Recombinant Human Nectin-4 (NECTIN4), partial (Active)

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Code CSB-MP822274HU
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Size $228
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
  • Activity
    Measured by its binding ability in a functional ELISA. Immobilized NECTIN4 at 2 μg/ml can bind anti-NECTIN4 antibody(CSB-RA822274A0HU)(enfortumab vedotin-like), the EC50 is 0.6029-0.7837 ng/mL. Biological Activity Assay
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Product Details

Purity
Greater than 95% as determined by SDS-PAGE.
Endotoxin
Less than 1.0 EU/ug as determined by LAL method.
Activity
Measured by its binding ability in a functional ELISA. Immobilized NECTIN4 at 2 μg/mL can bind anti-NECTIN4 antibody(CSB-RA822274A0HU)(enfortumab vedotin-like), the EC50 is 0.6029-0.7837 ng/mL.
Target Names
Uniprot No.
Research Area
Cell Biology
Alternative Names
(Ig superfamily receptor LNIR)(Nectin cell adhesion molecule 4)(Poliovirus receptor-related protein 4)
Molecular Characterization
Species
Homo sapiens (Human)
Source
Mammalian cell
Expression Region
32-349aa
Target Protein Sequence
GELETSDVVTVVLGQDAKLPCFYRGDSGEQVGQVAWARVDAGEGAQELALLHSKYGLHVSPAYEGRVEQPPPPRNPLDGSVLLRNAVQADEGEYECRVSTFPAGSFQARLRLRVLVPPLPSLNPGPALEEGQGLTLAASCTAEGSPAPSVTWDTEVKGTTSSRSFKHSRSAAVTSEFHLVPSRSMNGQPLTCVVSHPGLLQDQRITHILHVSFLAEASVRGLEDQNLWHIGREGAMLKCLSEGQPPPSYNWTRLDGPLPSGVRVDGDTLGFPPLTTEHSGIYVCHVSNEFSSRDSQVTVDVLDPQEDSGKQVDLVSAS
Mol. Weight
36.9 kDa
Protein Length
Partial
Tag Info
C-terminal 10xHis-tagged
Form
Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer
Lyophilized from a 0.2 μm filtered 20 mM Tris-HCl, 0.5 M NaCl, 6% Trehalose, pH 8.0
Reconstitution
We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting and FAQs
Storage Condition
Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life
The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time
Basically, we can dispatch the products out in 3-7 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA
Please contact us to get it.
Description

Co-introduction of the gene encoding the human Nectin-4 (NECTIN4) protein (32-349aa) with the C-terminal 10xHis-tag gene creates a recombinant plasmid, which is then transformed into mammalian cells. Mammalian cells that can endure a specific antibiotic are selected and cultured under conditions that encourage the expression of the gene of interest. Following expression, affinity purification is employed to isolate and purify the recombinant human NECTIN4 protein from the cell lysate. Its purity exceeds 95% and its endotoxin content is less than 1.0 EU/ug. Its activity has been validated through a functional ELISA.

Nectin-4 is a sticky molecule crucial for many cell activities. It's got several parts: a front end with three immunoglobulin-like pieces, a middle part that spans the cell membrane, and a tail that reaches into the cell's interior and hooks up with the cell's structural scaffold, called the actin cytoskeleton [1]. Belonging to the nectin family, it's involved in steering cells in the right direction, controlling how fast they grow, what they turn into, how they move, and whether they invade other tissues [2]. It teams up with a protein called afadin, which latches onto the cell's internal skeleton, to get its job done [3].

Nectin-4 mostly hangs out on tumor cells, which makes it a promising target for cancer treatments that harness the immune system [4]. It's especially abundant in urothelial carcinoma, suggesting it could be a bull's-eye for drugs in this type of cancer [5]. In some types of thyroid cancer, it's been tagged as a gene that helps tumors grow and spread [6]. It's even involved in the growth of new blood vessels, a process called angiogenesis, via a signaling pathway involving Src, making it a potential target in cancers like angiosarcoma [2]. And it's not just cancers - it's also a doorway for viruses like measles to invade cells [7][8][9][10][11]. Plus, it might have a role in a serious pregnancy complication called pre-eclampsia, and it's found in the skin, esophagus, bladder, and placenta tissues [12]. Lastly, it has been linked to the spread of cancer to other parts of the body and putting the brakes on the immune system in ovarian cancer [13].

