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Showing Protein Growth/differentiation factor 5 (HMDBP13847)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP13847
Secondary Accession Numbers None
Name Growth/differentiation factor 5
Synonyms
  1. GDF-5
  2. Bone morphogenetic protein 14
  3. Cartilage-derived morphogenetic protein 1
  4. Lipopolysaccharide-associated protein 4
  5. Radotermin
  6. BMP-14
  7. CDMP-1
  8. LAP-4
  9. LPS-associated protein 4
Gene Name GDF5
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Growth factor involved in bone and cartilage formation. During cartilage development regulates differentiation of chondrogenic tissue through two pathways. Firstly, positively regulates differentiation of chondrogenic tissue through its binding of high affinity with BMPR1B and of less affinity with BMPR1A, leading to induction of SMAD1-SMAD5-SMAD8 complex phosphorylation and then SMAD protein signaling transduction (PubMed:24098149, PubMed:21976273, PubMed:15530414, PubMed:25092592). Secondly, negatively regulates chondrogenic differentiation through its interaction with NOG (PubMed:21976273). Required to prevent excessive muscle loss upon denervation. This function requires SMAD4 and is mediated by phosphorylated SMAD1/5/8 (By similarity). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205).
Pathways
  • Cytokine-cytokine receptor interaction
  • Hippo signaling pathway
  • TGF-beta signaling pathway
Reactions Not Available
GO Classification
Biological Process
cell-cell signaling
negative regulation of neuron apoptotic process
response to mechanical stimulus
negative regulation of epithelial cell proliferation
SMAD protein signal transduction
positive regulation of neuron differentiation
BMP signaling pathway
chondroblast differentiation
forelimb morphogenesis
hindlimb morphogenesis
negative regulation of chondrocyte differentiation
negative regulation of mesenchymal cell apoptotic process
ossification involved in bone remodeling
positive regulation of pathway-restricted SMAD protein phosphorylation
regulation of SMAD protein signal transduction
embryonic limb morphogenesis
positive regulation of chondrocyte differentiation
regulation of multicellular organism growth
positive regulation of BMP signaling pathway
transforming growth factor beta receptor signaling pathway
Cellular Component
plasma membrane
extracellular region
extracellular space
Molecular Function
growth factor activity
BMP binding
cytokine activity
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 501
Molecular Weight 55410.15
Theoretical pI 9.788
Pfam Domain Function
Signals
  • 1-27;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P43026
UniProtKB/Swiss-Prot Entry Name GDF5_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052 ]
  3. Hotten G, Neidhardt H, Jacobowsky B, Pohl J: Cloning and expression of recombinant human growth/differentiation factor 5. Biochem Biophys Res Commun. 1994 Oct 28;204(2):646-52. doi: 10.1006/bbrc.1994.2508. [PubMed:7980526 ]
  4. Chang SC, Hoang B, Thomas JT, Vukicevic S, Luyten FP, Ryba NJ, Kozak CA, Reddi AH, Moos M Jr: Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J Biol Chem. 1994 Nov 11;269(45):28227-34. [PubMed:7961761 ]
  5. Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J, Luyten FP: A human chondrodysplasia due to a mutation in a TGF-beta superfamily member. Nat Genet. 1996 Mar;12(3):315-7. doi: 10.1038/ng0396-315. [PubMed:8589725 ]
  6. Triantafilou K, Triantafilou M, Dedrick RL: A CD14-independent LPS receptor cluster. Nat Immunol. 2001 Apr;2(4):338-45. doi: 10.1038/86342. [PubMed:11276205 ]
  7. Sengle G, Charbonneau NL, Ono RN, Sasaki T, Alvarez J, Keene DR, Bachinger HP, Sakai LY: Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J Biol Chem. 2008 May 16;283(20):13874-88. doi: 10.1074/jbc.M707820200. Epub 2008 Mar 13. [PubMed:18339631 ]
  8. Seemann P, Brehm A, Konig J, Reissner C, Stricker S, Kuss P, Haupt J, Renninger S, Nickel J, Sebald W, Groppe JC, Ploger F, Pohl J, Schmidt-von Kegler M, Walther M, Gassner I, Rusu C, Janecke AR, Dathe K, Mundlos S: Mutations in GDF5 reveal a key residue mediating BMP inhibition by NOGGIN. PLoS Genet. 2009 Nov;5(11):e1000747. doi: 10.1371/journal.pgen.1000747. Epub 2009 Nov 26. [PubMed:19956691 ]
  9. Schwaerzer GK, Hiepen C, Schrewe H, Nickel J, Ploeger F, Sebald W, Mueller T, Knaus P: New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. J Bone Miner Res. 2012 Feb;27(2):429-42. doi: 10.1002/jbmr.532. [PubMed:21976273 ]
  10. Degenkolbe E, Konig J, Zimmer J, Walther M, Reissner C, Nickel J, Ploger F, Raspopovic J, Sharpe J, Dathe K, Hecht JT, Mundlos S, Doelken SC, Seemann P: A GDF5 point mutation strikes twice--causing BDA1 and SYNS2. PLoS Genet. 2013;9(10):e1003846. doi: 10.1371/journal.pgen.1003846. Epub 2013 Oct 3. [PubMed:24098149 ]
  11. Stange K, Thieme T, Hertel K, Kuhfahl S, Janecke AR, Piza-Katzer H, Penttinen M, Hietala M, Dathe K, Mundlos S, Schwarz E, Seemann P: Molecular analysis of two novel missense mutations in the GDF5 proregion that reduce protein activity and are associated with brachydactyly type C. J Mol Biol. 2014 Sep 23;426(19):3221-3231. doi: 10.1016/j.jmb.2014.07.029. Epub 2014 Aug 1. [PubMed:25092592 ]
  12. Wang J, Yu T, Wang Z, Ohte S, Yao RE, Zheng Z, Geng J, Cai H, Ge Y, Li Y, Xu Y, Zhang Q, Gusella JF, Fu Q, Pregizer S, Rosen V, Shen Y: A New Subtype of Multiple Synostoses Syndrome Is Caused by a Mutation in GDF6 That Decreases Its Sensitivity to Noggin and Enhances Its Potency as a BMP Signal. J Bone Miner Res. 2016 Apr;31(4):882-9. doi: 10.1002/jbmr.2761. Epub 2015 Dec 28. [PubMed:26643732 ]
  13. Gutierrez-Amavizca BE, Brambila-Tapia AJ, Juarez-Vazquez CI, Holder-Espinasse M, Manouvrier-Hanu S, Escande F, Barros-Nunez P: A novel mutation in CDMP1 causes brachydactyly type C with "angel-shaped phalanx". A genotype-phenotype correlation in the mutational spectrum. Eur J Med Genet. 2012 Nov;55(11):611-4. doi: 10.1016/j.ejmg.2012.07.004. Epub 2012 Jul 22. [PubMed:22828468 ]
  14. Kotzsch A, Nickel J, Seher A, Sebald W, Muller TD: Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity. EMBO J. 2009 Apr 8;28(7):937-47. doi: 10.1038/emboj.2009.37. Epub 2009 Feb 19. [PubMed:19229295 ]
  15. Thomas JT, Kilpatrick MW, Lin K, Erlacher L, Lembessis P, Costa T, Tsipouras P, Luyten FP: Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nat Genet. 1997 Sep;17(1):58-64. doi: 10.1038/ng0997-58. [PubMed:9288098 ]
  16. Schwabe GC, Turkmen S, Leschik G, Palanduz S, Stover B, Goecke TO, Mundlos S: Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. Am J Med Genet A. 2004 Feb 1;124A(4):356-63. doi: 10.1002/ajmg.a.20349. [PubMed:14735582 ]
  17. Szczaluba K, Hilbert K, Obersztyn E, Zabel B, Mazurczak T, Kozlowski K: Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene. Am J Med Genet A. 2005 Nov 1;138(4):379-83. doi: 10.1002/ajmg.a.30969. [PubMed:16222676 ]
  18. Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, Stricker S, Pohl J, Ploger F, Staub E, Nickel J, Sebald W, Knaus P, Mundlos S: Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 2005 Sep;115(9):2373-81. doi: 10.1172/JCI25118. Epub 2005 Aug 25. [PubMed:16127465 ]
  19. Dawson K, Seeman P, Sebald E, King L, Edwards M, Williams J 3rd, Mundlos S, Krakow D: GDF5 is a second locus for multiple-synostosis syndrome. Am J Hum Genet. 2006 Apr;78(4):708-12. doi: 10.1086/503204. Epub 2006 Feb 24. [PubMed:16532400 ]
  20. Wang X, Xiao F, Yang Q, Liang B, Tang Z, Jiang L, Zhu Q, Chang W, Jiang J, Jiang C, Ren X, Liu JY, Wang QK, Liu M: A novel mutation in GDF5 causes autosomal dominant symphalangism in two Chinese families. Am J Med Genet A. 2006 Sep 1;140A(17):1846-53. doi: 10.1002/ajmg.a.31372. [PubMed:16892395 ]
  21. Douzgou S, Lehmann K, Mingarelli R, Mundlos S, Dallapiccola B: Compound heterozygosity for GDF5 in Du Pan type chondrodysplasia. Am J Med Genet A. 2008 Aug 15;146A(16):2116-21. doi: 10.1002/ajmg.a.32435. [PubMed:18629880 ]
  22. Ploger F, Seemann P, Schmidt-von Kegler M, Lehmann K, Seidel J, Kjaer KW, Pohl J, Mundlos S: Brachydactyly type A2 associated with a defect in proGDF5 processing. Hum Mol Genet. 2008 May 1;17(9):1222-33. doi: 10.1093/hmg/ddn012. Epub 2008 Jan 18. [PubMed:18203755 ]
  23. Yang W, Cao L, Liu W, Jiang L, Sun M, Zhang D, Wang S, Lo WHY, Luo Y, Zhang X: Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. J Hum Genet. 2008;53(4):368-374. doi: 10.1007/s10038-008-0253-7. Epub 2008 Feb 19. [PubMed:18283415 ]
  24. Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE: Mutations in GDF5 presenting as semidominant brachydactyly A1. Hum Mutat. 2010 Oct;31(10):1155-62. doi: 10.1002/humu.21338. [PubMed:20683927 ]
  25. Al-Qattan MM, Al-Motairi MI, Al Balwi MA: Two novel homozygous missense mutations in the GDF5 gene cause brachydactyly type C. Am J Med Genet A. 2015 Jul;167(7):1621-6. doi: 10.1002/ajmg.a.37040. Epub 2015 Mar 28. [PubMed:25820810 ]