Growth/differentiation factor 5

Details

Name
Growth/differentiation factor 5
Synonyms
  • BMP-14
  • BMP14
  • Bone morphogenetic protein 14
  • Cartilage-derived morphogenetic protein 1
  • CDMP-1
  • CDMP1
  • GDF-5
  • LAP-4
  • Lipopolysaccharide-associated protein 4
  • LPS-associated protein 4
  • Radotermin
Gene Name
GDF5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020629|Growth/differentiation factor 5
MRLPKLLTFLLWYLAWLDLEFICTVLGAPDLGQRPQGTRPGLAKAEAKERPPLARNVFRP
GGHSYGGGATNANARAKGGTGQTGGLTQPKKDEPKKLPPRPGGPEPKPGHPPQTRQATAR
TVTPKGQLPGGKAPPKAGSVPSSFLLKKAREPGPPREPKEPFRPPPITPHEYMLSLYRTL
SDADRKGGNSSVKLEAGLANTITSFIDKGQDDRGPVVRKQRYVFDISALEKDGLLGAELR
ILRKKPSDTAKPAAPGGGRAAQLKLSSCPSGRQPASLLDVRSVPGLDGSGWEVFDIWKLF
RNFKNSAQLCLELEAWERGRAVDLRGLGFDRAARQVHEKALFLVFGRTKKRDLFFNEIKA
RSGQDDKTVYEYLFSQRRKRRAPLATRQGKRPSKNLKARCSRKALHVNFKDMGWDDWIIA
PLEYEAFHCEGLCEFPLRSHLEPTNHAVIQTLMNSMDPESTPPTCCVPTRLSPISILFID
SANNVVYKQYEDMVVESCGCR
Number of residues
501
Molecular Weight
55410.15
Theoretical pI
10.41
GO Classification
Functions
BMP binding / cytokine activity / growth factor activity / identical protein binding / transforming growth factor beta receptor binding
Processes
BMP signaling pathway / cell development / cell-cell signaling / chondroblast differentiation / chondrocyte differentiation / embryonic limb morphogenesis / extracellular matrix organization / forelimb morphogenesis / growth / hindlimb morphogenesis / mitophagy in response to mitochondrial depolarization / negative regulation of chondrocyte differentiation / negative regulation of epithelial cell proliferation / negative regulation of mesenchymal cell apoptotic process / negative regulation of neuron apoptotic process / positive regulation of BMP signaling pathway / positive regulation of chondrocyte differentiation / positive regulation of neuron differentiation / positive regulation of pathway-restricted SMAD protein phosphorylation / regulation of apoptotic process / regulation of MAPK cascade / regulation of multicellular organism growth / SMAD protein import into nucleus / SMAD protein signal transduction / transforming growth factor beta receptor signaling pathway
Components
extracellular region / extracellular space / intracellular / plasma membrane
General Function
Transforming growth factor beta receptor binding
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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0020630|Growth/differentiation factor 5 (GDF5)
ATGAGACTCCCCAAACTCCTCACTTTCTTGCTTTGGTACCTGGCTTGGCTGGACCTGGAA
TTCATCTGCACTGTGTTGGGTGCCCCTGACTTGGGCCAGAGACCCCAGGGGACCAGGCCA
GGATTGGCCAAAGCAGAGGCCAAGGAGAGGCCCCCCCTGGCCCGGAACGTCTTCAGGCCA
GGGGGTCACAGCTATGGTGGGGGGGCCACCAATGCCAATGCCAGGGCAAAGGGAGGCACC
GGGCAGACAGGAGGCCTGACACAGCCCAAGAAGGATGAACCCAAAAAGCTGCCCCCCAGA
CCGGGCGGCCCTGAACCCAAGCCAGGACACCCTCCCCAAACAAGGCAGGCTACAGCCCGG
ACTGTGACCCCAAAAGGACAGCTTCCCGGAGGCAAGGCACCCCCAAAAGCAGGATCTGTC
CCCAGCTCCTTCCTGCTGAAGAAGGCCAGGGAGCCCGGGCCCCCACGAGAGCCCAAGGAG
CCGTTTCGCCCACCCCCCATCACACCCCACGAGTACATGCTCTCGCTGTACAGGACGCTG
TCCGATGCTGACAGAAAGGGAGGCAACAGCAGCGTGAAGTTGGAGGCTGGCCTGGCCAAC
ACCATCACCAGCTTTATTGACAAAGGGCAAGATGACCGAGGTCCCGTGGTCAGGAAGCAG
