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Q9UK05

- GDF2_HUMAN

UniProt

Q9UK05 - GDF2_HUMAN

Protein

Growth/differentiation factor 2

Gene

GDF2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    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

    1. protein binding Source: BHF-UCL

    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

    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

    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 strandi326 – 33510
    Turni336 – 3405
    Turni342 – 3443
    Beta strandi345 – 3473
    Beta strandi349 – 35911
    Helixi366 – 3683
    Helixi372 – 38312
    Turni385 – 3873
    Beta strandi393 – 40614
    Beta strandi412 – 42817

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ZKZX-ray2.33A320-429[»]
    4FAOX-ray3.36A/B/G/H/M/N/S/T/a/b/g/h320-429[»]
    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.
    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

    MCPGALWVAL PLLSLLAGSL QGKPLQSWGR GSAGGNAHSP LGVPGGGLPE    50
    HTFNLKMFLE NVKVDFLRSL NLSGVPSQDK TRVEPPQYMI DLYNRYTSDK 100
    STTPASNIVR SFSMEDAISI TATEDFPFQK HILLFNISIP RHEQITRAEL 150
    RLYVSCQNHV DPSHDLKGSV VIYDVLDGTD AWDSATETKT FLVSQDIQDE 200
    GWETLEVSSA VKRWVRSDST KSKNKLEVTV ESHRKGCDTL DISVPPGSRN 250
    LPFFVVFSND HSSGTKETRL ELREMISHEQ ESVLKKLSKD GSTEAGESSH 300
    EEDTDGHVAA GSTLARRKRS AGAGSHCQKT SLRVNFEDIG WDSWIIAPKE 350
    YEAYECKGGC FFPLADDVTP TKHAIVQTLV HLKFPTKVGK ACCVPTKLSP 400
    ISVLYKDDMG VPTLKYHYEG MSVAECGCR 429
    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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSiCCDS7219.1.
    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:
    EMBL
    GenBank
    DDBJ
    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 CCDS7219.1.
    RefSeqi NP_057288.1. NM_016204.2.
    UniGenei Hs.279463.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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 [» ]
    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.
    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

    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: October 1, 2014
    This is version 124 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