UniProt UniProt http://www.uniprot.org Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J. Clin. Invest. (0021-9738) 2005 imex curation Seemann P., Schwappacher R., Kjaer K.W., Krakow D., Lehmann K., Dawson K., Stricker S., Pohl J., Plöger F., Staub E., Nickel J., Sebald W., Knaus P., Mundlos S. Rare diseases - Interactions investigated in the context of Rare genetic disease BMPR-IA and BMPR-IB construct details according pmid 10692589 and 10880444. stefan.mundlos@charite.de,knaus@chemie.fu-berlin.de 22-Jan-2015: Contacted by IntAct-Help. Only protein-protein interactions in vitro In vitro spr surface plasmon resonance Optical biosensor BIAcore(r) BIAcore(r) Optical biosensor spr predetermined predetermined participant predetermined Seemann P., Schwappacher R., Kjaer K.W., Krakow D., Lehmann K., Dawson K., Stricker S., Pohl J., Plöger F., Staub E., Nickel J., Sebald W., Knaus P., Mundlos S. Rare diseases - Interactions investigated in the context of Rare genetic disease BMPR-IA and BMPR-IB construct details according pmid 10692589 and 10880444. stefan.mundlos@charite.de stefan.mundlos@charite.de,knaus@chemie.fu-berlin.de Accepted 2015-JAN-15 by ORCHARD J. Clin. Invest. (0021-9738) 2005 imex curation nogg_human Noggin NOG protein protein human Homo sapiens Human MERCPSLGVTLYALVVVLGLRATPAGGQHYLHIRPAPSDNLPLVDLIEHPDPIFDPKEKDLNETLLRSLLGGHYDPGFMATSPPEDRPGGGGGAAGGAEDLAELDQLLRQRPSGAMPSEIKGLEFSEGLAQGKKQRLSKKLRRKLQMWLWSQTFCPVLYAWNDLGSRFWPRYVKVGSCFSKRSCSVPEGMVCKPSKSVHLTVLRWRCQRRGGQRCGWIPIQYPIISECKCSC FCA0D8E1E2098580 gdf5_human Growth/differentiation factor 5 GDF5 CDMP1 Cartilage-derived morphogenetic protein 1 Radotermin BMP14 Bone morphogenetic protein 14 Lipopolysaccharide-associated protein 4 protein protein human Homo sapiens Human MRLPKLLTFLLWYLAWLDLEFICTVLGAPDLGQRPQGTRPGLAKAEAKERPPLARNVFRPGGHSYGGGATNANARAKGGTGQTGGLTQPKKDEPKKLPPRPGGPEPKPGHPPQTRQATARTVTPKGQLPGGKAPPKAGSVPSSFLLKKAREPGPPREPKEPFRPPPITPHEYMLSLYRTLSDADRKGGNSSVKLEAGLANTITSFIDKGQDDRGPVVRKQRYVFDISALEKDGLLGAELRILRKKPSDTAKPAAPGGGRAAQLKLSSCPSGRQPASLLDVRSVPGLDGSGWEVFDIWKLFRNFKNSAQLCLELEAWERGRAVDLRGLGFDRAARQVHEKALFLVFGRTKKRDLFFNEIKARSGQDDKTVYEYLFSQRRKRRAPLATRQGKRPSKNLKARCSRKALHVNFKDMGWDDWIIAPLEYEAFHCEGLCEFPLRSHLEPTNHAVIQTLMNSMDPESTPPTCCVPTRLSPISILFIDSANNVVYKQYEDMVVESCGCR mint 37985F2D15C4F5EF bmr1a_human Bone morphogenetic protein receptor type-1A ACVRLK3 ALK3 BMPR1A Serine/threonine-protein kinase receptor R5 Activin receptor-like kinase 3 protein protein human Homo sapiens Human MPQLYIYIRLLGAYLFIISRVQGQNLDSMLHGTGMKSDSDQKKSENGVTLAPEDTLPFLKCYCSGHCPDDAINNTCITNGHCFAIIEEDDQGETTLASGCMKYEGSDFQCKDSPKAQLRRTIECCRTNLCNQYLQPTLPPVVIGPFFDGSIRWLVLLISMAVCIIAMIIFSSCFCYKHYCKSISSRRRYNRDLEQDEAFIPVGESLKDLIDQSQSSGSGSGLPLLVQRTIAKQIQMVRQVGKGRYGEVWMGKWRGEKVAVKVFFTTEEASWFRETEIYQTVLMRHENILGFIAADIKGTGSWTQLYLITDYHENGSLYDFLKCATLDTRALLKLAYSAACGLCHLHTEIYGTQGKPAIAHRDLKSKNILIKKNGSCCIADLGLAVKFNSDTNEVDVPLNTRVGTKRYMAPEVLDESLNKNHFQPYIMADIYSFGLIIWEMARRCITGGIVEEYQLPYYNMVPSDPSYEDMREVVCVKRLRPIVSNRWNSDECLRAVLKLMSECWAHNPASRLTALRIKKTLAKMVESQDVKI DIP protein P36894 original sequence version: 180 DIP protein P36894 original sequence version: 179 DIP protein P36894 original sequence version: 185 00CE2DDDA3A44170 bmr1b_human Bone morphogenetic protein receptor type-1B BMPR1B protein protein human Homo sapiens Human MLLRSAGKLNVGTKKEDGESTAPTPRPKVLRCKCHHHCPEDSVNNICSTDGYCFTMIEEDDSGLPVVTSGCLGLEGSDFQCRDTPIPHQRRSIECCTERNECNKDLHPTLPPLKNRDFVDGPIHHRALLISVTVCSLLLVLIILFCYFRYKRQETRPRYSIGLEQDETYIPPGESLRDLIEQSQSSGSGSGLPLLVQRTIAKQIQMVKQIGKGRYGEVWMGKWRGEKVAVKVFFTTEEASWFRETEIYQTVLMRHENILGFIAADIKGTGSWTQLYLITDYHENGSLYDYLKSTTLDAKSMLKLAYSSVSGLCHLHTEIFSTQGKPAIAHRDLKSKNILVKKNGTCCIADLGLAVKFISDTNEVDIPPNTRVGTKRYMPPEVLDESLNRNHFQSYIMADMYSFGLILWEVARRCVSGGIVEEYQLPYHDLVPSDPSYEDMREIVCIKKLRPSFPNRWSSDECLRQMGKLMTECWAHNPASRLTALRVKKTLAKMSESQDIKL Defects in BMPR1B are a cause of brachydactyly type A2 (BDA2) [MIM:112600]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits. BDA2 was described first in a large Norwegian kindred. BDA2 is caused by mutations in BMPR1B gene and studies demonstrate that these mutations function as dominant negatives in vitro and in vivo On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMPS/OP-1 mint Defects in BMPR1B are the cause of acromesomelic chondrodysplasia with genital anomalies [MIM:609441]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers) B283D9BF45535C79 bmpr1a-gdf5-2 1 3 unspecified role unspecified role prey prey P43026:p.Arg438Leu mutation increasing strength mutation increasing interaction strength mutation increasing strength certain certain sequence position certain certain certain sequence position certain R L Variant in SYNS2 [MIM:610017] and SYM1B [MIM:615298]. UniProt FTId: VAR_026545 Wed May 02 16:05:56 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'arg438leu' Tue Jun 30 17:31:15 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Arg438Leu' mutation increases binding affinity to kd 8.4 nM P43026:p.Leu441Pro mutation disrupting rate mutation disrupting interaction rate mutation disrupting rate certain certain sequence position certain certain certain sequence position certain L P Variant in DPS [MIM:228900] and BDA2 [MIM:112600]. UniProt FTId: VAR_017408. Wed May 02 16:56:48 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu441pro' Tue Jun 30 18:54:02 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu441Pro' ecoli Escherichia coli (strain K12) 4 unspecified role unspecified role bait bait region biotin tag biotin tag undetermined undetermined sequence position undetermined undetermined undetermined sequence position undetermined n-terminus gsgama tag tag n-term range n-terminal range n-term range n-term range n-terminal range n-term range region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain ecoli Escherichia coli (strain K12) direct interaction direct interaction Table 1 bmpr1b-gdf5-9 1 3 unspecified role unspecified role prey prey P43026:p.Leu441Pro mutation decreasing strength mutation decreasing interaction strength mutation decreasing strength certain certain sequence position certain certain certain sequence position certain L P Wed May 02 19:38:56 BST 2018 This feature has been corrected as a result of our quality control procedures. The original label was 'leu441pro' Tue Jun 30 18:21:35 BST 2020 This feature has been corrected as a result of our quality control procedures. The original label was 'p.Leu441Pro' Involved in DPS (MIM:228900) and BDA2 (OMIM 112600); UniProt FTId: VAR_017408; dbSNP:rs28936683. Decreases affinity to receptor to KD 26.5 nM Variant/mutation arg438leu did not change the association. ecoli Escherichia coli (strain K12) 5 unspecified role unspecified role bait bait c-terminus lvprgs tag tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range c-terminus his tag his tag Hexa-His-tag 6-His-tag Histidine-tag Hexa-His-tag Histidine-tag 6-His-tag c-term range C-terminal range c-term range c-term range C-terminal range c-term range region sufficient to bind sufficient binding region sufficient to bind certain certain sequence position certain certain certain sequence position certain spofr-sf_9 Spodoptera frugiperda insect cells Fall armyworm sf_9 insect cells Derived from pupal ovarian tissue of the fall armyworm Cloned from the parent cell line, IPLB-SF-21-AE (SF-21) derived from immature ovaries of fall armyworm Spodoptera frugiperda pupae cells are susceptible to Baculovirus infection direct interaction direct interaction Table 1 nog-gdf5-1 1 3 unspecified role unspecified role prey prey ecoli Escherichia coli (strain K12) 2 unspecified role unspecified role bait bait direct interaction direct interaction Table 1 GDF5 variations/mutations arg438leu and leu441pro do not change the affinity