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]
Common aliases are UPF0705, FLJ22210, and MGC4707. [7]
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]
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]
| Name | Accession Number | Numbers of Exons | Size (bp) |
| Transcript Variant 1 | NM_001003676.3 | 8 | 1923 |
| Transcript Variant 2 | NM_001003677.3 | 9 | 1668 |
| Transcript Variant 3 | NM_024113.5 | 8 | 1650 |
| Transcript Variant 4 | NM_001003678.3 | 9 | 1159 |
| Transcript Variant 5 | NM_001278222.1 | 8 | 1619 |
| Transcript Variant 6 | NR_103471.2 | 10 | 1895 |
| Transcript Variant 7 | NR_103472.2 | 8 | 1519 |
Table 1. Known human mRNA transcript variants for C11orf49.
There are 5 known isoforms for the C11orf49 protein with isoform 2 being the most complete protein, encoded by transcript variant 2. [5]
| Name | Accession Number | Size (AA) |
| Isoform 1 | NP_001003676.1 | 274 |
| Isoform 2 | NP_001003677.1 | 337 |
| Isoform 3 | NP_077018.1 | 331 |
| Isoform 4 | NP_001003678.1 | 326 |
| Isoform 5 | NP_001265151.1 | 322 |
Table 2. Known human protein isoforms for C11orf49.
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]
The C11orf49 protein is predicted to contain a protein kinase domain near the N' terminus (residues 12-51) [8]
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.
i-Tasser predicted tertiary structure is included to the right of the page. [14]
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.
The C11orf49 protein is predicted to be sumoylated at positions 119 and 320, both lysine residues. [15]
The C11orf49 protein found in humans is predicted to be localized in the cytoplasm. [16]
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.
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.
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.
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.
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]
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]
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]
| Protein | Description |
| HTT | Huntingtin protein |
| APOE | Apolipoprotein E |
| PRKAR1A | cAMP-dependent protein kinase type I-alpha regulatory subunit |
| FH | Fumarate hydratase |
| GCA | Grancalcin |
| PHF1 | PHD finger protein 1 |
| VPS54 | Vacuolar protein sorting-associated protein 54 |
| ZFHX3 | Zinc finger homeobox protein 3 |
| RAB7L1 | RAS oncogene family-like 1 |
| NDRG1 | Stress responsive protein |
| PNMA5 | Paraneoplastic antigen-like protein 5 |
| TXN2 | Thioredoxin |
Table 6. List of proteins that interact with the C11orf49 protein found in humans.
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]
| Genus and Species | Common name | Taxonomic group | Divergence (MYA) | Accession # | AA length | Identity (%) | Similarity (%) |
| Mus musculus | Mouse | Rodentia | 89 | NP_780332.1 | 331 | 92 | 95.5 |
| Gallus gallus | Chicken | Aves | 318 | XP_015142672.1 | 331 | 76.7 | 83.5 |
| Chelonia mydas | Green Sea Turtle | Reptilia | 318 | XP_007054360.2 | 362 | 73.4 | 79.9 |
| Geotrypetes seraphini | Gaboon caecilian | Amphibia | 352 | XP_033784118.1 | 329 | 69.9 | 81.7 |
| Xenopus tropicalis | Tropical Clawed Frog | Amphibia | 352 | NM_001079316.1 | 330 | 61.9 | 77.3 |
| Danio rerio | Zebrafish | Cyprinoidae | 433 | NP_001002479.1 | 331 | 54.7 | 72.2 |
| Sacoglossus kowalevskii | Acorn Worm | Hemichordata | 627 | XP_006821066.1 | 299 | 43.6 | 58.2 |
| Nematostella vectensis | Starlet Sea Anemone | Cnidaria | 687 | XP_032240720.1 | 300 | 42.4 | 57.3 |
| Macrostomum lignano | Flatworm | Platyhelminthes | 692 | PAA77967.1 | 404 | 29.7 | 42.3 |
| Stegodyphus mimosarum | African Velvet Spider | Arthropoda | 736 | KFM74201.1 | 321 | 24.3 | 38.5 |
| Trichoplax adhaerens | Trichoplax | Placozoa | 747 | XP_002108042.1 | 263 | 24.7 | 39.6 |
| Salpingoeca rosetta | N/A | Choanoflagellate | 928 | XP_004994083.1 | 231 | 15.5 | 25.5 |
| Spizellomyces palustris | Australian fungus | Spizellomyces | 1017 | TPX67906.1 | 298 | 21.4 | 32.7 |
| Saprolegnia diclina | Cotton Mould | Oomycota | 1552 | XP_008621502.1 | 314 | 22.9 | 35.6 |
Table 7. List of selected orthologs of C11orf49.
Saprolegnia diclina is the most distantly related ortholog of C11orf49 known, with its divergence from ancestral humans approximately 1,552 MYA. [24] [26]
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.
C11orf49 is predicted to act as a cAMP-dependent protein kinase. [8]
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]
Protein YIF1A is a Yip1 domain family proteins that in humans is encoded by the YIF1A gene.
OCC-1 is a protein, which in humans is encoded by the gene C12orf75. The gene is approximately 40,882 bp long and encodes 63 amino acids. OCC-1 is ubiquitously expressed throughout the human body. OCC-1 has shown to be overexpressed in various colon carcinomas. Novel splice variant of this gene was also detected in various human cancer types; in addition to encoding a novel smaller protein, OCC-1 gene produces a non-protein coding RNA splice variant lncRNA.