References:
[1] R. Rotunno, A. Diociaiuti, M. Dentici, M. Rinelli, M. Callea, C. Retrosiet al., Ectodermal dysplasia-syndactyly syndrome with toe-only minimal syndactyly due to a novel mutation in nectin4: a case report and literature review, Genes, vol. 12, no. 5, p. 748, 2021. https://doi.org/10.3390/genes12050748
[2] Y. Tanaka, M. Murata, K. Tanegashima, Y. Oda, & T. Ito, Nectin cell adhesion molecule 4 regulates angiogenesis through src signaling and serves as a novel therapeutic target in angiosarcoma, Scientific Reports, vol. 12, no. 1, 2022. https://doi.org/10.1038/s41598-022-07727-x
[3] N. Reymond, S. Fabre, E. Lecocq, J. Adélaı̈de, P. Dubreuil, & M. Lopez, Nectin4/prr4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/prr1 through v domain interaction, Journal of Biological Chemistry, vol. 276, no. 46, p. 43205-43215, 2001. https://doi.org/10.1074/jbc.m103810200
[4] A. Reches, Y. Ophir, N. Stein, I. Kol, B. Isaacson, Y. Charpak-Amikamet al., Nectin4 is a novel tigit ligand which combines checkpoint inhibition and tumor specificity, Journal for Immunotherapy of Cancer, vol. 8, no. 1, p. e000266, 2020. https://doi.org/10.1136/jitc-2019-000266
[5] C. Chu, M. Sjöström, E. Egusa, E. Gibb, M. Badura, J. Zhuet al., Heterogeneity in nectin4 expression across molecular subtypes of urothelial cancer mediates sensitivity to enfortumab vedotin, Clinical Cancer Research, vol. 27, no. 18, p. 5123-5130, 2021. https://doi.org/10.1158/1078-0432.ccr-20-4175
[6] J. Chen, A. Bhandari, S. Hirachan, S. Lv, S. Mainali, C. Zhenget al., A specificity protein 1 assists the progression of the papillary thyroid cell
line by initiating nectin4, Endocrine Metabolic & Immune Disorders - Drug Targets, vol. 24, no. 7, p. 789-797, 2024. https://doi.org/10.2174/1871530323666230413134611
[7] M. Mühlebach, M. Mateo, P. Sinn, S. Prüfer, K. Uhlig, V. Léonardet al., Adherens junction protein nectin-4 is the epithelial receptor for measles virus, Nature, vol. 480, no. 7378, p. 530-533, 2011. https://doi.org/10.1038/nature10639
[8] B. Yang, Q. Xue, J. Guo, X. Wang, Y. Zhang, K. Guoet al., Autophagy induction by the pathogen receptor nectin4 and sustained autophagy contribute to peste des petits ruminants virus infectivity, Autophagy, vol. 16, no. 5, p. 842-861, 2019. https://doi.org/10.1080/15548627.2019.1643184
[9] M. Takeda, M. Tahara, N. Nagata, & F. Seki, Wild-type measles virus is intrinsically dual-tropic, Frontiers in Microbiology, vol. 2, 2012. https://doi.org/10.3389/fmicb.2011.00279
[10] N. Otsuki, T. Sekizuka, F. Seki, K. Sakai, T. Kubota, Y. Nakatsuet al., Canine distemper virus with the intact c protein has the potential to replicate in human epithelial cells by using human nectin4 as a receptor, Virology, vol. 435, no. 2, p. 485-492, 2013. https://doi.org/10.1016/j.virol.2012.10.033
[11] Y. Liu, S. Russell, C. Ayala-Breton, S. Russell, & K. Peng, Ablation of nectin4 binding compromises cd46 usage by a hybrid vesicular stomatitis virus/measles virus, Journal of Virology, vol. 88, no. 4, p. 2195-2204, 2014. https://doi.org/10.1128/jvi.02628-13
[12] M. Ito, H. Nishizawa, M. Tsutsumi, A. Kato, Y. Sakabe, Y. Nodaet al., Potential role for nectin-4 in the pathogenesis of pre-eclampsia: a molecular genetic study, BMC Medical Genetics, vol. 19, no. 1, 2018. https://doi.org/10.1186/s12881-018-0681-y
[13] J. Graumann, F. Finkernagel, S. Reinartz, T. Stief, D. Brödje, H. Renzet al., Multi-platform affinity proteomics identify proteins linked to metastasis and immune suppression in ovarian cancer plasma, Frontiers in Oncology, vol. 9, 2019. https://doi.org/10.3389/fonc.2019.01150"

