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

LRRIQ3
Identifiers
AliasesLRRIQ3, LRRC44, leucine-rich repeats and IQ motif containing 3, leucine rich repeats and IQ motif containing 3
External IDsOMIM: 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 MbChr 3: 154.8 – 154.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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[21] 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.[24]

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 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 (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]

References
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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