View source for Kinase Subfamily FAM20A

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[[kinase classification|Kinase Classification]]: [[Kinase_Group_PKL|Group PKL]]: [[Kinase_Family_GASK|Family GASK]]: Subfamily FAM20A


FAM20A is a subfamily of the  [[Kinase_Family_GASK|GASK]] ('''G'''olgi-'''As'''sociated '''K'''inase) family of secretory kinases. It consists of two genes (FAM20A and FAM20C) in humans and all other vertebrates, and one or more homologs in other deuterostomes, in insects and in nematodes.

====Evolution====
FAM20A is single copy in all vertebrates, but FAM20C is dynamic: it appears to be duplicated four-fold in most fish, though lost from some, and an additional likely paralog is found from amphibians to platypus, but not in placental mammals or fish. A single FAM20A-like gene is found in some invertebrate chordates (Branchiostoma and Saccoglossus) but it is apparently lost from Ciona. Urchins have two FAM20A genes, one similar to the invertebrate chordates, and the other highly divergent. Insects and nematodes also have just one copy.

====Domain Structure====
Like other FJ family kinases, FAM20A 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====
Human FAM20C interacts with 7 proteins from a single screen <cite>Vinayagam</cite>, all of which are linked to each other, with functions enriched for transcriptional and chromatin regulation. The Drosophila homolog, CG31145 has a single interaction with a dynein light chain, DLC90F. No other family members have known interactors

====Functions====
Mutations in FAM20C were found to cause bone disorders ([http://en.wikipedia.org/wiki/Raine_syndrome Raine Syndrome] / Lethal Osteosclerotic Bone Dysplasia) giving rise to abnormally hard and dense bone, usually lethal within hours of birth. Four different non-synonymous changes at 3 positions were found, along with several splice site mutations and a deletion <cite>Raine, Fradin, Simpson</cite>. The disorder is recessive, and while the mutant residues are conserved within vertebrates, they are not conserved within the whole family and do not effect the catalytic residues. Mouse FAM20C (aka DMP4) is selectively expressed in mineralizing bone, and in developing teeth, the differentiation of that [http://en.wikipedia.org/wiki/Odontoblast odontoblasts], the dentin (mineral)-secreting cells is modulated by FAM20C levels <cite>Hao, Wang</cite>.

A FAM20A mutation was also associated with  to Amelogenesis Imperfecta, a biomineralization disorder resulting in imperfect tooth enamel <cite>OSullivan</cite>. The mutation causes a premature stop of the protein at position 136 and is likely null. A deletion of the FAM20A region in mouse also caused a general postnatal growth retardation <cite>An</cite>


====References====
<biblio>
#An pmid=20847595
#Fradin pmid=20825432
#Vinayagam pmid=21900206
#Raine pmid=17924334
#Hao pmid=17369251
#Simpson pmid=19250384
#Wang pmid=20644212
#OSullivan pmid=21549343
</biblio>