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   27-MAR-2024, entry version 89.
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}, rdr
GN   {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}.
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   AlphaFoldDB; P85857; -.
DR   SMR; P85857; -.
DR   STRING; 7955.ENSDARP00000069999; -.
DR   GlyCosmos; P85857; 1 site, No reported glycans.
DR   PaxDb; 7955-ENSDARP00000069999; -.
DR   GeneID; 566470; -.
DR   KEGG; dre:566470; -.
DR   AGR; ZFIN:ZDB-GENE-980526-373; -.
DR   CTD; 566470; -.
DR   ZFIN; ZDB-GENE-980526-373; gdf6a.
DR   eggNOG; KOG3900; Eukaryota.
DR   HOGENOM; CLU_020515_0_0_1; -.
DR   InParanoid; P85857; -.
DR   OMA; KKSKYRC; -.
DR   OrthoDB; 2912454at2759; -.
DR   PhylomeDB; P85857; -.
DR   TreeFam; TF316134; -.
DR   SignaLink; P85857; -.
DR   PRO; PR:P85857; -.
DR   Proteomes; UP000000437; Chromosome 16.
DR   Bgee; ENSDARG00000053479; Expressed in germ layer and 77 other cell types or 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:0042462; P:eye photoreceptor cell development; IMP:ZFIN.
DR   GO; GO:0045635; P:negative regulation of melanocyte differentiation; 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: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   CDD; cd13766; TGF_beta_GDF5_6_7; 1.
DR   Gene3D; 2.60.120.970; -; 1.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 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:SF43; GROWTH_DIFFERENTIATION FACTOR 6; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 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
//