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 27-MAR-2024, entry version 188. 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"; 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 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 GlyCosmos; Q9UK05; 2 sites, No reported glycans. DR GlyGen; Q9UK05; 2 sites. DR iPTMnet; Q9UK05; -. DR PhosphoSitePlus; Q9UK05; -. DR BioMuta; GDF2; -. DR DMDM; 13124266; -. DR MassIVE; Q9UK05; -. DR PaxDb; 9606-ENSP00000463051; -. DR PeptideAtlas; Q9UK05; -. DR ProteomicsDB; 84699; -. DR Antibodypedia; 72423; 445 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 AGR; HGNC:4217; -. 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; 2912454at2759; -. 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; 16 hits in 1132 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 male germ line stem cell (sensu Vertebrata) in testis and 14 other cell types or tissues. 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; IDA:UniProt. DR GO; GO:0005125; F:cytokine activity; IGI:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IDA:BHF-UCL. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProt. 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:0071773; P:cellular response to BMP stimulus; IDA:BHF-UCL. DR GO; GO:0006879; P:intracellular iron ion homeostasis; TAS:DFLAT. 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: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:0045766; P:positive regulation of angiogenesis; IDA:DFLAT. DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; IDA:BHF-UCL. 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:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. 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:0030858; P:positive regulation of epithelial cell differentiation; IDA:BHF-UCL. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:BHF-UCL. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0001570; P:vasculogenesis; IEA:Ensembl. DR CDD; cd19400; TGF_beta_BMP9; 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:SF157; GROWTH_DIFFERENTIATION FACTOR 2; 1. DR PANTHER; PTHR11848; TGF-BETA FAMILY; 1. DR Pfam; PF00019; TGF_beta; 1. DR Pfam; PF00688; TGFb_propeptide; 1. DR PRINTS; PR00669; INHIBINA. 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. DR Genevisible; Q9UK05; HS. 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 //