Leucine rich repeat containing 57, also known as LRRC57, is a protein encoded in humans by the LRRC57 gene.
Function The exact function of LRRC57 is not known. It is a member of the leucine-rich repeat family of proteins, which are known to be involved in protein-protein interactions.
Protein sequence As is customary for leucine-rich repeat proteins, the sequence is shown below with the repeats starting on their own lines. The beginning of each repeat is a β-strand, which forms a β-sheet along the concave side of the protein. The convex side of the protein is formed by the latter half of each repeat, and may consist of a variety of structures, including α-helices, 310 helices, β-turns, and even short β-strands.
Note that the 5' and 3' UTR both are rich in leucines, suggesting that they may be degenerate repeats (the overall protein is 19.7% leucine and 7.5% asparagine, both very rich).
The following layout of the LRRC57 amino acid sequence makes it easy to discern the LxxLxLxxNxxL consensus sequence of LRRs.
Homology
LRRC57 is exceedingly well conserved, as shown by the following multiple sequence alignment, prepared using ClustalX2. The cyan and yellow highlights call out regions of high conservation and the repeats.
The following table provides a few details on orthologs of the human version of LRRC57. To save space, not all of these orthologs are included in the above multiple sequence alignment. These orthologs were gathered from BLAT. and BLAST searches
Species Organism common name NCBI accession Sequence identity Sequence similarity Length (AAs) Gene common name Homo sapiensHumanNP_694992100%100%239leucine rich repeat containing 57 Pan troglodytesChimpanzeeXP_51033899%100%165PREDICTED: hypothetical protein Orangutan99%99%238From BLAT – no GenBank record Macaca mulattaRhesus macaqueXP_00110063396%99%143PREDICTED: similar to CG3040-PA Mus musculusHouse mouseNP_07993395%99%239leucine rich repeat containing 57 Rattus norvegicusNorway ratNP_00101235495%99%239leucine rich repeat containing 57 Canis lupus familiarisDogXP_53544394%98%264PREDICTED: similar to CG3040-PA Equus caballusHorseXP_00150329894%97%273PREDICTED: similar to leucine rich repeat containing 57 Bos taurusCattleNP_00102692494%97%239leucine rich repeat containing 57 Monodelphis domesticaOpossumXP_00136268284%94%239PREDICTED: hypothetical protein Ornithorhynchus anatinusPlatypusXP_00152040376%92%99PREDICTED: hypothetical protein Gallus gallusChickenXP_42116085%92%238PREDICTED: hypothetical protein Taeniopygia guttataZebra finchXP_00220036985%92%238PREDICTED: leucine rich repeat containing 57 Xenopus laevisAfrican clawed frogNP_00108520876%88%238hypothetical protein LOC432302 Xenopus (Silurana) tropicalisWestern clawed frogNP_00112019976%87%238hypothetical protein LOC100145243 Danio rerioZebrafishNP_00100262769%83%238leucine rich repeat containing 57 Tetraodon nigroviridisSpotted green pufferfishCAF8964067%83%238unnamed protein product Branchiostoma floridaeFlorida lanceletXP_00220932557%78%237hypothetical protein BRAFLDRAFT_277364 Ciona intestinalis(a sea squirt)XP_00212999250%71%237PREDICTED: similar to Leucine rich repeat containing 57 Strongylocentrotus purpuratusPurple urchinXP_78298657%74%212PREDICTED: hypothetical protein Ixodes scapularisBlack-legged tickEEC1786957%73%237leucine rich domain-containing protein, putative Apis melliferaHoney beeXP_00112181853%72%238PREDICTED: similar to CG3040-PA Nasonia vitripennisJewel waspXP_00160119057%73%238PREDICTED: similar to ENSANGP00000011808 Tribolium castaneumRed flour beetleXP_97348656%70%238PREDICTED: similar to AGAP001491-PA Pediculus humanusBody louseEEB1784452%72%238leucine-rich repeat-containing protein, putative Aedes aegyptiYellow fever mosquitoXP_00165742050%66%239internalin A Culex quinquefasciatusSouthern house mosquitoXP_00186569149%67%238leucine-rich repeat-containing protein 57 Drosophila melanogasterFruit flyNP_57237250%67%238CG3040 Drosophila simulansXP_00210634449%67%238GD16172 Drosophila sechelliaXP_00204319249%67%238GM17488 Drosophila yakubaXP_00210131250%68%238GE17554 Drosophila erectaXP_00197850350%67%238GG17646 Drosophila ananassaeXP_00196415851%68%238GF20868 Drosophila pseudoobscuraXP_00135527149%66%238GA15818 Drosophila persimilisXP_00202529849%66%238GL13411 Drosophila virilisXP_00205696351%68%238GJ16607 Drosophila mojavensisXP_00201040851%68%238GI14698 Drosophila grimshawiXP_00199174552%68%238GH12826 Drosophila willistoniXP_00207164550%67%238GK10093 Anopheles gambiaeXP_32163046%66%238AGAP001491-PA Caenorhabditis elegans(a nematode)NP_74098343%63%485hypothetical protein ZK546.2 Caenorhabditis briggsae(a nematode)XP_00167988141%64%439Hypothetical protein CBG02285
Gene neighborhood
The LRRC57 gene has interesting relationships to its neighbors – HAUS2 upstream and SNAP23 downstream, as shown below for human.
Shown below is the neighborhood for the mouse ortholog. Note that the neighbors are the same, which is true for most vertebrates.
Note the close proximity between LRRC57 and HAUS2/CEP27 (the same gene by different names). In humans, the exons are 50bp apart, whereas in mouse, they overlap, as shown in the closeup, below. This close relationship may partially explain the high conservation of LRRC57, as it would require a mutation to be stable in both genes at the same time.
The relationship to the downstream neighbor, SNAP23 is also interesting. Quoting from the AceView entry: "373 bp of this gene are antisense to spliced gene SNAP23, raising the possibility of regulated alternate expression". Taking the reverse complement of the LRRC57 cDNA and aligning it with the SNAP23 cDNA does show high similarity, as shown in this partial alignment:
Predicted post-translational modifications
The tools on the ExPASy Proteomics site predict the following post-translational modifications:
Tool Predicted Modification Homo sapiens Mus musculus Gallus gallus Drosophila melanogaster YinOYangO-β-GlcNAcS166S166S165T16, T102 NetPhosphosphorylationS145, S149, S169, S199, S201, T27 T234S139, S145, S169, S199, S201, T27, T149, T234S148, S198, S200, T22S46, S69, S200, T179, T193, Y230 SulfinatorsulfationY224, Y227Y224, Y227Y223, Y226(none) SulfoSitesulfationY224Y224Y223Y223 SumoPlotsumoylationK86, K15, and K236(not checked)(not checked)(not checked) TerminatorN-terminusG2G2G2G2
The predicted modifications for Homo sapiens are shown on the following conceptual translation. The cyan highlights are predicted phosphorylation sites and the yellow highlights are as labeled. The red boxes show predictions that are conserved across all four organisms.
The sites for all four organisms are highlighted on the following multiple sequence alignment.
Note that the phosphorylation at S201 and the sulfation at Y224 are the only well conserved predictions across all four organisms.
Structure
The structure of LRRC57 is not known. However, a protein BLAST search against the protein databank returns a similar protein (), with an E-value of 3E−14. It is also a leucine rich repeat containing seven repeats of the same length as LRRC57, described as Eptatretus burgeri (inshore hagfish) variable lymphocyte receptors A29.
References