Leucine-rich repeat-containing protein 7 (LRRC7)
The protein contains 1537 amino acids for an estimated molecular weight of 172581 Da.
Required for normal synaptic spine architecture and function. Necessary for DISC1 and GRM5 localization to postsynaptic density complexes and for both N-methyl D-aspartate receptor-dependent and metabotropic glutamate receptor-dependent long term depression. (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| a breast cancer sample; somatic mutation | |
| dbSNP:rs12069888 |
No binding partner found
Biological Process
Cell-cell adhesion
Establishment or maintenance of epithelial cell apical/basal polarity
MAPK cascade
Neurotransmitter receptor transport postsynaptic membrane to endosome
Neurotransmitter receptor transport, endosome to postsynaptic membrane
Neutrophil degranulation
Positive regulation of neuron projection development
Receptor clustering
Receptor localization to synapse
Regulation of NMDA receptor activity
Cellular Component
Adherens junction
Axon initial segment
Basolateral plasma membrane
Cell junction
Cell-cell junction
Centrosome
Cytosol
Extracellular region
Neuron projection
Nucleoplasm
Plasma membrane
Postsynaptic density
Specific granule lumen
Synapse
Molecular Function
The reference OMIM entry for this protein is 614453
Leucine-rich repeat-containing protein 7; lrrc7
Densin
Densin 180
Kiaa1365
DESCRIPTION
LRRC7 is an abundant scaffold protein of postsynaptic densities that forms a high-affinity complex with alpha-CaM kinase II (CAMK2A; 114078) and alpha-actinin (see 102575) (Carlisle et al., 2011).CLONING
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) obtained a partial LRRC7 clone, which they designated KIAA1365. The translated sequence shares significant similarity with the C-terminal end of rat densin-180. RT-PCR ELISA detected LRRC7 expression in whole adult brain and weaker expression in fetal brain. LRRC7 was expressed in all specific adult brain regions examined except cerebellum, with highest expression in caudate nucleus. Little to no expression was detected in other adult or fetal tissues. By searching databases for sequences similar to rat densin-180, followed by PCR of a human brain cDNA library, Izawa et al. (2002) obtained full-length human densin-180. The deduced 1,537-amino acid protein contains 16 leucine-rich repeats, a putative transmembrane domain, and a PDZ domain. It was predicted to be phosphorylated by CAMK2. Densin-180 localized to synapses along dendrites of cultured rat hippocampal neurons.GENE FUNCTION
By yeast 2-hybrid screening of a human brain cDNA library, Izawa et al. (2002) found that the C-terminal cytosolic PDZ domain of human densin-180 bound the C terminus of NPRAP (CTNND2; 604275). Protein pull-down experiments confirmed the interaction. Immunoprecipitation analysis of transfected COS-7 cells and endogenous rat brain synaptosomal fractions showed that densin-180 interacted with both NPRAP and N-cadherin (CDH2; 114020).MAPPING
By radiation hybrid analysis, Nagase et al. (2000) mapped the LRRC7 gene to chromosome 1. Hartz (2012) mapped the LRRC7 gene to chromosome 1p31.1 based on an alignment of the LRRC7 sequence (GenBank GENBANK AB037786) with the genomic sequence (GRCh37).ANIMAL MODEL
Carlisle et al. (2011) obtained densin -/- mice at the expected mendelian ratio, but they had a mortality rate of about 20% and showed early growth retardation. Surviving mice were similar to wildtype in size by 11 weeks of age and had a normal life span. Densin -/- mice exhibited behavioral abnormalities, including grasping, impaired short-term memory, hyperactivity in response to stress or novelty, and absence of acoustic prepulse inhibition. Coordination, endurance, and balance were similar between densin -/- and wildtype mice. Histologic examination of densin -/- forebrains revealed no gross abnormalities; however, densin -/- hippocampal neurons showed abnormal synaptic spine morphology. Western blot analysis revealed reduced amount of alpha-actinin in whole densin -/- brain and reduced Disc1 (605210) and Mglur5 (GRM5; 604102) in isolated densin -/- postsynaptic densities. Loss of densin altered steady-state activation of Camk2 and activation of Camk2 in response to synaptic activity, and it impaired Nmdar (GRIN; 138249)- and Mglur-dependent long-term depression. Carlisle et al. (2011) concluded that densin is required for normal synaptic spine architecture and function. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614453 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).