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Gene Review

DENND6A  -  DENN/MADD domain containing 6A

Homo sapiens

Synonyms: AFI1A, DENN domain-containing protein 6A, FAM116A, FLJ34969, Protein DENND6A

Synonyms: FLJ34969 , hypothetical protein LOC20162711


Accession Number: NM_152678 (mRNA)11 and NP_689891 (Protein)11


Summary: FAM116A   is 4679 bp gene present in humans and has conserved   orthologs from P.troglodytes to O. sativa. The gene is located on the short arm of chromosome 3 at position 3p14.3. The mRNA of FAM116A contains an open reading frame coding for 20   exons and 608 amino acids. The FAM116A gene has a conserved and known differentially expressed in neoplastic vs normal cells (DENN) domain of unknown function that is, according to Marchler-Bauer et al., a domain which occurs in several proteins involved in Rab-mediated processes or regulation of MAPK signaling pathways1,10. The function of the protein is not yet well understood by the scientific community.


Gene Neighborhood and Location:


Gene neighborhood of FAM116A on chromosome 3; Location: 3p14.32


FAM116A is located on the short arm of chromosome 3 at position 3p14.35



FAM116A has conserved othologs in mammals, birds, amphibians, fish, invertebrates, insects, and plants. All of the orthologs contain a conserved DENN Domain. FAM116A has no known paralogs.


Postranslational Modifications:

Serine 127 is posttranslationally phosphorylated4.


Potential Protein interactions: In the Anopheles   gambiae FAM116A homologous protein a PTZ00009 domain, which codes for Heat Shock Protein 70 Kda (Hsp70), was bound to the FAM116A/DENN domain of the protein1,10. This phenomenon is what Reiner Veitia describes as the Rosetta   Stone method of protein interaction3. Future studies between the proteins may be fruitful for discovery of the function of the FAM116A protein.


Connection with Heat Shock:

  1. Rosetta Stone Hsp70 Protein Interaction with FAM116A in Anopheles gambiae10
  2. Up-regulation of FAM116A in Mus musculus over time in response to heat shock8,9
  3. Relation of the DENN Domain to MAP Kinases, which respond to extracellular stimuli including heat shock6
  4. ‘Heat Shock Factors’ family of ubiquitously expressed transcription factor predicted by MatInspector7
The relationship between FAM116A and heat shock is intriguing but experiments need to be conducted in order to verify protein-protein interaction, protein structure, and relevance in the body because the function of the protein is not yet well understood.




  1. CDD: a Conserved Domain Database for the functional annotation of proteins. Marchler-Bauer A et al. Nucleic Acids Res.39(D)225-9. (2011)
  2. Gene: Genes and mapped phenotypes. National Center for Biotechnology Information (NCBI).  
  3. Rosetta Stone proteins: “chance and necessity”?. Veitia R. Genome Biology, 3(2). (2002)
  4. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Olsen JV. Sci Signal 3. (2010)
  5. Genecards [ 
  6. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, Cobb MH Endocr. Rev. 22 (2): 153–83. (2001)
  7. Genomatix (MatInspector) [ 
  8. The role of heat shock transcription factor 1 in the genome-wide regulation of the mammalian heat shock response. Trinklein ND, Murray JI, Hartman SJ, Botstein D et al. Mol Biol Cell. 15(3):1254-61. (2004)
  9. National Center for Biotechnology Information. (GeProfiles) [ 
  10. National Center for Biotechnology Information. (Homologene) [ 
  11. National Center for Biotechnology Information (NCBI) [ 





















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