LRRC57

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Leucine rich repeat containing 57, also known as LRRC57, is a protein that in humans is encoded by the LRRC57 gene.[1]

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,[2] the sequence[1] 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.[2]

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.[2] 

  1  M G N S A L R A H V E T A Q K T G V F Q L K D R G L T E F P A D L Q K L T S N   39
 40  L R T I D L S N N K I E S L P P L L I G K F T L                                 63
 64  L K S L S L N N N K L T V L P D E I C N L K K                                   86
 87  L E T L S L N N N H L R E L P S T F G Q L S A                                  109
110  L K T L S L S G N Q L G A L P P Q L C S L R H                                  132
133  L D V M D L S K N Q I R S I P D S V G E L Q                                    154
155  V I E L N L N Q N Q I S Q I S V K I S C C P R                                  177
178  L K I L R L E E N C L E L S M L P Q S I L S D                                  200
201  S Q I C L L A V E G N L F E I K K L R E L E G Y D K Y M E R F T A T K K K F A  239
     L x x L x L x x N x L x x L x x x x x x L x

Homology

LRRC57 is exceedingly well conserved, as shown by the following multiple sequence alignment, prepared using ClustalX2.[3] The cyan and yellow highlights call out regions of high conservation and the repeats.

File:LRRC57-MSA.png

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.[4] and BLAST searches[5]

Species Organism common name NCBI accession Sequence identity Sequence similarity Length (AAs) Gene common name
Homo sapiens Human NP_694992 100% 100% 239 leucine rich repeat containing 57
Pan troglodytes Chimpanzee XP_510338 99% 100% 165 PREDICTED: hypothetical protein
Orangutan 99% 99% 238 From BLAT – no GenBank record
Macaca mulatta Rhesus macaque XP_001100633 96% 99% 143 PREDICTED: similar to CG3040-PA
Mus musculus House mouse NP_079933 95% 99% 239 leucine rich repeat containing 57
Rattus norvegicus Norway rat NP_001012354 95% 99% 239 leucine rich repeat containing 57
Canis lupus familiaris Dog XP_535443 94% 98% 264 PREDICTED: similar to CG3040-PA
Equus caballus Horse XP_001503298 94% 97% 273 PREDICTED: similar to leucine rich repeat containing 57
Bos taurus Cattle NP_001026924 94% 97% 239 leucine rich repeat containing 57
Monodelphis domestica Opossum XP_001362682 84% 94% 239 PREDICTED: hypothetical protein
Ornithorhynchus anatinus Platypus XP_001520403 76% 92% 99 PREDICTED: hypothetical protein
Gallus gallus Chicken XP_421160 85% 92% 238 PREDICTED: hypothetical protein
Taeniopygia guttata Zebra finch XP_002200369 85% 92% 238 PREDICTED: leucine rich repeat containing 57
Xenopus laevis African clawed frog NP_001085208 76% 88% 238 hypothetical protein LOC432302
Xenopus (Silurana) tropicalis Western clawed frog NP_001120199 76% 87% 238 hypothetical protein LOC100145243
Danio rerio Zebrafish NP_001002627 69% 83% 238 leucine rich repeat containing 57
Tetraodon nigroviridis Spotted green pufferfish CAF89640 67% 83% 238 unnamed protein product
Branchiostoma floridae Florida lancelet XP_002209325 57% 78% 237 hypothetical protein BRAFLDRAFT_277364
Ciona intestinalis (a sea squirt) XP_002129992 50% 71% 237 PREDICTED: similar to Leucine rich repeat containing 57
Strongylocentrotus purpuratus Purple urchin XP_782986 57% 74% 212 PREDICTED: hypothetical protein
Ixodes scapularis Black-legged tick EEC17869 57% 73% 237 leucine rich domain-containing protein, putative
Apis mellifera Honey bee XP_001121818 53% 72% 238 PREDICTED: similar to CG3040-PA
Nasonia vitripennis Jewel wasp XP_001601190 57% 73% 238 PREDICTED: similar to ENSANGP00000011808
Tribolium castaneum Red flour beetle XP_973486 56% 70% 238 PREDICTED: similar to AGAP001491-PA
Pediculus humanus Body louse EEB17844 52% 72% 238 leucine-rich repeat-containing protein, putative
Aedes aegypti Yellow fever mosquito XP_001657420 50% 66% 239 internalin A
Culex quinquefasciatus Southern house mosquito XP_001865691 49% 67% 238 leucine-rich repeat-containing protein 57
Drosophila melanogaster Fruit fly NP_572372 50% 67% 238 CG3040
Drosophila simulans XP_002106344 49% 67% 238 GD16172
Drosophila sechellia XP_002043192 49% 67% 238 GM17488
Drosophila yakuba XP_002101312 50% 68% 238 GE17554
Drosophila erecta XP_001978503 50% 67% 238 GG17646
Drosophila ananassae XP_001964158 51% 68% 238 GF20868
Drosophila pseudoobscura XP_001355271 49% 66% 238 GA15818
Drosophila persimilis XP_002025298 49% 66% 238 GL13411
Drosophila virilis XP_002056963 51% 68% 238 GJ16607
Drosophila mojavensis XP_002010408 51% 68% 238 GI14698
Drosophila grimshawi XP_001991745 52% 68% 238 GH12826
Drosophila willistoni XP_002071645 50% 67% 238 GK10093
Anopheles gambiae XP_321630 46% 66% 238 AGAP001491-PA
Caenorhabditis elegans (a nematode) NP_740983 43% 63% 485 hypothetical protein ZK546.2
Caenorhabditis briggsae (a nematode) XP_001679881 41% 64% 439 Hypothetical protein CBG02285

