C11orf49

CSTPP1
Identifiers
Aliases	CSTPP1, chromosome 11 open reading frame 49, C11orf49, centriolar satellite-associated tubulin polyglutamylase complex regulator 1
External IDs	MGI: 1915079 HomoloGene: 11471 GeneCards: CSTPP1
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11p11.2 Start 46,936,689 bp[1] End 47,164,385 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 E1 Start 91,105,413 bp[2] End 91,275,049 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in external globus pallidus Brodmann area 9 prefrontal cortex right uterine tube nucleus accumbens ganglionic eminence hypothalamus putamen caudate nucleus pons Top expressed in spermatocyte spermatid superior frontal gyrus ventromedial nucleus paraventricular nucleus of hypothalamus arcuate nucleus medial vestibular nucleus lateral hypothalamus entorhinal cortex medial geniculate nucleus More reference expression data BioGPS More reference expression data
Orthologs Species Human Mouse Entrez 79096 228356 Ensembl ENSG00000149179 ENSMUSG00000040591 UniProt Q9H6J7 Q8BHR8 RefSeq (mRNA) NM_001003676 NM_001003677 NM_001003678 NM_001278222 NM_024113 NM_175123 NM_001311144 NM_153797 RefSeq (protein) NP_001003676 NP_001003677 NP_001003678 NP_001265151 NP_077018 NP_001298073 NP_780332 Location (UCSC) Chr 11: 46.94 – 47.16 Mb Chr 2: 91.11 – 91.28 Mb PubMed search [3] [4]
Wikidata
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C11orf49 is a protein coding gene that in humans encodes for the C11orf49 protein.^[5] It is heavily expressed in brain tissue and peripheral blood mononuclear cells, with the latter being an important component of the immune system.^[6][7] It is predicted that the C11orf49 protein acts as a kinase, and has been shown to interact with HTT (determining protein for Huntington's disease) and APOE2 (risk protein for Alzheimer's).^[8][9]

Gene[edit]

Aliases[edit]

Common aliases are UPF0705, FLJ22210, and MGC4707.^[7]

Location[edit]

C11orf49 is found at locus p11.2 on human chromosome 11, with a plus strand orientation.^[7] The gene is 224,830 bp long including introns, and spans from position 46,936,806 to 47,161,635 on chromosome 11. ^[10]

Transcript Variants[edit]

There are 7 known transcript variants for the mRNA of C11orf49, with variant 2 encoding for the most complete protein. Variant 1 lacks a 3’ splice junction, which results in a truncated 3’ terminus compared to variant 2. Variant 3 contains an alternate splice site at the 3’ end, which lacks an internal region near the 3’ terminus compared to variant 2. Variant 4 has an alternate 3’ terminus exon, resulting in a truncated 3’ terminus compared to variant 2. Variant 5 lacks an exon in the 5’ coding region which results in an upstream start codon, and has alternate splice site near the 3’ region. This results in a distinct N-terminus and a missing internal region near the 3’ terminus compared to variant 2. Variants 6 and 7 are both represented as candidates for nonsense-mediated mRNA decay (NMD), and do not encode for viable proteins.^[5]

Table 1. Known human mRNA transcript variants for C11orf49.

Protein[edit]

Isoforms[edit]

There are 5 known isoforms for the C11orf49 protein with isoform 2 being the most complete protein, encoded by transcript variant 2.^[5]

Table 2. Known human protein isoforms for C11orf49.

Composition[edit]

The C11orf49 protein has a molecular weight of 38.1 kD, and an isoelectric point of about pH = 5.^[11] Protein composition falls under normal levels for each amino acid, and there are no conserved repeats, patterns, or charged clusters to be seen. There are no hydrophobic or transmembrane regions to be seen.^[12]

Protein Domain[edit]

The C11orf49 protein is predicted to contain a protein kinase domain near the N' terminus (residues 12-51)^[8]

Secondary Structure[edit]

Secondary structure prediction tools such as Ali2D, Phyre2, and i-Tasser all predict that the C11orf49 protein is mostly composed of alpha helices, with no predicted beta sheets.^[8][13][14] Information on where these alpha helices are located can be seen to the right of the page.

Tertiary Structure[edit]

i-Tasser predicted tertiary structure is included to the right of the page.^[14]

Post-Translational Modifications[edit]

Phosphorylation[edit]

The C11orf49 protein is predicted to be phosphorylated at 4 different sites, mainly on serine residues, but also on one threonine residue.^[15]

Table 3. Predicted phosphorylation sites for the C11orf49 human protein.

Sumoylation[edit]

The C11orf49 protein is predicted to be sumoylated at positions 119 and 320, both lysine residues.^[15]

Subcellular Localization[edit]

The C11orf49 protein found in humans is predicted to be localized in the cytoplasm.^[16]

Gene Level Regulation[edit]

Promoters[edit]

There are 7 promoters listed on Genomatix, however only one of the promoters (GXP_204543) starts at the beginning of the C11orf49 gene that is found in humans, and also has the greatest number of encoding transcripts.^[17]

Table 4. List of promoters associated with the C11orf49 human gene.

Transcription Factors[edit]

The following transcription factors are predicted to bind to the GXP_204543 promoter. ^[18] The higher the matrix score, the more likely the transcription factor is to bind to the promoter. Information on where these transcription factors bind on the GXP_204543 promoter is showcased in the image to the right of the page.

Table 5. List of binding transcription factors to the GXP_204543 promoter.

Gene Expression[edit]

Tissue Specific Expression[edit]

Both microarray expression patterns and RNA-Seq data show very high levels of expression in the brain.^[5][19] RNA-Seq data also shows high expression in lung fetal tissue.^[5] Additional information for other tissues is included to the right of the page.

Conditions of Differentiated Expression[edit]

C11orf49 expression is significantly increased after the overexpression of claudin-1 in lung adenocarcinoma cell lines.^[20] Claudin-1 specifically prevents paracellular diffusion of small molecules through tight junctions in the epidermis.

C11orf49 expression is significantly decreased after the treatment of camptothecin on a renal epithelial cell line.^[21] Camptothecin is an alkaloid that inhibits the nuclear enzyme DNA topoisomerase, and has exhibited antitumor activity. It has also shown the ability to cause apoptosis by changing the permeability of the mitochondrial membrane, releasing cytochrome C.

Post-Transcription Regulation[edit]

5' UTR[edit]

There is a predicted stem-loop structure in the 5' UTR of the C11orf49 transcript from nucleotides 15-26 shown to the right of the page.^[22]

3' UTR[edit]

There are predicted stem-loop structures and miRNA binding sites for the 3' UTR of the C11orf49 transcript shown to the right of the page.^[22][23]

Protein-Protein Interactions[edit]

The database provided by PSICQUIC indicates that the C11orf49 protein found in humans interacts with the following proteins listed in Table 6.^[9] All interactions were determined using two-hybrid screening experiments.^[9]

Table 6. List of proteins that interact with the C11orf49 protein found in humans.

Homology and Evolution[edit]

Orthologs and Paralogs[edit]

C11orf49 can be found among a wide variety of taxonomic groups, including but not limited to Mammalia, Aves, Reptilia, Amphibia, Cyprinidae, Hemichordata, Cnidaria, Platyhelminthes, Arthropoda, Placozoa, Choanoflagellate, Spizellomyces, and Oomycota.^[24][25] However, C11orf49 could not be found in Insecta or Plantae.^[24][25] There are no known paralogs of C11orf49.^[24][25]

Table 7. List of selected orthologs of C11orf49.

Evolution[edit]

History[edit]

Saprolegnia diclina is the most distantly related ortholog of C11orf49 known, with its divergence from ancestral humans approximately 1,552 MYA.^[24][26]

Evolutionary Rate[edit]

After performing a molecular clock analysis, C11orf49 has evolved at a faster rate than Cytochrome c but slower than Fibrinogen alpha. The graph containing this analysis is to the right of the page.

Function[edit]

Protein Kinase Activity[edit]

C11orf49 is predicted to act as a cAMP-dependent protein kinase.^[8]

Clinical Significance[edit]

C11orf49 has been shown to interact with proteins HTT and APOE2, which are associated with Huntington's disease and Alzheimer's, respectively.^[9] Due to the predicted function of C11orf49, this interaction could be kinase-oriented.

C11orf49 expression is significantly increased after the overexpression of Claudin-1 in lung adenocarcinoma cells.^[20]

C11orf49 expression is significantly decreased after the treatment of camptothecin on a renal epithelial cell line.^[21]

References[edit]