Recombinant Human Tyrosine-protein phosphatase non-receptor type substrate 1 (SIRPA), partial

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Code CSB-EP021334HU1
Size $224
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 90% as determined by SDS-PAGE.
Target Names
SIRPA
Uniprot No.
Research Area
Cardiovascular
Alternative Names
Signal regulatory protein alpha type 1; Bit; Brain Ig like molecule with tyrosine based activation motifs; Brain Ig-like molecule with tyrosine-based activation motifs; Brain immunoglobulin like molecule with tyrosine based activation motifs; CD172 antigen like family member A; CD172 antigen-like family member A; CD172a; CD172a antigen; Inhibitory receptor SHPS-1; Macrophage fusion receptor; MFR; MYD 1; Myd 1 antigen; MyD-1 antigen; p84; Protein tyrosine phosphatase non receptor type substrate 1; PTPNS1; SHP substrate 1; SHPS-1; SHPS1; SHPS1_HUMAN; Signal regulatory protein alpha 2; Signal regulatory protein alpha 3; Signal regulatory protein alpha; Signal regulatory protein alpha type 2; Signal-regulatory protein alpha-1; Signal-regulatory protein alpha-2; Signal-regulatory protein alpha-3; SIRP; Sirp-alpha-1; Sirp-alpha-2; Sirp-alpha-3; SIRPA; SIRPalpha; SIRPalpha1; SIRPalpha2; SIRPalpha3; Tyrosine phosphatase SHP substrate 1; Tyrosine protein phosphatase non receptor type substrate 1; Tyrosine-protein phosphatase non-receptor type substrate 1
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
31-373aa
Target Protein Sequence
EEELQVIQPDKSVSVAAGEEELQVIQPDKSVSVAAGESAILHCTVTSLIPVGPIQWFRGAGPARELIYNQKEGHFPRVTTVSESTKRENMDFSISISNITPADAGTYYCVKFRKGSPDTEFKSGAGTELSVRAKPSAPVVSGPAARATPQHTVSFTCESHGFSPRDITLKWFKNGNELSDFQTNVDPVGESVSYSIHSTAKVVLTREDVHSQVICEVAHVTLQGDPLRGTANLSETIRVPPTLEVTQQPVRAENQVNVTCQVRKFYPQRLQLTWLENGNVSRTETASTVTENKDGTYNWMSWLLVNVSAHRDDVKLTCQVEHDGQPAVSKSHDLKVSAHPKEQGSNTAAENTGSNERNIY
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
53.7kDa
Protein Length
Partial of BC026692
Tag Info
N-terminal 6xHis-SUMO-tagged
Form
Liquid or 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
If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 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
3-7 business days
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

The production of the recombinant Human SIRPA protein begins with the creation of the recombinant plasmid, which is synthesized by inserting the gene encoding the Human SIRPA protein (31-373aa) into a plasmid vector. The recombinant plasmid is introduced into e.coli cells. e.coli cells that can survive in the presence of a specific antibiotic are selected and then cultured under conditions conducive to the expression of the gene of interest. The protein is equipped with a N-terminal 6xHis-SUMO tag. Following expression, the recombinant SIRPA protein is isolated and purified from the cell lysate using affinity purification. Denaturing SDS-PAGE is then employed to resolve the resulting recombinant Human SIRPA protein, demonstrating a purity exceeding 90%.

