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 17-JUN-2020, entry version 73. 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 Cyprinidae; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR RefSeq; NP_001153466.1; NM_001159994.1. 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 eggNOG; ENOG410XT8Z; LUCA. DR GeneTree; ENSGT00940000160140; -. DR HOGENOM; CLU_020515_0_0_1; -. DR InParanoid; P85857; -. DR KO; K20012; -. DR OMA; LGNIPCF; -. DR OrthoDB; 749511at2759; -. DR PhylomeDB; P85857; -. DR TreeFam; TF316134; -. DR PRO; PR:P85857; -. DR Proteomes; UP000000437; Chromosome 16. DR Bgee; ENSDARG00000053479; Expressed in ectoderm and 65 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:0030509; P:BMP signaling pathway; IBA:GO_Central. 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 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 //