GDF2_HUMAN
ID GDF2_HUMAN Reviewed; 429 AA.
AC Q9UK05; Q5VSQ9; Q9Y571;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 179.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Celeste A.J.;
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 316-429.
RC TISSUE=Liver;
RA Zimmers T.A., Koniaris L.G., Sitzmann J.V., Lee S.-J.;
RT "Growth/differentiation factor-2, a new TGF-beta family member with bone
RT promoting activities.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18309101; DOI=10.1161/circresaha.107.165530;
RA David L., Mallet C., Keramidas M., Lamande N., Gasc J.M., Dupuis-Girod S.,
RA Plauchu H., Feige J.J., Bailly S.;
RT "Bone morphogenetic protein-9 is a circulating vascular quiescence
RT factor.";
RL Circ. Res. 102:914-922(2008).
RN [7]
RP INTERACTION WITH ACVR1.
RX PubMed=20628059; DOI=10.1074/jbc.m110.130518;
RA Luo J., Tang M., Huang J., He B.C., Gao J.L., Chen L., Zuo G.W., Zhang W.,
RA Luo Q., Shi Q., Zhang B.Q., Bi Y., Luo X., Jiang W., Su Y., Shen J.,
RA Kim S.H., Huang E., Gao Y., Zhou J.Z., Yang K., Luu H.H., Pan X.,
RA Haydon R.C., Deng Z.L., He T.C.;
RT "TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced
RT osteogenic signaling in mesenchymal stem cells.";
RL J. Biol. Chem. 285:29588-29598(2010).
RN [8]
RP INTERACTION WITH ENG.
RX PubMed=21737454; DOI=10.1074/jbc.m111.260133;
RA Castonguay R., Werner E.D., Matthews R.G., Presman E., Mulivor A.W.,
RA Solban N., Sako D., Pearsall R.S., Underwood K.W., Seehra J., Kumar R.,
RA Grinberg A.V.;
RT "Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10
RT via its orphan domain, inhibits blood vessel formation, and suppresses
RT tumor growth.";
RL J. Biol. Chem. 286:30034-30046(2011).
RN [9]
RP FUNCTION, AND INTERACTION WITH ACVRL1.
RX PubMed=22799562; DOI=10.1021/bi300942x;
RA Mahlawat P., Ilangovan U., Biswas T., Sun L.Z., Hinck A.P.;
RT "Structure of the Alk1 extracellular domain and characterization of its
RT bone morphogenetic protein (BMP) binding properties.";
RL Biochemistry 51:6328-6341(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=21710321; DOI=10.1007/s00018-011-0751-1;
RA Bidart M., Ricard N., Levet S., Samson M., Mallet C., David L.,
RA Subileau M., Tillet E., Feige J.J., Bailly S.;
RT "BMP9 is produced by hepatocytes and circulates mainly in an active mature
RT form complexed to its prodomain.";
RL Cell. Mol. Life Sci. 69:313-324(2012).
RN [11]
RP INTERACTION WITH ENG AND ACVRL1.
RX PubMed=22347366; DOI=10.1371/journal.pone.0029948;
RA Alt A., Miguel-Romero L., Donderis J., Aristorena M., Blanco F.J.,
RA Round A., Rubio V., Bernabeu C., Marina A.;
RT "Structural and functional insights into endoglin ligand recognition and
RT binding.";
RL PLoS ONE 7:E29948-E29948(2012).
RN [12]
RP FUNCTION.
RX PubMed=23300529; DOI=10.1371/journal.pone.0050920;
RA Nolan-Stevaux O., Zhong W., Culp S., Shaffer K., Hoover J.,
RA Wickramasinghe D., Ruefli-Brasse A.;
RT "Endoglin requirement for BMP9 signaling in endothelial cells reveals new
RT mechanism of action for selective anti-endoglin antibodies.";
RL PLoS ONE 7:E50920-E50920(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 320-429, AND DISULFIDE BONDS.
RX PubMed=15851468; DOI=10.1074/jbc.m503328200;
RA Brown M.A., Zhao Q., Baker K.A., Naik C., Chen C., Pukac L., Singh M.,
RA Tsareva T., Parice Y., Mahoney A., Roschke V., Sanyal I., Choe S.;
RT "Crystal structure of BMP-9 and functional interactions with pro-region and
RT receptors.";
RL J. Biol. Chem. 280:25111-25118(2005).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.36 ANGSTROMS) OF 320-429 IN COMPLEX WITH ACVRL1
RP AND ACVR2B, AND DISULFIDE BONDS.
