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Protein

Thrombopoietin

Gene

Thpo

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 - Biological processi

  1. cell proliferation Source: InterPro
  2. myeloid cell differentiation Source: MGI
  3. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  4. positive regulation of megakaryocyte differentiation Source: UniProtKB
  5. positive regulation of protein kinase B signaling Source: UniProtKB
  6. positive regulation of protein phosphorylation Source: UniProtKB
  7. thrombopoietin-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Hormone

Enzyme and pathway databases

ReactomeiREACT_296516. Platelet Aggregation (Plug Formation).

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:101875. Thpo.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 356335ThrombopoietinPRO_0000008412Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi28 ↔ 172Sequence Analysis
Disulfide bondi50 ↔ 106Sequence Analysis
Glycosylationi197 – 1971N-linked (GlcNAc...)Sequence Analysis
Glycosylationi206 – 2061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi235 – 2351N-linked (GlcNAc...)Sequence Analysis
Glycosylationi249 – 2491N-linked (GlcNAc...)Sequence Analysis
Glycosylationi256 – 2561N-linked (GlcNAc...)Sequence Analysis
Glycosylationi336 – 3361N-linked (GlcNAc...)Sequence Analysis
Glycosylationi351 – 3511N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP40226.

PTM databases

PhosphoSiteiP40226.

Expressioni

Tissue specificityi

Found mainly in the liver, kidney and skeletal muscle.

Inductioni

Expression in the liver and bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).1 Publication

Gene expression databases

BgeeiP40226.
CleanExiMM_THPO.
ExpressionAtlasiP40226. baseline and differential.
GenevestigatoriP40226.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000075756.

Structurei

3D structure databases

ProteinModelPortaliP40226.
SMRiP40226. Positions 28-172.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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

eggNOGiNOG84342.
HOGENOMiHOG000082495.
HOVERGENiHBG002468.
InParanoidiP40226.
KOiK06854.
OMAiCAKRAPP.
OrthoDBiEOG7PVWPW.
PhylomeDBiP40226.
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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P40226-1) [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
MELTDLLLAA MLLAVARLTL SSPVAPACDP RLLNKLLRDS HLLHSRLSQC
60 70 80 90 100
PDVDPLSIPV LLPAVDFSLG EWKTQTEQSK AQDILGAVSL LLEGVMAARG
110 120 130 140 150
QLEPSCLSSL LGQLSGQVRL LLGALQGLLG TQLPLQGRTT AHKDPNALFL
160 170 180 190 200
SLQQLLRGKV RFLLLVEGPT LCVRRTLPTT AVPSSTSQLL TLNKFPNRTS
210 220 230 240 250
GLLETNFSVT ARTAGPGLLS RLQGFRVKIT PGQLNQTSRS PVQISGYLNR
260 270 280 290 300
THGPVNGTHG LFAGTSLQTL EASDISPGAF NKGSLAFNLQ GGLPPSPSLA
310 320 330 340 350
PDGHTPFPPS PALPTTHGSP PQLHPLFPDP STTMPNSTAP HPVTMYPHPR

NLSQET
Length:356
Mass (Da):37,836
Last modified:February 1, 1995 - v1
Checksum:iD346DBAE8392053C
GO
Isoform 2 (identifier: P40226-2) [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:352
Mass (Da):37,384
Checksum:iB7121C4BC7CCAF4A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei133 – 1364Missing in isoform 2. 1 PublicationVSP_001452

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L34169 mRNA. Translation: AAA40436.1.
BC003803 mRNA. Translation: AAH03803.1.
CCDSiCCDS37292.1. [P40226-1]
PIRiS45330.
RefSeqiNP_001166976.1. NM_001173505.1. [P40226-1]
NP_001276823.1. NM_001289894.1. [P40226-2]
NP_033405.1. NM_009379.3. [P40226-1]
UniGeneiMm.3943.

Genome annotation databases

EnsembliENSMUST00000076422; ENSMUSP00000075756; ENSMUSG00000022847. [P40226-1]
ENSMUST00000115437; ENSMUSP00000111097; ENSMUSG00000022847. [P40226-1]
GeneIDi21832.
KEGGimmu:21832.
UCSCiuc007yra.2. mouse. [P40226-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L34169 mRNA. Translation: AAA40436.1.
BC003803 mRNA. Translation: AAH03803.1.
CCDSiCCDS37292.1. [P40226-1]
PIRiS45330.
RefSeqiNP_001166976.1. NM_001173505.1. [P40226-1]
NP_001276823.1. NM_001289894.1. [P40226-2]
NP_033405.1. NM_009379.3. [P40226-1]
UniGeneiMm.3943.

3D structure databases

ProteinModelPortaliP40226.
SMRiP40226. Positions 28-172.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000075756.

PTM databases

PhosphoSiteiP40226.

Proteomic databases

PRIDEiP40226.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000076422; ENSMUSP00000075756; ENSMUSG00000022847. [P40226-1]
ENSMUST00000115437; ENSMUSP00000111097; ENSMUSG00000022847. [P40226-1]
GeneIDi21832.
KEGGimmu:21832.
UCSCiuc007yra.2. mouse. [P40226-1]

Organism-specific databases

CTDi7066.
MGIiMGI:101875. Thpo.

Phylogenomic databases

eggNOGiNOG84342.
HOGENOMiHOG000082495.
HOVERGENiHBG002468.
InParanoidiP40226.
KOiK06854.
OMAiCAKRAPP.
OrthoDBiEOG7PVWPW.
PhylomeDBiP40226.
TreeFamiTF338084.

Enzyme and pathway databases

ReactomeiREACT_296516. Platelet Aggregation (Plug Formation).

Miscellaneous databases

NextBioi301278.
PROiP40226.
SOURCEiSearch...

Gene expression databases

BgeeiP40226.
CleanExiMM_THPO.
ExpressionAtlasiP40226. baseline and differential.
GenevestigatoriP40226.

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...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Kidney.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  3. "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 [MRNA] (ISOFORMS 1 AND 2).
  4. "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] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary gland.
  5. "Diurnal expression of the thrombopoietin gene is regulated by CLOCK."
    Tracey C.J., Pan X., Catterson J.H., Harmar A.J., Hussain M.M., Hartley P.S.
    J. Thromb. Haemost. 10:662-669(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

Entry informationi

Entry nameiTPO_MOUSE
AccessioniPrimary (citable) accession number: P40226
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 1, 2015
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.