AGGTACGTGTTTGACATTAGTGCCCTGGAGAAGGATGGGCTGCTGGGGGCCGAGCTGCGG
ATCTTGCGGAAGAAGCCCTCGGACACGGCCAAGCCAGCGGCCCCCGGAGGCGGGCGGGCT
GCCCAGCTGAAGCTGTCCAGCTGCCCCAGCGGCCGGCAGCCGGCCGCCTTGCTGGATGTG
CGCTCCGTGCCAGGCCTGGACGGATCTGGCTGGGAGGTGTTCGACATCTGGAAGCTCTTC
CGAAACTTTAAGAACTCGGCCCAGCTGTGCCTGGAGCTGGAGGCCTGGGAACGGGGCAGG
GCCGTGGACCTCCGTGGCCTGGGCTTCGACCGCGCCGCCCGGCAGGTCCACGAGAAAGCC
CTGTTCCTGGTGTTTGGCCGCACCAAGAAACGGGACCTGTTCTTTAATGAGATTAAGGCC
CGCTCTGGCCAGGACGATAAGACCGTGTATGAGTACCTGTTCAGCCAGCGGCGAAAACGG
CGGGCCCCACTGGCCACTCGCCAGGGCAAGCGACCCAGCAAGAACCTTAAGGCTCGCTGC
AGTCGGAAGGCACTGCATGTCAACTTCAAGGACATGGGCTGGGACGACTGGATCATCGCA
CCCCTTGAGTACGAGGCTTTCCACTGCGAGGGGCTGTGCGAGTTCCCATTGCGCTCCCAC
CTGGAGCCCACGAATCATGCAGTCATCCAGACCCTGATGAACTCCATGGACCCCGAGTCC
ACACCACCCACCTGCTGTGTGCCCACGCGGCTGAGTCCCATCAGCATCCTCTTCATTGAC
TCTGCCAACAACGTGGTGTATAAGCAGTATGAGGACATGGTCGTGGAGTCGTGTGGCTGC
AGGTAG
Chromosome Location
20
Locus
20q11.2
External Identifiers
ResourceLink
UniProtKB IDP43026
UniProtKB Entry NameGDF5_HUMAN
GenBank Gene IDX80915
GenAtlas IDGDF5
HGNC IDHGNC:4220
General References
  1. 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. [Article]
  2. 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. [Article]
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  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. [Article]
  6. Triantafilou K, Triantafilou M, Dedrick RL: A CD14-independent LPS receptor cluster. Nat Immunol. 2001 Apr;2(4):338-45. [Article]
  7. Bai X, Xiao Z, Pan Y, Hu J, Pohl J, Wen J, Li L: Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes. Biochem Biophys Res Commun. 2004 Dec 10;325(2):453-60. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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):3221-31. doi: 10.1016/j.jmb.2014.07.029. Epub 2014 Aug 1. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. Faiyaz-Ul-Haque M, Ahmad W, Zaidi SH, Haque S, Teebi AS, Ahmad M, Cohn DH, Tsui LC: Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome). Clin Genet. 2002 Jun;61(6):454-8. [Article]
  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. [Article]
  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. [Article]
  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. Epub 2005 Aug 25. [Article]
  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. Epub 2006 Feb 24. [Article]
  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. [Article]
  21. Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S, Ozaki K, Takigawa M, Tanaka T, Nakamura Y, Jiang Q, Ikegawa S: A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet. 2007 Apr;39(4):529-33. Epub 2007 Mar 25. [Article]
  22. 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. [Article]
  23. 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. [Article]
  24. Yang W, Cao L, Liu W, Jiang L, Sun M, Zhang D, Wang S, Lo WH, 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):368-74. doi: 10.1007/s10038-008-0253-7. Epub 2008 Feb 19. [Article]
  25. 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. [Article]
  26. 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. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails