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Thpo thrombopoietin [ Mus musculus (house mouse) ]

Gene ID: 21832, updated on 18-Sep-2024

Summary

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Official Symbol
Thpoprovided by MGI
Official Full Name
thrombopoietinprovided by MGI
Primary source
MGI:MGI:101875
See related
Ensembl:ENSMUSG00000022847 AllianceGenome:MGI:101875
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Ml; Tpo; Mgdf; Mpllg
Summary
This gene encodes a humoral growth factor necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. The encoded protein is a ligand for the product of the myeloproliferative leukemia virus oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Expression
Ubiquitous expression in liver adult (RPKM 4.4), cortex adult (RPKM 4.1) and 24 other tissues See more
Orthologs
human all
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Genomic context

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See Thpo in Genome Data Viewer
Location:
16 B1; 16 12.51 cM
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 16 NC_000082.7 (20543204..20553261, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 16 NC_000082.6 (20724454..20734511, complement)

Chromosome 16 - NC_000082.7Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 131, member A Neighboring gene STARR-seq mESC enhancer starr_40329 Neighboring gene chloride channel, voltage-sensitive 2 Neighboring gene STARR-positive B cell enhancer ABC_E1489 Neighboring gene polymerase (RNA) II (DNA directed) polypeptide H Neighboring gene STARR-seq mESC enhancer starr_40331 Neighboring gene chordin Neighboring gene predicted gene, 22741 Neighboring gene STARR-seq mESC enhancer starr_40332 Neighboring gene predicted gene, 46544

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Thrombopoietin maintains cell numbers of hematopoietic stem and progenitor cells with megakaryopoietic potential. O'Neill A, et al. Haematologica, 2021 Jul 1. PMID 32527954, Free PMC Article
  2. Thrombopoietin Metabolically Primes Hematopoietic Stem Cells to Megakaryocyte-Lineage Differentiation. Nakamura-Ishizu A, et al. Cell Rep, 2018 Nov 13. PMID 30428347
  3. Platelet deficiency in Tpo(-/-) mice can both promote and suppress the metastasis of experimental breast tumors in an organ-specific manner. Thiele W, et al. Clin Exp Metastasis, 2018 Oct. PMID 30043083
  4. Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance. Decker M, et al. Science, 2018 Apr 6. PMID 29622652, Free PMC Article
  5. Role of Megakaryocytes in Breast Cancer Metastasis to Bone. Jackson W 3rd, et al. Cancer Res, 2017 Apr 15. PMID 28202531

See all (129) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Notch1 regulates hepatic thrombopoietin production.
    Title: Notch1 regulates hepatic thrombopoietin production.
  2. Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.
    Title: Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.
  3. Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis.
    Title: Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis.
  4. Megakaryocyte/platelet-derived TGF-beta1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.
    Title: Megakaryocyte/platelet-derived TGF-β1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.
  5. Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver.
    Title: Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver.
  6. Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation.
    Title: Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation.
  7. Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts.
    Title: Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts.
  8. Thpo-regulated mitochondrial activity associated with mitochondrial translocation of STAT3 phosphorylated at serine 727.
    Title: Thrombopoietin Metabolically Primes Hematopoietic Stem Cells to Megakaryocyte-Lineage Differentiation.
  9. Authors demonstrate that thrombopoietin and its receptor MPL are critical for the human JAK2V617F-bearing MK-induced myeloproliferation in mice, both by directly affecting the quantity and quality of MKs and by altering the MK-endothelial interaction and vascular niche function.
    Title: JAK2V617F Megakaryocytes Promote Hematopoietic Stem/Progenitor Cell Expansion in Mice Through Thrombopoietin/MPL Signaling.
  10. Study of hepatocarcinogenesis induced by diethylnitrosamine in B6C3F1 mice, the BrafV637E mutation, corresponding to the human BRAFV600E mutation, suggested that the TPO-mediated macroenvironmental changes involving the liver and bone marrow may promote proliferation of the BRAFV600E-mutated hepatocytes, but cause hematological, renal, and pulmonary disorders that lead to death.
    Title: Overproduction of thrombopoietin by BRAFV600E-mutated mouse hepatocytes and contribution of thrombopoietin to hepatocarcinogenesis.
Submit: New GeneRIF Correction See all GeneRIFs (44)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables cytokine activity IEA
Inferred from Electronic Annotation
more info
  
enables hormone activity IEA
Inferred from Electronic Annotation
more info
  
enables signaling receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell surface receptor signaling pathway via STAT ISO
Inferred from Sequence Orthology
more info
  
involved_in megakaryocyte development ISO
Inferred from Sequence Orthology
more info
  
involved_in megakaryocyte differentiation ISO
Inferred from Sequence Orthology
more info
  
involved_in megakaryocyte differentiation ISS
Inferred from Sequence or Structural Similarity
more info
  
acts_upstream_of_or_within myeloid cell differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of ERK1 and ERK2 cascade IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of MAPK cascade ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of cell population proliferation ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of hematopoietic stem cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within positive regulation of hematopoietic stem cell proliferation ISO
Inferred from Sequence Orthology
more info
 PubMed 
involved_in positive regulation of megakaryocyte differentiation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISO
Inferred from Sequence Orthology
more info
  
involved_in positive regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in thrombopoietin-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in thrombopoietin-mediated signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in thrombopoietin-mediated signaling pathway ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
is_active_in extracellular region IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular space IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
thrombopoietin
Names
C-mpl ligand
megakaryocyte colony-stimulating factor
megakaryocyte growth and development factor
myeloproliferative leukemia virus oncogene ligand

