LRRC57 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | LRRC57 , leucine rich repeat containing 57 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 1913856 HomoloGene: 11995 GeneCards: LRRC57 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Leucine rich repeat containing 57, also known as LRRC57 is a protein encoded in humans by the LRRC57 gene. [5]
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.
As is customary for leucine-rich repeat proteins, [6] the sequence [5] 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. [6]
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. [6]
1 M G N S A '''<span style="color:orange">L</span>''' R A H V E T A Q K T G V F Q '''<span style="color:orange">L</span>''' K D R G L T E F P A D L Q K L T S N 39 40 '''<span style="color:orange">L</span>''' R T I D '''<span style="color:orange">L</span>''' S N '''<span style="color:orange">N</span>''' K I E S '''<span style="color:orange">L</span>''' P P L L I G K F T L 63 64 '''<span style="color:orange">L</span>''' K S '''<span style="color:orange">L</span>''' S '''<span style="color:orange">L</span>''' N N '''<span style="color:orange">N</span>''' K '''<span style="color:orange">L</span>''' T V '''<span style="color:orange">L</span>''' P D E I C N '''<span style="color:orange">L</span>''' K K 86 87 '''<span style="color:orange">L</span>''' E T <span style="color:orange">L</span> S <span style="color:orange">L</span> N N <span style="color:blue">N</span> H <span style="color:orange">L</span> R E <span style="color:orange">L</span> P S T F G Q <span style="color:orange">L</span> S A 109 110 <span style="color:orange">L</span> K T <span style="color:orange">L</span> S <span style="color:orange">L</span> S G <span style="color:blue">N</span> Q <span style="color:orange">L</span> G A <span style="color:orange">L</span> P P Q L C S <span style="color:orange">L</span> R H 132 133 <span style="color:orange">L</span> D V M D <span style="color:orange">L</span> S K <span style="color:blue">N</span> Q I R S I P D S V G E <span style="color:orange">L</span> Q 154 155 V I E <span style="color:orange">L</span> N <span style="color:orange">L</span> N Q <span style="color:blue">N</span> Q I S Q I S V K I S C C P R 177 178 <span style="color:orange">L</span> K I <span style="color:orange">L</span> R <span style="color:orange">L</span> E E <span style="color:blue">N</span> C <span style="color:orange">L</span> E L S M L P Q S I <span style="color:orange">L</span> S D 200 201 S Q I C L <span style="color:orange">L</span> A V E G N L F E I K K L R E <span style="color:orange">L</span> E G Y D K Y M E R F T A T K K K F A 239 <span style="color:orange">L</span> x x <span style="color:orange">L</span> x <span style="color:orange">L</span> x x <span style="color:blue">N</span> x <span style="color:orange">L</span> x x <span style="color:orange">L</span> x x x x x x <span style="color:orange">L</span> x
LRRC57 is exceedingly well conserved, as shown by the following multiple sequence alignment, prepared using ClustalX2. [7] 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. [8] and BLAST searches [9]
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 |
The LRRC57 gene has interesting relationships to its neighbors – HAUS2 upstream and SNAP23 downstream, as shown below for human. [10]
Shown below is the neighborhood for the mouse [11] 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 [12] 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:
The tools on the ExPASy Proteomics site [13] predict the following post-translational modifications:
Tool | Predicted Modification | Homo sapiens | Mus musculus | Gallus gallus | Drosophila melanogaster |
YinOYang [14] | O-β-GlcNAc | S166 | S166 | S165 | T16, T102 |
NetPhos [15] | 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 [16] | sulfation | Y224, Y227 | Y224, Y227 | Y223, Y226 | (none) |
SulfoSite [17] | sulfation | Y224 | Y224 | Y223 | Y223 |
SumoPlot [18] | sumoylation | K86, K15, and K236 | (not checked) | (not checked) | (not checked) |
Terminator [19] | 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.
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.
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. [22]
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) also known as G-protein coupled receptor 49 (GPR49) or G-protein coupled receptor 67 (GPR67) is a protein that in humans is encoded by the LGR5 gene. It is a member of GPCR class A receptor proteins. R-spondin proteins are the biological ligands of LGR5. LGR5 is expressed across a diverse range of tissue such as in the muscle, placenta, spinal cord and brain and particularly as a biomarker of adult stem cells in certain tissues.
Fibromodulin is a protein that in humans is encoded by the FMOD gene.
Leucine-rich repeat-containing protein 4 is a protein that in humans is encoded by the LRRC4 gene.
Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene.
Leucine-rich repeat-containing protein 8D is a protein that in humans is encoded by the LRRC8D gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8C, and LRRC8E, is a subunit of the heteromer protein Volume-Regulated Anion Channel. Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these channels have been linked to.
Leucine-rich repeat-containing protein 41 is a protein that in humans is encoded by the LRRC41 gene.
Leucine-rich repeat-containing protein 8A is a protein that in humans is encoded by the LRRC8A gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8B, LRRC8C, LRRC8D, and LRRC8E, is a subunit of the heteromer protein volume-regulated anion channel (VRAC). (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these channels have been linked to.
Asporin is a protein that in humans is encoded by the ASPN gene.
Leucine-rich repeat-containing protein 23 is a protein that in humans is encoded by the LRRC23 gene.
Leucine-rich repeat-containing protein 8E is a protein that in humans is encoded by the LRRC8E gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8C, and LRRC8D, is sometimes a subunit of the heteromer protein volume-regulated anion channel. Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these channels have been linked to.
Leucine-rich repeat-containing protein 17 is a protein that in humans is encoded by the LRRC17 gene.
Leucine-rich repeat-containing protein 50 is a protein that in humans is encoded by the LRRC50 gene.
Leucine-rich repeat neuronal protein 3, also known as neuronal leucine-rich repeat protein 3 (NLRR-3), is a protein that in humans is encoded by the LRRN3 gene.
Leucine rich repeat containing 40 (LRRC40) is a protein that in humans is encoded by the LRRC40 gene.
Leucine rich repeat containing 15 is a cell membrane expressed protein that in humans is encoded by the LRRC15 gene. located on chromosome 3 at 3q29 that belongs to the LRR superfamily, which is involved in cell–cell and cell–ECM interactions. There is preliminary evidence that expression may be related to the severity of COVID-19 and that it is an inhibitory accessory factor for SARS-CoV-2 entry to cells. LRRC15 lacks obvious intracellular domains. LRRC15 displays a highly restricted expression pattern, but is expressed in areas that make up innate immune barriers such as the placenta, skin, activated fibroblasts in wounds, and lymphoid tissues such as the spleen. LRRC15 may play some role in innate immunity. LRRC15 is aberrantly expressed in cancer. It is highly expressed in CAFs within the stroma of numerous solid tumors and directly expressed in mesenchymal tumors such as glioblastoma, sarcomas, and melanoma.
Leucine rich repeat containing 24 is a protein that, in humans, is encoded by the LRRC24 gene. The protein is represented by the official symbol LRRC24, and is alternatively known as LRRC14OS. The function of LRRC24 is currently unknown. It is a member of the leucine-rich repeat (LRR) superfamily of proteins.
Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene. Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel. Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane, and that is not the only function these channels have been linked to.
LRRIQ3, which is also known as LRRC44, is a protein that in humans is encoded by the LRRIQ3 gene. It is predominantly expressed in the testes, and is linked to a number of diseases.
Leucine rich repeat containing 26 (LRRC26) is a protein that in humans is encoded by the LRRC26 gene.
Leucine-rich repeat-containing protein 74A (LRRC74A), is a protein encoded by the LRRC74A gene. The protein LRRC74A 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.