P40226 (TPO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Thpo

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	356 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Tissue specificity	Found mainly in the liver, kidney and skeletal muscle.
Domain	Two-domain structure with an erythropoietin-like N-terminal and a Ser/Pro/Thr-rich C-terminal.
Sequence similarities	Belongs to the EPO/TPO family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Cytokine Hormone
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell proliferation Inferred from electronic annotation. Source: InterPro myeloid cell differentiation Inferred from direct assay PubMed 12393382. Source: MGI
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P40226-1)

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: P40226-2)

Also known as: TPO-2;

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Chain	22 – 356	335	Thrombopoietin		PRO_0000008412
Amino acid modifications
	Glycosylation	197	1	N-linked (GlcNAc...) Potential
	Glycosylation	206	1	N-linked (GlcNAc...) Potential
	Glycosylation	235	1	N-linked (GlcNAc...) Potential
	Glycosylation	249	1	N-linked (GlcNAc...) Potential
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
	Glycosylation	336	1	N-linked (GlcNAc...) Potential
	Glycosylation	351	1	N-linked (GlcNAc...) Potential
	Disulfide bond	28 ↔ 172		Potential
	Disulfide bond	50 ↔ 106		Potential
Natural variations
	Alternative sequence	133 – 136	4	Missing in isoform 2.		VSP_001452

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: D346DBAE8392053C	FASTA	356	37,836
	10 20 30 40 50 60 MELTDLLLAA MLLAVARLTL SSPVAPACDP RLLNKLLRDS HLLHSRLSQC PDVDPLSIPV 70 80 90 100 110 120 LLPAVDFSLG EWKTQTEQSK AQDILGAVSL LLEGVMAARG QLEPSCLSSL LGQLSGQVRL 130 140 150 160 170 180 LLGALQGLLG TQLPLQGRTT AHKDPNALFL SLQQLLRGKV RFLLLVEGPT LCVRRTLPTT 190 200 210 220 230 240 AVPSSTSQLL TLNKFPNRTS GLLETNFSVT ARTAGPGLLS RLQGFRVKIT PGQLNQTSRS 250 260 270 280 290 300 PVQISGYLNR THGPVNGTHG LFAGTSLQTL EASDISPGAF NKGSLAFNLQ GGLPPSPSLA 310 320 330 340 350 PDGHTPFPPS PALPTTHGSP PQLHPLFPDP STTMPNSTAP HPVTMYPHPR NLSQET
	Isoform 2 (TPO-2) [UniParc]. Checksum: B7121C4BC7CCAF4A	FASTA	352	37,384
	10 20 30 40 50 60 MELTDLLLAA MLLAVARLTL SSPVAPACDP RLLNKLLRDS HLLHSRLSQC PDVDPLSIPV 70 80 90 100 110 120 LLPAVDFSLG EWKTQTEQSK AQDILGAVSL LLEGVMAARG QLEPSCLSSL LGQLSGQVRL 130 140 150 160 170 180 LLGALQGLLG TQGRTTAHKD PNALFLSLQQ LLRGKVRFLL LVEGPTLCVR RTLPTTAVPS 190 200 210 220 230 240 STSQLLTLNK FPNRTSGLLE TNFSVTARTA GPGLLSRLQG FRVKITPGQL NQTSRSPVQI 250 260 270 280 290 300 SGYLNRTHGP VNGTHGLFAG TSLQTLEASD ISPGAFNKGS LAFNLQGGLP PSPSLAPDGH 310 320 330 340 350 TPFPPSPALP TTHGSPPQLH PLFPDPSTTM PNSTAPHPVT MYPHPRNLSQ ET

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo." Lok S., Kaushansky K., Holly R.D., Kuijper J.L., Lofton-Day C.E., Oort P.J., Grant F.J., Heipel M.D., Burkhead S.K., Kramer J.M., Bell L.A.N., Sprecher C.A., Blumberg H., Johnson R., Prunkard D., Ching A.F.T., Mathewes S.L., Bailey M.C. , Forstrom J.W., Buddle M.M., Osborn S.G., Evans S.J., Sheppard P.O., Presnell S.R., O'Hara P.J., Hagen F.S., Roth G.J., Foster D.C. Nature 369:565-568(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[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. , 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: 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L34169 mRNA. Translation: AAA40436.1. BC003803 mRNA. Translation: AAH03803.1.
IPI	IPI00108063. IPI00230271.
PIR	S45330.
RefSeq	NP_001166976.1. NM_001173505.1. NP_033405.1. NM_009379.3.
UniGene	Mm.3943.
3D structure databases
ProteinModelPortal	P40226.
SMR	P40226. Positions 28-172.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000075756.
PTM databases
PhosphoSite	P40226.
Proteomic databases
PRIDE	P40226.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000076422; ENSMUSP00000075756; ENSMUSG00000022847. ENSMUST00000115437; ENSMUSP00000111097; ENSMUSG00000022847.
GeneID	21832.
KEGG	mmu:21832.
UCSC	uc007yra.2. mouse.
Organism-specific databases
CTD	7066.
MGI	MGI:101875. Thpo.
Phylogenomic databases
eggNOG	NOG84342.
HOGENOM	HOG000082495.
HOVERGEN	HBG002468.
InParanoid	P40226.
KO	K06854.
OMA	CPDVNPL.
OrthoDB	EOG4HT8SV.
Gene expression databases
ArrayExpress	P40226.
Bgee	P40226.
CleanEx	MM_THPO.
Genevestigator	P40226.
GermOnline	ENSMUSG00000022847. Mus musculus.
Family and domain databases
Gene3D	1.20.1250.10. 1 hit.
InterPro	IPR009079. 4_helix_cytokine-like_core. IPR012351. 4_helix_cytokine_core. IPR019767. EPO/TPO_CS. IPR001323. EPO_TPO. IPR003978. Thrombopoeitin. [Graphical view]
PANTHER	PTHR10560. PTHR10560. 1 hit.
Pfam	PF00758. EPO_TPO. 1 hit. [Graphical view]
PRINTS	PR01485. THROMBOPTN.
SUPFAM	SSF47266. 4_helix_cytokine. 1 hit.
PROSITE	PS00817. EPO_TPO. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	301278.
SOURCE	Search...

Entry information

Entry name

TPO_MOUSE

Accession

Primary (citable) accession number: P40226

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 29, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program