Uncharacterized protein Chromosome 16 Open Reading Frame 71 is a protein in humans, encoded by the C16orf71 gene. The gene is expressed in epithelial tissue of the respiratory system, adipose tissue, and the testes. Predicted associated biological processes of the gene include regulation of the cell cycle, cell proliferation, apoptosis, and cell differentiation in those tissue types. 1357 bp of the gene are antisense to spliced genes ZNF500 and ANKS3, indicating the possibility of regulated alternate expression.
Uncharacterized protein C12orf60 is a protein that in humans is encoded by the C12orf60 gene. The gene is also known as LOC144608 or MGC47869. The protein lacks transmembrane domains and helices, but it is rich in alpha-helices. It is predicted to localize in the nucleus.
Uncharacterized protein C2orf73 is a protein that in humans is encoded by the C2orf73 gene. The protein is predicted to be localized to the nucleus.
TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.
Chromosome 4 open reading frame 51 (C4orf51) is a protein which in humans is encoded by the C4orf51 gene.
Cilia- and flagella-associated protein 299 (CFAP299), is a protein that in humans is encoded by the CFAP299 gene. CFAP299 is predicted to play a role in spermatogenesis and cell apoptosis.
Uncharacterized Protein C15orf32 is a protein which in humans is encoded by the C15orf32 gene and is located on chromosome 15, location 15q26.1. Variants of C15orf32 have been linked to bipolar disorder, alcohol use disorder, and acute myeloid leukemia.
C7orf50 is a gene in humans that encodes a protein known as C7orf50. This gene is ubiquitously expressed in the kidneys, brain, fat, prostate, spleen, among 22 other tissues and demonstrates low tissue specificity. C7orf50 is conserved in chimpanzees, Rhesus monkeys, dogs, cows, mice, rats, and chickens, along with 307 other organisms from mammals to fungi. This protein is predicted to be involved with the import of ribosomal proteins into the nucleus to be assembled into ribosomal subunits as a part of rRNA processing. Additionally, this gene is predicted to be a microRNA (miRNA) protein coding host gene, meaning that it may contain miRNA genes in its introns and/or exons.
Uncharacterized protein C17orf78 is a protein encoded by the C17orf78 gene in humans. The name denotes the location of the parent gene, being at the 78th open reading frame, on the 17th human chromosome. The protein is highly expressed in the small intestine, especially the duodenum. The function of C17orf78 is not well defined.
C2orf74, also known as LOC339804, is a protein encoding gene located on the short arm of chromosome 2 near position 15 (2p15). Isoform 1 of the gene is 19,713 base pairs long. C2orf74 has orthologs in 135 different species, including primarily placental mammals and some marsupials.
SMIM19, also known as Small Integral Membrane Protein 19, encodes the SMIM19 protein. SMIM19 is a confirmed single-pass transmembrane protein passing from outside to inside, 5' to 3' respectively. SMIM19 has ubiquitously high to medium expression with among varied tissues or organs. The validated function of SMIM19 remains under review because of on sub-cellular localization uncertainty. However, all linked proteins research to interact with SMIM19 are associated with the endoplasmic reticulum (ER), presuming SMIM19 ER association
The FAM214B, also known as protein family with sequence similarity 214, B (FAM214B) is a protein that, in humans, is encoded by the FAM214B gene located on the human chromosome 9. The protein has 538 amino acids. The gene contain 9 exon. There has been studies that there are low expression of this gene in patients with major depression disorder. In most organisms such as mammals, amphibians, reptiles, and birds, there are high levels of gene expression in the bone marrow and blood. For humans in fetal development, FAM214B is mostly expressed in the brains and bone marrow.
C6orf136 is a protein in humans encoded by the C6orf136 gene. The gene is conserved in mammals, mollusks, as well some porifera. While the function of the gene is currently unknown, C6orf136 has been shown to be hypermethylated in response to FOXM1 expression in Head Neck Squamous Cell Carcinoma (HNSCC) tissue cells. Additionally, elevated expression of C6orf136 has been associated with improved survival rates in patients with bladder cancer. C6orf136 has three known isoforms.
FAM120AOS, or family with sequence similarity 120A opposite strand, codes for uncharacterized protein FAM120AOS, which currently has no known function. The gene ontology describes the gene to be protein binding. Overall, it appears that the thyroid and the placenta are the two tissues with the highest expression levels of FAM120AOS across a majority of datasets.
Family with sequence 98, member C or FAM98C is a gene that encodes for FAM98C has two aliases FLJ44669 and hypothetical protein LOC147965. FAM98C has two paralogs in humans FAM98A and FAM98B. FAM98C can be characterized for being a Leucine-rich protein. The function of FAM98C is still not defined. FAM98C has orthologs in mammals, reptiles, and amphibians and has a distant orhtologs in Rhinatrema bivittatum and Nanorana parkeri.
Chromosome 5 open reading frame forty-nine, also known as C5orf49, is a protein that in humans is encoded by the C5orf49 gene. Aliases for C5orf49 include Chromosome 5 Open Reading Frame 49, Uncharacterized Protein C5orf49 and LOC134121. C5orf49 is predicted to localize to the cilia and have ciliary functions.
Chromosome 5 open reading frame 22 (c5orf22) is a protein-coding gene of poorly characterized function in Homo sapiens. The primary alias is unknown protein family 0489 (UPF0489).
C4orf36 is a protein that in humans is encoded by the c4orf36 gene.
