LRRC7

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Leucine rich repeat containing 7
Identifiers
Symbols LRRC7 ; DENSIN
External IDs OMIM614453 MGI2676665 HomoloGene10817 GeneCards: LRRC7 Gene
Orthologs
Species Human Mouse
Entrez 57554 242274
Ensembl ENSG00000033122 ENSMUSG00000028176
UniProt Q96NW7 Q80TE7
RefSeq (mRNA) NM_020794 NM_001081358
RefSeq (protein) NP_065845 NP_001074827
Location (UCSC) Chr 1:
70.03 – 70.62 Mb
Chr 3:
158.08 – 158.56 Mb
PubMed search [1] [2]

Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene.[1]

Structure[edit]

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.[2]

Interactions[edit]

LRRC7 has been shown to interact with CDH2.[3]

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 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/]

References[edit]

  1. ^ "Entrez Gene: LRRC7 leucine rich repeat containing 7". 
  2. ^ Thalhammer A, Trinidad JC, Burlingame AL, Schoepfer R (April 2009). "Densin-180: revised membrane topology, domain structure and phosphorylation status". J. Neurochem. 109 (2): 297–302. doi:10.1111/j.1471-4159.2009.05951.x. PMC 2846389. PMID 19187442. 
  3. ^ Izawa, Ichiro; Nishizawa Miwako; Ohtakara Kazuhiro; Inagaki Masaki (Feb 2002). "Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses". J. Biol. Chem. (United States) 277 (7): 5345–50. doi:10.1074/jbc.M110052200. ISSN 0021-9258. PMID 11729199. 

Further reading[edit]


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/