RX PubMed=22718755; DOI=10.1074/jbc.m112.377960;
RA Townson S.A., Martinez-Hackert E., Greppi C., Lowden P., Sako D., Liu J.,
RA Ucran J.A., Liharska K., Underwood K.W., Seehra J., Kumar R.,
RA Grinberg A.V.;
RT "Specificity and structure of a high affinity activin receptor-like kinase
RT 1 (ALK1) signaling complex.";
RL J. Biol. Chem. 287:27313-27325(2012).
RN [15] {ECO:0007744|PDB:4MPL}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 321-429, SUBUNIT, INTERACTION
RP WITH ACVRL1, SUBCELLULAR LOCATION, AND DISULFIDE BONDS.
RX PubMed=25237187; DOI=10.1074/jbc.m114.579771;
RA Wei Z., Salmon R.M., Upton P.D., Morrell N.W., Li W.;
RT "Regulation of bone morphogenetic protein 9 (BMP9) by redox-dependent
RT proteolysis.";
RL J. Biol. Chem. 289:31150-31159(2014).
RN [16] {ECO:0007744|PDB:4YCG, ECO:0007744|PDB:4YCI}
RP X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 320-429, FUNCTION, INTERACTION
RP WITH ACVRL1; BMPR2; ACVR2B AND ACVR2A, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=25751889; DOI=10.1073/pnas.1501303112;
RA Mi L.Z., Brown C.T., Gao Y., Tian Y., Le V.Q., Walz T., Springer T.A.;
RT "Structure of bone morphogenetic protein 9 procomplex.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:3710-3715(2015).
RN [17] {ECO:0007744|PDB:5HZW, ECO:0007744|PDB:5I05}
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 320-429, X-RAY CRYSTALLOGRAPHY
RP (4.45 ANGSTROMS) OF 320-429 IN COMPLEX WITH ENG, SUBUNIT, AND DISULFIDE
RP BONDS.
RX PubMed=28564608; DOI=10.1016/j.celrep.2017.05.011;
RA Saito T., Bokhove M., Croci R., Zamora-Caballero S., Han L., Letarte M.,
RA de Sanctis D., Jovine L.;
RT "Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP
RT Signaling and HHT1.";
RL Cell Rep. 19:1917-1928(2017).
RN [18]
RP VARIANTS HHT5 LEU-68; LEU-85 AND TRP-333, AND PROTEOLYTIC PROCESSING.
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:0000269|PubMed:18309101,
CC ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:22799562,
CC ECO:0000269|PubMed:23300529, ECO:0000269|PubMed:25237187}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:25237187,
CC PubMed:28564608). Detected in extracellular fluid as mature homodimer,
CC and in complex with its propeptide (PubMed:21710321, PubMed:25237187).
CC Interacts with ACVRL1, BMPR2 and ACVR2B with high affinity (in vitro)
CC (PubMed:22799562, PubMed:22347366, PubMed:25237187, PubMed:25751889).
CC Identified in a complex with ACVRL1 and ACVR2B (PubMed:22718755). Has
CC ten times lower affinity for ACVR2A (in vitro) (PubMed:25751889).
CC Interacts with ENG, forming a heterotetramer with a 2:2 stoichiometry
CC (PubMed:21737454, PubMed:28564608). Can form a heteromeric complex with
CC ENG and ACVRL1 (PubMed:28564608). Interacts with type I receptor ACVR1
CC (PubMed:20628059). {ECO:0000269|PubMed:15851468,
CC ECO:0000269|PubMed:20628059, ECO:0000269|PubMed:21710321,
CC ECO:0000269|PubMed:21737454, ECO:0000269|PubMed:22347366,
CC ECO:0000269|PubMed:22718755, ECO:0000269|PubMed:22799562,
CC ECO:0000269|PubMed:25751889, ECO:0000269|PubMed:28564608}.
CC -!- INTERACTION:
CC PRO_0000033903; P37023: ACVRL1; NbExp=2; IntAct=EBI-16227344, EBI-8043559;
CC PRO_0000033903; P17813: ENG; NbExp=10; IntAct=EBI-16227344, EBI-2834630;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18309101,
CC ECO:0000269|PubMed:21710321, ECO:0000269|PubMed:25237187}.
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (at protein level).
CC {ECO:0000269|PubMed:21710321}.
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:0000269|PubMed:25237187}.
CC -!- DISEASE: Telangiectasia, hereditary hemorrhagic, 5 (HHT5) [MIM:615506]:
CC A multisystemic vascular dysplasia leading to dilation of permanent
CC blood vessels and arteriovenous malformations of skin, mucosa, and
CC viscera. The disease is characterized by recurrent epistaxis and
CC gastro-intestinal hemorrhage. Visceral involvement includes
CC arteriovenous malformations of the lung, liver, and brain.
