# LRRIQ3

LRRIQ3 (Leucine-rich repeats and IQ motif containing 3), which is also known as LRRC44, is a protein that in humans is encoded by the LRRIQ3 gene. 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 at 1p31.1.

### Overall Structure

There are a total of 7 exons in the putative sequence of LRRIQ3.

## mRNA
### Expression

LRRIQ3 is expressed as 2 primary isoforms, 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 tissue. There are relatively high expression levels in T cells, the epididymis, the kidney, 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 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 residues, with a total of 82 lysines. It is also slightly low on glycines.

### Domains and Motifs

In total, there are 4 conserved domains within LRRIQ3: 3 leucine-rich repeats 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 in structure, including a long alpha-helical C-terminal domain. It is also predicted to function as a monomer.

### Post-translational Modifications

LRRIQ3 is predicted to undergo many post-translational modifications. These include O-GlcNAcylation, SUMOylation, ubiquitination, and phosphorylation. 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.

### Protein Interactions

There is evidence that LRRIQ3 interacts with a number of proteins from two-hybrid assays and affinity chromatography. The proteins LRRIQ3 interact with include LYN, NCK2, GNB4, and ABL1. These proteins are associated with cell signalling, cytoskeletal reorganization, and cell differentiation, as well as others.

## Homology and evolution
### Paralogs and Orthologs

No paralogs exists for LRRIQ3 in humans. However, there are a number of orthologs, as reported by BLAST, some of which are listed below. The number of years since divergence from the human protein, listed in "million of years ago (MYA)" below, were calculated using TimeTree.
Orthologs to Human LRRIQ3 Protein (NP_001099129.1) :
| Genus and Species | Common Name | Divergence from Human Lineage (MYA) | Accession Number | Sequence length (aa) | Sequence Identity to Human Protein | Sequence Similarity to Human Protein |
| Gorilla gorilla gorilla | Gorilla | 9.06 | XP_004026030.1 | 624 | 97% | 98% |
| Macaca mulatta | Rhesus monkey | 29.44 | XP_001097148.2 | 623 | 93% | 95% |
| Ursus maritimus | Polar bear | 96 | XP_008689049.1 | 625 | 76% | 87% |
| Felis catus | Domestic cat | 96 | XP_003990274.1 | 625 | 74% | 86% |
| Camelus ferus | Bactrian camel | 96 | XP_006178380.1 | 618 | 73% | 84% |
| Oryctolagus cuniculus | European rabbit | 90 | XP_002715603.1 | 622 | 71% | 83% |
| Bison bison bison | American bison | 96 | XP_010847739.1 | 625 | 70% | 82% |
| Trichechus manatus latirostris | Manatee | 105 | XP_004369192.1 | 623 | 70% | 82% |
| Loxodonta africana | African elephant | 105 | XP_003411181.1 | 625 | 68% | 80% |
| Condylura cristata | Star-nosed mole | 96 | XP_004679575.1 | 627 | 67% | 80% |
| Eptesicus fuscus | Big brown bat | 96 | XP_008137759.1 | 621 | 66% | 80% |
| Myotis davidii | Vesper bat | 96 | XP_006775977.1 | 618 | 65% | 79% |
| Rattus norvegicus | Norway rat | 90 | NP_001019478.1 | 633 | 62% | 77% |
| Mus Musculus | House mouse | 90 | NP_083214.2 | 633 | 63% | 76% |
| Sorex araneus | Common shrew | 96 | XP_004603704.1 | 612 | 55% | 73% |
| Chrysemys picta bellii | Painted turtle | 312 | XP_005285573.1 | 624 | 40% | 56% |
| Pogona vitticeps | Bearded dragon | 312 | XP_020650341.1 | 651 | 35% | 54% |
| Apteryx australis mantelli | Brown kiwi | 312 | XP_013800580.1 | 664 | 35% | 54% |
| Struthio camelus australis | Southern Ostrich | 312 | XP_009685099.1 | 628 | 34% | 51% |

## Clinical significance

LRRIQ3 is linked to a number of cancers. RNA-seq experiments have shown that LRRIQ3 is severely down-regulated (Log$_2$-fold changes between -3.4 and -4.2) in a number of disease states, including pancreatic cancer, colorectal cancer, and breast cancer.