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Protein

Growth/differentiation factor 2

Gene

GDF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

GO - Biological processi

  • activin receptor signaling pathway Source: BHF-UCL
  • angiogenesis Source: UniProtKB
  • blood vessel morphogenesis Source: DFLAT
  • BMP signaling pathway Source: BHF-UCL
  • cartilage development Source: DFLAT
  • cell development Source: GO_Central
  • cellular iron ion homeostasis Source: DFLAT
  • cellular response to BMP stimulus Source: BHF-UCL
  • growth Source: InterPro
  • negative regulation of angiogenesis Source: DFLAT
  • negative regulation of blood vessel endothelial cell migration Source: DFLAT
  • negative regulation of cell growth Source: BHF-UCL
  • negative regulation of DNA biosynthetic process Source: BHF-UCL
  • negative regulation of DNA replication Source: DFLAT
  • negative regulation of endothelial cell migration Source: BHF-UCL
  • negative regulation of endothelial cell proliferation Source: DFLAT
  • ossification Source: DFLAT
  • osteoblast differentiation Source: Ensembl
  • pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • patterning of blood vessels Source: DFLAT
  • positive regulation of angiogenesis Source: DFLAT
  • positive regulation of BMP signaling pathway Source: Ensembl
  • positive regulation of cartilage development Source: Ensembl
  • positive regulation of endothelial cell differentiation Source: Ensembl
  • positive regulation of endothelial cell proliferation Source: DFLAT
  • positive regulation of interleukin-8 production Source: BHF-UCL
  • positive regulation of osteoblast differentiation Source: Ensembl
  • positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of apoptotic process Source: GO_Central
  • regulation of MAPK cascade Source: GO_Central
  • SMAD protein signal transduction Source: GO_Central
  • vasculogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Angiogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Growth/differentiation factor 2
Short name:
GDF-2
Alternative name(s):
Bone morphogenetic protein 9
Short name:
BMP-9
Gene namesi
Name:GDF2
Synonyms:BMP9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:4217. GDF2.

Subcellular locationi

GO - Cellular componenti

  • cell Source: GOC
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Telangiectasia, hereditary hemorrhagic, 5 (HHT5)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:615506
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti68 – 681R → L in HHT5; impaired protein processing and function. 1 Publication
VAR_070689
Natural varianti85 – 851P → L in HHT5; impaired protein processing and function. 1 Publication
VAR_070690
Natural varianti333 – 3331R → W in HHT5; impaired protein processing and function. 1 Publication
VAR_070691

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi615506. phenotype.
Orphaneti774. Hereditary hemorrhagic telangiectasia.
PharmGKBiPA28632.

Polymorphism and mutation databases

BioMutaiGDF2.
DMDMi13124266.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Propeptidei23 – 319297By similarityPRO_0000033902Add
BLAST
Chaini320 – 429110Growth/differentiation factor 2PRO_0000033903Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi71 – 711N-linked (GlcNAc...)Sequence Analysis
Glycosylationi136 – 1361N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi327 ↔ 393
Disulfide bondi356 ↔ 426
Disulfide bondi360 ↔ 428
Disulfide bondi392 – 392Interchain

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UK05.
PRIDEiQ9UK05.

PTM databases

PhosphoSiteiQ9UK05.

Expressioni

Gene expression databases

BgeeiQ9UK05.
CleanExiHS_GDF2.
GenevisibleiQ9UK05. HS.

Organism-specific databases

HPAiCAB023357.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with ENG.5 Publications

Protein-protein interaction databases

BioGridi108928. 3 interactions.
STRINGi9606.ENSP00000249598.

Structurei

Secondary structure

1
429
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi328 – 3303Combined sources
Beta strandi333 – 3353Combined sources
Turni336 – 3405Combined sources
Turni342 – 3443Combined sources
Beta strandi345 – 3473Combined sources
Beta strandi349 – 3524Combined sources
Beta strandi355 – 3584Combined sources
Helixi366 – 3683Combined sources
Helixi372 – 38312Combined sources
Turni385 – 3873Combined sources
Beta strandi393 – 40614Combined sources
Beta strandi408 – 4103Combined sources
Beta strandi412 – 42817Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZKZX-ray2.33A320-429[»]
4FAOX-ray3.36A/B/G/H/M/N/S/T/a/b/g/h320-429[»]
4MPLX-ray1.90A321-429[»]
4YCGX-ray3.30C/D320-429[»]
4YCIX-ray3.25C/D320-429[»]
ProteinModelPortaliQ9UK05.
SMRiQ9UK05. Positions 323-429.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UK05.

