UniProtKB - P40225 (TPO_HUMAN)
Protein
Thrombopoietin
Gene
THPO
Organism
Homo sapiens (Human)
Status
Functioni
Lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from their committed progenitor cells. It acts at a late stage of megakaryocyte development. It may be the major physiological regulator of circulating platelets.
GO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- growth factor activity Source: ProtInc
- hormone activity Source: UniProtKB-KW
- signaling receptor binding Source: GO_Central
GO - Biological processi
- cell population proliferation Source: ProtInc
- megakaryocyte development Source: ARUK-UCL
- multicellular organism development Source: ProtInc
- positive regulation of cell population proliferation Source: ARUK-UCL
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of hematopoietic stem cell proliferation Source: MGI
- positive regulation of MAPK cascade Source: ARUK-UCL
- positive regulation of megakaryocyte differentiation Source: UniProtKB
- positive regulation of protein kinase B signaling Source: ARUK-UCL
- positive regulation of protein phosphorylation Source: UniProtKB
- receptor signaling pathway via STAT Source: ARUK-UCL
- thrombopoietin-mediated signaling pathway Source: ARUK-UCL
Keywordsi
Molecular function | Cytokine, Hormone |
Enzyme and pathway databases
PathwayCommonsi | P40225 |
Reactomei | R-HSA-76009, Platelet Aggregation (Plug Formation) |
SignaLinki | P40225 |
SIGNORi | P40225 |
Names & Taxonomyi
Protein namesi | Recommended name: ThrombopoietinAlternative name(s): C-mpl ligand Short name: ML Megakaryocyte colony-stimulating factor Megakaryocyte growth and development factor Short name: MGDF Myeloproliferative leukemia virus oncogene ligand |
Gene namesi | Name:THPO Synonyms:MGDF |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000090534.17 |
HGNCi | HGNC:11795, THPO |
MIMi | 600044, gene |
neXtProti | NX_P40225 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular region Source: GO_Central
- extracellular space Source: UniProtKB-KW
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Thrombocythemia 1 (THCYT1)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
Related information in OMIMOrganism-specific databases
DisGeNETi | 7066 |
MalaCardsi | THPO |
MIMi | 187950, phenotype |
OpenTargetsi | ENSG00000090534 |
Orphaneti | 71493, Familial thrombocytosis 397692, Hereditary isolated aplastic anemia 329319, Thrombocythemia with distal limb defects |
PharmGKBi | PA36506 |
Miscellaneous databases
Pharosi | P40225, Tbio |
Chemistry databases
ChEMBLi | CHEMBL1293256 |
Polymorphism and mutation databases
BioMutai | THPO |
DMDMi | 730982 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Add BLAST | 21 | |
ChainiPRO_0000008411 | 22 – 353 | ThrombopoietinAdd BLAST | 332 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 22 | O-linked (GalNAc...) serine1 Publication | 1 | |
Disulfide bondi | 28 ↔ 172 | |||
Disulfide bondi | 50 ↔ 106 | |||
Glycosylationi | 58 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Glycosylationi | 131 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Glycosylationi | 179 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Glycosylationi | 180 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Glycosylationi | 184 | O-linked (GalNAc...) serine1 Publication | 1 | |
Glycosylationi | 197 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Glycosylationi | 206 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Glycosylationi | 213 | O-linked (GalNAc...) threonine1 Publication | 1 | |
Glycosylationi | 234 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Glycosylationi | 255 | N-linked (GlcNAc...) (complex) asparagine1 Publication | 1 | |
Glycosylationi | 265 | O-linked (GalNAc...) serine1 Publication | 1 | |
Glycosylationi | 340 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 348 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | P40225 |
PaxDbi | P40225 |
PeptideAtlasi | P40225 |
PRIDEi | P40225 |
ProteomicsDBi | 55350 [P40225-1] 55351 [P40225-2] 55352 [P40225-3] |
PTM databases
GlyConnecti | 592, 12 N-Linked glycans, 4 O-Linked glycans |
GlyGeni | P40225, 14 sites, 12 N-linked glycans (1 site) |
iPTMneti | P40225 |
PhosphoSitePlusi | P40225 |
UniCarbKBi | P40225 |
Expressioni
Gene expression databases
Bgeei | ENSG00000090534, Expressed in right lobe of liver and 103 other tissues |
ExpressionAtlasi | P40225, baseline and differential |
Genevisiblei | P40225, HS |
Organism-specific databases
HPAi | ENSG00000090534, Tissue enriched (liver) |
Interactioni
GO - Molecular functioni
- cytokine activity Source: UniProtKB-KW
- growth factor activity Source: ProtInc
- hormone activity Source: UniProtKB-KW
- signaling receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 112922, 3 interactors |
DIPi | DIP-5729N |
ELMi | P40225 |
IntActi | P40225, 3 interactors |
STRINGi | 9606.ENSP00000204615 |
Miscellaneous databases
RNActi | P40225, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P40225 |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 285 – 337 | Pro-richAdd BLAST | 53 |
Domaini
Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal.
