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Protein

Thrombopoietin

Gene

THPO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

Keywordsi

Molecular functionCytokine, Hormone

Enzyme and pathway databases

ReactomeiR-HSA-76009 Platelet Aggregation (Plug Formation)
SignaLinkiP40225
SIGNORiP40225

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombopoietin
Alternative 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000090534.17
HGNCiHGNC:11795 THPO
MIMi600044 gene
neXtProtiNX_P40225

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & 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.
See also OMIM:187950

Organism-specific databases

DisGeNETi7066
MalaCardsiTHPO
MIMi187950 phenotype
OpenTargetsiENSG00000090534
Orphaneti71493 Familial thrombocytosis
397692 Hereditary isolated aplastic anemia
329319 Thrombocythemia with distal limb defects
PharmGKBiPA36506

Chemistry databases

ChEMBLiCHEMBL1293256

Polymorphism and mutation databases

BioMutaiTHPO
DMDMi730982

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Add BLAST21
ChainiPRO_000000841122 – 353ThrombopoietinAdd BLAST332

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi22O-linked (GalNAc...) serine1 Publication1
Disulfide bondi28 ↔ 172
Disulfide bondi50 ↔ 106
Glycosylationi58O-linked (GalNAc...) threonine1 Publication1
Glycosylationi131O-linked (GalNAc...) threonine1 Publication1
Glycosylationi179O-linked (GalNAc...) threonine1 Publication1
Glycosylationi180O-linked (GalNAc...) threonine1 Publication1
Glycosylationi184O-linked (GalNAc...) serine1 Publication1
Glycosylationi197N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi206N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi213O-linked (GalNAc...) threonine1 Publication1
Glycosylationi234N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi255N-linked (GlcNAc...) (complex) asparagine1 Publication1
Glycosylationi265O-linked (GalNAc...) serine1 Publication1
Glycosylationi340N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi348N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP40225
PeptideAtlasiP40225
PRIDEiP40225
ProteomicsDBi55350
55351 [P40225-2]
55352 [P40225-3]

PTM databases

GlyConnecti592
iPTMnetiP40225
PhosphoSitePlusiP40225
UniCarbKBiP40225

Miscellaneous databases

PMAP-CutDBiP40225

Expressioni

Gene expression databases

BgeeiENSG00000090534 Expressed in 85 organ(s), highest expression level in right lobe of liver
CleanExiHS_THPO
ExpressionAtlasiP40225 baseline and differential
GenevisibleiP40225 HS

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112922, 3 interactors
DIPiDIP-5729N
ELMiP40225
IntActiP40225, 3 interactors
STRINGi9606.ENSP00000204615

Structurei

Secondary structure

1353
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP40225
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40225

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi285 – 337Pro-richAdd BLAST53

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

Signal

Phylogenomic databases

eggNOGiENOG410IVHV Eukaryota
ENOG41116B9 LUCA
GeneTreeiENSGT00390000006294
HOVERGENiHBG002468
InParanoidiP40225
KOiK06854
OMAiPLNGTHG
OrthoDBiEOG091G0DW3
PhylomeDBiP40225
TreeFamiTF338084

Family and domain databases

InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR019767 EPO/TPO_CS
IPR001323 EPO_TPO
IPR003978 Thrombopoeitin
PANTHERiPTHR10560 PTHR10560, 1 hit
PfamiView protein in Pfam
PF00758 EPO_TPO, 1 hit
PRINTSiPR01485 THROMBOPTN
SUPFAMiSSF47266 SSF47266, 1 hit
PROSITEiView protein in PROSITE
PS00817 EPO_TPO, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 2 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 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:353
Mass (Da):37,823
Last modified:February 1, 1995 - v1
Checksum:iF0AB5449B72E5526
GO
Isoform 2 (identifier: P40225-2) [UniParc]FASTAAdd to basket
Also known as: TPO-2

The sequence of this isoform differs from the canonical sequence as follows:
     133-136: Missing.

Show »
Length:349
Mass (Da):37,387
Checksum:iC7348E1148DAA58C
GO
Isoform 3 (identifier: P40225-3) [UniParc]FASTAAdd to basket
Also known as: Truncated

The sequence of this isoform differs from the canonical sequence as follows:
     160-198: Missing.

