GDF2_DANRE
ID GDF2_DANRE Reviewed; 389 AA.
AC F1QWZ4; D2CN90;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Growth/differentiation factor 2;
DE Short=GDF-2;
DE AltName: Full=Bone morphogenetic protein 9;
DE Short=BMP-9;
DE Flags: Precursor;
GN Name=gdf2; Synonyms=bmp9;
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shravage B.V., Roman B.L.;
RT "Cloning and developmental expression of BMP9 and BMP3b from Zebrafish.";
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=23972370; DOI=10.1016/j.ajhg.2013.07.004;
RA Wooderchak-Donahue W.L., McDonald J., O'Fallon B., Upton P.D., Li W.,
RA Roman B.L., Young S., Plant P., Fulop G.T., Langa C., Morrell N.W.,
RA Botella L.M., Bernabeu C., Stevenson D.A., Runo J.R., Bayrak-Toydemir P.;
RT "BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap
RT with hereditary hemorrhagic telangiectasia.";
RL Am. J. Hum. Genet. 93:530-537(2013).
CC -!- FUNCTION: Potent circulating inhibitor of angiogenesis. Signals through
CC the type I activin receptor ACVRL1 but not other Alks. Signaling
CC through SMAD1 in endothelial cells requires TGF-beta coreceptor
CC endoglin/eng. {ECO:0000250|UniProtKB:Q9UK05}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:Q9UK05}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9UK05}.
CC -!- PTM: A reversible disulfide bond can be formed between the two subunits
CC in the homodimer; this has no effect on gdf2 activity.
CC {ECO:0000250|UniProtKB:Q9UK05}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes slight
CC decreases in both anterior-posterior and dorsal-ventral axes, while
CC trunk and tail anatomy are otherwise normal. Vascular patterning is
CC relatively normal, although defects are detected in maturation of the
CC caudal vein: the caudal venous plexus fails to resolve and both dorsal
CC and ventral veins continue to carry blood flow.
CC {ECO:0000269|PubMed:23972370}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; EU352209; ACA57846.1; -; mRNA.
DR EMBL; CR450691; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001165057.2; NM_001171586.2.
DR AlphaFoldDB; F1QWZ4; -.
DR SMR; F1QWZ4; -.
DR STRING; 7955.ENSDARP00000076657; -.
DR PaxDb; F1QWZ4; -.
DR Ensembl; ENSDART00000082220; ENSDARP00000076657; ENSDARG00000059173.
DR GeneID; 563287; -.
DR KEGG; dre:563287; -.
DR CTD; 2658; -.
DR ZFIN; ZDB-GENE-100107-1; gdf2.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159802; -.
DR HOGENOM; CLU_020515_2_0_1; -.
DR InParanoid; F1QWZ4; -.
DR OMA; GTFDLRM; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; F1QWZ4; -.
DR TreeFam; TF316134; -.
DR Reactome; R-DRE-201451; Signaling by BMP.
DR PRO; PR:F1QWZ4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 12.
DR Bgee; ENSDARG00000059173; Expressed in liver and 2 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:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Angiogenesis; Cleavage on pair of basic residues; Cytokine; Disulfide bond;
KW Glycoprotein; Growth factor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..280
FT /evidence="ECO:0000250"
FT /id="PRO_0000425903"
FT CHAIN 281..389
FT /note="Growth/differentiation factor 2"
FT /id="PRO_0000425904"
FT REGION 263..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 232
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 288..354
FT /evidence="ECO:0000250|UniProtKB:Q9UK05"
FT DISULFID 317..386
FT /evidence="ECO:0000250|UniProtKB:Q9UK05"
FT DISULFID 321..388
FT /evidence="ECO:0000250|UniProtKB:Q9UK05"
FT DISULFID 353
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9UK05"
FT CONFLICT 27
FT /note="G -> A (in Ref. 1; ACA57846)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="R -> G (in Ref. 1; ACA57846)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="V -> VF (in Ref. 1; ACA57846)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 45080 MW; 5A77104E1A86EA7C CRC64;
MWRVGHLLLL MSIVFRITEE KSLGDAGSLE DSMFIQEQKL VEDDDLNKVE SFLGFMKEDF
LRKLNLSGVP QEHRKVQPPQ FMIELYNRYA SDKNSIPRSD VIRSFVVQDV IYSIRQGNKT
QHRLLFNVSI PNHEEITSVQ LRLFTLWHRH KPACDDLFTS INVYDVEYEQ NAKILHLLDG
RDVRESINTW EAFDVTGAVR IWHESRRGAG EIQVEVQHSC DSFDISLSLE DNSSAVVIVF
SDDLGNRKEE SMRKVKEMLV REQQQVGNQA PVSNRHRRRK RKAKNNYCRR TSLKVNFKDI
GWDKWIVAPP EYDAYECKGV CYFPLTDDVS PSRHAVIQTL VNLSNPKKAN MACCVPTKLD
PIAVMYQEKG VITVRHLYEE MKVAKCGCR
