Leucine Rich Repeating Containing 73 (LRRC73) is a protein-coding gene, which, in Homo sapiens, is encoded by the LRRC73 gene..
Aliases: C6orf154, Chromosome 6 Open Reading Frame 154
Bioinformation: Accession number: NM_001012974.4 (mRNA), NP_001012992 (Protein); Genomic location: NC_000006.12: 43506968-43510346 (-) Gene In the human genome, LRRC73 is located on chromosome 6, specifically at 6p21.1, on the negative-sense strand. The LRRC73 sequence spans 1,782 base pairs, consisting of 6 exons. The LRRC73 gene has one protein-coding sequence.
mRNA LRRC73 mRNA encodes three protein isoforms. Two of which are encoded from complete transcripts, while the remaining isoform is truncated and only carboxyl (COOH) terminus complete. +Alternate IsoformsIsoform VariantAccession #Length (nt)Exons9Protein IsoformAccession #Length (aa)Variant 1NM_001012974.41,7821,2,3,4,5,61NP_001012992.1316Variant 2NM_001271882.21,0901,2,3,4,5,62NP_001258811.1193
Protein LRRC73 protein consists of 2 isoforms. Isoform one stands as the longer isoform composed of 316 amino acids. Isoform two stands as the smaller isoform and is lacking part of the 5’ coding region and has a shorter N-terminus with 193 amino acids. LRRC73 is a leucine-rich repeat-containing protein mostly involved in mediating protein-protein interactions.
Composition
LRRC73 Isoform 1 has a theoretical molecular weight of 33 KDa and theoretical isoelectric point of 4.73. Amino acid composition analysis indicates the human LRRC73 protein to have lower-than-normal levels of phenylalanine, lysine, tyrosine, and higher-than-normal levels of leucine. LRRC73 exhibited a highly hydrophobic core (LVIFM 28%-32%), a localized negative charge cluster from residues 245 to 274 which consists of 11 acidic residues within a 30-residue window, along with an absence of transmembrane regions.
Motifs and modification sites Motifscan predicted seven LRRC73 protein motifs through NCBI-CDD. Most of these motifs correspond to leucine-rich repeat (LRR) families. The most significant matches, based on E-values, include the RAN GTPase-activating protein, as well as, LRR_RI and generic LRR motifs from residues spanning from 5-255.
No transmembrane helices, catalytic signatures, linear motifs, or phosphorylation were found. The remaining three motifs for LRRC73 consist of E-values above significant thresholds and were therefore not further interpreted. +Motifs for human protein LRRC73 isoform 1NCBI-CDDPositionDescriptionE-value44407228..254COG5238, RNA1, Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis].7.00E-202380645..255cd00116, LRR_RI, Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily.1.00E-1644391449..243COG4886, LRR, Leucine-rich repeat (LRR) protein [Transcription].2.00E-0627538050..243sd00033, LRR_RI, leucine-rich repeats, ribonuclease inhibitor (RI)-like subfamily.1.00E-04236849158..223PRK11109, PRK11109, fused PTS fructose transporter subunit IIA/HPr protein.0.14215382188..227PLN02712, PLN02712, arogenate dehydrogenase.0.57275378139..243sd00031, LRR_1, leucine-rich repeats.0.86
Protein interactions LRRC73 is situated in a genomic locus alongslide yip1 domain family member 3 (YIPF3) upstream and tight junction associated protein 1 (TJAP1) downstream.
Human proteins Source: ANKRD13D (Ankyrin repeat domain-containing protein 13D) TEPSIN (AP-4 complex accessory subunit Tepsin) VSIG10 (V-set and immunoglobulin domain containing 10) DOCK3 (Dedicator of cytokinesis protein 3) TBC1D5 (TBC1 domain family member 5) NPRL2 (GATOR complex protein NPRL2) POLR3H (DNA-directed RNA polymerase III subunit RPC8) OR10A4 (Olfactory receptor 10A4) VPS26B (Vacuolar protein sorting-associated protein 26B) VPS35 (Vacuolar protein sorting-associated protein 35)
Conceptual translation Sources:
Tissue localization and expression
Localization LRRC73 is predicted to be located intracellularly, the protein is sublocalized to the cytosol and nuclear bodies. Expression patterns include ciliary rootlets of glandular cells within the fallopian tube, respiratory epithelia, and the nuclei of cells in seminiferous ducts.
