Kinase Subfamily FAM20B

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Kinase Classification: Group PKL: Family GASK: Subfamily FAM20B


FAM20B is a animal-specific subfamily of the GASK (Golgi-Associated Kinase) of secretory kinases. It has been implicated in phosphorylation and control of proteoglycans.

Protein Structure

Like other FJ family kinases, FAM20B has a conserved signal peptide but no predicted transmembrane domain. The PKL-type kinase domain is at the C-terminus, with a variable (~200? AA) N-terminus with no known domain and lower sequence conservation than the kinase domain.

Protein Interactions

Neither human nor Drosophila FAM20B proteins have reported protein interactions (Feb 2012).

Evolution

FAM20B consists of a single gene in humans, all other vertebrates, some other chordates and echinoderms, insects and cnidarians and a sponge. It is not found in nematodes or outside of the metazoans.

Functions

FAM20B was shown to have in vitro kinase activity on glycosylated proteins, specifically phosphorylating xylose residues [1]. Thus it has a protein substrate, but phosphorylates a sugar moiety rather than an amino acid. The level of chondroitin and heparan sulfate in HeLa cells was shown to correlate positively with the level of FAM20B expression.

Zebrafish FAM20B has also been implicated in proteoglycan production: A conference abstract found two of three mutations in a screen for cartilage formation in zebrafish to be in FAM20B. These mutations, and morpholinos against FAM20B caused increased production of cartilage matrix and decreased perichondral bone formation during endochondral ossification (bone formation) [2]. The other mutation was found in a proteoglycan enzyme, and it was shown that the two proteins operate together in the formation of proteoglycans.

Phosphosite shows a single phosphorylation, on Y138 (upstream of the kinase domain, conserved in most but not all FAM20B), from multiple published and unpublished studies (FAM20A and FAM20C are not known to be phosphorylated).

FAM20B has been found in a proteome survey of lung cancer cell line conditioned media [3] and in a commercial list of CSF fluid proteome NextGen Sciences

Gerard 20:39, 8 February 2012 (UTC)

References

  1. Koike T, Izumikawa T, Tamura J, and Kitagawa H. FAM20B is a kinase that phosphorylates xylose in the glycosaminoglycan-protein linkage region. Biochem J. 2009 Jun 26;421(2):157-62. DOI:10.1042/BJ20090474 | PubMed ID:19473117 | HubMed [Koike]
  2. Eames BF, Yan YL, Swartz ME, Levic DS, Knapik EW, Postlethwait JH, and Kimmel CB. Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation. PLoS Genet. 2011 Aug;7(8):e1002246. DOI:10.1371/journal.pgen.1002246 | PubMed ID:21901110 | HubMed [Eames]
  3. Planque C, Kulasingam V, Smith CR, Reckamp K, Goodglick L, and Diamandis EP. Identification of five candidate lung cancer biomarkers by proteomics analysis of conditioned media of four lung cancer cell lines. Mol Cell Proteomics. 2009 Dec;8(12):2746-58. DOI:10.1074/mcp.M900134-MCP200 | PubMed ID:19776420 | HubMed [Planque]
All Medline abstracts: PubMed | HubMed