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{{Infobox_gene}}
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'''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]].<ref name="entrez">{{cite web | title = Entrez Gene: LRRC7 leucine rich repeat containing 7| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57554| accessdate = }}</ref>
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== Structure ==
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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 repeat]]s (LRRs) within the 500 [[N-terminus|N-terminal]] residues, and one Psd95/Discs large/Zona occludens ([[PDZ domain|PDZ]]) domain within the 200 [[C-terminus|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 [[cytoplasm]]ic; [[palmitoylation]] is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD.<ref name="pmid19187442">{{cite journal |vauthors=Thalhammer A, Trinidad JC, Burlingame AL, Schoepfer R | title = Densin-180: revised membrane topology, domain structure and phosphorylation status | journal = J. Neurochem. | volume = 109 | issue = 2 | pages = 297–302 |date=April 2009 | pmid = 19187442 | doi = 10.1111/j.1471-4159.2009.05951.x | url = | issn = | pmc = 2846389 }}</ref>
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==Interactions==
LRRC7 has been shown to [[Protein-protein interaction|interact]] with [[CDH2]].<ref name=pmid11729199>{{cite journal |last=Izawa |first=Ichiro |authorlink= |author2=Nishizawa Miwako |author3=Ohtakara Kazuhiro |author4=Inagaki Masaki  |date=Feb 2002 |title=Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses |journal=J. Biol. Chem. |volume=277 |issue=7 |pages=5345–50 |publisher= |location = United States| issn = 0021-9258| pmid = 11729199 |doi = 10.1074/jbc.M110052200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}</ref>


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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/]
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Leucine rich repeat containing 7
| HGNCid = 18531
| Symbol = LRRC7
| AltSymbols =; DKFZp686I1147; KIAA1365; MGC144918
| OMIM = 
| ECnumber = 
| Homologene = 10817
| MGIid = 2676665
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component =
| Process =
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 57554
    | Hs_Ensembl = ENSG00000033122
    | Hs_RefseqProtein = NP_065845
    | Hs_RefseqmRNA = NM_020794
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 69806669
    | Hs_GenLoc_end = 70361752
    | Hs_Uniprot = Q96NW7
    | Mm_EntrezGene = 242274
    | Mm_Ensembl = ENSMUSG00000028176
    | Mm_RefseqmRNA = XM_143575
    | Mm_RefseqProtein = XP_143575
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 158018188
    | Mm_GenLoc_end = 158496649
    | Mm_Uniprot = Q3URB9
  }}
}}
'''Leucine rich repeat containing 7''', also known as '''LRRC7''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: LRRC7 leucine rich repeat containing 7| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57554| accessdate = }}</ref>