Show »
Length:314
Mass (Da):33,604
Checksum:i183A09670C9FAEE4
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W6L1F8W6L1_HUMAN
Thrombopoietin
THPO
286Annotation score:
A0A2R8Y734A0A2R8Y734_HUMAN
Thrombopoietin
THPO
12Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46R → K in AAB03392 (Ref. 8) Curated1
Sequence conflicti46R → K in AAB03393 (Ref. 8) Curated1
Sequence conflicti46R → K in AAB03394 (Ref. 8) Curated1
Sequence conflicti76M → MSQ in AAA74083 (PubMed:7822271).Curated1
Sequence conflicti113Q → E in AAA50553 (PubMed:8020099).Curated1
Sequence conflicti131T → P in AAA74083 (PubMed:7822271).Curated1
Sequence conflicti277G → E in AAB03393 (Ref. 8) Curated1
Sequence conflicti277G → E in AAB03394 (Ref. 8) Curated1
Sequence conflicti346S → C in AAB03393 (Ref. 8) Curated1
Sequence conflicti346S → C in AAB03394 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01179514L → P. Corresponds to variant dbSNP:rs1042346Ensembl.1
Natural variantiVAR_011796116G → E. Corresponds to variant dbSNP:rs1126665Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001450133 – 136Missing in isoform 2. 1 Publication4
Alternative sequenceiVSP_001451160 – 198Missing in isoform 3. CuratedAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33410 mRNA Translation: AAA59857.1
U11025 mRNA Translation: AAA50553.1
L36051 Genomic DNA Translation: AAC37568.1
L36052 mRNA Translation: AAC37566.1
D32046 Genomic DNA Translation: BAA06807.1
S76771 Genomic DNA Translation: AAB33390.1
D32047 mRNA Translation: BAA21930.1
U59493 mRNA Translation: AAB03392.1
U59494 mRNA Translation: AAB03393.1
U59495 mRNA Translation: AAB03394.1
U17071 Genomic DNA Translation: AAA74083.1
BC130322 mRNA Translation: AAI30323.1
BC136338 mRNA Translation: AAI36339.1
BC143982 mRNA Translation: AAI43983.1
CCDSiCCDS3265.1 [P40225-1]
CCDS54693.1 [P40225-2]
PIRiG02729
I59281 I80105
RefSeqiNP_000451.1, NM_000460.3 [P40225-1]
NP_001171068.1, NM_001177597.2 [P40225-2]
NP_001171069.1, NM_001177598.2
NP_001276926.1, NM_001289997.1
NP_001276927.1, NM_001289998.1 [P40225-1]
NP_001276932.1, NM_001290003.1
NP_001276951.1, NM_001290022.1 [P40225-2]
NP_001276955.1, NM_001290026.1
NP_001276956.1, NM_001290027.1
NP_001276957.1, NM_001290028.1 [P40225-1]
UniGeneiHs.1166
Hs.734657

Genome annotation databases

EnsembliENST00000204615; ENSP00000204615; ENSG00000090534 [P40225-1]
ENST00000445696; ENSP00000410763; ENSG00000090534 [P40225-2]
ENST00000645603; ENSP00000494281; ENSG00000090534 [P40225-1]
ENST00000647395; ENSP00000494504; ENSG00000090534 [P40225-1]
GeneIDi7066
KEGGihsa:7066
UCSCiuc003fol.2 human [P40225-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33410 mRNA Translation: AAA59857.1
U11025 mRNA Translation: AAA50553.1
L36051 Genomic DNA Translation: AAC37568.1
L36052 mRNA Translation: AAC37566.1
D32046 Genomic DNA Translation: BAA06807.1
S76771 Genomic DNA Translation: AAB33390.1
D32047 mRNA Translation: BAA21930.1
U59493 mRNA Translation: AAB03392.1
U59494 mRNA Translation: AAB03393.1
U59495 mRNA Translation: AAB03394.1
U17071 Genomic DNA Translation: AAA74083.1
BC130322 mRNA Translation: AAI30323.1
BC136338 mRNA Translation: AAI36339.1
BC143982 mRNA Translation: AAI43983.1
CCDSiCCDS3265.1 [P40225-1]
CCDS54693.1 [P40225-2]
PIRiG02729
I59281 I80105
RefSeqiNP_000451.1, NM_000460.3 [P40225-1]
NP_001171068.1, NM_001177597.2 [P40225-2]
NP_001171069.1, NM_001177598.2
NP_001276926.1, NM_001289997.1
NP_001276927.1, NM_001289998.1 [P40225-1]
NP_001276932.1, NM_001290003.1
NP_001276951.1, NM_001290022.1 [P40225-2]
NP_001276955.1, NM_001290026.1
NP_001276956.1, NM_001290027.1
NP_001276957.1, NM_001290028.1 [P40225-1]
UniGeneiHs.1166
Hs.734657