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Target Background

Function
Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function. Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.
Gene References into Functions
  1. Accumulation of SIRPalpha-inhibited macrophages in tumors favored tumor regression for 1-2 weeks, but donor macrophages quickly differentiated toward non-phagocytic, high-SIRPalpha TAMs. PMID: 28669759
  2. SIRP alpha protein is under-expressed in low and high-grades of astrocytoma from patients' brain samples. PMID: 27900675
  3. Anti-SIRPA antibody immunotherapy enhances neutrophil and macrophage antitumor activity. PMID: 29158380
  4. SIRPalpha might play an important role in the progression of oral leukoplakia and oral cancer, and could be a pivotal therapeutic target in oral squamous cell carcinoma, regulating the phenotype of macrophages via targeting NF-kappaB signaling. PMID: 27793032
  5. TTI-621 (SIRPalphaFc) is a fully human recombinant fusion protein that blocks the CD47-SIRPalpha axis by binding to human CD47 and enhancing phagocytosis of malignant cells..These data indicate that TTI-621 is active across a broad range of human tumors. PMID: 27856600
  6. data suggest that TTI-621 may be efficacious in triggering the destruction of cancer cells by a diverse population of TAMs found in vivo and support possible combination approaches to augment the activity of CD47 blockade PMID: 29084248
  7. CD47, TSP1, and to a lesser extent SIRPalpha facilitate exosome-mediated myeloid-derived suppressor cells chemotaxis and migration. PMID: 27728760
  8. exploited by Hepatitis E virus to negative regulated IFN-beta of the host innate immune system to promote viral infection PMID: 26492885
  9. Data suggest a reduction in the CD47 antigen/signal-regulatory protein alpha (SIRPalpha) pathway by programmed cell death protein 1 (PD-1) blockade, which regulates Myeloid-derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs). PMID: 26573233
  10. agents that block the CD47:SIRP-alpha engagement are attractive therapeutic targets as a monotherapy or in combination with additional immune-modulating agents for activating antitumor T cells in vivo PMID: 26116271
  11. the data suggest that combinatorial actions of ADAM10 and gamma-secretase on SIRPalpha cleavage promote inflammatory signaling. PMID: 26534964
  12. Loss of cell surface CD47 clustering formation and binding avidity to SIRPalpha facilitate apoptotic cell clearance by macrophages. PMID: 26085683
  13. Velcro" engineering of high affinity CD47 ectodomain as signal regulatory protein alpha (SIRPalpha) antagonists that enhance antibody-dependent cellular phagocytosis PMID: 25837251
  14. negatively regulates neutrophil accumulation during inflammation PMID: 24516072
  15. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. PMID: 24968096
  16. These results suggest that thrombospondin-1 binding to SIRP-alpha on nonphagocytic cells activates NADPH oxidase, limits vasodilation, and promotes renal ischemia reperfusion injury. PMID: 24511121
  17. 'clustering' SIRPalpha into plasma membrane microdomains is essential for activated monocytes and macrophages to effectively interact with CD47 and initiate intracellular signaling PMID: 24143245
  18. Polymorphisms in the human inhibitory signal-regulatory protein alpha do not affect binding to its ligand CD47. PMID: 24550402
  19. SIRPA plays a protective role in cardiac hypertrophy through negative regulation of the Toll-like receptor 4/nuclear factor-kappaB pathway. PMID: 24101669
  20. These results demonstrate a SIRPalpha-based mechanism that dynamically regulates polymorphonuclear leukocyte inflammatory responses. PMID: 24026300
  21. Signal regulatory protein alpha is associated with tumor-polarized macrophages phenotype switch and plays a pivotal role in tumor progression. PMID: 23504854
  22. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells. PMID: 23669395
  23. Expression of SIRPalpha on two low SIRPalpha acute myeloid leukemia (AML) expressing cell lines could be upregulated upon differentiation of the cells. PMID: 23320069
  24. SHPS-1 negatively regulates the MyD88-dependent TLR signaling pathway through the inhibition of NF-kappaB activation PMID: 23314616
  25. IFN-beta and IFN-gamma/TNF-alpha decrease erythrophagocytosis by human monocytes in vitro, and this effect does not apparently require an increase in SIRP-alpha or SHP-1 expression. PMID: 22738830