Sequence similaritiesi
Belongs to the EPO/TPO family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502S9T0, Eukaryota |
GeneTreei | ENSGT00390000006294 |
HOGENOMi | CLU_039844_0_0_1 |
InParanoidi | P40225 |
OMAi | AHPHFQN |
OrthoDBi | 906192at2759 |
PhylomeDBi | P40225 |
TreeFami | TF338084 |
Family and domain databases
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR019767, EPO/TPO_CS IPR001323, EPO_TPO IPR003978, Thrombopoietin |
PANTHERi | PTHR10560, PTHR10560, 1 hit |
Pfami | View protein in Pfam PF00758, EPO_TPO, 1 hit |
PRINTSi | PR01485, THROMBOPTN |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00817, EPO_TPO, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P40225-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MELTELLLVV MLLLTARLTL SSPAPPACDL RVLSKLLRDS HVLHSRLSQC
60 70 80 90 100
PEVHPLPTPV LLPAVDFSLG EWKTQMEETK AQDILGAVTL LLEGVMAARG
110 120 130 140 150
QLGPTCLSSL LGQLSGQVRL LLGALQSLLG TQLPPQGRTT AHKDPNAIFL
160 170 180 190 200
SFQHLLRGKV RFLMLVGGST LCVRRAPPTT AVPSRTSLVL TLNELPNRTS
210 220 230 240 250
GLLETNFTAS ARTTGSGLLK WQQGFRAKIP GLLNQTSRSL DQIPGYLNRI
260 270 280 290 300
HELLNGTRGL FPGPSRRTLG APDISSGTSD TGSLPPNLQP GYSPSPTHPP
310 320 330 340 350
TGQYTLFPLP PTLPTPVVQL HPLLPDPSAP TPTPTSPLLN TSYTHSQNLS
QEG
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5FBX8 | Q5FBX8_HUMAN | Thrombopoietin | THPO | 319 | Annotation score: | ||
A0A3B3ITS0 | A0A3B3ITS0_HUMAN | Thrombopoietin | THPO hCG_40497 | 493 | Annotation score: | ||
F8W6L1 | F8W6L1_HUMAN | Thrombopoietin | THPO | 286 | Annotation score: | ||
A0A2R8Y734 | A0A2R8Y734_HUMAN | Thrombopoietin | THPO | 12 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 46 | R → K in AAB03392 (Ref. 8) Curated | 1 | |
Sequence conflicti | 46 | R → K in AAB03393 (Ref. 8) Curated | 1 | |
Sequence conflicti | 46 | R → K in AAB03394 (Ref. 8) Curated | 1 | |
Sequence conflicti | 76 | M → MSQ in AAA74083 (PubMed:7822271).Curated | 1 | |
Sequence conflicti | 113 | Q → E in AAA50553 (PubMed:8020099).Curated | 1 | |
Sequence conflicti | 131 | T → P in AAA74083 (PubMed:7822271).Curated | 1 | |
Sequence conflicti | 277 | G → E in AAB03393 (Ref. 8) Curated | 1 | |
Sequence conflicti | 277 | G → E in AAB03394 (Ref. 8) Curated | 1 | |
Sequence conflicti | 346 | S → C in AAB03393 (Ref. 8) Curated | 1 | |
Sequence conflicti | 346 | S → C in AAB03394 (Ref. 8) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_011795 | 14 | L → P. Corresponds to variant dbSNP:rs1042346Ensembl. | 1 | |
Natural variantiVAR_011796 | 116 | G → E. Corresponds to variant dbSNP:rs1126665Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_001450 | 133 – 136 | Missing in isoform 2. 1 Publication | 4 | |
Alternative sequenceiVSP_001451 | 160 – 198 | Missing in isoform 3. CuratedAdd BLAST | 39 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000445696; ENSP00000410763; ENSG00000090534 [P40225-2] ENST00000647395; ENSP00000494504; ENSG00000090534 [P40225-1] |
GeneIDi | 7066 |
KEGGi | hsa:7066 |
UCSCi | uc003fol.2, human [P40225-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1V7M | X-ray | 2.51 | V/X | 22-184 | [»] | |
1V7N | X-ray | 3.30 | V/X/Y/Z | 22-184 | [»] | |
