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 16-OCT-2019, entry version 70. 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., RA Wittbrodt J., 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 RP 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 RT dorsal 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., RA Lehmann O.J.; RT "Contribution of growth differentiation factor 6-dependent cell RT survival to 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 CC apoptosis during retinal development. Establishes dorsal-ventral CC positional information in the retina and controls the formation of CC the retinotectal map. Functions maternally in dorsal/ventral CC patterning to induce the expression of the zygotic bmp2b and bmp4 CC genes and ventralize embryos. Zygotic expression does not appear CC to regulate axis specification, but instead functions to establish CC the integrity of the axial vessels during embryonic development. CC May be involved in maintaining the identity of cells of the CC dorsal-most neural tube and of at least a subset of neural crest CC cells. {ECO:0000269|PubMed:10415343, ECO:0000269|PubMed:11091070, CC ECO:0000269|PubMed:12413901, ECO:0000269|PubMed:12601179, CC ECO:0000269|PubMed:19164594, ECO:0000269|PubMed:23307924, CC ECO:0000269|PubMed:23847306, ECO:0000269|PubMed:7734395}. CC -!- SUBUNIT: Homodimer; disulfide-linked. CC {ECO:0000250|UniProtKB:P39905}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. CC -!- TISSUE SPECIFICITY: First expressed in late gastrula stage embryos CC (9.5 hours post fertilization (hpf)) in anterior neuroectoderm CC corresponding to the future dorsal part of the brain. Shortly CC after tailbud formation (11 hpf), expression expands to the entire CC neural region and is subsequently expressed in derivatives of the CC lateral neural plate and migrating neural crest cells, with the CC future midbrain and hindbrain showing strong expression. Also CC expressed weakly and transiently in the posterior embryo from 11.5 CC hpf to 15 hpf in the lateral mesoderm, and in ectoderm above the CC neural keel. At 14 hpf, expressed along the entire length of the CC embryo and starting around the 16-somite stage, expressed in the CC dorsal quadrant of the retina, representing the distal tip of the CC eye anlage. At this stage, also expressed in the hatching gland CC and the hypochord. At 24 hpf, expressed in the roof plate CC outlining the fourth brain ventricle, in the posterior hypochord, CC the primitive gut endoderm, the ventral tail mesenchyme, the CC dorsal part of the neural tube and the dorsal fin. Weakly CC expressed in the dorsal part of the posterior spinal cord and in CC blood cell precursors. {ECO:0000269|PubMed:10415343, CC ECO:0000269|PubMed:11091070, ECO:0000269|PubMed:12413901, CC 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 CC obscured by overgrown skin and misshapen irides. Mutants at 2 CC weeks of age show profound alterations in the morphology of CC individual photoreceptor subtypes and UV cones. At later CC timepoints loss of normal retinal lamination is observed, together CC with a disorganization of Mueller glia cells. Adults, cone CC photoreceptors are dysmorphic and reduced in abundance. CC {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; HOG000231514; -. 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 66 organ(s), highest expression level in ectoderm. 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:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central. 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:0048468; P:cell development; IBA:GO_Central. 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:0042981; P:regulation of apoptotic process; 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:0043408; P:regulation of MAPK cascade; IBA:GO_Central. 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: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; Complete proteome; KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT PROPEP 25 284 {ECO:0000255}. FT /FTId=PRO_0000342703. FT CHAIN 285 404 Growth/differentiation factor 6-A. FT {ECO:0000255}. FT /FTId=PRO_0000342704. FT CARBOHYD 91 91 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 303 369 {ECO:0000250|UniProtKB:P39905}. FT DISULFID 332 401 {ECO:0000250|UniProtKB:P39905}. FT DISULFID 336 403 {ECO:0000250|UniProtKB:P39905}. FT DISULFID 368 368 Interchain. FT {ECO:0000250|UniProtKB:P39905}. FT CONFLICT 51 51 E -> R (in Ref. 2; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 70 70 V -> L (in Ref. 2; no nucleotide entry). FT {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 //