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P85857

- GDF6A_DANRE

UniProt

P85857 - GDF6A_DANRE

Protein

Growth/differentiation factor 6-A

Gene

gdf6a

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 45 (01 Oct 2014)
      Sequence version 1 (01 Jul 2008)
      Previous versions | rss
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    Functioni

    Growth factor that controls proliferation and cellular differentiation in the retina. Plays a key role in regulating apoptosis during retinal development. Establishes dorsal-ventral positional information in the retina and controls the formation of the retinotectal map. Functions maternally in dorsal/ventral patterning to induce the expression of the zygotic bmp2b and bmp4 genes and ventralize embryos. Zygotic expression does not appear to regulate axis specification, but instead functions to establish the integrity of the axial vessels during embryonic development. May be involved in maintaining the identity of cells of the dorsal-most neural tube and of at least a subset of neural crest cells.8 Publications

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. growth Source: InterPro
    3. multicellular organismal development Source: UniProtKB-KW
    4. retinal cell apoptotic process Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein, Growth factor

    Keywords - Biological processi

    Apoptosis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Growth/differentiation factor 6-A
    Short name:
    GDF-6-A
    Alternative name(s):
    Growth differentiation factor 6A
    Protein radar
    Gene namesi
    Name:gdf6a
    Synonyms:radar1 Publication, rdr1 Publication
    OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
    Taxonomic identifieri7955 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
    ProteomesiUP000000437: Chromosome 16

    Subcellular locationi

    Secreted By similarity

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Disruption phenotypei

    Adults display microphthalmia, with eyes obscured by overgrown skin and misshapen irides. Mutants at 2 weeks of age show profound alterations in the morphology of individual photoreceptor subtypes and UV cones. At later timepoints loss of normal retinal lamination is observed, together with a disorganization of Mueller glia cells. Adults, cone photoreceptors are dysmorphic and reduced in abundance.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Propeptidei25 – 284260Sequence AnalysisPRO_0000342703Add
    BLAST
    Chaini285 – 404120Growth/differentiation factor 6-ASequence AnalysisPRO_0000342704Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi91 – 911N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi303 ↔ 369By similarity
    Disulfide bondi332 ↔ 401By similarity
    Disulfide bondi336 ↔ 403By similarity
    Disulfide bondi368 – 368InterchainBy similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

    Expressioni

    Tissue specificityi

    First expressed in late gastrula stage embryos (9.5 hours post fertilization (hpf)) in anterior neuroectoderm corresponding to the future dorsal part of the brain. Shortly after tailbud formation (11 hpf), expression expands to the entire neural region and is subsequently expressed in derivatives of the lateral neural plate and migrating neural crest cells, with the future midbrain and hindbrain showing strong expression. Also expressed weakly and transiently in the posterior embryo from 11.5 hpf to 15 hpf in the lateral mesoderm, and in ectoderm above the neural keel. At 14 hpf, expressed along the entire length of the embryo and starting around the 16-somite stage, expressed in the dorsal quadrant of the retina, representing the distal tip of the eye anlage. At this stage, also expressed in the hatching gland and the hypochord. At 24 hpf, expressed in the roof plate outlining the fourth brain ventricle, in the posterior hypochord, the primitive gut endoderm, the ventral tail mesenchyme, the dorsal part of the neural tube and the dorsal fin. Weakly expressed in the dorsal part of the posterior spinal cord and in blood cell precursors.4 Publications

    Developmental stagei

    Expressed both maternally and zygotically. Expressed from early cleavage stage until blastula sphere stage. Expression is then barely detectable until the end of gastrulation (tailbud stage) when expression is resumed.2 Publications

    Gene expression databases

    BgeeiP85857.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked.By similarity

    Protein-protein interaction databases

    STRINGi7955.ENSDARP00000069999.

    Structurei

    3D structure databases

    ProteinModelPortaliP85857.
    SMRiP85857. Positions 300-404.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the TGF-beta family.Sequence Analysis

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG317866.
    GeneTreeiENSGT00730000110209.
    HOGENOMiHOG000231514.
    HOVERGENiHBG107938.
    KOiK04664.
    OMAiFTRSQRK.
    OrthoDBiEOG7WMCK0.
    PhylomeDBiP85857.
    TreeFamiTF316134.

    Family and domain databases

    Gene3Di2.10.90.10. 1 hit.
    InterProiIPR029034. Cystine-knot_cytokine.
    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]
    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.