  26. neutrophils reduce their SIRPalpha expression during apoptosis, which may be part of the functional down-regulation seen in apoptotic neutrophils. PMID: 23271705
  27. thymic Sirpalpha(+) cDCs crucially contribute to a process of intrathymic tumor immune tolerance that involves CCR2 and CCL2 PMID: 22815949
  28. In the glomeruli of CNS patients carrying mutations in NPHS1, where SD formation is disrupted, the expression of SIRPalpha as well as Neph1 and nephrin was significantly decreased, indicating that SIRPalpha is closely associated with the nephrin complex PMID: 22747997
  29. Surfactant protein D (Sp-D) binds to membrane-proximal domain (D3) of signal regulatory protein alpha (SIRPalpha), a site distant from binding domain of CD47, while also binding to analogous region on signal regulatory protein beta (SIRPbeta). PMID: 22511785
  30. SIRPalpha1 in hepatic sinusoid Kupffer cells is associated with the extent of autoimmune hepatitis. PMID: 22409853
  31. data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor phagocytosis and elimination PMID: 22451913
  32. SIRPalpha/CD172a and FHOD1 are unique markers of littoral cells, a recently evolved major cell population of red pulp of human spleen. PMID: 22490440
  33. Sensing of cell surface CD47 expression by phagocyte SIRPalpha is a critical determinant of T- and natural killer-cell homeostasis under steady-state conditions in vivo. PMID: 21788504
  34. hSIRPa-transgenic Rag2(-/-)gamma(c)(-/-) mice represent a unique mouse strain supporting high levels of human cell engraftment. PMID: 21788509
  35. The prolactin receptor (PRLr)-SIRPalpha-integrin complex provides a basis for integrin-PRLr cross-talk that contributes to the biology of breast cancer. PMID: 20826546
  36. the relationships between SIRPalpha1 and beta-catenin in leukemia cells. PMID: 21369691
  37. Single Nucleotide Polymorphisms in PTPNS1 is associated with inflammatory bowel disease. PMID: 21225905
  38. SHP-2 as an essential component of tumor suppression and anoikis mediated by SIRPalpha1 in human breast carcinoma cells as well as in v-Src-transformed cells. PMID: 21169408
  39. Poor prognosis of breast cancer patients with high expression of CD47 is due to an active CD47/SIRPA signaling pathway in circulating cells. PMID: 20705613
  40. The role of cis dimerization of signal regulatory protein alpha (SIRPalpha) in binding to CD47. PMID: 20826801
  41. Findings reveal a novel mechanism for recruitment of PDK1 to the SHPS-1 signaling complex, which is required for IGF-I-stimulated AKT Thr(308) phosphorylation and inhibition of apoptosis. PMID: 20643654
  42. Inhibition of engulfment correlates with affinity of CD47 for SIRPA - but only at low levels of CD47. PMID: 20299253
  43. SIRPalpha1 specifically affects the SHP-2/FAK/Grb2/Sos-1/MAPK activation loop to downmodulate EGFRvIII-mediated migration and transformation. PMID: 20473329
  44. Insulin-like growth factor-I-stimulated insulin receptor substrate-1 negatively regulates Src homology 2 domain-containing protein-tyrosine phosphatase substrate-1 function in vascular smooth muscle cells. PMID: 20207740
  45. SIRP alpha gene expression is higher in monocytes from autoimmune hemolytic anemia patients, compared with basal expression. PMID: 19874234
  46. CD47/SIRP-alpha interactions are implicated in the pathogenesis of DC-driven allergic airway inflammation. PMID: 19748659
  47. Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration PMID: 11792697
  48. The interaction of SHPS-1 with CD47 may contribute to the recruitment of B lymphocytes via endothelial cells under steady state conditions. PMID: 11907074
  49. MyD-1-coupling to this PI 3-kinase-dependent signaling pathway may therefore present a novel target for the development of therapeutic strategies for combating TNFalpha production and consequent inflammatory disease. PMID: 12805067
  50. Expression of SIRPalpha1 on astrocytomas may be of considerable importance in brain tumor biology. PMID: 14729615

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Subcellular Location
Membrane; Single-pass type I membrane protein.
Tissue Specificity
Ubiquitous. Highly expressed in brain. Detected on myeloid cells, but not T-cells. Detected at lower levels in heart, placenta, lung, testis, ovary, colon, liver, small intestine, prostate, spleen, kidney, skeletal muscle and pancreas.
Database Links

HGNC: 9662

OMIM: 602461

KEGG: hsa:140885

STRING: 9606.ENSP00000348307

UniGene: Hs.581021

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