smooth muscle cell migration after renal and vessel damage, respectively. Secondly, suppresses the development of tolerogenic dendric cells thereby inhibiting the differentiation of regulatory T cells and also promote T cell expansion through NFAT signaling and Th1 cell differentiation. Promotes tissue regeneration after injury or trauma. After heart damage negatively regulates the recruitment of inflammatory cells and mediates cell survival through activation of anti-apoptotic signaling pathways via MAPKs and AKT pathways through the activation of angiogenesis. Also facilitates liver regeneration as well as bone repair by recruiting macrophage at trauma site and by promoting cartilage development by facilitating chondrocyte differentiation. Plays a role in brain by promoting neural precursor cells survival and growth through interaction with heparan sulfate proteoglycans. Binds PTPRZ1 and promotes neuronal migration and embryonic neurons survival. Binds SDC3 or GPC2 and mediates neurite outgrowth and cell adhesion. Binds chondroitin sulfate E and heparin leading to inhibition of neuronal cell adhesion induced by binding with GPC2. Binds CSPG5 and promotes elongation of oligodendroglial precursor-like cells. Also binds ITGA6:ITGB1 complex; this interaction mediates MDK-induced neurite outgrowth. Binds LRP1; promotes neuronal survival. Binds ITGA4:ITGB1 complex; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation. 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. Promotes epithelial to mesenchymal transition through interaction with NOTCH2. During arteriogenesis, plays a role in vascular endothelial cell proliferation by inducing VEGFA expression and release which in turn induces nitric oxide synthase expression. Moreover activates vasodilation through nitric oxide synthase activation. Negatively regulates bone formation in response to mechanical load by inhibiting Wnt/beta-catenin signaling in osteoblasts. In addition plays a role in hippocampal development, working memory, auditory response, early fetal adrenal gland development and the female reproductive system.
Subcellular Location Secreted.
Protein Families Pleiotrophin family
Database References
Tissue Specificity Expressed in various tumor cell lines. In insulinoma tissue predominantly expressed in precancerous lesions.

