GDF6A_DANRE
ID GDF6A_DANRE Reviewed; 404 AA.
AC P85857;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=Growth/differentiation factor 6-A;
DE Short=GDF-6-A;
DE AltName: Full=Growth differentiation factor 6A;
DE AltName: Full=Protein radar;
DE Flags: Precursor;
GN Name=gdf6a;
GN Synonyms=radar {ECO:0000303|PubMed:7734395},
GN rdr {ECO:0000303|PubMed:10415343};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-56, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10415343; DOI=10.1016/s0925-4773(99)00026-x;
RA Delot E., Kataoka H., Goutel C., Yan Y.-L., Postlethwait J., Wittbrodt J.,
RA Rosa F.M.;
RT "The BMP-related protein radar: a maintenance factor for dorsal
RT neuroectoderm cells?";
RL Mech. Dev. 85:15-25(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-404, FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo {ECO:0000269|PubMed:7734395};
RX PubMed=7734395; DOI=10.1016/0925-4773(94)00320-m;
RA Rissi M., Wittbrodt J., Delot E., Naegeli M., Rosa F.M.;
RT "Zebrafish Radar: a new member of the TGF-beta superfamily defines dorsal
RT regions of the neural plate and the embryonic retina.";
RL Mech. Dev. 49:223-234(1995).
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11091070; DOI=10.1016/s0925-4773(00)00470-6;
RA Goutel C., Kishimoto Y., Schulte-Merker S., Rosa F.M.;
RT "The ventralizing activity of Radar, a maternally expressed bone
RT morphogenetic protein, reveals complex bone morphogenetic protein
RT interactions controlling dorso-ventral patterning in zebrafish.";
RL Mech. Dev. 99:15-27(2000).
RN [4] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12413901; DOI=10.1006/dbio.2002.0794;
RA Hall C.J., Flores M.V.C., Davidson A.J., Crosier K.E., Crosier P.S.;
RT "Radar is required for the establishment of vascular integrity in the
RT zebrafish.";
RL Dev. Biol. 251:105-117(2002).
RN [5] {ECO:0000305}
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=12601179; DOI=10.1073/pnas.0530115100;
RA Sidi S., Goutel C., Peyrieras N., Rosa F.M.;
RT "Maternal induction of ventral fate by zebrafish radar.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:3315-3320(2003).
RN [6] {ECO:0000305}
RP REVIEW.
RX PubMed=12682283; DOI=10.1073/pnas.0931010100;
RA Wilm T.P., Solnica-Krezel L.;
RT "Radar breaks the fog: insights into dorsoventral patterning in
RT zebrafish.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4363-4365(2003).
RN [7]
RP FUNCTION.
RX PubMed=19164594; DOI=10.1073/pnas.0803202106;
RA Gosse N.J., Baier H.;
RT "An essential role for Radar (Gdf6a) in inducing dorsal fate in the
RT zebrafish retina.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:2236-2241(2009).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23307924; DOI=10.1093/hmg/dds560;
RA Asai-Coakwell M., March L., Dai X.H., Duval M., Lopez I., French C.R.,
RA Famulski J., De Baere E., Francis P.J., Sundaresan P., Sauve Y.,
RA Koenekoop R.K., Berry F.B., Allison W.T., Waskiewicz A.J., Lehmann O.J.;
RT "Contribution of growth differentiation factor 6-dependent cell survival to
RT early-onset retinal dystrophies.";
RL Hum. Mol. Genet. 22:1432-1442(2013).
RN [9]
RP FUNCTION IN APOPTOSIS.
RX PubMed=23847306; DOI=10.1167/iovs.12-11315;
RA Pant S.D., March L.D., Famulski J.K., French C.R., Lehmann O.J.,
RA Waskiewicz A.J.;
RT "Molecular mechanisms regulating ocular apoptosis in zebrafish gdf6a
RT mutants.";
RL Invest. Ophthalmol. Vis. Sci. 54:5871-5879(2013).
CC -!- FUNCTION: Growth factor that controls proliferation and cellular
CC differentiation in the retina. Plays a key role in regulating apoptosis
CC during retinal development. Establishes dorsal-ventral positional
CC information in the retina and controls the formation of the
CC retinotectal map. Functions maternally in dorsal/ventral patterning to
CC induce the expression of the zygotic bmp2b and bmp4 genes and
CC ventralize embryos. Zygotic expression does not appear to regulate axis
CC specification, but instead functions to establish the integrity of the
CC axial vessels during embryonic development. May be involved in
CC maintaining the identity of cells of the dorsal-most neural tube and of
CC at least a subset of neural crest cells. {ECO:0000269|PubMed:10415343,
CC ECO:0000269|PubMed:11091070, ECO:0000269|PubMed:12413901,
CC ECO:0000269|PubMed:12601179, ECO:0000269|PubMed:19164594,
CC ECO:0000269|PubMed:23307924, ECO:0000269|PubMed:23847306,
CC ECO:0000269|PubMed:7734395}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:P39905}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: First expressed in late gastrula stage embryos (9.5
CC hours post fertilization (hpf)) in anterior neuroectoderm corresponding
CC to the future dorsal part of the brain. Shortly after tailbud formation
CC (11 hpf), expression expands to the entire neural region and is
CC subsequently expressed in derivatives of the lateral neural plate and
CC migrating neural crest cells, with the future midbrain and hindbrain
CC showing strong expression. Also expressed weakly and transiently in the
CC posterior embryo from 11.5 hpf to 15 hpf in the lateral mesoderm, and
CC in ectoderm above the neural keel. At 14 hpf, expressed along the
CC entire length of the embryo and starting around the 16-somite stage,
CC expressed in the dorsal quadrant of the retina, representing the distal
CC tip of the eye anlage. At this stage, also expressed in the hatching
CC gland and the hypochord. At 24 hpf, expressed in the roof plate
CC outlining the fourth brain ventricle, in the posterior hypochord, the
CC primitive gut endoderm, the ventral tail mesenchyme, the dorsal part of
CC the neural tube and the dorsal fin. Weakly expressed in the dorsal part
CC of the posterior spinal cord and in blood cell precursors.
