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Q9UK05

- GDF2_HUMAN

UniProt

Q9UK05 - GDF2_HUMAN

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Protein

Growth/differentiation factor 2

Gene

GDF2

Organism
Homo sapiens (Human)
Status
Reviewed - 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 - Biological processi

  1. activin receptor signaling pathway Source: BHF-UCL
  2. angiogenesis Source: UniProtKB
  3. blood vessel morphogenesis Source: DFLAT
  4. BMP signaling pathway Source: BHF-UCL
  5. cartilage development Source: DFLAT
  6. cellular iron ion homeostasis Source: DFLAT
  7. cellular response to BMP stimulus Source: BHF-UCL
  8. growth Source: InterPro
  9. negative regulation of angiogenesis Source: DFLAT
  10. negative regulation of blood vessel endothelial cell migration Source: DFLAT
  11. negative regulation of cell growth Source: BHF-UCL
  12. negative regulation of DNA biosynthetic process Source: BHF-UCL
  13. negative regulation of DNA replication Source: DFLAT
  14. negative regulation of endothelial cell migration Source: BHF-UCL
  15. negative regulation of endothelial cell proliferation Source: DFLAT
  16. ossification Source: DFLAT
  17. osteoblast differentiation Source: Ensembl
  18. pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  19. patterning of blood vessels Source: DFLAT
  20. positive regulation of angiogenesis Source: DFLAT
  21. positive regulation of BMP signaling pathway Source: Ensembl
  22. positive regulation of endothelial cell differentiation Source: Ensembl
  23. positive regulation of endothelial cell proliferation Source: DFLAT
  24. positive regulation of interleukin-8 production Source: BHF-UCL
  25. positive regulation of osteoblast differentiation Source: Ensembl
  26. positive regulation of pathway-restricted SMAD protein phosphorylation Source: BHF-UCL
  27. positive regulation of transcription, DNA-templated Source: BHF-UCL
  28. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  29. 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: Chromosome 10

Organism-specific databases

HGNCiHGNC:4217. GDF2.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. extracellular space Source: UniProtKB-KW
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
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.

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.
GenevestigatoriQ9UK05.

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[»]
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.

Polymorphism databases

DMDMi13124266.

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 .
CCDSi CCDS73118.1.
RefSeqi NP_057288.1. NM_016204.2.
UniGenei Hs.279463.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ZKZ X-ray 2.33 A 320-429 [» ]
4FAO X-ray 3.36 A/B/G/H/M/N/S/T/a/b/g/h 320-429 [» ]
4MPL X-ray 1.90 A 321-429 [» ]
ProteinModelPortali Q9UK05.
SMRi Q9UK05. Positions 323-429.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108928. 3 interactions.
STRINGi 9606.ENSP00000249598.

PTM databases

PhosphoSitei Q9UK05.

Polymorphism databases

DMDMi 13124266.

Proteomic databases

PaxDbi Q9UK05.
PRIDEi Q9UK05.

Protocols and materials databases

DNASUi 2658.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000581492 ; ENSP00000463051 ; ENSG00000263761 .
GeneIDi 2658.
KEGGi hsa:2658.
UCSCi uc001jfa.1. human.

Organism-specific databases

CTDi 2658.
GeneCardsi GC10M048413.
HGNCi HGNC:4217. GDF2.
HPAi CAB023357.
MIMi 605120. gene.
615506. phenotype.
neXtProti NX_Q9UK05.
Orphaneti 774. Hereditary hemorrhagic telangiectasia.
PharmGKBi PA28632.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG280573.
GeneTreei ENSGT00760000118883.
HOGENOMi HOG000249477.
HOVERGENi HBG106648.
InParanoidi Q9UK05.
KOi K05503.
OMAi ENMKVDF.
OrthoDBi EOG7ZD1V3.
PhylomeDBi Q9UK05.
TreeFami TF316134.

Miscellaneous databases

EvolutionaryTracei Q9UK05.
GeneWikii GDF2.
GenomeRNAii 2658.
NextBioi 10496.
PROi Q9UK05.
SOURCEi Search...

Gene expression databases

Bgeei Q9UK05.
CleanExi HS_GDF2.
Genevestigatori Q9UK05.

Family and domain databases

Gene3Di 2.10.90.10. 1 hit.
InterProi IPR029034. Cystine-knot_cytokine.
IPR002405. Inhibin_asu.
IPR001839. TGF-b_C.
IPR001111. TGF-b_N.
IPR015615. TGF-beta-rel.
IPR017948. TGFb_CS.
[Graphical view ]
PANTHERi PTHR11848. PTHR11848. 1 hit.
Pfami PF00019. TGF_beta. 1 hit.
PF00688. TGFb_propeptide. 1 hit.
[Graphical view ]
PRINTSi PR00669. INHIBINA.
SMARTi SM00204. TGFB. 1 hit.
[Graphical view ]
SUPFAMi SSF57501. SSF57501. 1 hit.
PROSITEi PS00250. TGF_BETA_1. 1 hit.
PS51362. TGF_BETA_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: November 26, 2014
This is version 126 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