GPALPP motifs-containing protein 1, also known as LSR7 (lipopolysaccharide-specific response protein 7), is a protein that in humans is encoded by the GPALPP1 (GPALPP motifs containing 1) gene (previously KIAA1704). The function of the protein GPALPP1 is not yet well understood. GPALPP1 contains one domain of unknown function, DUF3752. The protein contains a conserved, uncharged, repeated motif GPALPP(GF) near the N terminus and an unusual, conserved, mixed charge throughout (alternating readily between positive and negative charges). It is predicted to be localized to the nucleus.
Clinical significance
GPALPP1 has at least a 5 fold expression loss associated with mantle cell lymphoma.
In a second study, researchers used a linkage disequilibrium mapping study of locus 13q13-14 to investigate potential susceptibility for autism over a 1.5 Mb linkage peak, including GPALPP1. A single marker PDTPhase analysis was performed for four SNPs for GPALPP1; however, none of the SNPs were statistically significant in associating the marker with the loci.
An expression study found that GPALPP1 is significantly up-regulated in U937 cells (macrophage-like human cell line) when treated with nicotine.
Properties Number of Exons mRNA sequence length (bp) Protein sequence length (aa) Molecular Weight (kD) Isoelectric point 8 1431 340 38.1 5.0526
Gene
Location GPALPP1 is found on the chromosome 13, at locus q14.12, with the genomic sequence starting at 45,563,687 bp and ending at 45,602,405 bp.
Gene Neighborhood
GPALPP1 is located on the positive strand surrounded by 5 nearby genes.
Positive Orientation General Transcription Factor IIF (GTF2F2) is further downstream directed in the same orientation. Functionally, it binds to RNA Polymerase II. Negative Orientation Nuclear Fragile X Mental Retardation Protein Interacting Protein 1 (NUFIp1) shows RNA-binding activity with specific nuclear role for FMRP. This is an RNA-binding protein associated with Fragile X. Start sites are antisense to start of GPALPP1. Potassium Channel Tetramerisation Domain Containing 4 (KCTD4) proposed to participate in potassium ion transport. Tumor protein translationally controlled 1 (TPT1) is involved in calcium binding and microtubule stabilization. Small nucleolar RNA, H/ACA box 31 (SNORA31) does not have a known function at this time.
Expression
GPALPP1 has ubiquitous low to moderate expression patterns across body tissues (below 50%)
Promoter
Using GenoMatix ElDorado analysis tools, the promoter was predicted to be 727 base pairs in length projecting into exon 1. There are two predicted transcriptional start sites for this promoter, shown on the adjacent image.
GPALPP1 promoter showed significant histone 3 lysine 4 trimethylation peaks in K562 cells (erythroid cell line). It also showed increased relative expression in erythroid progenitors along with gene neighbors, NUFIP1 and TPT1.
An additional study found that the proximal promoter is one of many thousand direct targets of transcription factor, Myc, in vivo.
mRNA
Splice Variants
According to Ensembl, there are four coding splice variants. None of the alternative splice forms have experimental evidence associated. One splice variant undergoes non-sense mediated decay while another is predicted to splice the gene directly in half and retain amino acids 171–340.
Conservation
NCBI BLAST searches reveal that known mRNA orthologs exist in mammals, reptiles, birds, frogs, and fish with at least 65% sequence identity.
Protein
General Properties
Composition
Shown in the table below, GPALPP1 has significantly higher percentages of charged amino acids (D, K, KR, KRED) than the normal human protein and is mostly conserved within its orthologous proteins.
Compositional Analysis Amino Acid (AA) Abundance H. sapiens AA Abundance Mus musculus AA Abundance Gallus gallus AA Abundance Xenopus tropicales D++ 42 (12.4%) 37 (10.7%) 35 (10%) 33 (9.8%) V-- 6 (1.8%) 9 (2.6%) 9 (2.6%) ----- K+ 37 (10.9%) 37 (10.7%) ----- ----- L- 17 (5.0%) 17 (4.9%) 19 (5.4%) ----- KR+ 62 (18.2%) 62 (17.9%) 60 (17.1%) 56 (16.6%) KRED++ 134 (39.4%) 135 (39.0%) 135 (38.6%) 122 (36.1%) ED+ 72 (21.2%) 73 (21.1%) 75 (21.4%) 66 (19.5%) LVIFM- 54 (15.9%) 59 (17.1%) 58 (16.6%) 57 (16.9%)
Conservation
GPALPP1 has protein orthologs extending through plants, shown in descending order of identity in the table below. Mammals have the highest level of conservation with 89 percent identity followed by birds, frogs, fish, invertebrates, insects, and plants.
Genus and Species Common name Accession number Sequence length (aa) Sequence identity to Human protein (%) ! !Sequence similarity to Human Protein (%) Evolutionary Time to Human Divergence (Million years) Homo sapiens Human NP_061029.2 340 100 100 0 Pan troglodytes Chimpanzee XP_509661.2 340 99 100 6.4 Macaca mulatta Rhesus monkey XP_001094145 344 97 98 29.2 Loxodonta africana African savanna elephant XP_003412655 341 95 98 98.8 Sus scrofa Wild boar XP_001924228 346 89 95 92.4 Mus musculus Mouse NP_080453.2 346 89 93 94.4 Gallus gallus Chicken NP_001006270 350 67 78 371.2 Taeniopygia guttata Zebra finch XP_002198724 342 70 81 400.1 Xenopus tropicales Western clawed frog NP_001072786 338 62 74 400.1 Xenopus laevis African clawed frog NP_001089474 337 61 74 661.2 Danio rerio Zebrafish NP_001003473 405 49 61 782.7 Saccoglossus kowalevskii Acorn worm XP_002738946 350 43 60 1369 Culex quinquefasciatus Southern house mosquito XP_001847636.1 335 41 57 782.7 Drosophila ananassae Fruit fly XP_001954135 348 34 50 1215.8 Glycine max Soybean XP_003556198 569 32 51 1369 Puccinia graminis Stem rust XP_003328471 346 29 46 1215.8
Conserved domains
Concerning conserved domains, thus far, there does not appear to be much information about conserved motif, GPALPP(GF). This motif represents the neutral segments in this highly charged protein.
DUF3752 is generally found in Eukaryotes and is between 140 and 163 amino acids in length. It belongs to pfam12572, member of superfamily cl13947
Conserved Region H. sapiens Amino Acid Site Charge (Acidic, Basic, Neutral) Poly-serine 41-49 Neutral Poly-aspartic Acid 81-88 Acidic GPALPP(GF) 7–14; 32–37; 92–99; 112-119 Neutral IIGP 110–113; 146-149 Neutral DUF3752 196-333 Basic (pI=10.51) Information provided by Statistical Analysis of Proteins (SAPS) tool.
Post Translation Modifications
GPALPP1 is predicted by ExPASy tools to undergo several conserved post translational modifications including glycation, o-linked glycosylation, serine phosphorylation, threonine phosphorylation, and several kinase specific phosphorylation (PKC, PKA, and CKII).
Secondary Structure
There are four conserved predicted alpha helices located towards the C terminus of the protein. The N terminus is predicted to be dominated by coiled regions.
Subcellular Localization
ExPASy PSORT predicts 74% chance of being localized to the nucleus.
References