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Target Background

Function
Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells.; (Microbial infection) Acts as a receptor for measles virus.
Gene References into Functions
  1. We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer. PMID: 28778498
  2. Nectin-4 promotes cell-cell adhesion/aggregation, migration, and proliferation of ovarian tumor cells. PMID: 28038455
  3. Nectin-4 is not only a BCSC marker but also a breast cancer metastasis marker PMID: 28600142
  4. This study suggests that PVRL4 is post-transcriptionally regulated by miR-128 and miR-31. PMID: 27507538
  5. High Nectin-4 expression is associated with neoplasms. PMID: 27013195
  6. We show that Measles virus gains entry into MCF7, DLD-1, and HTB-20 cancer cells through a PVRL4-mediated macropinocytosis pathway and identified the typical cellular GTPase and kinase involved. PMID: 28250131
  7. nectin-4 serves as a stimulatory co-receptor for the prolactin receptor by regulating the feedback inhibition of SOCS1 in the JAK2-STAT5a signaling pathway PMID: 28258213
  8. Nectin-4 is both a new promising prognostic biomarker and specific therapeutic target for Triple-negative breast cancers PMID: 27998973
  9. ADAM17 and ADAM10 cleave Nectin-4 and release soluble Nectin-4 (sN4). PMID: 28232483
  10. The data presented in this study suggested that nectin-4 may be a therapeutic target for systemic lupus erythematous through affecting the cell apoptosis PMID: 26617807
  11. Nectin-4 is critical for gallbladder cancer cell progression via PI3K/AKT pathway activation of Rac1. PMID: 26949052
  12. Nectin-4 expression, when compared with control group, was higher in endometriotic lesions of patients having ovarian endometriosis and peritoneal endometriosis. This difference was significant in the endometrium of patients having endometriosis. PMID: 27328518
  13. Transformation of breast cancer cells is dependent on PVRL4. PMID: 23682311
  14. Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer. PMID: 25888293
  15. In airway epithelial cells, measles virus spread requires the nectin-4/afadin complex and is based on cytoplasm transfer between columnar cells. PMID: 25926640
  16. The present study described clinical investigation of the EDSS1 identified in a large consanguineous family; DNA sequence analysis revealed a novel homozygous nonsense mutation (181C>T, p.Asp61*) in the PVRL4 gene. PMID: 25529316
  17. Ovarian tissue expression and serum nectin 4 appear to be potential markers in ovarian cancer. PMID: 25019423
  18. Authors show that the same key residues in the BC and FG loops of nectin-4 govern binding to the measles virus attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. PMID: 25275122
  19. data outline a synergistic action of nectin-1 and -4 in the early steps of AJ formation and implicate this interaction in modulating the Rac1 signaling pathway PMID: 24577405
  20. Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus. PMID: 24335299
  21. Thus, while nectin-4 and CD46 interact functionally with the measles virus H protein beta4-beta5 hydrophobic groove, SLAM merely covers it. PMID: 23760251
  22. Data suggest that expression of nectin-4 is up-regulated in eutopic endometrium of patients with endometriosis compared with control subjects. PMID: 22926846
  23. We show that human nectin4 is fully functional as a canince distemper virus receptor. PMID: 23174504
  24. structure of the membrane-distal domain of nectin-4 in complex with measles virus hemagglutinin (MV-H; structure shows nectin-4 binds the MV-H beta4-beta5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions PMID: 23202587
  25. crystals of nectin-4 diffracted to 1.8 A resolution and belonged to space group P2(1), with unit-cell parameters a = 33.1, b = 51.7, c = 56.9 A, beta = 94.7 degrees PMID: 22869128
  26. measles virus targets nectin-4 to emerge in the airways PMID: 22048310
  27. Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a property that is characteristic of receptor-associated viral infections. PMID: 21901103
  28. The findings of study suggest that increased expression of Nectin-4 may indicate a worse prognosis in breast cancer patients. PMID: 21526486
  29. Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing EDSS1 PMID: 21346770
  30. Ectoderma dysplasia-syndactyly syndrome. Second example of "nectinopathy". PMID: 21333831
  31. nectin 4 may serve as a potential biomarker that helps discriminate benign gynecologic diseases from ovarian cancer in a panel with CA125. PMID: 20959669
  32. Ectodermal dysplasia-syndactyly syndrome is the second known "nectinopathy" caused by mutations in a nectin adhesion molecule. PMID: 20691405
  33. the active form of TACE is overexpressed in breast tumors and may indicate that TACE is responsible for Nectin-4 shedding not only in vitro but also in vivo PMID: 15784625
  34. Nectin-4 was not detected in normal breast epithelium; by contrast Nectin-4 was expressed in ductal breast carcinoma. PMID: 17474988
  35. Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target. PMID: 19679554

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Involvement in disease
Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1)
Subcellular Location
Cell membrane; Single-pass type I membrane protein. Cell junction, adherens junction. Note=Colocalizes with AFDN at cadherin-based adherens junctions (PubMed:11544254).; [Processed poliovirus receptor-related protein 4]: Secreted. Note=The secreted form is found in breast tumor patients (PubMed:15784625).
Protein Families
Nectin family
Tissue Specificity
Predominantly expressed in placenta. Not detected in normal breast epithelium but expressed in breast carcinoma.
Database Links

HGNC: 19688

OMIM: 609607

KEGG: hsa:81607

STRING: 9606.ENSP00000356991

UniGene: Hs.492490

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