LRRIQ3

Last updated
LRRIQ3
Identifiers
Aliases LRRIQ3 , LRRC44, leucine-rich repeats and IQ motif containing 3, leucine rich repeats and IQ motif containing 3
External IDs OMIM: 617957 MGI: 1921685 HomoloGene: 23668 GeneCards: LRRIQ3
Orthologs
SpeciesHumanMouse
Entrez

127255

74435

Ensembl

ENSG00000162620

ENSMUSG00000028182

UniProt

A6PVS8
H0Y5F9

Q14DL3

RefSeq (mRNA)

NM_001105659
NM_145258
NM_001322315

NM_028938

RefSeq (protein)

NP_001099129
NP_001309244

NP_083214

Location (UCSC) Chr 1: 74.03 – 74.2 Mb Chr 3: 154.8 – 154.9 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] It is predominantly expressed in the testes, and is linked to a number of diseases. [6]

Contents

Gene

Locus

LRRIQ3 is found on the minus strand of the end of the short arm of human chromosome 1 at 1p31.1. [7]

Overall Structure

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

mRNA

Expression

LRRIQ3 is expressed as 2 primary isoforms, which produce proteins of length 624 amino acids and 464 amino acids respectively. [7] It is expressed at low levels in human and brown rat tissues, [8] [9] 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. [10]

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). [11] Additionally, there is strong evidence that human LRRIQ3 localizes to the plasma membrane from antibody staining. [12] LRRIQ3 is rich in lysine residues, with a total of 82 lysines. It is also slightly low on glycines. [13]

Domains and Motifs

In total, there are 4 conserved domains within LRRIQ3: 3 leucine-rich repeats and 1 IQ calmodulin-binding motif. [13] Leucine-rich repeats are typically involved in protein-protein interactions, and form a characteristic α/β horseshoe fold. [14] [15] An IQ motif provides a binding site for calmodulin (CaM) or CaM-like proteins. [16]

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. [17] [18] [19] [20]

The best model generated by I-TASSER for LRRIQ3. The 3 leucine-rich repeats are shown in red, salmon, and magenta respectively. The IQ calmodulin-binding domain is shown in green. LRRIQ3 I-TASSER Model.png
The best model generated by I-TASSER for LRRIQ3. The 3 leucine-rich repeats are shown in red, salmon, and magenta respectively. The IQ calmodulin-binding domain is shown in green.

Post-translational Modifications

LRRIQ3 is predicted to undergo many post-translational modifications. These include O-GlcNAcylation, SUMOylation, ubiquitination, and phosphorylation. [22] [23] LRRIQ3 is predicted to have 4 well conserved SUMOylation sites and 1 well conserved ubiquitination site. [22] A representation of these post-translational modifications is shown in the figure below.

A representation of the domains, motif, and post-translational modification sites of LRRIQ3, generated using DOG 2.0. LRRIQ3 Domains and Motifs.png
A representation of the domains, motif, and post-translational modification sites of LRRIQ3, generated using DOG 2.0.

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. [25] [26] These proteins are associated with cell signalling, cytoskeletal reorganization, and cell differentiation, as well as others. [27] [28] [29] [30]

Homology and evolution

Paralogs and Orthologs

No paralogs exists for LRRIQ3 in humans. [6] However, there are a number of orthologs, as reported by BLAST, some of which are listed below. [31] The number of years since divergence from the human protein, listed in "million of years ago (MYA)" below, were calculated using TimeTree. [32]

Orthologs to Human LRRIQ3 Protein (NP_001099129.1)
Genus and SpeciesCommon NameDivergence from Human Lineage (MYA)Accession NumberSequence length (aa)Sequence Identity to Human ProteinSequence Similarity to Human Protein
Gorilla gorilla gorillaGorilla9.06XP_004026030.162497%98%
Macaca mulattaRhesus monkey29.44XP_001097148.262393%95%
Ursus maritimusPolar bear96XP_008689049.162576%87%
Felis catusDomestic cat96XP_003990274.162574%86%
Camelus ferusBactrian camel96XP_006178380.161873%84%
Oryctolagus cuniculusEuropean rabbit90XP_002715603.162271%83%
Bison bison bisonAmerican bison96XP_010847739.162570%82%
Trichechus manatus latirostrisManatee105XP_004369192.162370%82%
Loxodonta africanaAfrican elephant105XP_003411181.162568%80%
Condylura cristataStar-nosed mole96XP_004679575.162767%80%
Eptesicus fuscusBig brown bat96XP_008137759.162166%80%
Myotis davidiiVesper bat96XP_006775977.161865%79%
Rattus norvegicusNorway rat90NP_001019478.163362%77%
Mus MusculusHouse mouse90NP_083214.263363%76%
Sorex araneusCommon shrew96XP_004603704.161255%73%
Chrysemys picta belliiPainted turtle312XP_005285573.162440%56%
Pogona vitticepsBearded dragon312XP_020650341.165135%54%
Apteryx australis mantelliBrown kiwi312XP_013800580.166435%54%
Struthio camelus australisSouthern Ostrich312XP_009685099.162834%51%

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. [33] [34] [35]

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References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028182 - Ensembl, May 2017
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  32. ↑ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2018-05-06.
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  34. ↑ github.com/gxa/atlas/graphs/contributors, EMBL-EBI Expression Atlas development team. "Search results < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-04-30.{{cite web}}: |last= has generic name (help)
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