    P85857-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDALRAVAFY ALFVFLWSLP CCQSAALISQ KRSKGARSAF DGQRSHKFLK    50
    EILASSPGAS RRDDFKDPVV PHDYMISIYR TYSAAEKLGL NASFFRSSKS 100
    ANTITSFVDK GKDDLTLSPL RRQTYLFDVS TLSDKEELVG AELRIFRKSP 150
    GDVQPSPSGV YNLHLLSCRS ERPLASRSID LQDSRKAEWE VLDVWGIFKH 200
    RHQENQLCLQ LKVTYGKSDT EIDLKQLGFH RHSRTQQERA ILVVYTRSKK 250
    RENLFNEMKE KIKSRGDDDE EESALQFKAR RRRRTALNNR HGKRHGKKSK 300
    SRCSKKALHV NFKELGWDDW IIAPLDYEAY HCEGVCDFPL RSHLEPTNHA 350
    IIQTLMNSMD PNSTPPSCCV PTKLSPISIL YIDSGNNVVY KQYEDMVVEQ 400
    CGCR 404
    Length:404
    Mass (Da):46,290
    Last modified:July 1, 2008 - v1
    Checksum:i23233847DF96E197
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti51 – 511E → R no nucleotide entry (PubMed:7734395)Curated
    Sequence conflicti70 – 701V → L no nucleotide entry (PubMed:7734395)Curated

    Sequence databases

    RefSeqiNP_001153466.1. NM_001159994.1.
    UniGeneiDr.16432.

    Genome annotation databases

    EnsembliENSDART00000075517; ENSDARP00000069999; ENSDARG00000053479.
    GeneIDi566470.
    KEGGidre:566470.

    Cross-referencesi

    Sequence databases

    RefSeqi NP_001153466.1. NM_001159994.1.
    UniGenei Dr.16432.

    3D structure databases

    ProteinModelPortali P85857.
    SMRi P85857. Positions 300-404.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 7955.ENSDARP00000069999.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSDART00000075517 ; ENSDARP00000069999 ; ENSDARG00000053479 .
    GeneIDi 566470.
    KEGGi dre:566470.

    Organism-specific databases

    CTDi 566470.

    Phylogenomic databases

    eggNOGi NOG317866.
    GeneTreei ENSGT00730000110209.
    HOGENOMi HOG000231514.
    HOVERGENi HBG107938.
    KOi K04664.
    OMAi FTRSQRK.
    OrthoDBi EOG7WMCK0.
    PhylomeDBi P85857.
    TreeFami TF316134.

    Miscellaneous databases

    NextBioi 20888199.
    PROi P85857.

    Gene expression databases

    Bgeei P85857.

    Family and domain databases

    Gene3Di 2.10.90.10. 1 hit.
    InterProi IPR029034. Cystine-knot_cytokine.
    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 ]
    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. "The BMP-related protein radar: a maintenance factor for dorsal neuroectoderm cells?"
      Delot E., Kataoka H., Goutel C., Yan Y.-L., Postlethwait J., Wittbrodt J., Rosa F.M.
      Mech. Dev. 85:15-25(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-56, FUNCTION, TISSUE SPECIFICITY.
    2. "Zebrafish Radar: a new member of the TGF-beta superfamily defines dorsal regions of the neural plate and the embryonic retina."
      Rissi M., Wittbrodt J., Delot E., Naegeli M., Rosa F.M.
      Mech. Dev. 49:223-234(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-404, FUNCTION, TISSUE SPECIFICITY.
      Tissue: Embryo1 Publication.
    3. "The ventralizing activity of Radar, a maternally expressed bone morphogenetic protein, reveals complex bone morphogenetic protein interactions controlling dorso-ventral patterning in zebrafish."
      Goutel C., Kishimoto Y., Schulte-Merker S., Rosa F.M.
      Mech. Dev. 99:15-27(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    4. "Radar is required for the establishment of vascular integrity in the zebrafish."
      Hall C.J., Flores M.V.C., Davidson A.J., Crosier K.E., Crosier P.S.
      Dev. Biol. 251:105-117(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    5. Cited for: FUNCTION, DEVELOPMENTAL STAGE.
    6. "Radar breaks the fog: insights into dorsoventral patterning in zebrafish."
      Wilm T.P., Solnica-Krezel L.
      Proc. Natl. Acad. Sci. U.S.A. 100:4363-4365(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    7. "An essential role for Radar (Gdf6a) in inducing dorsal fate in the zebrafish retina."
      Gosse N.J., Baier H.
      Proc. Natl. Acad. Sci. U.S.A. 106:2236-2241(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    9. "Molecular mechanisms regulating ocular apoptosis in zebrafish gdf6a mutants."
      Pant S.D., March L.D., Famulski J.K., French C.R., Lehmann O.J., Waskiewicz A.J.
      Invest. Ophthalmol. Vis. Sci. 54:5871-5879(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN APOPTOSIS.

    Entry informationi

    Entry nameiGDF6A_DANRE
    AccessioniPrimary (citable) accession number: P85857
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 2008
    Last sequence update: July 1, 2008
    Last modified: October 1, 2014
    This is version 45 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3