LRRC7

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.[5]

LRRC7
Identifiers
Aliases	LRRC7, DENSIN, leucine rich repeat containing 7
External IDs	OMIM: 614453 MGI: 2676665 HomoloGene: 10817 GeneCards: LRRC7
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.1 Start 69,568,261 bp[1] End 70,151,945 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 H4 Start 158,082,891 bp[2] End 158,562,221 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • ionotropic glutamate receptor binding • Ras guanyl-nucleotide exchange factor activity Cellular component • cell junction • postsynaptic membrane • synapse • membrane • GO:0097483, GO:0097481 postsynaptic density • extracellular region • specific granule lumen • cytoplasm • cell membrane • neuron projection • intercellular junction • ionotropic glutamate receptor complex • basolateral plasma membrane • axon initial segment • cytosol Biological process • neutrophil degranulation • signal transduction • positive regulation of neuron projection development • receptor clustering • establishment or maintenance of epithelial cell apical/basal polarity • receptor localization to synapse • cell-cell adhesion • neurotransmitter receptor transport, endosome to postsynaptic membrane • neurotransmitter receptor transport postsynaptic membrane to endosome • MAPK cascade • regulation of NMDA receptor activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	57554	242274
Ensembl	ENSG00000033122	ENSMUSG00000028176
UniProt	Q96NW7	Q80TE7
RefSeq (mRNA)	NM_020794 NM_001330635 NM_001350216 NM_001366836 NM_001366837 NM_001366838 NM_001366839 NM_001366840 NM_001366841 NM_001366842 NM_001370785	NM_001081358 NM_001291452 NM_001291453 NM_001370781 NM_001370782
RefSeq (protein)	NP_001317564 NP_001337145 NP_001353765 NP_001353766 NP_001353767 NP_001353768 NP_001353769 NP_001353770 NP_001353771 NP_001357714	NP_001074827 NP_001278381 NP_001278382 NP_001357710 NP_001357711
Location (UCSC)	Chr 1: 69.57 – 70.15 Mb	Chr 3: 158.08 – 158.56 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

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.[6]

Interactions

LRRC7 has been shown to interact with CDH2.[7]

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

1. GRCh38: Ensembl release 89: ENSG00000033122 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028176 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: LRRC7 leucine rich repeat containing 7".
6. 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.
7. 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

• 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. doi:10.1523/JNEUROSCI.16-21-06839.1996. PMC 6579252. PMID 8824323.
• 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. PMID 10718198.
• 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. doi:10.1523/JNEUROSCI.21-02-00423.2001. PMC 6763799. PMID 11160423.
• 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. PMID 11729199.
• Ohtakara K, Nishizawa M, Izawa I, et al. (2003). "Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1". Genes Cells. 7 (11): 1149–60. doi:10.1046/j.1365-2443.2002.00589.x. PMID 12390249.
• 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. PMID 12525888.
• Ahola H, Heikkilä E, Aström E, et al. (2003). "A novel protein, densin, expressed by glomerular podocytes". J. Am. Soc. Nephrol. 14 (7): 1731–7. doi:10.1097/01.ASN.0000075553.33781.9F. PMID 12819232.
• Goodchild RE, Dauer WT (2005). "The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein". J. Cell Biol. 168 (6): 855–62. doi:10.1083/jcb.200411026. PMC 2171781. PMID 15767459.
• 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. PMID 16120608.
• Gregory SG, Barlow KF, McLay KE, et al. (2006). "The DNA sequence and biological annotation of human chromosome 1". Nature. 441 (7091): 315–21. Bibcode:2006Natur.441..315G. doi:10.1038/nature04727. PMID 16710414.
• 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. PMID 16741999.
• 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. PMID 17039495.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• 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. PMID 17581699.

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/