##gff-version 3 P43026 UniProtKB Signal peptide 1 27 . . . Ontology_term=ECO:0000255;evidence=ECO:0000255 P43026 UniProtKB Propeptide 28 381 . . . ID=PRO_0000033912;Ontology_term=ECO:0000255;evidence=ECO:0000255 P43026 UniProtKB Chain 382 501 . . . ID=PRO_0000033913;Note=Growth/differentiation factor 5 P43026 UniProtKB Region 29 169 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P43026 UniProtKB Region 246 265 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P43026 UniProtKB Glycosylation 189 189 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000255;evidence=ECO:0000255 P43026 UniProtKB Disulfide bond 400 466 . . . Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19229295;Dbxref=PMID:19229295 P43026 UniProtKB Disulfide bond 429 498 . . . Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19229295;Dbxref=PMID:19229295 P43026 UniProtKB Disulfide bond 433 500 . . . Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19229295;Dbxref=PMID:19229295 P43026 UniProtKB Disulfide bond 465 465 . . . Note=Interchain;Ontology_term=ECO:0000250;evidence=ECO:0000250 P43026 UniProtKB Natural variant 163 163 . . . ID=VAR_037977;Note=R->G;Dbxref=dbSNP:rs34534075 P43026 UniProtKB Natural variant 173 173 . . . ID=VAR_037978;Note=In BDC. M->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:14735582;Dbxref=dbSNP:rs28936397,PMID:14735582 P43026 UniProtKB Natural variant 201 201 . . . ID=VAR_073139;Note=In BDC%3B decrease of induction of SMAD protein signal transduction with either BMPR1A or BMPR1B%3B less induction of chondrgenesis%3B no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex%3B reduction of protein level%3B abnormal proteolysis product. T->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25092592;Dbxref=PMID:25092592 P43026 UniProtKB Natural variant 203 203 . . . ID=VAR_074161;Note=In BDC. T->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25820810;Dbxref=PMID:25820810 P43026 UniProtKB Natural variant 263 263 . . . ID=VAR_073140;Note=In BDC%3B no induction of SMAD protein signal transduction via BMPR1A%3B less induction of chondrgenesis%3B no phosphorylation of SMAD1-SMAD5-SMAD8 protein complex%3B reduction of protein level%3B abnormal proteolysis product. L->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25092592;Dbxref=PMID:25092592 P43026 UniProtKB Natural variant 276 276 . . . ID=VAR_026120;Note=A->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15489334,ECO:0000269|PubMed:7980526;Dbxref=dbSNP:rs224331,PMID:15489334,PMID:7980526 P43026 UniProtKB Natural variant 373 373 . . . ID=VAR_054909;Note=In SYM1B%3B the mature GDF5 protein is detected as the wild-type in the supernatant derived from the mutant transfected cells. L->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18283415;Dbxref=dbSNP:rs121909349,PMID:18283415 P43026 UniProtKB Natural variant 378 378 . . . ID=VAR_054910;Note=In AMD2B. R->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18629880;Dbxref=dbSNP:rs121909350,PMID:18629880 P43026 UniProtKB Natural variant 380 380 . . . ID=VAR_046743;Note=In BDA2%3B reduces activity%3B impairs processing. R->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18203755;Dbxref=dbSNP:rs397514668,PMID:18203755 P43026 UniProtKB Natural variant 399 399 . . . ID=VAR_064416;Note=In BDA1C%3B less effective than wild-type in stimulating chondrogenesis%3B impairs BMP signaling through BMPR1A. R->C;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:20683927,ECO:0000269|PubMed:24098149;Dbxref=dbSNP:rs397514519,PMID:20683927,PMID:24098149 P43026 UniProtKB Natural variant 400 400 . . . ID=VAR_017407;Note=In AMD2A. C->Y;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:9288098;Dbxref=dbSNP:rs74315387,PMID:9288098 P43026 UniProtKB Natural variant 414 414 . . . ID=VAR_073141;Note=In SYNS2 and BDA1C%3B reduced interaction with NOG%3B reduces affinity to BMPR1A%3B impairs BMP signaling through BMPR1A%3B impairs chondrogenesis. W->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:24098149;Dbxref=PMID:24098149 P43026 UniProtKB Natural variant 436 436 . . . ID=VAR_054911;Note=In AMD2B. P->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:18629880;Dbxref=dbSNP:rs121909351,PMID:18629880 P43026 UniProtKB Natural variant 437 437 . . . ID=VAR_037979;Note=In AMD2B%3B located on the same allele as T-439 and L-440. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16222676;Dbxref=PMID:16222676 P43026 UniProtKB Natural variant 438 438 . . . ID=VAR_026545;Note=In SYNS2 and SYM1B%3B increased biological activity when compared to wild-type%3B normal binding to BMPR1B ectodomain but increased binding to that of BMPR1A. R->L;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:16127465,ECO:0000269|PubMed:16532400;Dbxref=dbSNP:rs74315388,PMID:16127465,PMID:16532400 P43026 UniProtKB Natural variant 439 439 . . . ID=VAR_037980;Note=In AMD2B%3B located on the same allele as L-437 del and L-440. S->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16222676;Dbxref=PMID:16222676 P43026 UniProtKB Natural variant 440 440 . . . ID=VAR_037981;Note=In AMD2B%3B located on the same allele as L-437 del and T-439. H->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16222676;Dbxref=PMID:16222676 P43026 UniProtKB Natural variant 441 441 . . . ID=VAR_017408;Note=In AMD2B%2C SYNS2 and BDA2%3B the mutant is almost inactive%3B loss of binding to BMPR1A and BMPR1B ectodomains%3B no induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation%3B impairs nuclear translocation of phosphotylated SMAD1-SMAD5-SMAD8 protein complex%3B no ability to induce SMAD protein signal transduction%3B binds to NOG. L->P;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:12121354,ECO:0000269|PubMed:16127465,ECO:0000269|PubMed:21976273;Dbxref=dbSNP:rs28936683,PMID:12121354,PMID:16127465,PMID:21976273 P43026 UniProtKB Natural variant 445 445 . . . ID=VAR_073142;Note=In SYNS2. N->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19956691;Dbxref=PMID:19956691 P43026 UniProtKB Natural variant 445 445 . . . ID=VAR_073143;Note=In SYNS2%3B resistant to NOG inhibition%3B no change in binding with MPR1A and BMPR1B%3B strong induction of chondrogenesis. N->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:19956691;Dbxref=PMID:19956691 P43026 UniProtKB Natural variant 475 475 . . . ID=VAR_037982;Note=In SYNS2%3B reduction in binding affinity with BMPR2%3B no change in binding affinity with BMPR1A%3B no change in binding affinity with BMPR1B%3B decreases induction of SMAD1-SMAD5-SMAD8 protein complex phosphorylation%3B delay of phosphotylated SMAD1-SMAD5-SMAD8 protein complex nuclear translocation%3B strong reduction of SMAD protein signal transduction%3B reduction of chondrocyte differentiation%3B strong improvement of chondrogenesis%3B decrease of NOG binding%3B resistant to NOG inhibition%3B no chondrogenesis inhibition. S->N;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:21976273,ECO:0000269|Ref.18;Dbxref=dbSNP:rs121909347,PMID:21976273 P43026 UniProtKB Natural variant 486 486 . . . ID=VAR_074162;Note=In BDC. V->M;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:25820810;Dbxref=PMID:25820810 P43026 UniProtKB Natural variant 491 491 . . . ID=VAR_037983;Note=In SYM1B. E->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16892395;Dbxref=dbSNP:rs74315389,PMID:16892395 P43026 UniProtKB Mutagenesis 490 490 . . . Note=Resitant to NOG inhibition. Y->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:26643732;Dbxref=PMID:26643732 P43026 UniProtKB Sequence conflict 38 38 . . . Note=T->S;Ontology_term=ECO:0000305;evidence=ECO:0000305 P43026 UniProtKB Sequence conflict 254 258 . . . Note=APGGG->VPRSR;Ontology_term=ECO:0000305;evidence=ECO:0000305 P43026 UniProtKB Sequence conflict 321 321 . . . Note=A->T;Ontology_term=ECO:0000305;evidence=ECO:0000305 P43026 UniProtKB Sequence conflict 384 384 . . . Note=L->S;Ontology_term=ECO:0000305;evidence=ECO:0000305 P43026 UniProtKB Beta strand 399 403 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 406 408 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Turn 409 413 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Turn 415 417 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 418 420 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 422 425 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 428 432 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Helix 439 441 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Helix 445 456 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Turn 458 460 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 465 479 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF P43026 UniProtKB Beta strand 481 483 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:3QB4 P43026 UniProtKB Beta strand 485 501 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7ZJF