LRRC7
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Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
which in humans is encoded by the ''LRRC7''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


Structure

Found to be densely associated to the
postsynaptic density The postsynaptic density (PSD) is a protein dense ''specialization'' attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron. The PSD is in ...
(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 repeat A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe tertiary structure, fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These Pr ...
s (LRRs) within the 500
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
residues, and one Psd95/Discs large/Zona occludens ( PDZ) domain within the 200
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
residues. Originally postulated to have an apparent transmembrane domain, it has now been shown that the protein has numerous
phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
sites both N- and C-term of this domain, and that protein is therefore
cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...
ic;
palmitoylation In molecular biology, palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typic ...
is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD.


Interactions

LRRC7 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
CDH2 Cadherin-2 also known as Neural cadherin (N-cadherin), is a protein that in humans is encoded by the ''CDH2'' gene. CDH2 has also been designated as CD325 ( cluster of differentiation 325). Cadherin-2 is a transmembrane protein expressed in mult ...
. 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/]


References


Further reading

* * * * * * * * * * * * * * {{refend 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/ LRR proteins