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1V7MX-ray2.51V/X22-184[»]
1V7NX-ray3.30V/X/Y/Z22-184[»]
ProteinModelPortaliP40225
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112922, 3 interactors
DIPiDIP-5729N
ELMiP40225
IntActiP40225, 3 interactors
STRINGi9606.ENSP00000204615

Chemistry databases

ChEMBLiCHEMBL1293256

PTM databases

GlyConnecti592
iPTMnetiP40225
PhosphoSitePlusiP40225
UniCarbKBiP40225

Polymorphism and mutation databases

BioMutaiTHPO
DMDMi730982

Proteomic databases

PaxDbiP40225
PeptideAtlasiP40225
PRIDEiP40225
ProteomicsDBi55350
55351 [P40225-2]
55352 [P40225-3]

Protocols and materials databases

DNASUi7066
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000204615; ENSP00000204615; ENSG00000090534 [P40225-1]
ENST00000445696; ENSP00000410763; ENSG00000090534 [P40225-2]
ENST00000645603; ENSP00000494281; ENSG00000090534 [P40225-1]
ENST00000647395; ENSP00000494504; ENSG00000090534 [P40225-1]
GeneIDi7066
KEGGihsa:7066
UCSCiuc003fol.2 human [P40225-1]

Organism-specific databases

CTDi7066
DisGeNETi7066
EuPathDBiHostDB:ENSG00000090534.17
GeneCardsiTHPO
HGNCiHGNC:11795 THPO
MalaCardsiTHPO
MIMi187950 phenotype
600044 gene
neXtProtiNX_P40225
OpenTargetsiENSG00000090534
Orphaneti71493 Familial thrombocytosis
397692 Hereditary isolated aplastic anemia
329319 Thrombocythemia with distal limb defects
PharmGKBiPA36506
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVHV Eukaryota
ENOG41116B9 LUCA
GeneTreeiENSGT00390000006294
HOVERGENiHBG002468
InParanoidiP40225
KOiK06854
OMAiPLNGTHG
OrthoDBiEOG091G0DW3
PhylomeDBiP40225
TreeFamiTF338084

Enzyme and pathway databases

ReactomeiR-HSA-76009 Platelet Aggregation (Plug Formation)
SignaLinkiP40225
SIGNORiP40225

Miscellaneous databases

ChiTaRSiTHPO human
EvolutionaryTraceiP40225
GeneWikiiThrombopoietin
GenomeRNAii7066
PMAP-CutDBiP40225
PROiPR:P40225
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090534 Expressed in 85 organ(s), highest expression level in right lobe of liver
CleanExiHS_THPO
ExpressionAtlasiP40225 baseline and differential
GenevisibleiP40225 HS

Family and domain databases

InterProiView protein in InterPro
IPR009079 4_helix_cytokine-like_core
IPR019767 EPO/TPO_CS
IPR001323 EPO_TPO
IPR003978 Thrombopoeitin
PANTHERiPTHR10560 PTHR10560, 1 hit
PfamiView protein in Pfam
PF00758 EPO_TPO, 1 hit
PRINTSiPR01485 THROMBOPTN
SUPFAMiSSF47266 SSF47266, 1 hit
PROSITEiView protein in PROSITE
PS00817 EPO_TPO, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTPO_HUMAN
AccessioniPrimary (citable) accession number: P40225
Secondary accession number(s): A1L3Y0
, B7ZLR8, B9EGA8, Q13020, Q15790, Q15791, Q15792
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 7, 2018
This is version 173 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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