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Q9UK05 (GDF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth/differentiation factor 2

Short name=GDF-2
Alternative name(s):
Bone morphogenetic protein 9
Short name=BMP-9
Gene names
Name:GDF2
Synonyms:BMP9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length429 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG. Ref.6 Ref.8 Ref.10

Subunit structure

Homodimer; disulfide-linked. Interacts with ENG. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Subcellular location

Secreted Ref.6.

Involvement in disease

Telangiectasia, hereditary hemorrhagic, 5 (HHT5) [MIM:615506]: A multisystemic vascular dysplasia leading to dilation of permanent blood vessels and arteriovenous malformations of skin, mucosa, and viscera. The disease is characterized by recurrent epistaxis and gastro-intestinal hemorrhage. Visceral involvement includes arteriovenous malformations of the lung, liver, and brain.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the TGF-beta family.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentSecreted
   DiseaseDisease mutation
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

activin receptor signaling pathway

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

blood vessel morphogenesis

Inferred from direct assay PubMed 20406889. Source: DFLAT

cartilage development

Traceable author statement PubMed 20406889. Source: DFLAT

cellular iron ion homeostasis

Traceable author statement PubMed 20406889. Source: DFLAT

growth

Inferred from electronic annotation. Source: InterPro

negative regulation of DNA biosynthetic process

Inferred from direct assay PubMed 19366699. Source: BHF-UCL

negative regulation of DNA replication

Traceable author statement PubMed 20406889. Source: DFLAT

negative regulation of angiogenesis

Traceable author statement PubMed 20406889. Source: DFLAT

negative regulation of blood vessel endothelial cell migration

Traceable author statement PubMed 20406889. Source: DFLAT

negative regulation of cell growth

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

negative regulation of endothelial cell migration

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

negative regulation of endothelial cell proliferation

Inferred from direct assay PubMed 20406889. Source: DFLAT

ossification

Traceable author statement PubMed 20406889. Source: DFLAT

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

patterning of blood vessels

Inferred from direct assay PubMed 20406889. Source: DFLAT

positive regulation of BMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of angiogenesis

Inferred from direct assay PubMed 20406889. Source: DFLAT

positive regulation of endothelial cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell proliferation

Inferred from direct assay PubMed 20406889. Source: DFLAT

positive regulation of interleukin-8 production

Inferred from direct assay PubMed 19366699. Source: BHF-UCL

positive regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of pathway-restricted SMAD protein phosphorylation

Inferred from direct assay PubMed 17068149PubMed 19366699PubMed 19903896. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19366699. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17068149. Source: BHF-UCL

vasculogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 319297 By similarity
PRO_0000033902
Chain320 – 429110Growth/differentiation factor 2
PRO_0000033903

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation1361N-linked (GlcNAc...) Potential
Disulfide bond327 ↔ 393 Ref.11 Ref.12
Disulfide bond356 ↔ 426 Ref.11 Ref.12
Disulfide bond360 ↔ 428 Ref.11 Ref.12
Disulfide bond392Interchain Ref.11 Ref.12

Natural variations

Natural variant681R → L in HHT5; impaired protein processing and function. Ref.13
VAR_070689
Natural variant851P → L in HHT5; impaired protein processing and function. Ref.13
VAR_070690
Natural variant3331R → W in HHT5; impaired protein processing and function. Ref.13
VAR_070691

Secondary structure

................... 429
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UK05 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 5AC15DCA205FF086

FASTA42947,320
        10         20         30         40         50         60 
MCPGALWVAL PLLSLLAGSL QGKPLQSWGR GSAGGNAHSP LGVPGGGLPE HTFNLKMFLE 

        70         80         90        100        110        120 
NVKVDFLRSL NLSGVPSQDK TRVEPPQYMI DLYNRYTSDK STTPASNIVR SFSMEDAISI 

       130        140        150        160        170        180 
TATEDFPFQK HILLFNISIP RHEQITRAEL RLYVSCQNHV DPSHDLKGSV VIYDVLDGTD 

       190        200        210        220        230        240 
AWDSATETKT FLVSQDIQDE GWETLEVSSA VKRWVRSDST KSKNKLEVTV ESHRKGCDTL 

       250        260        270        280        290        300 
DISVPPGSRN LPFFVVFSND HSSGTKETRL ELREMISHEQ ESVLKKLSKD GSTEAGESSH 

       310        320        330        340        350        360 
EEDTDGHVAA GSTLARRKRS AGAGSHCQKT SLRVNFEDIG WDSWIIAPKE YEAYECKGGC 

       370        380        390        400        410        420 
FFPLADDVTP TKHAIVQTLV HLKFPTKVGK ACCVPTKLSP ISVLYKDDMG VPTLKYHYEG 