Family & Domainsi

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG280573.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000249477.
HOVERGENiHBG106648.
InParanoidiQ9UK05.
KOiK05503.
OMAiENMKVDF.
OrthoDBiEOG7ZD1V3.
PhylomeDBiQ9UK05.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9UK05-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCPGALWVAL PLLSLLAGSL QGKPLQSWGR GSAGGNAHSP LGVPGGGLPE
60 70 80 90 100
HTFNLKMFLE NVKVDFLRSL NLSGVPSQDK TRVEPPQYMI DLYNRYTSDK
110 120 130 140 150
STTPASNIVR SFSMEDAISI TATEDFPFQK HILLFNISIP RHEQITRAEL
160 170 180 190 200
RLYVSCQNHV DPSHDLKGSV VIYDVLDGTD AWDSATETKT FLVSQDIQDE
210 220 230 240 250
GWETLEVSSA VKRWVRSDST KSKNKLEVTV ESHRKGCDTL DISVPPGSRN
260 270 280 290 300
LPFFVVFSND HSSGTKETRL ELREMISHEQ ESVLKKLSKD GSTEAGESSH
310 320 330 340 350
EEDTDGHVAA GSTLARRKRS AGAGSHCQKT SLRVNFEDIG WDSWIIAPKE
360 370 380 390 400
YEAYECKGGC FFPLADDVTP TKHAIVQTLV HLKFPTKVGK ACCVPTKLSP
410 420
ISVLYKDDMG VPTLKYHYEG MSVAECGCR
Length:429
Mass (Da):47,320
Last modified:May 1, 2000 - v1
Checksum:i5AC15DCA205FF086
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti68 – 681R → L in HHT5; impaired protein processing and function. 1 Publication
VAR_070689
Natural varianti85 – 851P → L in HHT5; impaired protein processing and function. 1 Publication
VAR_070690
Natural varianti333 – 3331R → W in HHT5; impaired protein processing and function. 1 Publication
VAR_070691

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS73118.1.
RefSeqiNP_057288.1. NM_016204.2.
UniGeneiHs.279463.

Genome annotation databases

EnsembliENST00000581492; ENSP00000463051; ENSG00000263761.
GeneIDi2658.
KEGGihsa:2658.
UCSCiuc001jfa.1. human.

Cross-referencesi

Web resourcesi

Wikipedia

GDF2 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS73118.1.
RefSeqiNP_057288.1. NM_016204.2.
UniGeneiHs.279463.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZKZX-ray2.33A320-429[»]
4FAOX-ray3.36A/B/G/H/M/N/S/T/a/b/g/h320-429[»]
4MPLX-ray1.90A321-429[»]
4YCGX-ray3.30C/D320-429[»]
4YCIX-ray3.25C/D320-429[»]
ProteinModelPortaliQ9UK05.
SMRiQ9UK05. Positions 323-429.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108928. 3 interactions.
STRINGi9606.ENSP00000249598.

PTM databases

PhosphoSiteiQ9UK05.

Polymorphism and mutation databases

BioMutaiGDF2.
DMDMi13124266.

Proteomic databases

PaxDbiQ9UK05.
PRIDEiQ9UK05.

Protocols and materials databases

DNASUi2658.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000581492; ENSP00000463051; ENSG00000263761.
GeneIDi2658.
KEGGihsa:2658.
UCSCiuc001jfa.1. human.

Organism-specific databases

CTDi2658.
GeneCardsiGC10M048413.
HGNCiHGNC:4217. GDF2.
HPAiCAB023357.
MIMi605120. gene.
615506. phenotype.
neXtProtiNX_Q9UK05.
Orphaneti774. Hereditary hemorrhagic telangiectasia.
PharmGKBiPA28632.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG280573.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000249477.
HOVERGENiHBG106648.
InParanoidiQ9UK05.
KOiK05503.
OMAiENMKVDF.
OrthoDBiEOG7ZD1V3.
PhylomeDBiQ9UK05.
TreeFamiTF316134.

Miscellaneous databases

EvolutionaryTraceiQ9UK05.
GeneWikiiGDF2.
GenomeRNAii2658.
NextBioi10496.
PROiQ9UK05.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UK05.
CleanExiHS_GDF2.
GenevisibleiQ9UK05. HS.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiIPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view]
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiPF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view]
PRINTSiPR00669. INHIBINA.
SMARTiSM00204. TGFB. 1 hit.
[Graphical view]
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiPS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. Cited for: VARIANTS HHT5 LEU-68; LEU-85 AND TRP-333, PROTEOLYTIC PROCESSING.

Entry informationi

Entry nameiGDF2_HUMAN
AccessioniPrimary (citable) accession number: Q9UK05
Secondary accession number(s): Q5VSQ9, Q9Y571
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: July 22, 2015
This is version 132 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 10
    Human chromosome 10: 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

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.