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P40225 (TPO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:THPO
Synonyms:MGDF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length353 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subcellular location

Secreted.

Domain

Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal.

Involvement in disease

Thrombocythemia 1 (THCYT1) [MIM:187950]: A myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the EPO/TPO family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P40225-1)

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.
Isoform 2 (identifier: P40225-2)

Also known as: TPO-2;

The sequence of this isoform differs from the canonical sequence as follows:
     133-136: Missing.
Isoform 3 (identifier: P40225-3)

Also known as: Truncated;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Chain22 – 353332Thrombopoietin
PRO_0000008411

Regions

Compositional bias285 – 33753Pro-rich

Amino acid modifications

Glycosylation221O-linked (GalNAc...) Ref.11
Glycosylation581O-linked (GalNAc...) Ref.11
Glycosylation1311O-linked (GalNAc...) Ref.11
Glycosylation1791O-linked (GalNAc...) Ref.11
Glycosylation1801O-linked (GalNAc...) Ref.11
Glycosylation1841O-linked (GalNAc...) Ref.11
Glycosylation1971N-linked (GlcNAc...) (complex) Ref.11
Glycosylation2061N-linked (GlcNAc...) (complex) Ref.11
Glycosylation2131O-linked (GalNAc...) Ref.11
Glycosylation2341N-linked (GlcNAc...) (complex) Ref.11
Glycosylation2551N-linked (GlcNAc...) (complex) Ref.11
Glycosylation2651O-linked (GalNAc...) Ref.11
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Potential
Disulfide bond28 ↔ 172 Ref.11 Ref.12
Disulfide bond50 ↔ 106 Ref.11 Ref.12

Natural variations

Alternative sequence133 – 1364Missing in isoform 2.
VSP_001450
Alternative sequence160 – 19839Missing in isoform 3.
VSP_001451
Natural variant141L → P.
Corresponds to variant rs1042346 [ dbSNP | Ensembl ].
VAR_011795
Natural variant1161G → E.
Corresponds to variant rs1126665 [ dbSNP | Ensembl ].
VAR_011796

Experimental info

Sequence conflict461R → K in AAB03392. Ref.8
Sequence conflict461R → K in AAB03393. Ref.8
Sequence conflict461R → K in AAB03394. Ref.8
Sequence conflict761M → MSQ in AAA74083. Ref.7
Sequence conflict1131Q → E in AAA50553. Ref.2
Sequence conflict1311T → P in AAA74083. Ref.7
Sequence conflict2771G → E in AAB03393. Ref.8
Sequence conflict2771G → E in AAB03394. Ref.8
Sequence conflict3461S → C in AAB03393. Ref.8
Sequence conflict3461S → C in AAB03394. Ref.8

Secondary structure

.......................... 353
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: F0AB5449B72E5526

FASTA35337,823
        10         20         30         40         50         60 
MELTELLLVV MLLLTARLTL SSPAPPACDL RVLSKLLRDS HVLHSRLSQC PEVHPLPTPV 

        70         80         90        100        110        120 
LLPAVDFSLG EWKTQMEETK AQDILGAVTL LLEGVMAARG QLGPTCLSSL LGQLSGQVRL 

       130        140        150        160        170        180 
LLGALQSLLG TQLPPQGRTT AHKDPNAIFL SFQHLLRGKV RFLMLVGGST LCVRRAPPTT 

       190        200        210        220        230        240 
AVPSRTSLVL TLNELPNRTS GLLETNFTAS ARTTGSGLLK WQQGFRAKIP GLLNQTSRSL 

       250        260        270        280        290        300 
DQIPGYLNRI HELLNGTRGL FPGPSRRTLG APDISSGTSD TGSLPPNLQP GYSPSPTHPP 

       310        320        330        340        350 
TGQYTLFPLP PTLPTPVVQL HPLLPDPSAP TPTPTSPLLN TSYTHSQNLS QEG 

« Hide

Isoform 2 (TPO-2) [UniParc].

Checksum: C7348E1148DAA58C
Show »

FASTA34937,387
Isoform 3 (Truncated) [UniParc].

Checksum: 183A09670C9FAEE4
Show »

