KIAA1704

KIAA1704, also known as LSR7 (lipopolysaccharide-specific response protein 7), is a is_associated_with::protein that in humans is encoded by the GPALPP1 (GPALPP motifs containing 1) is_associated_with::gene. The function of KIAA1704 is not yet well understood. KIAA1704 contains one is_associated_with::domain of unknown function, DUF3752. The protein contains a conserved, uncharged, repeated motif GPALPP(GF) near the is_associated_with::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
KIAA1704 has at least a 5 fold expression loss associated with mantle cell lymphoma. In a second study, researchers used a is_associated_with::linkage disequilibrium mapping study of locus 13q13-14 to investigate potential susceptibility for autism over a 1.5 Mb linkage peak, including KIAA1704. A single marker PDTPhase analysis was performed for four SNPs for KIAA1704; however, none of the SNPs were statistically significant in associating the marker with the loci.

An expression study found that KIAA1704 is significantly up-regulated in U937 cells (macrophage-like human cell line) when treated with nicotine.

Location
KIAA1704 is found on the is_associated_with::chromosome 13, at locus q14.12, with the is_associated_with::genomic sequence starting at 45,563,687 bp and ending at 45,602,405 bp.

Gene Neighborhood


KIAA1704 is located on the positive strand surrounded by 5 nearby genes.

Positive Orientation Negative Orientation
 * General Transcription Factor IIF (GTF2F2) is further downstream directed in the same orientation. Functionally, it binds to RNA Polymerase II.
 * Nuclear Fragile X Mental Retardation Protein Interacting Protein 1 (NUFIp1) shows RNA-binding activity with specific nuclear role for is_associated_with::FMRP. This is an RNA-binding protein associated with Fragile X. Start sites are antisense to start of KIAA1704.
 * 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
KIAA1704 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 image to the right.

KIAA1704 promoter showed significant is_associated_with::histone 3 lysine 4 trimethylation peaks in K562 cells (is_associated_with::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 is_associated_with::transcription factor, is_associated_with::Myc, in vivo.

Splice Variants
According to is_associated_with::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 is_associated_with::BLAST searches reveal that known mRNA is_associated_with::orthologs exist in mammals, reptiles, birds, frogs, and fish with at least 65% sequence identity.

Composition
Shown in the table below, KIAA1704 has significantly higher percentages of charged amino acids (D, K, KR, KRED) than the normal human protein and is mostly conserved within its is_associated_with::orthologous proteins.

Conservation
KIAA1704 has protein is_associated_with::orthologs extending through plants, shown in descending order of identity in the table below. is_associated_with::Mammals have the highest level of conservation with 89 percent identity followed by is_associated_with::birds, is_associated_with::frogs, is_associated_with::fish, is_associated_with::invertebrates, is_associated_with::insects, and is_associated_with::plants.

Conserved domains
Concerning conserved domains, thus far, there does not appear to be much information about conserved motif, GPALPP(GF). It is interesting to note that this motif represents the neutral segments in this highly charged protein.

DUF3752 is generally found in is_associated_with::Eukaryotes and is between 140-163 is_associated_with::amino acids in length. It belongs to is_associated_with::pfam12572, member of superfamily cl13947

Information provided by Statistical Analysis of Proteins (SAPS) tool.

Post Translation Modifications
KIAA1704 is predicted by is_associated_with::ExPASy tools to undergo several conserved post translational modifications including is_associated_with::glycation, is_associated_with::o-linked glycosylation, is_associated_with::serine phosphorylation, is_associated_with::threonine phosphorylation, and several is_associated_with::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
is_associated_with::ExPASy PSORT predicts 74% chance of being localized to the nucleus.