LRRN3
Encyclopedia
Leucine-rich repeat neuronal protein 3, also known as neuronal leucine-rich repeat protein 3 (NLRR-3), is a protein
that in humans is encoded by the LRRN3 gene
.
produces five different mRNAs that appear to differ by truncation of the 3' end. There are only three main transcript variants that actually encode for the LRRN3 protein, with the longest transcript variant being 3744 base pairs in length. All three of these transcript variants have differing lengths and number of exon
s, but they all have the exon that includes the entire coding sequence for the LRRN3 protein. There are also two paralogs to the LRRN3 gene. These include the LRRN1
and LRRN2
genes, both of which have the same leucine-rich repeats that are characteristic to this family of genes.
The LRRN3 protein contains 12 leucine-rich repeats, along with an LRRNT and an LRR_RI domain. Leucine-rich repeat
s are unusually rich in the hydrophobic amino acid leucine
. They are common in protein-protein interaction motifs and are typically 20-29 amino acids in length. All major classes of LRRs are known to have a curved horseshoe structure with a parallel beta sheet
on the concave side and mostly helical elements on the convex side. The LRRN3 protein also has an immunoglobulin domain, a fibronectin
type III domain, and a transmembrane region toward the end of the protein. The composition of this protein is shown below.
species. A multiple sequence alignment
has shown this very high conservation of the LRRN3 gene among many different species. All 12 of the leucine-rich repeats, along with the LRRNT and the LRR_RI regions, are highly conserved in all vertebrates for which orthologs of this protein have been obtained. The Ig and FN3 domains also show high conservation in all of the orthologous sequences for mammals and birds, but are not as highly conserved for the rest of the homologous sequences. The high conservation of the leucine-rich repeats, the Ig domain, and the FN3 domain show that these regions must be of importance to the functionality of the LRRN3 gene.
data has shown that the LRRN3 gene is expressed at very high levels in humans, about 2.3 times the average gene. It is most highly expressed in brain
, heart
, and testes tissues. It is also slightly expressed in kidney, muscle, pharynx, placental, and thymus tissue. The highest expression of the LRRN3 gene for the developmental stages is the fetal stage, but it is also expressed in the infant, juvenile, and adult stages, as can be seen in the EST profile.
The expression data for the LRRN3 gene shows that it has its highest expression in the brain. Overall, the LRRN3 gene seems to have high to moderate expression throughout the majority of brain tissue. The highest expression being found in the cerebral cortex
, the hippocampal formation, the cerebellar cortex, and the paraflocculus. All of these regions play a role in some key cognitive function, involving the processing of language and sensory stimuli, memory, and oculomotor behavior. The high expression of the LRRN3 gene in these regions of the brain could show that the LRRN3 gene has some importance in these cognitive function.
Comparison of the LRRN3 protein with the chain A of the crystal structure of the LINGO1
ectodomain
shows that the LRRN3 protein takes on the characteristic horseshoe shape of most leucine-rich repeat proteins. The LINGO1 ectodomain also has a very long stretch of leucine-rich repeats which is the region that has the best alignment with the LRRN3 protein. This similar region shows that the LRRN3 protein has a structure that includes mostly beta-strands that are connected by loops, with a few alpha helices throughout.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the LRRN3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Gene
The LRRN3 is located on human chromosome 7, at 7q31.1. It contains 6 distinct gt-ag introns, and transcriptionTranscription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
produces five different mRNAs that appear to differ by truncation of the 3' end. There are only three main transcript variants that actually encode for the LRRN3 protein, with the longest transcript variant being 3744 base pairs in length. All three of these transcript variants have differing lengths and number of exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
s, but they all have the exon that includes the entire coding sequence for the LRRN3 protein. There are also two paralogs to the LRRN3 gene. These include the LRRN1
LRRN1
Leucine-rich repeat neuronal protein 1 is a protein that in humans is encoded by the LRRN1 gene.-Further reading:...
and LRRN2
LRRN2
Leucine-rich repeat neuronal protein 2 is a protein that in humans is encoded by the LRRN2 gene.-Further reading:...
genes, both of which have the same leucine-rich repeats that are characteristic to this family of genes.