FASTA31433,604

References

« Hide 'large scale' references
[1]"Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand."
de Sauvage F.J., Hass P.E., Spencer S.D., Malloy B.E., Gurney A.L., Spencer S.A., Darbonne W.C., Henzel W.J., Wong S.C., Kuang W.-J., Oles K.J., Hultgren B., Solberg L.A. Jr., Goeddel D.V., Eaton D.L.
Nature 369:533-538(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal liver.
[2]"Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl."
Bartley T.D., Bogenberger J., Hunt P., Li Y.-S., Lu H.S., Martin F., Chang M.-S., Samal B.B., Nichol J.L., Swift S., Johnson M.J., Hsu R.-Y., Parker V.P., Suggs S., Skrine J.D., Merewether L.A., Clogson C., Hsu E. expand/collapse author list , Hokom M.M., Hornkohl A., Choi E., Pangelinan M., Sun Y., Mar V., McNich J., Simonet L., Jacobsen F., Xie C., Shutter J., Chute H., Basu R., Selander L., Trollinger D., Sieu L., Padilla D., Trail G., Elliott G., Izumi R., Covey T., Crouse J., Garcia A., Xu W., del Castillo J., Biron J., Cole S., Hu M.C.-T., Pacifici R., Ponting I., Saris C., Wen D., Yung Y.P., Lin H., Bosselman R.A.
Cell 77:1117-1124(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal liver.
[3]"Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization."
Foster D.C., Sprecher C.A., Grant F.J., Kramer J.M., Kuijper J.L., Holly R.D., Whitmore T.E., Heipel M.D., Bell L.A.N., Ching A.F., McGrane V., Hart C., O'Hara P.J., Lok S.
Proc. Natl. Acad. Sci. U.S.A. 91:13023-13027(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[4]"Molecular cloning and chromosomal localization of the human thrombopoietin gene."
Sohma Y., Akahori H., Seki N., Hori T.-A., Ogami K., Kawamura K., Miyazaki H.
FEBS Lett. 353:57-61(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]"Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin."
Gurney A.L., Kuang W.-J., Xie M.-H., Malloy B.E., Eaton D.L., de Sauvage F.J.
Blood 85:981-988(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[6]"Purification and characterization of thrombopoietin."
Kato T., Ogami K., Shimada Y., Iwamatsu A., Sohma Y., Akahori H., Horie K., Kokubo A., Kudo Y., Maeda E., Kobayashi K., Ohashi H., Ozawa T., Inoue H., Kawamura K., Miyazaki H.
J. Biochem. 118:229-236(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[7]"Cloning and characterization of the human megakaryocyte growth and development factor (MGDF) gene."
Chang M., McNinch J., Basu R., Shutter J., Hsu R., Perkins C., Mar V., Suggs S., Welcher A., Li L., Lu H., Bartley T., Hunt P., Martin F., Samal B., Bogenberger J.
J. Biol. Chem. 270:511-514(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Tissue: Placenta.
[8]"Cloning and sequencing of human thrombopoietin."
Im S.H., Lee W.S., Chung K.H.
Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain and Testis.
[10]"An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia."
Wiestner A., Schlemper R.J., van der Maas A.P.C., Skoda R.C.
Nat. Genet. 18:49-52(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DISEASE.
[11]"Peptide, disulfide, and glycosylation mapping of recombinant human thrombopoietin from ser1 to Arg246."
Hoffman R.C., Andersen H., Walker K., Krakover J.D., Patel S., Stamm M.R., Osborn S.G.
Biochemistry 35:14849-14861(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS, GLYCOSYLATION AT SER-22; THR-58; THR-131; THR-179; THR-180; SER-184; ASN-197; ASN-206; THR-213; ASN-234; ASN-255 AND SER-265.
[12]"Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment."
Feese M.D., Tamada T., Kato Y., Maeda Y., Hirose M., Matsukura Y., Shigematsu H., Muto T., Matsumoto A., Watarai H., Ogami K., Tahara T., Kato T., Miyazaki H., Kuroki R.
Proc. Natl. Acad. Sci. U.S.A. 101:1816-1821(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 22-184 IN COMPLEX WITH ANTIBODY, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3265.1. [P40225-1]
CCDS54693.1. [P40225-2]
PIRG02729.
I80105. I59281.
RefSeqNP_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]
UniGeneHs.1166.
Hs.734657.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1V7MX-ray2.51V/X22-184[»]
1V7NX-ray3.30V/X/Y/Z22-184[»]
ProteinModelPortalP40225.
SMRP40225. Positions 28-172.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112922. 3 interactions.
DIPDIP-5729N.
IntActP40225. 3 interactions.
STRING9606.ENSP00000204615.

Chemistry

ChEMBLCHEMBL1293256.

PTM databases

PhosphoSiteP40225.

Polymorphism databases

DMDM730982.

Proteomic databases

PaxDbP40225.
PRIDEP40225.

Protocols and materials databases

DNASU7066.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000204615; ENSP00000204615; ENSG00000090534. [P40225-1]
ENST00000445696; ENSP00000410763; ENSG00000090534. [P40225-2]
GeneID7066.
KEGGhsa:7066.
UCSCuc003fol.1. human. [P40225-1]
uc003fom.2. human. [P40225-2]

Organism-specific databases

CTD7066.
GeneCardsGC03M184089.
HGNCHGNC:11795. THPO.
MIM187950. phenotype.
600044. gene.
neXtProtNX_P40225.
Orphanet71493. Familial thrombocytosis.
329319. Hereditary thrombocytosis with transverse limb defect.
PharmGKBPA36506.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG84342.
HOVERGENHBG002468.
InParanoidP40225.
KOK06854.
OMAEQSKAQD.
OrthoDBEOG7PVWPW.
PhylomeDBP40225.
TreeFamTF338084.

Enzyme and pathway databases

ReactomeREACT_604. Hemostasis.
SignaLinkP40225.

Gene expression databases

ArrayExpressP40225.
BgeeP40225.
CleanExHS_THPO.
GenevestigatorP40225.

Family and domain databases

Gene3D1.20.1250.10. 1 hit.
InterProIPR009079. 4_helix_cytokine-like_core.
IPR012351. 4_helix_cytokine_core.
IPR019767. EPO/TPO_CS.
IPR001323. EPO_TPO.
IPR003978. Thrombopoeitin.
[Graphical view]
PANTHERPTHR10560. PTHR10560. 1 hit.
PfamPF00758. EPO_TPO. 1 hit.
[Graphical view]
PRINTSPR01485. THROMBOPTN.
SUPFAMSSF47266. SSF47266. 1 hit.
PROSITEPS00817. EPO_TPO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP40225.
GeneWikiThrombopoietin.
GenomeRNAi7066.
NextBio27627.
PMAP-CutDBP40225.
PROP40225.
SOURCESearch...

Entry information

Entry nameTPO_HUMAN
AccessionPrimary (citable) accession number: P40225
Secondary accession number(s): A1L3Y0 expand/collapse secondary AC list , B7ZLR8, B9EGA8, Q13020, Q15790, Q15791, Q15792
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM