ID GDF11_HUMAN Reviewed; 407 AA. AC O95390; Q9UID1; Q9UID2; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 13-FEB-2019, entry version 152. DE RecName: Full=Growth/differentiation factor 11 {ECO:0000303|PubMed:10391213}; DE Short=GDF-11; DE AltName: Full=Bone morphogenetic protein 11 {ECO:0000303|PubMed:10075854}; DE Short=BMP-11; DE Flags: Precursor; GN Name=GDF11; Synonyms=BMP11 {ECO:0000303|PubMed:10075854}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX PubMed=10075854; DOI=10.1006/dbio.1998.9191; RA Gamer L.W., Wolfman N.M., Celeste A.J., Hattersley G., Hewick R., RA Rosen V.; RT "A novel BMP expressed in developing mouse limb, spinal cord, and tail RT bud is a potent mesoderm inducer in Xenopus embryos."; RL Dev. Biol. 208:222-232(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=10391213; DOI=10.1038/10320; RA McPherron A.C., Lawler A.M., Lee S.-J.; RT "Regulation of anterior/posterior patterning of the axial skeleton by RT growth/differentiation factor 11."; RL Nat. Genet. 22:260-264(1999). RN [3] {ECO:0000244|PDB:5E4G} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 299-407, DISULFIDE BONDS, RP AND SUBUNIT. RX PubMed=26919518; DOI=10.1107/S2053230X16001588; RA Padyana A.K., Vaidialingam B., Hayes D.B., Gupta P., Franti M., RA Farrow N.A.; RT "Crystal structure of human GDF11."; RL Acta Crystallogr. F 72:160-164(2016). RN [4] {ECO:0000244|PDB:5JHW, ECO:0000244|PDB:5UHM} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 299-407 IN COMPLEX WITH FST, RP DISULFIDE BONDS, AND FUNCTION. RX PubMed=28257634; DOI=10.1186/s12915-017-0350-1; RA Walker R.G., Czepnik M., Goebel E.J., McCoy J.C., Vujic A., Cho M., RA Oh J., Aykul S., Walton K.L., Schang G., Bernard D.J., Hinck A.P., RA Harrison C.A., Martinez-Hackert E., Wagers A.J., Lee R.T., RA Thompson T.B.; RT "Structural basis for potency differences between GDF8 and GDF11."; RL BMC Biol. 15:19-19(2017). CC -!- FUNCTION: Secreted signal that acts globally to specify positional CC identity along the anterior/posterior axis during development. May CC play critical roles in patterning both mesodermal and neural CC tissues and in establishing the skeletal pattern (By similarity). CC Signals through activin receptors type-2, ACVR2A and ACVR2B, and CC activin receptors type-1, ACVR1B, ACVR1C and TGFBR1 leading to the CC phosphorylation of SMAD2 and SMAD3 (PubMed:28257634). CC {ECO:0000250|UniProtKB:Q9Z1W4, ECO:0000269|PubMed:28257634}. CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:26919518). Interacts CC directly with ACVR2B (By similarity). Interacts directly with CC ACVR2A (By similarity). Interacts with ACVR1B, TGFBR1 and ACVR1C CC in an ACVR2B-dependent manner (By similarity). Interacts with FST CC isoform 2/FS-288 (PubMed:28257634). {ECO:0000250|UniProtKB:Q9Z1W4, CC ECO:0000269|PubMed:26919518, ECO:0000269|PubMed:28257634}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- PTM: Synthesized as large precursor molecule that undergoes CC proteolytic cleavage. The mature C-terminal portion of the CC molecule is bound non-covalently to its N-terminal propeptide CC rendering it inactive. Ligand activation requires additional CC cleavage of the prodomain by a tolloid-like metalloproteinase. CC {ECO:0000250|UniProtKB:Q9Z1W4}. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. 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; AF100907; AAC72852.1; -; mRNA. DR EMBL; AF028333; AAF21630.1; -; mRNA. DR EMBL; AF028334; AAF21631.1; -; Genomic_DNA. DR CCDS; CCDS8891.1; -. DR RefSeq; NP_005802.1; NM_005811.4. DR RefSeq; XP_006719257.1; XM_006719194.3. DR UniGene; Hs.600883; -. DR PDB; 5E4G; X-ray; 1.50 A; A=299-407. DR PDB; 5JHW; X-ray; 2.35 A; A/B=299-407. DR PDB; 5UHM; X-ray; 1.90 A; A/B=299-407. DR PDBsum; 5E4G; -. DR PDBsum; 5JHW; -. DR PDBsum; 5UHM; -. DR ProteinModelPortal; O95390; -. DR SMR; O95390; -. DR BioGrid; 115515; 21. DR IntAct; O95390; 6. DR MINT; O95390; -. DR STRING; 9606.ENSP00000257868; -. DR iPTMnet; O95390; -. DR PhosphoSitePlus; O95390; -. DR BioMuta; GDF11; -. DR jPOST; O95390; -. DR PaxDb; O95390; -. DR PeptideAtlas; O95390; -. DR PRIDE; O95390; -. DR ProteomicsDB; 50842; -. DR DNASU; 10220; -. DR Ensembl; ENST00000257868; ENSP00000257868; ENSG00000135414. DR GeneID; 