Gene neighborhood

The LRRC57 gene has interesting relationships to its neighbors – HAUS2 upstream and SNAP23 downstream, as shown below for human.[6]

File:LRRC57-Human-Neighbors.png

Shown below is the neighborhood for the mouse[7] ortholog. Note that the neighbors are the same, which is true for most vertebrates.

File:LRRC57-Mouse-Neighbors.png

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.

File:LRRC57-Mouse-Neighbors-Zoom.png

The relationship to the downstream neighbor, SNAP23 is also interesting. Quoting from the AceView[8] 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:

File:Snap23-lrrc57-alignment.png

Predicted post-translational modifications

The tools on the ExPASy Proteomics site[9] predict the following post-translational modifications:

Tool Predicted Modification Homo sapiens Mus musculus Gallus gallus Drosophila melanogaster
YinOYang[10] O-β-GlcNAc S166 S166 S165 T16, T102
NetPhos[11] phosphorylation S145, S149, S169, S199, S201, T27 T234 S139, S145, S169, S199, S201, T27, T149, T234 S148, S198, S200, T22 S46, S69, S200, T179, T193, Y230
Sulfinator[12] sulfation Y224, Y227 Y224, Y227 Y223, Y226 (none)
SulfoSite[13] sulfation Y224 Y224 Y223 Y223
SumoPlot[14] sumoylation K86, K15, and K236 (not checked) (not checked) (not checked)
Terminator[15] N-terminus G2 G2 G2 G2

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.

File:LRRC57-PostMod-Predicts.png

The sites for all four organisms are highlighted on the following multiple sequence alignment.

File:LRRC57-PostMod-Alignment.png

Note that the phosphorylation at S201 and the sulfation at Y224 are the only well conserved predictions across all four organisms.

Structure

File:LRRC57-Structure.png
Crystallographic structure of the leucine-rich repeat region of the variable lymphocyte receptor based on the PDB: 2O6Q​ coordinates. The seven leucine rich repeats are labeled as LRR 1–7. This figure was rendered using Cn3D.[16][17]

The structure of LRRC57 is not known. However, a protein BLAST search against the protein databank returns a similar protein (PDB: 2O6Q​), 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.[18]

References

  1. ↑ 1.0 1.1 "Entrez Gene: LRRC57 leucine rich repeat containing 57". Retrieved 4 May 2009.
  2. ↑ 2.0 2.1 2.2 Bella J, Hindle KL, McEwan PA, Lovell SC (August 2008). "The leucine-rich repeat structure". Cellular and Molecular Life Sciences. 65 (15): 2307–33. doi:10.1007/s00018-008-8019-0. PMID 18408889.
  3. ↑ "Clustal Home Page". Retrieved 4 May 2009.
  4. ↑ "BLAT Search Genome". Retrieved 4 May 2009.
  5. ↑ "BLAST". Retrieved 4 May 2009.
  6. ↑ "Human (Homo sapiens) Genome Browser Gateway". Retrieved 27 Apr 2009.
  7. ↑ "Mouse (Mus musculus) Genome Browser Gateway". Retrieved 27 Apr 2009.
  8. ↑ "AceView: Homo sapiens gene LRRC57, encoding leucine rich repeat containing 57". Retrieved 1 May 2009.
  9. ↑ "ExPASy Proteomics tools". Retrieved 24 Apr 2009.
  10. ↑ "YinOYang". Retrieved 24 Apr 2009.
  11. ↑ "NetPhos". Retrieved 24 Apr 2009.
  12. ↑ "Sulfinator". Retrieved 24 Apr 2009.
  13. ↑ "SulfoSite". Retrieved 24 Apr 2009.
  14. ↑ "SumoPlot". Retrieved 24 Apr 2009.
  15. ↑ "Terminator". Retrieved 24 Apr 2009.
  16. ↑ "Cn3D Home Page". Cn3D. National Center for Biotechnology Information, United States National Institutes of Health. 2008-04-24. Retrieved 2009-05-06.
  17. ↑ Wang Y, Geer LY, Chappey C, Kans JA, Bryant SH (June 2000). "Cn3D: sequence and structure views for Entrez". Trends in Biochemical Sciences. 25 (6): 300–2. doi:10.1016/S0968-0004(00)01561-9. PMID 10838572.
  18. ↑ Kim HM, Oh SC, Lim KJ, Kasamatsu J, Heo JY, Park BS, Lee H, Yoo OJ, Kasahara M, Lee JO (2007). "Structural diversity of the hagfish variable lymphocyte receptors". J Biol Chem. 282 (9): 6726–32. doi:10.1074/jbc.M608471200. PMID 17192264.
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