LRRC74A

Last updated
LRRC74A
Identifiers
Aliases LRRC74A , C14orf166B, LRRC74, leucine rich repeat containing 74A
External IDs MGI: 3646959 HomoloGene: 19331 GeneCards: LRRC74A
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_194287
NM_001385106
NM_001385107
NM_001385108

NM_001195767

RefSeq (protein)

NP_919263

NP_001182696

Location (UCSC) Chr 14: 76.83 – 76.87 Mb Chr 12: 86.78 – 86.81 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Leucine-rich repeat-containing protein 74A (LRRC74A), is a protein encoded by the LRRC74A gene. The protein LRRC74A (aliases C14orf166B, 14q24.3) is localized in the cytoplasm. It has a calculated molecular weight of approximately 55 kDa. [5] The LRRC74A protein is nominally expressed in the testis, salivary gland, and pancreas. [6]

Contents

Gene

The LRRC74A gene, also known as C14orf166B, is located on the positive-sense strand of locus 14q24.3. The full unspliced gene contains 17 exons. [7] LRRC74A spans from 76,826,408 to 76,870,304 for a total length of 43.9 kpb. [8]


Transcripts

LRRC74A has four transcript variants. The most abundant variant is LRRC74A transcript variant 1, which is 1710 nucleotides in length. [7]

LRRC74A transcript variants
Accession numberTranscript lengthNumber of exonsProtein lengthIsoform
NM_194287.31710144881
NM_001322426.2186154712
NM_001105519.371842013
NM_001105519.371842014

Protein

The LRRC74A protein is 488 amino acids in length with a predicted molecular weight of 55 kDA and an isoelectric point of 5.22. [9] It has higher than normal levels of methionine and asparagine. [10]

Domains and structure

The LRRC74A protein contains eight leucine-rich repeat domains in its sequence. [11] LRRC74A isoform 1 secondary structure is made up of alternating alpha helices and beta sheets. [12] Tertiary structure predictions show a horseshoe-shaped protein with high similarity to ribonuclease inhibitor [13]

LRRC74A Tertiary Structure prediction by I-TASSER Lrrc74aITASSER.gif
LRRC74A Tertiary Structure prediction by I-TASSER

[14]

Isoforms

LRRC74A has four splice isoforms. The most abundant isoform is LRRC74A protein isoform 1 which is 488 amino acids in length. [7]

LRRC74A protein isoforms
NameTranscript variantPeptide lengthDomains present
Isoform 11488 aa8 LRR domains
Isoform 22471 aa6 LRR domains
Isoform 33464 aa6 LRR domains
Isoform 44427 aa7 LRR domains

Regulation

Expression pattern

LRRC74A has overall low levels of expression compared to other proteins but within the tissues it is expressed in, it appears most prominently in the testes, salivary gland, and pancreas. [7] Within the cell, LRRC74A is localized to the cytosol. [15]

Transcript level regulation

Predicted 5' UTR folding structure of LRRC74A Lrrc74a5UTR.png
Predicted 5' UTR folding structure of LRRC74A

The 5' UTR of LRRC74A transcript variant 1 is 91 bp in length. [16] Analysis of potential folding structures identifies two possible stemloop structures. [17]

Predicted folding structure of the 3' UTR of LRRC74A Lrrc74a3utr.png
Predicted folding structure of the 3' UTR of LRRC74A

The 3' UTR is 158 bp in length and contains one polyadenylation signal. [16] It contains four predicted stemloop structures, with three loops closer to the 5' end of the UTR and one loop closer to the 3' end of the UTR.

Homology and evolution

Paralogs

The human LRRC74A gene has one paralog called LRRC74B. It is located at 22q11.21 [18]

Orthologs

LRRC74A has orthologs in species as distant as tunicates. Mammalian orthologs are moderately similar to human LRRC74A, with percent similarity greater than 80%. Orthologs in reptiles, birds and amphibians range from 65% to 40%. In fish and invertebrates, identity ranges from 40% to 20%. No orthologs were found in fungi, bacteria or plants.

Unrooted phylogenetic tree depicting the evolution of LRRC74A Lrrc74atree.png
Unrooted phylogenetic tree depicting the evolution of LRRC74A
Genus speciesCommon nameTaxonomic orderEstimated date of divergence (MYA)Accession numberSequence length (aa)Sequence identity (%)Sequence similarity (%)
Mammalia Homo sapiens Human Primates 0NP_919263.2488100100
Mus musculus Mouse Rodentia 87NP_001182696.148765.777.4
Gulo gulo Wolverine Carnivora 94KAI5767761.148874.686.3
Ursus maritimus Polar bear Carnivora 94XP_040497188.154860.670.6
Balaenoptera musculus Blue whale Artiodactyla 94XP_036697954.148268.980.1
Gracilinanus agilia Agile gracile opossum Marsupialia 106XP_044518037.146852.571.5
Aves Gallus gallus Chicken Galliformes 319XP_040528719.147642.860.9
Melopsittacus undulatus Budgerigar Psittaciformes 319XP_005149032.149446.464.6
Aquila chrysaetos Golden eagle Accipitriformes 319XP_029863093.14924662.1
Phaethon lepturus White-tailed tropicbird Phaethontiformes 319XP_010285698.147844.361.5
Reptilia Pelodiscus sinensis Chinese softshell turtle Testudines 319XP_025037771.148649.568
Pogona vitticeps Central bearded dragon Squamata 319XP_020649579.14834864.5
Notechis scutatus Tiger snake Squamata 319XP_026520078.149145.261.9
Amphibia Geotrypetes seraphini Gaboon caecilian Gymnophiona 353XP_033809167.154035.650.3
Bufo bufo Common toad Anura 353XP_040268304.153634.551.4
Fish Latimeria chalumnae West Indian Ocean coelacanth Latimeriidae 414XP_014341482.145647.566.2
Lepisosteus oculatus Spotted gar Lepisosteiformes 431XP_015205589.14504262.5
Salmo salar Atlantic salmon Salmoniformes 431XP_045549789.164832.345.1
Carcharodon carcharias Great white shark Chondrichthyes 464XP_041070161.17272437.4
Petromyzon marinus Sea lamprey Agnatha 510XP_032820627.151032.149.6
Invertebrata Ciona intestinalis Vase tunicate Enterogona 603XP_002120047.166124.540.6

Evolution

Lrrc74aevorate.png

The LRRC74A gene appears most distantly in tunicates which diverged from humans approximately 603 million years ago. [19] Orthologs of LRRC74A and LRRC74B also occur in tunicates. LRRC74A evolves at a moderately fast rate; a 1% change in amino acid sequence required around 10 million years. Based on sequence similarity of orthologs, LRRC74A evolves at a rate in the middle of cytochrome c and fibrinogen alpha.


Clinical significance

Disease association

COVID-19

A GWAS evaluating genetic mutations and clinical outcomes of patients who contracted COVID-19 found that a mutation in the LRRC74A gene was associated with higher mortality rates in infected patients, with the mutation being 7.4% more prevalent in deceased patients than living patients. [20]

Related Research Articles

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<span class="mw-page-title-main">NOXRED1</span> Human gene

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References

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