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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
{{PBB_Summary
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/]
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| summary_text =
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==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Apperson ML, Moon IS, Kennedy MB |title=Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. |journal=J. Neurosci. |volume=16 |issue= 21 |pages= 6839-52 |year= 1996 |pmid= 8824323 |doi=  }}
*{{cite journal  |vauthors=Apperson ML, Moon IS, Kennedy MB |title=Characterization of densin-180, a new brain-specific synaptic protein of the O-sialoglycoprotein family. |journal=J. Neurosci. |volume=16 |issue= 21 |pages= 6839–52 |year= 1996 |pmid= 8824323 |doi=  }}
*{{cite journal | author=Nagase T, Kikuno R, Ishikawa KI, ''et al.'' |title=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. |journal=DNA Res. |volume=7 |issue= 1 |pages= 65-73 |year= 2000 |pmid= 10718198 |doi=  }}
*{{cite journal   |vauthors=Nagase T, Kikuno R, Ishikawa KI, etal |title=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. |journal=DNA Res. |volume=7 |issue= 1 |pages= 65–73 |year= 2000 |pmid= 10718198 |doi=10.1093/dnares/7.1.65 }}
*{{cite journal | author=Walikonis RS, Oguni A, Khorosheva EM, ''et al.'' |title=Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin. |journal=J. Neurosci. |volume=21 |issue= 2 |pages= 423-33 |year= 2001 |pmid= 11160423 |doi=  }}
*{{cite journal   |vauthors=Walikonis RS, Oguni A, Khorosheva EM, etal |title=Densin-180 forms a ternary complex with the (alpha)-subunit of Ca2+/calmodulin-dependent protein kinase II and (alpha)-actinin. |journal=J. Neurosci. |volume=21 |issue= 2 |pages= 423–33 |year= 2001 |pmid= 11160423 |doi=  }}
*{{cite journal  | author=Izawa I, Nishizawa M, Ohtakara K, Inagaki M |title=Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses. |journal=J. Biol. Chem. |volume=277 |issue= 7 |pages= 5345-50 |year= 2002 |pmid= 11729199 |doi= 10.1074/jbc.M110052200 }}
*{{cite journal  |vauthors=Izawa I, Nishizawa M, Ohtakara K, Inagaki M |title=Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses. |journal=J. Biol. Chem. |volume=277 |issue= 7 |pages= 5345–50 |year= 2002 |pmid= 11729199 |doi= 10.1074/jbc.M110052200 }}
*{{cite journal | author=Ohtakara K, Nishizawa M, Izawa I, ''et al.'' |title=Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1. |journal=Genes Cells |volume=7 |issue= 11 |pages= 1149-60 |year= 2003 |pmid= 12390249 |doi=  }}
*{{cite journal   |vauthors=Ohtakara K, Nishizawa M, Izawa I, etal |title=Densin-180, a synaptic protein, links to PSD-95 through its direct interaction with MAGUIN-1. |journal=Genes Cells |volume=7 |issue= 11 |pages= 1149–60 |year= 2003 |pmid= 12390249 |doi=10.1046/j.1365-2443.2002.00589.x }}
*{{cite journal | author=Wang L, Xu J, Wu Q, ''et al.'' |title=Cloning and characterization of a novel splice variant of the brain-specific protein densin-180. |journal=Int. J. Mol. Med. |volume=11 |issue= 2 |pages= 257-60 |year= 2003 |pmid= 12525888 |doi=  }}
*{{cite journal   |vauthors=Wang L, Xu J, Wu Q, etal |title=Cloning and characterization of a novel splice variant of the brain-specific protein densin-180. |journal=Int. J. Mol. Med. |volume=11 |issue= 2 |pages= 257–60 |year= 2003 |pmid= 12525888 |doi=  10.3892/ijmm.11.2.257}}
*{{cite journal | author=Ahola H, Heikkilä E, Aström E, ''et al.'' |title=A novel protein, densin, expressed by glomerular podocytes. |journal=J. Am. Soc. Nephrol. |volume=14 |issue= 7 |pages= 1731-7 |year= 2003 |pmid= 12819232 |doi=  }}
*{{cite journal   |vauthors=Ahola H, Heikkilä E, Aström E, etal |title=A novel protein, densin, expressed by glomerular podocytes. |journal=J. Am. Soc. Nephrol. |volume=14 |issue= 7 |pages= 1731–7 |year= 2003 |pmid= 12819232 |doi=10.1097/01.ASN.0000075553.33781.9F }}
*{{cite journal  | author=Goodchild RE, Dauer WT |title=The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. |journal=J. Cell Biol. |volume=168 |issue= 6 |pages= 855-62 |year= 2005 |pmid= 15767459 |doi= 10.1083/jcb.200411026 }}
*{{cite journal  |vauthors=Goodchild RE, Dauer WT |title=The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein. |journal=J. Cell Biol. |volume=168 |issue= 6 |pages= 855–62 |year= 2005 |pmid= 15767459 |doi= 10.1083/jcb.200411026 | pmc=2171781 }}
*{{cite journal | author=Robison AJ, Bass MA, Jiao Y, ''et al.'' |title=Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. |journal=J. Biol. Chem. |volume=280 |issue= 42 |pages= 35329-36 |year= 2005 |pmid= 16120608 |doi= 10.1074/jbc.M502191200 }}
*{{cite journal   |vauthors=Robison AJ, Bass MA, Jiao Y, etal |title=Multivalent interactions of calcium/calmodulin-dependent protein kinase II with the postsynaptic density proteins NR2B, densin-180, and alpha-actinin-2. |journal=J. Biol. Chem. |volume=280 |issue= 42 |pages= 35329–36 |year= 2005 |pmid= 16120608 |doi= 10.1074/jbc.M502191200 }}
*{{cite journal | author=Gregory SG, Barlow KF, McLay KE, ''et al.'' |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315-21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
*{{cite journal   |vauthors=Gregory SG, Barlow KF, McLay KE, etal |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
*{{cite journal | author=Rinta-Valkama J, Aaltonen P, Lassila M, ''et al.'' |title=Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes. |journal=Diabetes Metab. Res. Rev. |volume=23 |issue= 2 |pages= 119-26 |year= 2007 |pmid= 16741999 |doi= 10.1002/dmrr.655 }}
*{{cite journal   |vauthors=Rinta-Valkama J, Aaltonen P, Lassila M, etal |title=Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes. |journal=Diabetes Metab. Res. Rev. |volume=23 |issue= 2 |pages= 119–26 |year= 2007 |pmid= 16741999 |doi= 10.1002/dmrr.655 }}
*{{cite journal  | author=Lassila M, Juhila J, Heikkilä E, Holthöfer H |title=Densin is a novel cell membrane protein of Sertoli cells in the testis. |journal=Mol. Reprod. Dev. |volume=74 |issue= 5 |pages= 641-5 |year= 2007 |pmid= 17039495 |doi= 10.1002/mrd.20659 }}
*{{cite journal  |vauthors=Lassila M, Juhila J, Heikkilä E, Holthöfer H |title=Densin is a novel cell membrane protein of Sertoli cells in the testis. |journal=Mol. Reprod. Dev. |volume=74 |issue= 5 |pages= 641–5 |year= 2007 |pmid= 17039495 |doi= 10.1002/mrd.20659 }}
*{{cite journal | author=Ewing RM, Chu P, Elisma F, ''et al.'' |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  |pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134 }}
*{{cite journal   |vauthors=Ewing RM, Chu P, Elisma F, etal |title=Large-scale mapping of human protein-protein interactions by mass spectrometry. |journal=Mol. Syst. Biol. |volume=3 |issue=  1|pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134 | pmc=1847948 }}
*{{cite journal | author=Heikkilä E, Ristola M, Endlich K, ''et al.'' |title=Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions. |journal=Mol. Cell. Biochem. |volume=305 |issue= 1-2 |pages= 9-18 |year= 2007 |pmid= 17581699 |doi= 10.1007/s11010-007-9522-6 }}
*{{cite journal   |vauthors=Heikkilä E, Ristola M, Endlich K, etal |title=Densin and beta-catenin form a complex and co-localize in cultured podocyte cell junctions. |journal=Mol. Cell. Biochem. |volume=305 |issue= 1–2 |pages= 9–18 |year= 2007 |pmid= 17581699 |doi= 10.1007/s11010-007-9522-6 }}
}}
}}
{{refend}}
{{refend}}


{{protein-stub}}
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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/
 
[[Category:LRR proteins]]

Revision as of 22:13, 31 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

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

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 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. ↑ "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


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/

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