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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. Signals through the type I activin receptor ACVRL1 but not other Alks. Signaling through SMAD1 in endothelial cells requires TGF-beta coreceptor endoglin/ENG.5 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
  • branching involved in blood vessel morphogenesis Source: DFLAT
  • cartilage development Source: DFLAT
  • cell development Source: GO_Central
  • cellular iron ion homeostasis Source: DFLAT
  • cellular response to BMP stimulus Source: BHF-UCL
  • 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
  • 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

Keywordsi

Molecular functionCytokine, Growth factor
Biological processAngiogenesis

Enzyme and pathway databases

ReactomeiR-HSA-201451. Signaling by BMP.
SIGNORiQ9UK05.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000263761.2.
HGNCiHGNC:4217. GDF2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_07068968R → L in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs200330818Ensembl.1
Natural variantiVAR_07069085P → L in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs199804679Ensembl.1
Natural variantiVAR_070691333R → W in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs35129734Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2658.
MalaCardsiGDF2.
MIMi615506. phenotype.
OpenTargetsiENSG00000263761.
Orphaneti774. Hereditary hemorrhagic telangiectasia.
PharmGKBiPA28632.

Chemistry databases

ChEMBLiCHEMBL3831181.

Polymorphism and mutation databases

BioMutaiGDF2.
DMDMi13124266.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000003390223 – 319By similarityAdd BLAST297
ChainiPRO_0000033903320 – 429Growth/differentiation factor 2Add BLAST110

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi136N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi327 ↔ 393Combined sources1 Publication
Disulfide bondi356 ↔ 426Combined sources
Disulfide bondi360 ↔ 428Combined sources
Disulfide bondi392InterchainCombined sources1 Publication

Post-translational modificationi

A reversible disulfide bond can be formed between the two subunits in the homodimer; this has no effect on GDF2 activity.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9UK05.
PaxDbiQ9UK05.
PeptideAtlasiQ9UK05.
PRIDEiQ9UK05.

PTM databases

iPTMnetiQ9UK05.
PhosphoSitePlusiQ9UK05.

Expressioni

Tissue specificityi

Detected in blood plasma (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000263761.
CleanExiHS_GDF2.
GenevisibleiQ9UK05. HS.

Organism-specific databases

HPAiCAB023357.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (PubMed:25237187, PubMed:28564608). Detected in extracellular fluid as mature homodimer, and in complex with its propeptide (PubMed:21710321, PubMed:25237187). Interacts with ACVRL1, BMPR2 and ACVR2B with high affinity (in vitro) (PubMed:22799562, PubMed:22347366, PubMed:25237187, PubMed:25751889). Identified in a complex with ACVRL1 and ACVR2B (PubMed:22718755). Has ten times lower affinity for ACVR2A (in vitro) (PubMed:25751889). Interacts with ENG, forming a heterotetramer with a 2:2 stoichiometry (PubMed:21737454, PubMed:28564608). Can form a heteromeric complex with ENG and ACVRL1 (PubMed:28564608).8 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108928. 3 interactors.
STRINGi9606.ENSP00000249598.

Structurei

Secondary structure

1429
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi328 – 330Combined sources3
Beta strandi333 – 335Combined sources3
Turni336 – 340Combined sources5
Turni342 – 344Combined sources3
Beta strandi345 – 347Combined sources3
Beta strandi349 – 352Combined sources4
Beta strandi355 – 358Combined sources4
Helixi366 – 368Combined sources3
Helixi372 – 383Combined sources12
Turni385 – 387Combined sources3
Beta strandi393 – 406Combined sources14
Beta strandi408 – 410Combined sources3
Beta strandi412 – 428Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5HZWX-ray4.45B320-429[»]
5I05X-ray1.87A320-429[»]
ProteinModelPortaliQ9UK05.
SMRiQ9UK05.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UK05.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni412 – 416Interaction with ENG1 Publication5

Sequence similaritiesi

Belongs to the TGF-beta family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3900. Eukaryota.
ENOG410XT8Z. LUCA.
GeneTreeiENSGT00760000118883.
HOGENOMiHOG000249477.
HOVERGENiHBG106648.
InParanoidiQ9UK05.
KOiK05503.
OMAiILYKDDM.
OrthoDBiEOG091G075U.
PhylomeDBiQ9UK05.
TreeFamiTF316134.

Family and domain databases

Gene3Di2.10.90.10. 1 hit.
InterProiView protein in InterPro
IPR029034. Cystine-knot_cytokine.
IPR001839. TGF-b_C.
IPR001111. TGF-b_propeptide.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
PANTHERiPTHR11848. PTHR11848. 1 hit.
PfamiView protein in Pfam
PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
SMARTiView protein in SMART
SM00204. TGFB. 1 hit.
SUPFAMiSSF57501. SSF57501. 1 hit.
PROSITEiView protein in PROSITE
PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_07068968R → L in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs200330818Ensembl.1
Natural variantiVAR_07069085P → L in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs199804679Ensembl.1
Natural variantiVAR_070691333R → W in HHT5; impaired protein processing and function. 1 PublicationCorresponds to variant dbSNP:rs35129734Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF188285 mRNA. Translation: AAD56960.1.
AL731561 Genomic DNA. No translation available.
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_016204.3.
UniGeneiHs.279463.

Genome annotation databases

EnsembliENST00000581492; ENSP00000463051; ENSG00000263761.
GeneIDi2658.
KEGGihsa:2658.
UCSCiuc001jfa.2. human.

Similar proteinsi

Entry informationi

Entry nameiGDF2_HUMAN
AccessioniPrimary (citable) accession number: Q9UK05
Secondary accession number(s): Q5VSQ9, Q9Y571
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: May 1, 2000
Last modified: September 27, 2017
This is version 151 of the entry and version 1 of the sequence. See 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

Caution

Can promote osteogenic differentiation in vitro (PubMed:25237187, PubMed:25751889). This is probably not physiologically relevant.Curated2 Publications

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