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
Aliases
Common aliases are UPF0705, FLJ22210, and MGC4707.[7]
Location
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
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]
The C11orf49 protein is predicted to contain a protein kinase domain near the N' terminus (residues 12-51)[8]
Secondary Structure
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.
The C11orf49 protein is predicted to be phosphorylated at 4 different sites, mainly on serine residues, but also on one threonine residue.[15]
Position
AA
Kinase
310
Serine
AGC/Akt
48
Threonine
AGC/Akt/AKT1
66
Serine
AGC/Akt
318
Serine
AGC/Akt
Table 3. Predicted phosphorylation sites for the C11orf49 human protein.
Sumoylation
The C11orf49 protein is predicted to be sumoylated at positions 119 and 320, both lysine residues.[15]
Subcellular Localization
The C11orf49 protein found in humans is predicted to be localized in the cytoplasm.[16]
Gene Level Regulation
Promoters
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]
Promoter ID
Start Position
End Position
Size (bp)
Orientation
Total # of transcripts
GXP_204543
46935524
46936819
1296
plus strand
32
GXP_3162280
47050923
47051962
1040
plus strand
1
GXP_3162281
47051454
47052500
1047
plus strand
2
GXP_3162283
47136696
47137735
1040
plus strand
1
GXP_3162284
47153395
47154434
1040
plus strand
1
GXP_3162285
47153944
47154983
1040
plus strand
1
GXP_204542
47159105
47160144
1040
plus strand
1
Table 4. List of promoters associated with the C11orf49 human gene.
Transcription Factors
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.
Matrix Family
Detailed Family Info
Detailed Matrix Info
Matrix Score
V$NKXH
NKX homeodomain factors
Homeodomain factor NKX-2.5
1
V$GATA
GATA binding factor
GATA-binding factor 3
0.992
V$LEFF
LEF1/TCF
Involved in the Wnt signal pathway
0.991
O$VTBP
Vertebrate TATA binding factor
Cellular and viral TATA box elements
0.99
V$KLFS
Krueppel like TFs
Gut-enriched Krueppel-like TF
0.982
V$MYBL
Cellular and Viral myb-like TFs
V-Myb
0.978
V$E2FF
E2F-myc activator
E2F TF 1
0.976
V$MEF3
MEF3 binding sites
Sine oculis homeobox homolog 2
0.972
V$XBBF
X-box binding factors
X-box binding protein RFX1
0.966
V$ETSF
Human and murine ETS1 factors
Elk-1
0.958
V$PBXC
PBX-MEIS complexes
Pre-B-cell leukemia homeobox 3
0.949
V$CAAT
CCAAT binding factors
Cellular and viral CCAAT box
0.927
V$HEAT
Heat shock factors
Heat shock factor 1
0.927
V$MYT1
MYT1 C2HC zinc finger protein
Myelin TF 1-like, neuronal C2H2 ZF 1
0.925
V$GCMF
Chorion-specific TFs
Glial cells missing homolog 1
0.902
V$ZF04
C2H2 zinc finger TF 4
Zinc finger and BTB domain
0.9
V$MAZF
Myc associated zinc fingers (MAZ)
MAZ
0.875
V$PAX9
Pax-9 binding sites
Zebrafish Pax-9 binding site
0.848
V$DMRT
DM domain-containing TFs
Mab-3 related TF 1
0.817
Table 5. List of binding transcription factors to the GXP_204543 promoter.
Gene Expression
Tissue Specific Expression
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
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 enzymeDNA 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
5' UTR
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
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
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]
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
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
Protein Kinase Activity
C11orf49 is predicted to act as a cAMP-dependent protein kinase.[8]
Clinical Significance
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]