CC {ECO:0000269|PubMed:23972370}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- CAUTION: Can promote osteogenic differentiation in vitro
CC (PubMed:25237187, PubMed:25751889). This is probably not
CC physiologically relevant. {ECO:0000269|PubMed:25237187,
CC ECO:0000269|PubMed:25751889, ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=GDF2 entry;
CC URL="https://en.wikipedia.org/wiki/GDF2";
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DR EMBL; AF188285; AAD56960.1; -; mRNA.
DR EMBL; AL731561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471251; EAW50660.1; -; Genomic_DNA.
DR EMBL; BC069643; AAH69643.1; -; mRNA.
DR EMBL; BC074921; AAH74921.1; -; mRNA.
DR EMBL; AF156891; AAD40309.1; -; mRNA.
DR CCDS; CCDS73118.1; -.
DR RefSeq; NP_057288.1; NM_016204.3.
DR PDB; 1ZKZ; X-ray; 2.33 A; A=320-429.
DR PDB; 4FAO; X-ray; 3.36 A; A/B/G/H/M/N/S/T/a/b/g/h=320-429.
DR PDB; 4MPL; X-ray; 1.90 A; A=321-429.
DR PDB; 4YCG; X-ray; 3.30 A; C/D=320-429.
DR PDB; 4YCI; X-ray; 3.25 A; C/D=320-429.
DR PDB; 5HZW; X-ray; 4.45 A; B=320-429.
DR PDB; 5I05; X-ray; 1.87 A; A=320-429.
DR PDBsum; 1ZKZ; -.
DR PDBsum; 4FAO; -.
DR PDBsum; 4MPL; -.
DR PDBsum; 4YCG; -.
DR PDBsum; 4YCI; -.
DR PDBsum; 5HZW; -.
DR PDBsum; 5I05; -.
DR AlphaFoldDB; Q9UK05; -.
DR SMR; Q9UK05; -.
DR BioGRID; 108928; 6.
DR IntAct; Q9UK05; 2.
DR STRING; 9606.ENSP00000463051; -.
DR ChEMBL; CHEMBL3831181; -.
DR GlyGen; Q9UK05; 2 sites.
DR iPTMnet; Q9UK05; -.
DR PhosphoSitePlus; Q9UK05; -.
DR BioMuta; GDF2; -.
DR DMDM; 13124266; -.
DR MassIVE; Q9UK05; -.
DR PaxDb; Q9UK05; -.
DR PeptideAtlas; Q9UK05; -.
DR PRIDE; Q9UK05; -.
DR ProteomicsDB; 84699; -.
DR Antibodypedia; 72423; 376 antibodies from 35 providers.
DR DNASU; 2658; -.
DR Ensembl; ENST00000581492.3; ENSP00000463051.1; ENSG00000263761.3.
DR GeneID; 2658; -.
DR KEGG; hsa:2658; -.
DR MANE-Select; ENST00000581492.3; ENSP00000463051.1; NM_016204.4; NP_057288.1.
DR UCSC; uc001jfa.2; human.
DR CTD; 2658; -.
DR DisGeNET; 2658; -.
DR GeneCards; GDF2; -.
DR HGNC; HGNC:4217; GDF2.
DR HPA; ENSG00000263761; Tissue enriched (liver).
DR MalaCards; GDF2; -.
DR MIM; 605120; gene.
DR MIM; 615506; phenotype.
DR neXtProt; NX_Q9UK05; -.
DR OpenTargets; ENSG00000263761; -.
DR Orphanet; 774; Hereditary hemorrhagic telangiectasia.
DR PharmGKB; PA28632; -.
DR VEuPathDB; HostDB:ENSG00000263761; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159802; -.
DR HOGENOM; CLU_020515_2_0_1; -.
DR InParanoid; Q9UK05; -.
DR OMA; GTFDLRM; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; Q9UK05; -.
DR TreeFam; TF316134; -.
DR PathwayCommons; Q9UK05; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR SignaLink; Q9UK05; -.
DR SIGNOR; Q9UK05; -.
DR BioGRID-ORCS; 2658; 15 hits in 1054 CRISPR screens.
DR EvolutionaryTrace; Q9UK05; -.
DR GeneWiki; GDF2; -.
DR GenomeRNAi; 2658; -.
DR Pharos; Q9UK05; Tbio.
DR PRO; PR:Q9UK05; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UK05; protein.
DR Bgee; ENSG00000263761; Expressed in right lobe of liver and 13 other tissues.
DR Genevisible; Q9UK05; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
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:0032924; P:activin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0048514; P:blood vessel morphogenesis; IDA:DFLAT.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IDA:DFLAT.
