LRRC57


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 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
SpeciesOrganism common nameNCBI accessionSequence identitySequence similarityLength Gene common name
Homo sapiensHuman100%100%239leucine rich repeat containing 57
Pan troglodytesChimpanzee99%100%165PREDICTED: hypothetical protein
Orangutan99%99%238From BLAT – no GenBank record
Macaca mulattaRhesus macaque96%99%143PREDICTED: similar to CG3040-PA
Mus musculusHouse mouse95%99%239leucine rich repeat containing 57
Rattus norvegicusNorway rat95%99%239leucine rich repeat containing 57
Canis lupus familiarisDog94%98%264PREDICTED: similar to CG3040-PA
Equus caballusHorse94%97%273PREDICTED: similar to leucine rich repeat containing 57
Bos taurusCattle94%97%239leucine rich repeat containing 57
Monodelphis domesticaOpossum84%94%239PREDICTED: hypothetical protein
Ornithorhynchus anatinusPlatypus76%92%99PREDICTED: hypothetical protein
Gallus gallusChicken85%92%238PREDICTED: hypothetical protein
Taeniopygia guttataZebra finch85%92%238PREDICTED: leucine rich repeat containing 57
Xenopus laevisAfrican clawed frog76%88%238hypothetical protein LOC432302
Xenopus tropicalisWestern clawed frog76%87%238hypothetical protein LOC100145243
Danio rerioZebrafish69%83%238leucine rich repeat containing 57
Tetraodon nigroviridisSpotted green pufferfish67%83%238unnamed protein product
Branchiostoma floridaeFlorida lancelet57%78%237hypothetical protein BRAFLDRAFT_277364
Ciona intestinalis50%71%237PREDICTED: similar to Leucine rich repeat containing 57
Strongylocentrotus purpuratusPurple urchin57%74%212PREDICTED: hypothetical protein
Ixodes scapularisBlack-legged tick57%73%237leucine rich domain-containing protein, putative
Apis melliferaHoney bee53%72%238PREDICTED: similar to CG3040-PA
Nasonia vitripennisJewel wasp57%73%238PREDICTED: similar to ENSANGP00000011808
Tribolium castaneumRed flour beetle56%70%238PREDICTED: similar to AGAP001491-PA
Pediculus humanusBody louse52%72%238leucine-rich repeat-containing protein, putative
Aedes aegyptiYellow fever mosquito50%66%239internalin A
Culex quinquefasciatusSouthern house mosquito49%67%238leucine-rich repeat-containing protein 57
Drosophila melanogasterFruit fly50%67%238CG3040
Drosophila simulans49%67%238GD16172
Drosophila sechellia49%67%238GM17488
Drosophila yakuba50%68%238GE17554
Drosophila erecta50%67%238GG17646
Drosophila ananassae51%68%238GF20868
Drosophila pseudoobscura49%66%238GA15818
Drosophila persimilis49%66%238GL13411
Drosophila virilis51%68%238GJ16607
Drosophila mojavensis51%68%238GI14698
Drosophila grimshawi52%68%238GH12826
Drosophila willistoni50%67%238GK10093
Anopheles gambiae46%66%238AGAP001491-PA
Caenorhabditis elegans43%63%485hypothetical protein ZK546.2
Caenorhabditis briggsae41%64%439Hypothetical protein CBG02285
------

Gene neighborhood

The LRRC57 gene has interesting relationships to its neighbors – 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. 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:
ToolPredicted ModificationHomo sapiensMus musculusGallus gallusDrosophila 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
SulfoSitesulfationY224Y224Y223Y223
SumoPlotsumoylationK86, K15, and K236
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 variable lymphocyte receptors A29.