CC {ECO:0000269|PubMed:10415343, ECO:0000269|PubMed:11091070,
CC ECO:0000269|PubMed:12413901, ECO:0000269|PubMed:7734395}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed from early cleavage stage until blastula sphere stage.
CC Expression is then barely detectable until the end of gastrulation
CC (tailbud stage) when expression is resumed.
CC {ECO:0000269|PubMed:11091070, ECO:0000269|PubMed:12601179}.
CC -!- DISRUPTION PHENOTYPE: Adults display microphthalmia, with eyes obscured
CC by overgrown skin and misshapen irides. Mutants at 2 weeks of age show
CC profound alterations in the morphology of individual photoreceptor
CC subtypes and UV cones. At later timepoints loss of normal retinal
CC lamination is observed, together with a disorganization of Mueller glia
CC cells. Adults, cone photoreceptors are dysmorphic and reduced in
CC abundance. {ECO:0000269|PubMed:23307924}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000255}.
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DR RefSeq; NP_001153466.1; NM_001159994.1.
DR AlphaFoldDB; P85857; -.
DR SMR; P85857; -.
DR STRING; 7955.ENSDARP00000069999; -.
DR PaxDb; P85857; -.
DR PRIDE; P85857; -.
DR Ensembl; ENSDART00000075517; ENSDARP00000069999; ENSDARG00000053479.
DR GeneID; 566470; -.
DR KEGG; dre:566470; -.
DR CTD; 566470; -.
DR ZFIN; ZDB-GENE-980526-373; gdf6a.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000160140; -.
DR HOGENOM; CLU_020515_0_0_1; -.
DR InParanoid; P85857; -.
DR OMA; KKSKYRC; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; P85857; -.
DR TreeFam; TF316134; -.
DR SignaLink; P85857; -.
DR PRO; PR:P85857; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 16.
DR Bgee; ENSDARG00000053479; Expressed in germ layer and 77 other tissues.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0001955; P:blood vessel maturation; IMP:ZFIN.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0043010; P:camera-type eye development; IMP:ZFIN.
DR GO; GO:0060219; P:camera-type eye photoreceptor cell differentiation; IGI:ZFIN.
DR GO; GO:0048264; P:determination of ventral identity; IDA:ZFIN.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:ZFIN.
DR GO; GO:0031076; P:embryonic camera-type eye development; IMP:ZFIN.
DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IMP:ZFIN.
DR GO; GO:0048706; P:embryonic skeletal system development; IMP:ZFIN.
DR GO; GO:1900747; P:negative regulation of vascular endothelial growth factor signaling pathway; IMP:ZFIN.
DR GO; GO:0046552; P:photoreceptor cell fate commitment; IMP:ZFIN.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:ZFIN.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IMP:ZFIN.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:ZFIN.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:ZFIN.
DR GO; GO:0001895; P:retina homeostasis; IMP:ZFIN.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IMP:ZFIN.
DR GO; GO:1990009; P:retinal cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0042670; P:retinal cone cell differentiation; IMP:ZFIN.
DR GO; GO:0042671; P:retinal cone cell fate determination; IMP:ZFIN.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IMP:ZFIN.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cleavage on pair of basic residues; Developmental protein;
KW Disulfide bond; Glycoprotein; Growth factor; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..284
FT /evidence="ECO:0000255"
FT /id="PRO_0000342703"
FT CHAIN 285..404
FT /note="Growth/differentiation factor 6-A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000342704"
FT REGION 263..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 263..279
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 280..304
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 303..369
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 332..401
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 336..403
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT DISULFID 368
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P39905"
FT CONFLICT 51
FT /note="E -> R (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="V -> L (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 404 AA; 46290 MW; 23233847DF96E197 CRC64;
MDALRAVAFY ALFVFLWSLP CCQSAALISQ KRSKGARSAF DGQRSHKFLK EILASSPGAS
RRDDFKDPVV PHDYMISIYR TYSAAEKLGL NASFFRSSKS ANTITSFVDK GKDDLTLSPL
RRQTYLFDVS TLSDKEELVG AELRIFRKSP GDVQPSPSGV YNLHLLSCRS ERPLASRSID
LQDSRKAEWE VLDVWGIFKH RHQENQLCLQ LKVTYGKSDT EIDLKQLGFH RHSRTQQERA
ILVVYTRSKK RENLFNEMKE KIKSRGDDDE EESALQFKAR RRRRTALNNR HGKRHGKKSK
SRCSKKALHV NFKELGWDDW IIAPLDYEAY HCEGVCDFPL RSHLEPTNHA IIQTLMNSMD
PNSTPPSCCV PTKLSPISIL YIDSGNNVVY KQYEDMVVEQ CGCR