MSVAECGCR 

« Hide

References

« Hide 'large scale' references
[1]Celeste A.J.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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].
[5]"Growth/differentiation factor-2, a new TGF-beta family member with bone promoting activities."
Zimmers T.A., Koniaris L.G., Sitzmann J.V., Lee S.-J.
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 316-429.
Tissue: Liver.
[6]"Bone morphogenetic protein-9 is a circulating vascular quiescence factor."
David L., Mallet C., Keramidas M., Lamande N., Gasc J.M., Dupuis-Girod S., Plauchu H., Feige J.J., Bailly S.
Circ. Res. 102:914-922(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth."
Castonguay R., Werner E.D., Matthews R.G., Presman E., Mulivor A.W., Solban N., Sako D., Pearsall R.S., Underwood K.W., Seehra J., Kumar R., Grinberg A.V.
J. Biol. Chem. 286:30034-30046(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ENG.
[8]"Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties."
Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P.
Biochemistry 51:6328-6341(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ACVRL1.
[9]"Structural and functional insights into endoglin ligand recognition and binding."
Alt A., Miguel-Romero L., Donderis J., Aristorena M., Blanco F.J., Round A., Rubio V., Bernabeu C., Marina A.
PLoS ONE 7:E29948-E29948(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ENG.
[10]"Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies."
Nolan-Stevaux O., Zhong W., Culp S., Shaffer K., Hoover J., Wickramasinghe D., Ruefli-Brasse A.
PLoS ONE 7:E50920-E50920(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Crystal structure of BMP-9 and functional interactions with pro-region and receptors."
Brown M.A., Zhao Q., Baker K.A., Naik C., Chen C., Pukac L., Singh M., Tsareva T., Parice Y., Mahoney A., Roschke V., Sanyal I., Choe S.
J. Biol. Chem. 280:25111-25118(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 320-429, DISULFIDE BONDS.
[12]"Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex."
Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J., Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R., Grinberg A.V.
J. Biol. Chem. 287:27313-27325(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 320-429 IN COMPLEX WITH ACVRL1 AND ACVR2B, DISULFIDE BONDS.
[13]"BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia."
Wooderchak-Donahue W.L., McDonald J., O'Fallon B., Upton P.D., Li W., Roman B.L., Young S., Plant P., Fulop G.T., Langa C., Morrell N.W., Botella L.M., Bernabeu C., Stevenson D.A., Runo J.R., Bayrak-Toydemir P.
Am. J. Hum. Genet. 93:530-537(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHT5 LEU-68; LEU-85 AND TRP-333, PROTEOLYTIC PROCESSING.
+Additional computationally mapped references.

Web resources

Wikipedia

GDF2 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF188285 mRNA. Translation: AAD56960.1.
AL731561 Genomic DNA. Translation: CAH74046.1.
CH471251 Genomic DNA. Translation: EAW50660.1.
BC069643 mRNA. Translation: AAH69643.1.
BC074921 mRNA. Translation: AAH74921.1.
AF156891 mRNA. Translation: AAD40309.1.
RefSeqNP_057288.1. NM_016204.2.
UniGeneHs.279463.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZKZX-ray2.33A320-429[»]
4FAOX-ray3.36A/B/G/H/M/N/S/T/a/b/g/h320-429[»]
ProteinModelPortalQ9UK05.
SMRQ9UK05. Positions 323-429.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108928. 3 interactions.
STRING9606.ENSP00000249598.

PTM databases

PhosphoSiteQ9UK05.

Polymorphism databases

DMDM13124266.

Proteomic databases

PaxDbQ9UK05.
PRIDEQ9UK05.

Protocols and materials databases

DNASU2658.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000249598; ENSP00000249598; ENSG00000128802.
ENST00000581492; ENSP00000463051; ENSG00000263761.
GeneID2658.
KEGGhsa:2658.
UCSCuc001jfa.1. human.

Organism-specific databases

CTD2658.
GeneCardsGC10M048413.
HGNCHGNC:4217. GDF2.
HPACAB023357.
MIM605120. gene.
615506. phenotype.
neXtProtNX_Q9UK05.
Orphanet774. Hereditary hemorrhagic telangiectasia.
PharmGKBPA28632.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG280573.
HOGENOMHOG000249477.
HOVERGENHBG106648.
InParanoidQ9UK05.
KOK05503.
OMAENMKVDF.
OrthoDBEOG7ZD1V3.
PhylomeDBQ9UK05.
TreeFamTF316134.

Gene expression databases

BgeeQ9UK05.
CleanExHS_GDF2.
GenevestigatorQ9UK05.

Family and domain databases

InterProIPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERPTHR11848. PTHR11848. 1 hit.
PfamPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSPR00669. INHIBINA.
SMARTSM00204. TGFB. 1 hit.
[Graphical view]
PROSITEPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UK05.
GeneWikiGDF2.
GenomeRNAi2658.
NextBio10496.
PROQ9UK05.
SOURCESearch...

Entry information

Entry nameGDF2_HUMAN
AccessionPrimary (citable) accession number: Q9UK05
Secondary accession number(s): Q5VSQ9, Q9Y571
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 119 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 10

Human chromosome 10: entries, gene names and cross-references to MIM