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001173505.1 → NP_001166976.1  thrombopoietin isoform 1 precursor

    See identical proteins and their annotated locations for NP_001166976.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) encodes the longest isoform (1, also known as Tpo1). Both variants 1 and 2 encode the same isoform 1.
    Source sequence(s)
    AI314551, AK047512, CT010490
    Consensus CDS
    CCDS37292.1
    UniProtKB/Swiss-Prot
    P40226
    UniProtKB/TrEMBL
    A0A338P6S5, Q543R9
    Related
    ENSMUSP00000075756.6, ENSMUST00000076422.13
    Conserved Domains (1) summary
    pfam00758
    Location:25 → 175
    EPO_TPO; Erythropoietin/thrombopoietin

  2. NM_001289894.1 → NP_001276823.1  thrombopoietin isoform 2 precursor

    See identical proteins and their annotated locations for NP_001276823.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate splice site in the 3' coding region, compared to variant 2. The resulting isoform (2, also known as Tpo2) lacks an internal 4aa peptide, compared to isoform 1.
    Source sequence(s)
    CT010490
    UniProtKB/TrEMBL
    A0A338P6S5
    Conserved Domains (1) summary
    pfam00758
    Location:25 → 171
    EPO_TPO; Erythropoietin/thrombopoietin

  3. NM_001289896.1 → NP_001276825.1  thrombopoietin isoform 3 precursor

    See identical proteins and their annotated locations for NP_001276825.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate splice site in the 3' coding region, which results in a reading frameshift, compared to variant 2. The resulting isoform (3, also known as Tpo4) has a shorter and distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    CT010490
    UniProtKB/TrEMBL
    A0A338P6C8
    Related
    ENSMUSP00000155914.2, ENSMUST00000231826.2
    Conserved Domains (1) summary
    pfam00758
    Location:25 → 119
    EPO_TPO; Erythropoietin/thrombopoietin

  4. NM_009379.3 → NP_033405.1  thrombopoietin isoform 1 precursor

    See identical proteins and their annotated locations for NP_033405.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Both variants 1 and 2 encode the same isoform 1.
    Source sequence(s)
    AK047512
    Consensus CDS
    CCDS37292.1
    UniProtKB/Swiss-Prot
    P40226
    UniProtKB/TrEMBL
    A0A338P6S5, Q543R9
    Related
    ENSMUSP00000111097.3, ENSMUST00000115437.4
    Conserved Domains (1) summary
    pfam00758
    Location:25 → 175
    EPO_TPO; Erythropoietin/thrombopoietin

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000082.7 Reference GRCm39 C57BL/6J

    Range
    20543204..20553261 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017316926.3 → XP_017172415.1  thrombopoietin isoform X2

    Conserved Domains (2) summary
    pfam05109
    Location:409 → 528
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00758
    Location:208 → 354
    EPO_TPO; Erythropoietin/thrombopoietin

  2. XM_017316929.3 → XP_017172418.1  thrombopoietin isoform X1

    Conserved Domains (2) summary
    pfam05109
    Location:413 → 532
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00758
    Location:208 → 358
    EPO_TPO; Erythropoietin/thrombopoietin

  3. XM_017316927.2 → XP_017172416.1  thrombopoietin isoform X3

    Conserved Domains (2) summary
    pfam05109
    Location:396 → 515
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00758
    Location:191 → 341
    EPO_TPO; Erythropoietin/thrombopoietin

  4. XM_017316928.1 → XP_017172417.1  thrombopoietin isoform X4

    Conserved Domains (2) summary
    pfam05109
    Location:392 → 511
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00758
    Location:191 → 337
    EPO_TPO; Erythropoietin/thrombopoietin

  5. XM_006521987.3 → XP_006522050.1  thrombopoietin isoform X7

    UniProtKB/TrEMBL
    A0A338P6S5
    Conserved Domains (2) summary
    pfam05109
    Location:300 → 419
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00758
    Location:95 → 245
    EPO_TPO; Erythropoietin/thrombopoietin

  6. XM_017316930.3 → XP_017172419.1  thrombopoietin isoform X5

    Conserved Domains (1) summary
    pfam00758
    Location:208 → 302
    EPO_TPO; Erythropoietin/thrombopoietin

  7. XM_017316932.3 → XP_017172421.1  thrombopoietin isoform X8

    Conserved Domains (1) summary
    pfam00758
    Location:208 → 302
    EPO_TPO; Erythropoietin/thrombopoietin

  8. XM_017316931.1 → XP_017172420.1  thrombopoietin isoform X6

    Conserved Domains (1) summary
    pfam00758
    Location:191 → 285
    EPO_TPO; Erythropoietin/thrombopoietin

  9. XM_017316933.2 → XP_017172422.1  thrombopoietin isoform X9

    Conserved Domains (1) summary
    pfam00758
    Location:191 → 285
    EPO_TPO; Erythropoietin/thrombopoietin

  10. XM_036159871.1 → XP_036015764.1  thrombopoietin isoform X10

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P40226.1 GenPept UniProtKB/Swiss-Prot:P40226

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