Gene Functions References

  1. Studied levels of mucin 16 (CA125), adenosine deaminase and midkine as tumor markers in nonsmall cell lung cancer-associated malignant pleural effusion. PMID: 29797475
  2. we show that MK can potentially be used as a surrogate biomarker for predicting DTC metastases when Tg is not suitable due to TgAb positivity. PMID: 28240744
  3. Midkine expression is not significantly linked to metastatic disease in pancreatic ductal adenocarcinoma. PMID: 29355490
  4. High midkine expression is associated with invasion and metastasis in Hepatocellular Carcinoma. PMID: 29936723
  5. This study has demonstrated an important association between increased serum MK (midkine)levels and risk factors of atherosclerosis such as HT(Hypertension),increased total and LDL cholesterol. PMID: 29984722
  6. Midkine can be considered as both a differentiating factor and a molecular-targeted therapy in odontogenic lesions PMID: 29383694
  7. Positive expression of MK predicts poor prognosis in patients with resectable combined hepatocellular cholangiocarcinoma. PMID: 29486735
  8. The data of this study showed that the serum MK concentration in ASD patients is significantly higher than healthy controls. PMID: 29164967
  9. MDK promoted gemcitabine resistance of biliary tract cancer through inducing epithelial to mesenchymal transition via upregulating Notch1. PMID: 29344648
  10. These results demonstrate that analysis of IHC expression patterns of MK and NANOG in pretreatment biopsy specimens during the work-up period can provide a more definitive prognosis prediction for each oral squamous cell carcinoma (OSCC) patient that can help clinicians to develop a more precise individual treatment modality. PMID: 29113102
  11. Elevated plasma midkine and pleiotrophin levels in systemic lupus erythematosus (SLE) patients suggest their involvement in this disease. PMID: 27903979
  12. Urinary midkine may be an effective biological marker for early diagnosis of acute kidney injury. PMID: 27530994
  13. suppression of midkine gene promoted the antitumoral effect of cisplatin on human gastric cell line AGS in vitro and in vivo via Notch signaling pathway. PMID: 28656262
  14. Results revealed that ectopic overexpression of midkine in HCC cell lines with IGF-1R inhibition markedly rescued inhibition of HCC cell proliferation, migration, and invasion. These data imply that inhibition of IGF-1R suppresses HCC growth and invasion via down-regulating midkine expression. PMID: 27813495
  15. Midkine is involved in bowel inflammation in UC and lymph node metastasis in CRC, rendering midkine an attractive target for their treatment. PMID: 27692729
  16. According to our results, serum MK has greater diagnostic value in diagnosing cancer, however, more reliable studies in larger cohort should be conducted to evaluate the diagnostic accuracy of serum MK. PMID: 28686647
  17. Data suggest that mature KLK9 (kallikrein 9) is a glycosylated chymotrypsin-like enzyme with strong preference for tyrosine over phenylalanine at P1 cleavage position; substrate specificity of KLK9 appears to extend to KLK10 and midkine; enzyme activity is enhanced by Mg2+ and Ca2+, but is reversibly attenuated by Zn2+; KLK9 is inhibited in vitro by many naturally occurring or synthetic protease inhibitors. PMID: 28559305
  18. this paper shows that measurement of serum levels of MK is helpful in confirming the diagnosis of Henoch-Schonlein purpura and predicting related nephritis in Chinese children PMID: 27497193
  19. midkine may be a good inflammatory marker in renal transplant recipients as in other inflammatory diseases. Moreover, it seems that it is not affected by factors other than inflammation during the post-transplantation period. PMID: 27470002
  20. MK high expression is an independent adverse prognostic factor in childhood ALL. Its level may be incorporated into an improved risk classification system for ALL and suggest the need of alternative regimens. PMID: 26352402
  21. Study shows that overexpression of serum MK levels in patients with head and neck squamous cell carcinoma are associated with poor prognosis. PMID: 26798989
  22. MK was significantly elevated in vitamin D deficiency and associated with anti-Saccharomyces cerevisiae antibodies positivity which was significantly increased in vitamin D deficiency PMID: 26566633
  23. MDK plays an important role in non-small cell lung cancer progression and prognosis and may act as a convincing prognostic indicator for non-small cell lung cancer patients. PMID: 26656665
  24. The concentration of MDK in amniotic fluid declined with gestational age.MDK concentrations in amniotic fluid were far higher than in maternal plasma. PMID: 27089523
  25. The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture. PMID: 25787827
  26. overexpression of midkine protein serves as an unfavorable prognostic biomarker in breast cancer patients PMID: 26159850
  27. our results suggest that midkine expression could be a clinically useful marker in predicting the presence of multiple lymph node metastases in BRAFV600E papillary thyroid carcinoma. PMID: 26297257
  28. PLSCR1 positively regulates hepatic carcinoma cell proliferation and migration through interacting with midkine PMID: 26642712
  29. Use hybrid-type modified chitosan derivative nanoparticles to deliver midkine-siRNA to HepG2 cells. PMID: 25655295
  30. Data shows the possibility that Staphylococcus aureus modulates and corrupts host airway defense lines such as MK by fragmentation in both immuno-competent and -suppressed patient groups. PMID: 24043271
  31. SP1 directly up-regulated the expression of midkine (MDK), and the SP1-MDK axis cooperated in glioma tumorigenesis. PMID: 25428991
  32. Results from targeted sequencing in patients with acute lymphoblastic leukemia identified KMT2D and KIF1B as novel putative driver genes and a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. PMID: 25355294
  33. MK expression in glioma was higher than in paratumor tissues. Overexpression was associated with the WHO grade, low Karnofsky score, time to recurrence, and poor survival. Co-expression of pleiotrophin and MK had a worse prognosis than either alone. PMID: 25001988
  34. midkine is as good as or even better than thyroglobulin to screen patients with thyroid nodules for differentiated thyroid cancer before surgery, and to predict whether metastases exist PMID: 25817231
  35. MK was expressed in adipocytes and regulated by inflammatory modulators. a significant increase in MK levels was observed in adipose tissue of obese ob/ob mice as well as in serum of overweight/obese subjects when compared with their respective controls. PMID: 24516630
  36. High expression levels of Midkine in gastric cardiac adenocarcinoma tissues may indicate a differentiation stage that is characteristic of malignancy, a late clinical stage and a poor prognosis. PMID: 25017879
  37. Midkine protein level is significantly higher in the papillary thyroid cancer than in the multi-nodular goiter patients. PMID: 25283079
  38. High levels of midkine in severe peripheral artery disease patients introduce this cytokine as a possible novel effector in the advanced atherosclerotic process. PMID: 25056169
  39. frequently expressed in pancreatic cancer and associated with perineural invasion PMID: 24659893
  40. Study presents novel MK functions and new upstream signaling effectors that induce its expression to promote PDAC. PMID: 24567526
  41. Midkine is specifically expressed in papillary thyroid cancer tissues and is associated with clinicopathological features and BRAF mutation. PMID: 24272599
  42. MK might play an important role in the progression of HNSCC and may be a useful prognostic factor PMID: 24164595
  43. PKCdelta/midkine axis mediates hypoxic proliferation and differentiation of lung epithelial cells. PMID: 24500281
  44. Circulating Midkine is significantly higher in malignant and non-malignant colorectal diseases than in apparently healthy individuals with more pronounced elevation in colorectal cancer than in non-malignant conditions. PMID: 23899719
  45. serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred. PMID: 23719264
  46. High MK expression was found in cystic fibrosis lung tissue compared with control samples, involving epithelia of the large and small airways, alveoli, and cells of the submucosa (i.e., neutrophils and mast cells). PMID: 23815177
  47. This study shows that airway epithelial cells of large airways and alveoli have a constitutive production of MK that is part of the bactericidal activity present in the air surface liquid, at least in vitro, and may thus be an important part of this arm of airway host defense. PMID: 23391998
  48. The MDK signal peptide contains both subdominant and cryptic CD4+ T cell epitopes. PMID: 23553629
  49. Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. PMID: 22562257
  50. MDK upregulation in castration resistant prostate cancer is associated with neuroendicrine differentiation (shown by its relation to CGA and TUBB3). PMID: 23129424


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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.

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