Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

MPL

Uniprot No.

P40238

Research Area

Immunology

Alternative Names

C MPL; CD110; mpl; MPLV; Myeloproliferative leukemia protein; Myeloproliferative leukemia virus oncogene; Proto-oncogene c-Mpl; THCYT2; Thrombopoietin receptor; TPO R; TPO-R; TPOR; TPOR_HUMAN

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

26-491aa

Target Protein Sequence

QDVSLLASDSEPLKCFSRTFEDLTCFWDEEEAAPSGTYQLLYAYPREKPRACPLSSQSMPHFGTRYVCQFPDQEEVRLFFPLHLWVKNVFLNQTRTQRVLFVDSVGLPAPPSIIKAMGGSQPGELQISWEEPAPEISDFLRYELRYGPRDPKNSTGPTVIQLIATETCCPALQRPHSASALDQSPCAQPTMPWQDGPKQTSPSREASALTAEGGSCLISGLQPGNSYWLQLRSEPDGISLGGSWGSWSLPVTVDLPGDAVALGLQCFTLDLKNVTCQWQQQDHASSQGFFYHSRARCCPRDRYPIWENCEEEEKTNPGLQTPQFSRCHFKSRNDSIIHILVEVTTAPGTVHSYLGSPFWIHQAVRLPTPNLHWREISSGHLELEWQHPSSWAAQETCYQLRYTGEGHQDWKVLEPPLGARGGTLELRPRSRYRLQLRARLNGPTYQGPWSSWSDPTRVETATETAW
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

56.5kDa

Protein Length

Extracellular Domain

Tag Info

N-terminal 6xHis-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.

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

Protein 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 Recombinant Human MPL protein is a protein encoded by recombinant DNA that was cloned in an expression vector that supported the expression of MPL gene. This recombinant MPL protein was expressed in the host. The expression region is 26-491aa of the Human MPL. In the production, the expression vector contains N-terminal 6xHis tag. Every production step was performed with a strict QC system. The purity of this protein is 90%+ determined by SDS-PAGE.

The thrombopoietin receptor, MPL, is a member of the type 1 homodimeric cytokine receptor family together with the EPO, prolactin, growth hormone, and granulocyte-colony stimulating factor receptors. Among this receptor family, MPL is unique because it has a reduplicated extracellular CRHD, of which, the distal CRHD is the site of THPO binding. The distal CRHD is also the site of germline SNP causing benign familial thrombocytosis, a hot spot for the mutations causing CAMT as well as the site of terminal sialylation during receptor maturation, which is impaired in the MPN. Like the other hematopoietic growth factor receptors, MPL is responsible for the metabolism of its cognate ligand, but in contrast to the other hematopoietic growth factors, the production of which is mainly regulated by demand. MPL offers a selective therapeutic target in the myeloproliferative neoplasms since impaired MPL processing is unique to the involved stem cells, while MPL is required for hematopoietic stem cell survival and quiescent in their bone marrow niches.