Expression LRRC73 showed little to no expression across most human tissues in the body. The highest expression levels have been observed in the adrenal gland, brain, and testis. RNA sequencing of total RNA from 20 human tissues showed mean expression of approximately 0.401 RPKM in the adrenal gland and 0.662 RPKM in the brain. HPA RNA-seq normal tissues showed mean expression levels of 12.679 ± 5.142 RPKM in the testis.
Protein abundance data from PaxDB indicated low protein expression of LRRC73 in testis, with an abundance of approximately 0.33 parts per million (ppm), ranking 10199 out of 15744.
Homology
Orthologs +LRRC73 Orthologs and Related PropertiesGenus and SpeciesCommon NameTaxonomic GroupDate of Divergence from the Human Lineage (MYA)Accession NumberSequence Length (aa)Sequence Identity to Human ProteinSequence Similarity to Human ProteinMammaliaHomo sapiensHumansPrimates0 MYANP_001012992.1316100%100%Mus musculusHouse MouseRodentia87 MYANP_001104612.131698.73%99.10%Balaenoptera acutorostrataMinke whaleArtiodactyla94 MYAXP_007193842.131699.68%99.70%Chrysochloris asiaticaCape golden moleAfrosoricida99 MYAXP_006860555.131697.15%99.10%BirdsOenanthe melanoleucaEastern black-eared wheatearPasseriformes319 MYAXP_056342448.131385.88%80.60%Struthio camelusAfrican ostrichStruthioniformes319 MYAXP_009684978.230380.06%88.00%Numenius arquataEurasian curlewCharadriiformes319 MYAXP_074025247.131879.13%88.20%Pezoporus wallicusGround ParrotPsittaciformes319 MYAXP_057271434.130379.11%88.30%ReptiliaEmydura macquarii macquariiMurray River turtleTestudines319 MYAXP_067420797.130379.43%87.00%Gopherus flavomarginatusMexican gopher tortoiseTestudines319 MYAXP_050807631.130379.43%86.80%Carettochelys insculptaPitted-shelled turtleTestudines319 MYAXP_074845841.130379.11%87.70%Pelodiscus sinensisChinese soft-shelled turtleTestudines319 MYAXP_075781124.130878.50%86.90%AmphibiaEleutherodactylus coquiCommon coquíAnura352 MYAXP_066450569.130469.94%81.00%Bufo bufoCommon toadAnura352 MYAXP_040283598.130469.06%80.00%Pseudophryne corroboreeCorroboree frogAnura352 MYAXP_063774856.130268.04%81.30%Pelobates fuscusCommon spadefoot toadAnura352 MYAXP_063300254.130267.72%75.43%FishSilurus meridionalisChinese large-mouth catfishSiluriformes429 MYAXP_046731911.132672.78%81.80%Brienomyrus brachyistiusBaby WhaleOsteoglossiformes429 MYAXP_048865752.132869.44%79.50%Cartilaginous fishHemitrygon akajeiRed stingrayMyliobatiformes462 MYAXP_072912304.130573.10%84.20%Callorhinchus miliiElephant sharkChondrichthyes462 MYAXP_007896433.126361.08%69.30% Twenty orthologs of the LRRC73 protein were identified across various taxa, including mammals (97%-99%), birds (79%-85%), reptiles and amphibians (67%-79%), fish (69%-72%), and cartilaginous fish (61%-73%). Sequence identity data were derived using of NCBI’s BLAST, EMBOSS NEEDLE, and Timetree,,.
LRRC73 is seen to have no paralogs
Evolutionary divergence The comparative LRRC73 evolutionary scatter plot illustrates the relationship between corrected percent divergence (m) and estimated date of divergence (million years ago) between the LRRC73 protein, fibrinogen alpha, and cytochrome c. Evolutionary rate comparisons place LRRC73 at an intermediate pace in comparison to the highly conserved cytochrome c and rapidly evolving fibrinogen alpha chain.
Evolution
LRRC73 belongs to the leucine rich repeat containing (LRR) family, whose members share the conserved LRR domains. Orthologs of LRRC73 have been identified in vertebrate species and not in any invertebrates, with the first appearance found approximately between 400 and 500 million years ago in cartilaginous fishes.
Clinical significance Genome-wide association studies (GWAS) have identified 95% credible sets that prioritize LRRC73 as a likely gene associated with placenta praevia. According to GeneCards, LRRC73 has also been reported to show an association with human cytomegalovirus (HCMV) infection, however, the clinical significance of this association has not been established.
References