LRRC57

LRRC57
Identifiers
Aliases	LRRC57 , leucine rich repeat containing 57
External IDs	MGI: 1913856; HomoloGene: 11995; GeneCards: LRRC57; OMA:LRRC57 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q15.2 Start 42,537,820 bp [1] End 42,548,802 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 E5 Start 120,434,719 bp [2] End 120,440,001 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in amniotic fluid pancreatic epithelial cell gonad palpebral conjunctiva monocyte Achilles tendon rectum endothelial cell ventricular zone stromal cell of endometrium Top expressed in seminiferous tubule spermatid secondary oocyte zygote morula primary oocyte granulocyte dentate gyrus of hippocampal formation granule cell ascending aorta neural layer of retina More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 255252 66606 Ensembl ENSG00000180979 ENSMUSG00000027286 UniProt Q8N9N7 Q9D1G5 RefSeq (mRNA) NM_153260 NM_001159609 NM_001159610 NM_001159612 NM_025657 RefSeq (protein) NP_694992 n/a Location (UCSC) Chr 15: 42.54 – 42.55 Mb Chr 2: 120.43 – 120.44 Mb PubMed search [3] [4]
Wikidata
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Leucine rich repeat containing 57, also known as LRRC57 is a protein encoded in humans by the LRRC57 gene. ^[5]

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, ^[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 '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' R A H V E T A Q K T G V F Q '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" 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  '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' R T I D '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' S N '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">N</span>''' K I E S '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' P P L L I G K F T L                                 63   64  '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' K S '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' S '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' N N '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">N</span>''' K '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' T V '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' P D E I C N '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' K K                                   86   87  '''<templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span>''' E T <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> N N <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> H <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> R E <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> P S T F G Q <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S A                                  109  110  <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> K T <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S G <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> Q <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> G A <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> P P Q L C S <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> R H                                  132  133  <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> D V M D <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S K <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> Q I R S I P D S V G E <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> Q                                    154  155  V I E <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> N <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> N Q <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> Q I S Q I S V K I S C C P R                                  177  178  <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> K I <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> R <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> E E <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> C <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> E L S M L P Q S I <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> S D                                  200  201  S Q I C L <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> A V E G N L F E I K K L R E <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> E G Y D K Y M E R F T A T K K K F A  239       <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:blue">N</span> x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x x x x x x <templatestyles src="Template:Color/styles.css" /><span class="tmp-color" style="color:orange">L</span> x

Homology

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

Gene neighborhood

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:

Predicted post-translational modifications

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.

Structure

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.

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]

References

1. GRCh38: Ensembl release 89: ENSG00000180979 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027286 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: LRRC57 leucine rich repeat containing 57" . Retrieved 4 May 2009.
6. 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. PMC   11131621 . PMID   18408889. S2CID   10222798.
7. "Clustal Home Page" . Retrieved 4 May 2009.
8. "BLAT Search Genome" . Retrieved 4 May 2009.
9. "BLAST" . Retrieved 4 May 2009.
10. "Human (Homo sapiens) Genome Browser Gateway" . Retrieved 27 Apr 2009.
11. "Mouse (Mus musculus) Genome Browser Gateway" . Retrieved 27 Apr 2009.
12. "AceView: Homo sapiens gene LRRC57, encoding leucine rich repeat containing 57" . Retrieved 1 May 2009.
13. "ExPASy Proteomics tools" . Retrieved 24 Apr 2009.
14. "YinOYang" . Retrieved 24 Apr 2009.
15. "NetPhos" . Retrieved 24 Apr 2009.
16. "Sulfinator" . Retrieved 24 Apr 2009.
17. "SulfoSite". Archived from the original on 24 July 2008. Retrieved 24 Apr 2009.
18. "SumoPlot". Archived from the original on 20 April 2009. Retrieved 24 Apr 2009.
19. "Terminator". Archived from the original on 16 April 2008. Retrieved 24 Apr 2009.
20. "Cn3D Home Page". Cn3D. National Center for Biotechnology Information, United States National Institutes of Health. 2008-04-24. Retrieved 2009-05-06.
21. 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.
22. 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.