DR GO; GO:0051216; P:cartilage development; TAS:DFLAT.
DR GO; GO:0006879; P:cellular iron ion homeostasis; TAS:DFLAT.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IDA:BHF-UCL.
DR GO; GO:0016525; P:negative regulation of angiogenesis; TAS:DFLAT.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; TAS:DFLAT.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0008156; P:negative regulation of DNA replication; TAS:DFLAT.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:DFLAT.
DR GO; GO:0001503; P:ossification; TAS:DFLAT.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:DFLAT.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:DFLAT.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl.
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 3D-structure; Angiogenesis; Cleavage on pair of basic residues; Cytokine;
KW Disease variant; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..319
FT /evidence="ECO:0000250"
FT /id="PRO_0000033902"
FT CHAIN 320..429
FT /note="Growth/differentiation factor 2"
FT /id="PRO_0000033903"
FT REGION 283..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..416
FT /note="Interaction with ENG"
FT /evidence="ECO:0000269|PubMed:28564608"
FT COMPBIAS 283..307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 71
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 327..393
FT /evidence="ECO:0000269|PubMed:25237187,
FT ECO:0007744|PDB:1ZKZ, ECO:0007744|PDB:4FAO,
FT ECO:0007744|PDB:4MPL, ECO:0007744|PDB:4YCG,
FT ECO:0007744|PDB:4YCI, ECO:0007744|PDB:5HZW,
FT ECO:0007744|PDB:5I05"
FT DISULFID 356..426
FT /evidence="ECO:0007744|PDB:1ZKZ, ECO:0007744|PDB:4FAO,
FT ECO:0007744|PDB:4MPL, ECO:0007744|PDB:4YCG,
FT ECO:0007744|PDB:4YCI, ECO:0007744|PDB:5HZW,
FT ECO:0007744|PDB:5I05"
FT DISULFID 360..428
FT /evidence="ECO:0007744|PDB:1ZKZ, ECO:0007744|PDB:4FAO,
FT ECO:0007744|PDB:4MPL, ECO:0007744|PDB:4YCG,
FT ECO:0007744|PDB:4YCI, ECO:0007744|PDB:5HZW,
FT ECO:0007744|PDB:5I05"
FT DISULFID 392
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:25237187,
FT ECO:0007744|PDB:4FAO"
FT VARIANT 68
FT /note="R -> L (in HHT5; impaired protein processing and
FT function; dbSNP:rs200330818)"
FT /evidence="ECO:0000269|PubMed:23972370"
FT /id="VAR_070689"
FT VARIANT 85
FT /note="P -> L (in HHT5; impaired protein processing and
FT function; dbSNP:rs199804679)"
FT /evidence="ECO:0000269|PubMed:23972370"
FT /id="VAR_070690"
FT VARIANT 333
FT /note="R -> W (in HHT5; impaired protein processing and
FT function; dbSNP:rs35129734)"
FT /evidence="ECO:0000269|PubMed:23972370"
FT /id="VAR_070691"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:5I05"
FT TURN 336..340
FT /evidence="ECO:0007829|PDB:5I05"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 355..359
FT /evidence="ECO:0007829|PDB:5I05"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:5I05"
FT HELIX 372..383
FT /evidence="ECO:0007829|PDB:5I05"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 393..406
FT /evidence="ECO:0007829|PDB:5I05"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:4MPL"
FT STRAND 412..428
FT /evidence="ECO:0007829|PDB:5I05"
SQ SEQUENCE 429 AA; 47320 MW; 5AC15DCA205FF086 CRC64;
MCPGALWVAL PLLSLLAGSL QGKPLQSWGR GSAGGNAHSP LGVPGGGLPE HTFNLKMFLE
NVKVDFLRSL NLSGVPSQDK TRVEPPQYMI DLYNRYTSDK STTPASNIVR SFSMEDAISI
TATEDFPFQK HILLFNISIP RHEQITRAEL RLYVSCQNHV DPSHDLKGSV VIYDVLDGTD
AWDSATETKT FLVSQDIQDE GWETLEVSSA VKRWVRSDST KSKNKLEVTV ESHRKGCDTL
DISVPPGSRN LPFFVVFSND HSSGTKETRL ELREMISHEQ ESVLKKLSKD GSTEAGESSH
EEDTDGHVAA GSTLARRKRS AGAGSHCQKT SLRVNFEDIG WDSWIIAPKE YEAYECKGGC
FFPLADDVTP TKHAIVQTLV HLKFPTKVGK ACCVPTKLSP ISVLYKDDMG VPTLKYHYEG
MSVAECGCR
