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Protein

Thrombopoietin

Gene

THPO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • growth factor activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Hormone

Enzyme and pathway databases

BioCyciZFISH:ENSG00000090534-MONOMER.
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

HGNCiHGNC:11795. THPO.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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. Hereditary thrombocytosis with transverse limb defect.
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...)1 Publication1
Disulfide bondi28 ↔ 172
Disulfide bondi50 ↔ 106
Glycosylationi58O-linked (GalNAc...)1 Publication1
Glycosylationi131O-linked (GalNAc...)1 Publication1
Glycosylationi179O-linked (GalNAc...)1 Publication1
Glycosylationi180O-linked (GalNAc...)1 Publication1
Glycosylationi184O-linked (GalNAc...)1 Publication1
Glycosylationi197N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi206N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi213O-linked (GalNAc...)1 Publication1
Glycosylationi234N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi255N-linked (GlcNAc...) (complex)1 Publication1
Glycosylationi265O-linked (GalNAc...)1 Publication1
Glycosylationi340N-linked (GlcNAc...)Sequence analysis1
Glycosylationi348N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP40225.
PeptideAtlasiP40225.
PRIDEiP40225.

PTM databases

iPTMnetiP40225.
PhosphoSitePlusiP40225.
UniCarbKBiP40225.

Miscellaneous databases

PMAP-CutDBP40225.

Expressioni

Gene expression databases

BgeeiENSG00000090534.
CleanExiHS_THPO.
ExpressionAtlasiP40225. baseline and differential.
GenevisibleiP40225. HS.

Interactioni

GO - Molecular functioni

  • growth factor activity Source: ProtInc

Protein-protein interaction databases

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

Structurei

Secondary structure

1353
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 45Combined sources14
Helixi46 – 48Combined sources3
Beta strandi49 – 52Combined sources4
Beta strandi60 – 63Combined sources4
Helixi70 – 74Combined sources5
Helixi77 – 98Combined sources22
Turni99 – 101Combined sources3
Beta strandi104 – 106Combined sources3
Helixi107 – 110Combined sources4
Helixi113 – 129Combined sources17
Beta strandi139 – 143Combined sources5
Helixi145 – 147Combined sources3
Helixi148 – 157Combined sources10
Turni158 – 160Combined sources3
Helixi161 – 163Combined sources3
Beta strandi165 – 167Combined sources3

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...

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.
OMAiCPEVNPL.
OrthoDBiEOG091G0DW3.
PhylomeDBiP40225.
TreeFamiTF338084.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003978. Thrombopoeitin.
[Graphical view]
PANTHERiPTHR10560. PTHR10560. 1 hit.
PfamiPF00758. EPO_TPO. 1 hit.
[Graphical view]
PRINTSiPR01485. THROMBOPTN.
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00817. EPO_TPO. 1 hit.
[Graphical view]

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

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

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 rs1042346dbSNPEnsembl.1
Natural variantiVAR_011796116G → E.Corresponds to variant rs1126665dbSNPEnsembl.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]
GeneIDi7066.
KEGGihsa:7066.
UCSCiuc003fol.2. human. [P40225-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
IntActiP40225. 3 interactors.
STRINGi9606.ENSP00000204615.

Chemistry databases

ChEMBLiCHEMBL1293256.

PTM databases

iPTMnetiP40225.
PhosphoSitePlusiP40225.
UniCarbKBiP40225.

Polymorphism and mutation databases

BioMutaiTHPO.
DMDMi730982.

Proteomic databases

PaxDbiP40225.
PeptideAtlasiP40225.
PRIDEiP40225.

Protocols and materials databases

DNASUi7066.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7066.
DisGeNETi7066.
GeneCardsiTHPO.
HGNCiHGNC:11795. THPO.
MalaCardsiTHPO.
MIMi187950. phenotype.
600044. gene.
neXtProtiNX_P40225.
OpenTargetsiENSG00000090534.
Orphaneti71493. Familial thrombocytosis.
397692. Hereditary isolated aplastic anemia.
329319. Hereditary thrombocytosis with transverse limb defect.
PharmGKBiPA36506.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IVHV. Eukaryota.
ENOG41116B9. LUCA.
GeneTreeiENSGT00390000006294.
HOVERGENiHBG002468.
InParanoidiP40225.
KOiK06854.
OMAiCPEVNPL.
OrthoDBiEOG091G0DW3.
PhylomeDBiP40225.
TreeFamiTF338084.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000090534-MONOMER.
ReactomeiR-HSA-76009. Platelet Aggregation (Plug Formation).
SignaLinkiP40225.
SIGNORiP40225.

Miscellaneous databases

ChiTaRSiTHPO. human.
EvolutionaryTraceiP40225.
GeneWikiiThrombopoietin.
GenomeRNAii7066.
PMAP-CutDBP40225.
PROiP40225.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000090534.
CleanExiHS_THPO.
ExpressionAtlasiP40225. baseline and differential.
GenevisibleiP40225. HS.

Family and domain databases

Gene3Di1.20.1250.10. 1 hit.
InterProiIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003978. Thrombopoeitin.
[Graphical view]
PANTHERiPTHR10560. PTHR10560. 1 hit.
PfamiPF00758. EPO_TPO. 1 hit.
[Graphical view]
PRINTSiPR01485. THROMBOPTN.
SUPFAMiSSF47266. SSF47266. 1 hit.
PROSITEiPS00817. EPO_TPO. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTPO_HUMAN
AccessioniPrimary (citable) accession number: P40225
Secondary accession number(s): A1L3Y0
, B7ZLR8, B9EGA8, Q13020, Q15790, Q15791, Q15792
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: November 2, 2016
This is version 163 of the entry and version 1 of the sequence. [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. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.