10220; -. DR KEGG; hsa:10220; -. DR UCSC; uc001shq.4; human. DR CTD; 10220; -. DR DisGeNET; 10220; -. DR EuPathDB; HostDB:ENSG00000135414.9; -. DR GeneCards; GDF11; -. DR HGNC; HGNC:4216; GDF11. DR HPA; HPA060985; -. DR HPA; HPA069609; -. DR MIM; 603936; gene. DR neXtProt; NX_O95390; -. DR OpenTargets; ENSG00000135414; -. DR PharmGKB; PA28631; -. DR eggNOG; KOG3900; Eukaryota. DR eggNOG; ENOG410XT8Z; LUCA. DR GeneTree; ENSGT00940000161052; -. DR HOGENOM; HOG000006566; -. DR HOVERGEN; HBG000217; -. DR InParanoid; O95390; -. DR KO; K22679; -. DR OMA; GSHECSA; -. DR OrthoDB; 892873at2759; -. DR PhylomeDB; O95390; -. DR TreeFam; TF318514; -. DR SignaLink; O95390; -. DR SIGNOR; O95390; -. DR ChiTaRS; GDF11; human. DR GeneWiki; GDF11; -. DR GenomeRNAi; 10220; -. DR PRO; PR:O95390; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000135414; Expressed in 202 organ(s), highest expression level in pigmented layer of retina. DR ExpressionAtlas; O95390; baseline and differential. DR Genevisible; O95390; HS. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. 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:0048593; P:camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0048468; P:cell development; IBA:GO_Central. DR GO; GO:0048469; P:cell maturation; IEA:Ensembl. DR GO; GO:0007498; P:mesoderm development; TAS:UniProtKB. DR GO; GO:0001656; P:metanephros development; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0031016; P:pancreas development; IEA:Ensembl. 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:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0060021; P:roof of mouth development; IEA:Ensembl. DR GO; GO:0001501; P:skeletal system development; TAS:UniProtKB. DR GO; GO:0060395; P:SMAD protein signal transduction; IMP:UniProtKB. DR GO; GO:0021512; P:spinal cord anterior/posterior patterning; IEA:Ensembl. DR GO; GO:0001657; P:ureteric bud development; 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; Cleavage on pair of basic residues; Complete proteome; KW Cytokine; Disulfide bond; Glycoprotein; Growth factor; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT PROPEP 25 298 {ECO:0000250}. FT /FTId=PRO_0000033986. FT CHAIN 299 407 Growth/differentiation factor 11. FT /FTId=PRO_0000033987. FT COMPBIAS 29 41 Poly-Ala. FT COMPBIAS 210 215 Poly-Gly. FT SITE 121 122 Cleavage; by BMP1. FT {ECO:0000250|UniProtKB:Q9Z1W4}. FT CARBOHYD 94 94 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 304 314 {ECO:0000244|PDB:5E4G, FT ECO:0000244|PDB:5JHW, FT ECO:0000244|PDB:5UHM, FT ECO:0000269|PubMed:26919518, FT ECO:0000269|PubMed:28257634}. FT DISULFID 313 372 {ECO:0000244|PDB:5E4G, FT ECO:0000244|PDB:5JHW, FT ECO:0000244|PDB:5UHM, FT ECO:0000269|PubMed:26919518, FT ECO:0000269|PubMed:28257634}. FT DISULFID 341 404 {ECO:0000244|PDB:5E4G, FT ECO:0000244|PDB:5JHW, FT ECO:0000244|PDB:5UHM, FT ECO:0000269|PubMed:26919518, FT ECO:0000269|PubMed:28257634}. FT DISULFID 345 406 {ECO:0000244|PDB:5E4G, FT ECO:0000244|PDB:5JHW, FT ECO:0000244|PDB:5UHM, FT ECO:0000269|PubMed:26919518, FT ECO:0000269|PubMed:28257634}. FT DISULFID 371 371 Interchain. {ECO:0000244|PDB:5E4G, FT ECO:0000244|PDB:5JHW, FT ECO:0000244|PDB:5UHM, FT ECO:0000269|PubMed:26919518, FT ECO:0000269|PubMed:28257634}. FT STRAND 301 304 {ECO:0000244|PDB:5UHM}. FT STRAND 312 316 {ECO:0000244|PDB:5E4G}. FT STRAND 319 321 {ECO:0000244|PDB:5E4G}. FT TURN 322 326 {ECO:0000244|PDB:5E4G}. FT STRAND 330 332 {ECO:0000244|PDB:5E4G}. FT STRAND 334 337 {ECO:0000244|PDB:5E4G}. FT STRAND 340 342 {ECO:0000244|PDB:5E4G}. FT TURN 347 350 {ECO:0000244|PDB:5E4G}. FT HELIX 355 362 {ECO:0000244|PDB:5E4G}. FT STRAND 371 385 {ECO:0000244|PDB:5E4G}. FT STRAND 387 389 {ECO:0000244|PDB:5E4G}. FT STRAND 391 407 {ECO:0000244|PDB:5E4G}. SQ SEQUENCE 407 AA; 45091 MW; E8FF48E363635BA8 CRC64; MVLAAPLLLG FLLLALELRP RGEAAEGPAA AAAAAAAAAA AGVGGERSSR PAPSVAPEPD GCPVCVWRQH SRELRLESIK SQILSKLRLK EAPNISREVV KQLLPKAPPL QQILDLHDFQ GDALQPEDFL EEDEYHATTE TVISMAQETD PAVQTDGSPL CCHFHFSPKV MFTKVLKAQL WVYLRPVPRP ATVYLQILRL KPLTGEGTAG GGGGGRRHIR IRSLKIELHS RSGHWQSIDF KQVLHSWFRQ PQSNWGIEIN AFDPSGTDLA VTSLGPGAEG LHPFMELRVL ENTKRSRRNL GLDCDEHSSE SRCCRYPLTV DFEAFGWDWI IAPKRYKANY CSGQCEYMFM QKYPHTHLVQ QANPRGSAGP CCTPTKMSPI NMLYFNDKQQ IIYGKIPGMV VDRCGCS //