LRRIQ3 (Leucine-rich repeats and IQ motif containing 3), which is also known as LRRC44, 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 ...

that in humans is encoded by the LRRIQ3

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 ...

. It is predominantly expressed in the testes, and is linked to a number of diseases.

Gene

Locus

LRRIQ3 is found on the minus strand of the end of the short arm of human

chromosome 1 Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 249 million nucleotide base pairs, which a ...

at 1p31.1.

Overall Structure

There are a total of 7

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

s in the putative sequence of LRRIQ3.

mRNA

Expression

LRRIQ3 is expressed as 2 primary

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

, which produce proteins of length 624 amino acids and 464 amino acids respectively. It is expressed at low levels in human and brown rat tissues, with highest expression levels in

testes A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone. The ...

tissue. There are relatively high expression levels in

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s, the

epididymis The epididymis (; : epididymides or ) is an elongated tubular genital organ attached to the posterior side of each one of the two male reproductive glands, the testicles. It is a single, narrow, tightly coiled tube in adult humans, in length; ...

, the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

, and a number of glands.

Protein

General Characteristics and Compositional Features

Human protein LRRIQ3 Isoform 1 consists of 624 amino acids, and has a molecular weight of 73.7 kDa. The isoelectric point of LRRIQ3 is 9.73, which suggests that LRRIQ3 is

basic Basic or BASIC may refer to: Science and technology * BASIC, a computer programming language * Basic (chemistry), having the properties of a base * Basic access authentication, in HTTP Entertainment * Basic (film), ''Basic'' (film), a 2003 film ...

at normal physiological pH (~7.4). Additionally, there is strong evidence that human LRRIQ3 localizes to the plasma membrane from antibody staining. LRRIQ3 is rich in

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

residues, with a total of 82 lysines. It is also slightly low on

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

Domains and Motifs

In total, there are 4 conserved domains within LRRIQ3: 3

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 and 1 IQ calmodulin-binding motif. Leucine-rich repeats are typically involved in protein-protein interactions, and form a characteristic α/β horseshoe fold. An IQ motif provides a binding site for calmodulin (CaM) or CaM-like proteins.

Secondary and Tertiary Structure

LRRIQ3 is predicted to be mostly

alpha-helical An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...

structure A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

, including a long alpha-helical

C-terminal domain 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 ...

. It is also predicted to function as a

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

Post-translational Modifications

LRRIQ3 is predicted to undergo many

post-translational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...

s. These include O-GlcNAcylation,

SUMOylation In molecular biology, SUMO (Small Ubiquitin-like Modifier) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function. This process is called SUMOylation (pronounced ...

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

ation, and

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 ...

. LRRIQ3 is predicted to have 4 well conserved SUMOylation sites and 1 well conserved ubiquitination site. A representation of these post-translational modifications is shown in the figure below. LRRIQ3_Domains_and_Motifs

Protein Interactions

There is evidence that LRRIQ3 interacts with a number of proteins from two-hybrid assays and

affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

. The proteins LRRIQ3 interact with include

LYN Lyn or LYN may refer to: People * Lyn (singer), South Korean singer * Lyn (gamer), South Korean ''Warcraft III'' player * Lyn (given name) * Lyn (surname) In science and technology * Lynx (constellation), standard abbreviation * Lyn (locomotive ...

NCK2 Cytoplasmic protein NCK2 (also known as NCK-beta and Grb4) is a protein that in humans is encoded by the ''NCK2'' gene. Function NCK belongs to family of adaptor proteins. There are two mammalian NCK genes, NCK1 and NCK2. NCK1 is located in c ...

, GNB4, and

ABL1 Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ''ABL1'' gene (previous symbol ''ABL'') located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammali ...

. These proteins are associated with

cell signalling In biology, cell signaling (cell signalling in British English) is the process by which a cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all cellular life in both prokaryotes and eukary ...

cytoskeletal The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all Cell (biology), cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane ...

reorganization, and

cell differentiation Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...

, as well as others.

Homology and evolution

Paralogs and Orthologs

paralog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

s exists for LRRIQ3 in humans. However, there are a number of

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

, as reported by

BLAST Blast or The Blast may refer to: *Explosion, a rapid increase in volume and release of energy in an extreme manner *Detonation, an exothermic front accelerating through a medium that eventually drives a shock front *A planned explosion in a mine, ...

, some of which are listed below. The number of years since

divergence In vector calculus, divergence is a vector operator that operates on a vector field, producing a scalar field giving the rate that the vector field alters the volume in an infinitesimal neighborhood of each point. (In 2D this "volume" refers to ...

from the human protein, listed in "million of years ago (MYA)" below, were calculated using TimeTree.

Clinical significance

LRRIQ3 is linked to a number of cancers. RNA-seq experiments have shown that LRRIQ3 is severely down-regulated (Log₂-fold changes between -3.4 and -4.2) in a number of disease states, including pancreatic cancer, colorectal cancer, and breast cancer.

References

{{reflist Proteins Genes on human chromosome 1