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. The LRRC74A protein is nominally expressed in the testis, salivary gland, and pancreas.
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. LRRC74A spans from 76,826,408 to 76,870,304 for a total length of 43.9 kpb.
Transcripts LRRC74A has four transcript variants. The most abundant variant is LRRC74A transcript variant 1, which is 1710 nucleotides in length.
+LRRC74A transcript variantsAccession numberTranscript lengthNumber of exonsProtein lengthIsoformNM_194287.31710144881NM_001322426.2186154712NM_001105519.371842013NM_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. It has higher than normal levels of methionine and asparagine.
Domains and structure The LRRC74A protein contains eight leucine-rich repeat domains in its sequence. LRRC74A isoform 1 secondary structure is made up of alternating alpha helices and beta sheets. Tertiary structure predictions show a horseshoe-shaped protein with high similarity to ribonuclease inhibitor
Isoforms LRRC74A has four splice isoforms. The most abundant isoform is LRRC74A protein isoform 1 which is 488 amino acids in length. +LRRC74A protein isoformsNameTranscript variantPeptide lengthDomains presentIsoform 11488 aa8 LRR domainsIsoform 22471 aa6 LRR domainsIsoform 33464 aa6 LRR domainsIsoform 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. Within the cell, LRRC74A is localized to the cytosol.
Transcript level regulation
The 5' UTR of LRRC74A transcript variant 1 is 91 bp in length. Analysis of potential folding structures identifies two possible stemloop structures.
The 3' UTR is 158 bp in length and contains one polyadenylation signal. 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
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.
Genus species Common name Taxonomic order Estimated date of divergence (MYA) Accession number Sequence length (aa) Sequence identity (%) Sequence similarity (%)MammaliaHomo sapiensHumanPrimates0NP_919263.2488100100Mus musculusMouseRodentia87NP_001182696.148765.777.4Gulo guloWolverineCarnivora94KAI5767761.148874.686.3Ursus maritimusPolar bearCarnivora94XP_040497188.154860.670.6Balaenoptera musculusBlue whaleArtiodactyla94XP_036697954.148268.980.1Gracilinanus agiliaAgile gracile opossumMarsupialia106XP_044518037.146852.571.5AvesGallus gallusChickenGalliformes319XP_040528719.147642.860.9Melopsittacus undulatusBudgerigarPsittaciformes319XP_005149032.149446.464.6Aquila chrysaetosGolden eagleAccipitriformes319XP_029863093.14924662.1Phaethon lepturusWhite-tailed tropicbirdPhaethontiformes319XP_010285698.147844.361.5ReptiliaPelodiscus sinensisChinese softshell turtleTestudines319XP_025037771.148649.568Pogona vitticepsCentral bearded dragonSquamata319XP_020649579.14834864.5Notechis scutatusTiger snakeSquamata319XP_026520078.149145.261.9AmphibiaGeotrypetes seraphiniGaboon caecilianGymnophiona353XP_033809167.154035.650.3Bufo bufoCommon toadAnura353XP_040268304.153634.551.4FishLatimeria chalumnaeWest Indian Ocean coelacanthLatimeriidae414XP_014341482.145647.566.2Lepisosteus oculatusSpotted garLepisosteiformes431XP_015205589.14504262.5Salmo salarAtlantic salmonSalmoniformes431XP_045549789.164832.345.1Carcharodon carchariasGreat white sharkChondrichthyes464XP_041070161.17272437.4Petromyzon marinusSea lampreyAgnatha510XP_032820627.151032.149.6InvertebrataCiona intestinalisVase tunicateEnterogona603XP_002120047.166124.540.6
Evolution
The LRRC74A gene appears most distantly in tunicates which diverged from humans approximately 603 million years ago. 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.
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