Protein
The LRRN3 protein is 708 amino acids in length. The molecular weight of this protein is 79,424 Daltons, with an isoelectric point of 8.02. It is known to be a single-pass type I membrane protein because it spans the membrane once, with its N-terminus on the extracellular side of the membrane, and its signal sequence is removed.The LRRN3 protein contains 12 leucine-rich repeats, along with an LRRNT and an LRR_RI domain. Leucine-rich repeat
Leucine-rich repeat
A leucine-rich repeat is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine...
s are unusually rich in the hydrophobic amino acid leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
. They are common in protein-protein interaction motifs and are typically 20-29 amino acids in length. All major classes of LRRs are known to have a curved horseshoe structure with a parallel beta sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...
on the concave side and mostly helical elements on the convex side. The LRRN3 protein also has an immunoglobulin domain, a fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
type III domain, and a transmembrane region toward the end of the protein. The composition of this protein is shown below.
Gene Conservation
The LRRN3 gene has been shown to be extremely highly conserved. There are 21 orthologs and homologs for this gene going back to zebra fish. This gene has not been found in any invertebrates or plantPlant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...
species. A multiple sequence alignment
Multiple sequence alignment
A multiple sequence alignment is a sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. In many cases, the input set of query sequences are assumed to have an evolutionary relationship by which they share a lineage and are descended from a common ancestor...
has shown this very high conservation of the LRRN3 gene among many different species. All 12 of the leucine-rich repeats, along with the LRRNT and the LRR_RI regions, are highly conserved in all vertebrates for which orthologs of this protein have been obtained. The Ig and FN3 domains also show high conservation in all of the orthologous sequences for mammals and birds, but are not as highly conserved for the rest of the homologous sequences. The high conservation of the leucine-rich repeats, the Ig domain, and the FN3 domain show that these regions must be of importance to the functionality of the LRRN3 gene.
Gene Expression
Gene ExpressionGene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
data has shown that the LRRN3 gene is expressed at very high levels in humans, about 2.3 times the average gene. It is most highly expressed in brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, and testes tissues. It is also slightly expressed in kidney, muscle, pharynx, placental, and thymus tissue. The highest expression of the LRRN3 gene for the developmental stages is the fetal stage, but it is also expressed in the infant, juvenile, and adult stages, as can be seen in the EST profile.
The expression data for the LRRN3 gene shows that it has its highest expression in the brain. Overall, the LRRN3 gene seems to have high to moderate expression throughout the majority of brain tissue. The highest expression being found in the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, the hippocampal formation, the cerebellar cortex, and the paraflocculus. All of these regions play a role in some key cognitive function, involving the processing of language and sensory stimuli, memory, and oculomotor behavior. The high expression of the LRRN3 gene in these regions of the brain could show that the LRRN3 gene has some importance in these cognitive function.
Structure
The characteristic shape of leucine-rich repeat proteins is an arc or horseshoe shape. This horseshoe shape of the protein is created by a parallel beta sheet on the concave side and mostly helical elements on the convex side. Eleven residue segments of the LRRs, corresponding to the beta-strand and adjacent loop regions are conserved in LRR proteins, whereas the remaining parts of the repeats may be different. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structures of some LRR protein-ligand complexes show that the concave surfact of the LRR domain is ideal for interaction with alpha-helix, thus supporting the conclusions that the elongated and curved LRR structure provides a framework for achieving diverse protein-protein interactions.Comparison of the LRRN3 protein with the chain A of the crystal structure of the LINGO1
LINGO1
Leucine rich repeat and Ig domain containing 1 also known as LINGO-1 is a protein which in humans is encoded by the LINGO1 gene.- Structure :...
ectodomain
Ectodomain
An ectodomain is the domain of a membrane protein that extends into the extracellular space . Ectodomains are usually the part of a protein that initiate contact with surface which leads to signal transduction. In SARS-CoV the ectodomain of the spike protein is responsible for attachment to and...
shows that the LRRN3 protein takes on the characteristic horseshoe shape of most leucine-rich repeat proteins. The LINGO1 ectodomain also has a very long stretch of leucine-rich repeats which is the region that has the best alignment with the LRRN3 protein. This similar region shows that the LRRN3 protein has a structure that includes mostly beta-strands that are connected by loops, with a few alpha helices throughout.