ModBasei | Search... | |||||
SWISS-MODEL-Workspacei | Submit a new modelling project... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112922, 3 interactors |
DIPi | DIP-5729N |
ELMi | P40225 |
IntActi | P40225, 3 interactors |
STRINGi | 9606.ENSP00000204615 |
Chemistry databases
ChEMBLi | CHEMBL1293256 |
PTM databases
GlyConnecti | 592, 12 N-Linked glycans, 4 O-Linked glycans |
GlyGeni | P40225, 14 sites, 12 N-linked glycans (1 site) |
iPTMneti | P40225 |
PhosphoSitePlusi | P40225 |
UniCarbKBi | P40225 |
Polymorphism and mutation databases
BioMutai | THPO |
DMDMi | 730982 |
Proteomic databases
MassIVEi | P40225 |
PaxDbi | P40225 |
PeptideAtlasi | P40225 |
PRIDEi | P40225 |
ProteomicsDBi | 55350 [P40225-1] 55351 [P40225-2] 55352 [P40225-3] |
Protocols and materials databases
ABCDi | P40225, 1 sequenced antibody |
Antibodypediai | 19145, 598 antibodies |
DNASUi | 7066 |
Genome annotation databases
Ensembli | ENST00000445696; ENSP00000410763; ENSG00000090534 [P40225-2] ENST00000647395; ENSP00000494504; ENSG00000090534 [P40225-1] |
GeneIDi | 7066 |
KEGGi | hsa:7066 |
UCSCi | uc003fol.2, human [P40225-1] |
Organism-specific databases
CTDi | 7066 |
DisGeNETi | 7066 |
EuPathDBi | HostDB:ENSG00000090534.17 |
GeneCardsi | THPO |
HGNCi | HGNC:11795, THPO |
HPAi | ENSG00000090534, Tissue enriched (liver) |
MalaCardsi | THPO |
MIMi | 187950, phenotype 600044, gene |
neXtProti | NX_P40225 |
OpenTargetsi | ENSG00000090534 |
Orphaneti | 71493, Familial thrombocytosis 397692, Hereditary isolated aplastic anemia 329319, Thrombocythemia with distal limb defects |
PharmGKBi | PA36506 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502S9T0, Eukaryota |
GeneTreei | ENSGT00390000006294 |
HOGENOMi | CLU_039844_0_0_1 |
InParanoidi | P40225 |
OMAi | AHPHFQN |
OrthoDBi | 906192at2759 |
PhylomeDBi | P40225 |
TreeFami | TF338084 |
Enzyme and pathway databases
PathwayCommonsi | P40225 |
Reactomei | R-HSA-76009, Platelet Aggregation (Plug Formation) |
SignaLinki | P40225 |
SIGNORi | P40225 |
Miscellaneous databases
BioGRID-ORCSi | 7066, 5 hits in 842 CRISPR screens |
ChiTaRSi | THPO, human |
EvolutionaryTracei | P40225 |
GeneWikii | Thrombopoietin |
GenomeRNAii | 7066 |
Pharosi | P40225, Tbio |
PROi | PR:P40225 |
RNActi | P40225, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000090534, Expressed in right lobe of liver and 103 other tissues |
ExpressionAtlasi | P40225, baseline and differential |
Genevisiblei | P40225, HS |
Family and domain databases
InterProi | View protein in InterPro IPR009079, 4_helix_cytokine-like_core IPR019767, EPO/TPO_CS IPR001323, EPO_TPO IPR003978, Thrombopoietin |
PANTHERi | PTHR10560, PTHR10560, 1 hit |
Pfami | View protein in Pfam PF00758, EPO_TPO, 1 hit |
PRINTSi | PR01485, THROMBOPTN |
SUPFAMi | SSF47266, SSF47266, 1 hit |
PROSITEi | View protein in PROSITE PS00817, EPO_TPO, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TPO_HUMAN | |
Accessioni | P40225Primary (citable) accession number: P40225 Secondary accession number(s): A1L3Y0 Q15792 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | December 2, 2020 | |
This is version 187 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations