Found to be densely associated to the postsynaptic density (PSD), it has been characterised as a 188 kDa (originally thought to be 180 kDa, hence nomenclature), 1495 residues long, brain-specific protein containing 16 leucine-rich repeats (LRRs) within the 500 N-terminal residues, and one Psd95/Discs large/Zona occludens (PDZ) domain within the 200 C-terminal residues. Originally postulated to have an apparent transmembrane domain, it has now been shown that the protein has numerous phosphorylation sites both N- and C-term of this domain, and that protein is therefore cytoplasmic; palmitoylation is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD.
The currently exposed interactions of Densin-180 portray the protein as a promiscuous player amongst key synaptic players, fitting with the original observation of the protein’s dense presence among core PSD proteins by Mary B. Kennedy's Laboratory. Identified interaction partners include: CaMKII-alpha, alpha-Actinin and NR2B (via CaMKII-alpha), Cav1.3 (L-type Ca2+) channels, MAGUIN-1, Shank, PSD-95 (via Shank and MAGUIN-1), beta-Catenin, delta-Catenins and NCadherin (via the Catenins). The nature and function of these interactions, detailed in tables 1-1 and 1-2, portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. [number of sources - referenced in - Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/]
It is also quite possible that Densin-180 dimerises or multimerises through interactions between its PDZ domain and its own terminal amino acid residues. [Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/]
Apperson ML, Moon IS, Kennedy MB (1996). "Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family". J. Neurosci. 16 (21): 6839–52. PMID8824323.
Nagase T, Kikuno R, Ishikawa KI, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID10718198.
Walikonis RS, Oguni A, Khorosheva EM, et al. (2001). "Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin". J. Neurosci. 21 (2): 423–33. PMID11160423.
Izawa I, Nishizawa M, Ohtakara K, Inagaki M (2002). "Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses". J. Biol. Chem. 277 (7): 5345–50. doi:10.1074/jbc.M110052200. PMID11729199.
Wang L, Xu J, Wu Q, et al. (2003). "Cloning and characterization of a novel splice variant of the brain-specific protein densin-180". Int. J. Mol. Med. 11 (2): 257–60. doi:10.3892/ijmm.11.2.257. PMID12525888.
Robison AJ, Bass MA, Jiao Y, et al. (2005). "Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2". J. Biol. Chem. 280 (42): 35329–36. doi:10.1074/jbc.M502191200. PMID16120608.
Rinta-Valkama J, Aaltonen P, Lassila M, et al. (2007). "Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes". Diabetes Metab. Res. Rev. 23 (2): 119–26. doi:10.1002/dmrr.655. PMID16741999.
Lassila M, Juhila J, Heikkilä E, Holthöfer H (2007). "Densin is a novel cell membrane protein of Sertoli cells in the testis". Mol. Reprod. Dev. 74 (5): 641–5. doi:10.1002/mrd.20659. PMID17039495.
Heikkilä E, Ristola M, Endlich K, et al. (2007). "Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions". Mol. Cell. Biochem. 305 (1–2): 9–18. doi:10.1007/s11010-007-9522-6. PMID17581699.
Add—a very detailed thesis with preliminary experiments and theories about the function of Densin-180 entitled Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells http://discovery.ucl.ac.uk/1322972/