Target Background

Function

Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

Gene References into Functions

JAK2V617F mutation was found in 37 (61.7%) patients with ET. Among 23 patients without JAK2V617F mutation, 7 (11.7%) had CALR mutation and 1 (1.7%) had MPL mutation. Fifteen (25.0%) patients were negative for all 3 mutations: JAK2V617F(-), CALR(-), and MPL(-). PMID: 29390868
MPL and CALR genotypes show a similar clinical picture at essential thrombocythaemia diagnosis. Bone marrow histology in MPL-mutated ET is characterized by prominent megakaryocytic proliferation. PMID: 29934356
These results indicate that lusutrombopag acts on human TPOR to upregulate differentiation and proliferation of megakaryocytic cells, leading to platelet production. PMID: 29274361
The expression of TPO and c-Mpl was significantly decreased in the cITP group compared to the nITP group, suggesting that TPO and its receptor may play important roles in childhood cITP pathogenesis. PMID: 29313460
A novel germ-line mutation of c-mpl gene in a sporadic case of essential thrombocythemia. PMID: 28391042
This study demonstrated that absence of MPL mutation in stroke. PMID: 28625126
MPL mutations and splenomegaly are risk factors for essential thrombocythemia progression into primary nyelofibrosis. PMID: 27768091
goals were: (i) to identify other MPL mutations that should be tested in MPN patients by mutation-specific PCR; and (ii) to determine the amino acid requirements at position 515 to prevent TpoR self-activation PMID: 26437785
Concurrent MPL W515L and Y591D mutations in a patient with myelofibrosis. PMID: 27519934
MPL is up regulated in JAK2(V617F) ECs and contributes to the maintenance/expansion of the JAK2(V617F) clone over JAK2(WT) clone in vitro PMID: 27865175
In tumor cell cultures, exogenous expression of MPL led to constitutive activation of STAT3 and 5, ERK1/2, and AKT, cytokine-independent growth, and reduction of apoptosis similar to the effects seen in the spontaneously outgrown cells. PMID: 27177927
Essential Thrombocythemia and Primary Myelofibrosis patients with MPL mutations are at high risk for Thrombotic Events. PMID: 28766534
Results show that mutant CALR induces autocrine, but not paracrine activation of MPL in myeloproliferative neoplasm. [review] PMID: 28741795
these results demonstrate that MPL P106L is a receptor with an incomplete defect in trafficking. PMID: 28034873
A newborn girl with congenitcal amegakaryocytic thrombocytopenia had a homozygous missense Trp154-to- Arg mutation in exon 4 of c-MPL. The same heterozygote mutation was detected in her mother, father, and 2 siblings. PMID: 26316487
Normal FLT3 and negative expression of CD34 and cMPL may predict a longer overall survival in aute myeloid leukemia. PMID: 27993871
we show that the positive charge of the CALR mutant C-terminus is necessary to transform hematopoietic cells by enabling binding between mutant CALR and the thrombopoietin receptor MPL. PMID: 26951227
In essential thrombocythemia, MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis. PMID: 26890983
PARP-1 has an important role in the progression of acute myeloid leukemia by suppressing the myeloproliferative leukemia virus oncogene PMID: 26314963
mutant CALR promotes myeloproliferative neoplasm development by activating c-MPL and its downstream pathway. PMID: 26817954
Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. PMID: 26668133
we describe a Mpl W515K somatic mutation in a paediatric case of ET who presented with Budd-Chiari syndrome. No paediatric patient harbouring a Mpl W515K mutation has been previously reported. PMID: 25970554
His(499) regulates the activation of human TpoR and provides additional protection against activating mutations, such as oncogenic Asn mutations in the TM domain PMID: 26627830
this study has shown that in a fraction of the so-called triple-negative ETs a significant proportion of patients have mutations in signaling molecules, more particularly in MPL. PMID: 26450985
erythrocyte lineage enforces exclusivity through upregulation of EKLF and its lineage-specific cytokine receptor (EpoR) while inhibiting both FLI-1 and the receptor TpoR (also known as MPL) for the opposing megakaryocyte lineage PMID: 26159733
Compared to normal controls, the frequency of the JAK246/1 haplotype was significantly higher among patients with JAK2V617F, JAK2Ex12del, or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients PMID: 26614694
Flow cytometric detection of MPL (CD110) as a diagnostic tool for differentiation of congenital thrombocytopenias. PMID: 25911549
Using C-mannosylation defective mutant of c-Mpl, the C-mannosylated tryptophan residues at four sites (Trp(269), Trp(272), Trp(474), and Trp(477)) are essential for c-Mpl-mediated JAK-STAT signaling. PMID: 26505790
MPL gene mutations are associated with essential thrombocythaemia and major thrombotic complications. PMID: 25573593
Letter/Meta-analysis: thrombopoietin receptor agonists significantly increase the risk of portal vein thrombosis in liver diseases. PMID: 25761530
MPL mutation is associated with myeloproliferative neoplasms. PMID: 25398833
The effects of inhibition of the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells. PMID: 24085601
The data supports the proposal of including MPL exon 10 mutations as major diagnostic markers for myeloproliferative neoplasms. PMID: 26071474
CALR mutation, MPL mutation and triple negativity may have roles in lowering vascular risk in primary myelofibrosis PMID: 25482134
Both immature and mature Mpl reach the cell surface. PMID: 24931576
The P106L mutation functionally separates The activity of c-Mpl in downstream signaling from that in maintaining platelet homeostasis. PMID: 25538044
Amino acid substitutions in a thrombopoietin receptor (Mpl)--containing cell growth switch (CGS) extending receptor stability improve the expansion capacity of human cord blood CD34(+) cells in the absence of exogenous cytokines. PMID: 25343958
OTT1 regulates the alternative splicing of Mpl-TR, a truncated isoform of c-Mpl, which modulates Thrombopoietin-mediated signaling. PMID: 25468569
Studies demonstrate that progression to AML is part of the natural history of MPL W515L-associated disease. PMID: 20823136
Impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies congenital amegakaryocytic thrombocytopenia. PMID: 23908116
These experiments define a novel VEGF-miR-1-Mpl-P-selectin effector pathway in lung Th2 inflammation and herald the utility of miR-1 and Mpl as potential therapeutic targets for asthma. PMID: 24043765
In migrating cancer stem cells isolated from primary human colorectal cancers, CD110(+) and CDCP1(+) subpopulations mediate organ-specific lung and liver metastasis. PMID: 23747337
MPL W515L mutation in pediatric essential thrombocythemia. PMID: 23441089
Different mutations of the human c-mpl gene indicate distinct hematopoietic diseases. PMID: 23351976
Loss of heterozygosity of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms. PMID: 23575445
MPL Baltimore mutation is associated with thrombocytosis. PMID: 23511495
Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation. PMID: 23359689
Up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis. PMID: 22613795
High MPL expression is associated with leukemia. PMID: 22337712
This study shows for the first time a link between homozygous MPL mutations and familial aplastic anemia. It also highlights the important role of MPL in trilineage hematopoiesis. PMID: 22180433

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Involvement in disease

Congenital amegakaryocytic thrombocytopenia (CAMT); Thrombocythemia 2 (THCYT2); Myelofibrosis with myeloid metaplasia (MMM)

Subcellular Location

Cell membrane; Single-pass type I membrane protein. Golgi apparatus. Cell surface.

Protein Families

Type I cytokine receptor family, Type 1 subfamily

Tissue Specificity

Expressed at a low level in a large number of cells of hematopoietic origin. Isoform 1 and isoform 2 are always found to be coexpressed.

Database Links

HGNC: 7217

OMIM: 159530

KEGG: hsa:4352

STRING: 9606.ENSP00000361548

UniGene: Hs.82906

Code	CSB-EP014755HU
Abbreviation	Recombinant Human MPL protein, partial
MSDS	MSDS Datasheet
Size	$224
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Recombinant Human Thrombopoietin receptor (MPL), partial

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