Centriolar satellite-associated tubulin polyglutamylase complex regulator 1 is a protein that in humans is encoded by the gene CSTPP1 (previously C11orf49). Recent research suggests that it is involved in cytoskeleton organization indirectly by regulating the assembly and stability of a related protein complex called the tubulin polyglutamylase complex.
Gene
Aliases Common aliases are UPF0705, FLJ22210, and MGC4707.
Location C11orf49 is found at locus p11.2 on human chromosome 11, with a plus strand orientation. The gene is 224,830 bp long including introns, and spans from position 46,936,806 to 47,161,635 on chromosome 11.
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. NameAccession NumberNumbers of ExonsSize (bp)Transcript Variant 1NM_001003676.381923Transcript Variant 2NM_001003677.391668Transcript Variant 3NM_024113.581650Transcript Variant 4NM_001003678.391159Transcript Variant 5NM_001278222.181619Transcript Variant 6NR_103471.2101895Transcript Variant 7NR_103472.281519 Table 1. Known human mRNA transcript variants for C11orf49.
Protein
Isoforms There are 5 known isoforms for the C11orf49 protein with isoform 2 being the most complete protein, encoded by transcript variant 2. NameAccession NumberSize (AA)Isoform 1NP_001003676.1274Isoform 2NP_001003677.1337Isoform 3NP_077018.1331Isoform 4NP_001003678.1326Isoform 5NP_001265151.1322 Table 2. Known human protein isoforms for C11orf49.
Composition The C11orf49 protein has a molecular weight of 38.1 kD, and an isoelectric point of about pH = 5. 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.
Protein Domain The C11orf49 protein is predicted to contain a protein kinase domain near the N' terminus (residues 12-51)
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. Information on where these alpha helices are located can be seen to the right of the page.
Tertiary Structure i-Tasser predicted tertiary structure is included to the right of the page.
Post-Translational Modifications Phosphorylation The C11orf49 protein is predicted to be phosphorylated at 4 different sites, mainly on serine residues, but also on one threonine residue. PositionAAKinase310SerineAGC/Akt48ThreonineAGC/Akt/AKT166SerineAGC/Akt318SerineAGC/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.
Subcellular Localization The C11orf49 protein found in humans is predicted to be localized in the cytoplasm.
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. Promoter IDStart PositionEnd PositionSize (bp)OrientationTotal # of transcriptsGXP_20454346935524469368191296plus strand32 GXP_316228047050923470519621040plus strand1 GXP_316228147051454470525001047plus strand2 GXP_316228347136696471377351040plus strand1 GXP_316228447153395471544341040plus strand1 GXP_316228547153944471549831040plus strand1 GXP_20454247159105471601441040plus strand1 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. 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 FamilyDetailed Family InfoDetailed Matrix InfoMatrix ScoreV$NKXHNKX homeodomain factorsHomeodomain factor NKX-2.51V$GATAGATA binding factorGATA-binding factor 30.992V$LEFFLEF1/TCFInvolved in the Wnt signal pathway0.991O$VTBPVertebrate TATA binding factorCellular and viral TATA box elements0.99V$KLFSKrueppel like TFsGut-enriched Krueppel-like TF0.982V$MYBLCellular and Viral myb-like TFsV-Myb0.978V$E2FFE2F-myc activatorE2F TF 10.976V$MEF3MEF3 binding sitesSine oculis homeobox homolog 20.972V$XBBFX-box binding factorsX-box binding protein RFX10.966V$ETSFHuman and murine ETS1 factorsElk-10.958V$PBXCPBX-MEIS complexesPre-B-cell leukemia homeobox 30.949V$CAATCCAAT binding factorsCellular and viral CCAAT box0.927V$HEATHeat shock factorsHeat shock factor 10.927V$MYT1MYT1 C2HC zinc finger proteinMyelin TF 1-like, neuronal C2H2 ZF 10.925V$GCMFChorion-specific TFsGlial cells missing homolog 10.902V$ZF04C2H2 zinc finger TF 4Zinc finger and BTB domain0.9V$MAZFMyc associated zinc fingers (MAZ)MAZ0.875V$PAX9Pax-9 binding sitesZebrafish Pax-9 binding site0.848V$DMRTDM domain-containing TFsMab-3 related TF 10.817 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. RNA-Seq data also shows high expression in lung fetal tissue. 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. 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. 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
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.
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.
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. All interactions were determined using two-hybrid screening experiments. ProteinDescriptionHTTHuntingtin proteinAPOEApolipoprotein EPRKAR1AcAMP-dependent protein kinase type I-alpha regulatory subunitFHFumarate hydrataseGCAGrancalcinPHF1PHD finger protein 1VPS54Vacuolar protein sorting-associated protein 54ZFHX3Zinc finger homeobox protein 3RAB7L1RAS oncogene family-like 1NDRG1Stress responsive proteinPNMA5Paraneoplastic antigen-like protein 5TXN2Thioredoxin Table 6. List of proteins that interact with the C11orf49 protein found in humans.
Homology and Evolution
Orthologs and Paralogs 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. However, C11orf49 could not be found in Insecta or Plantae. There are no known paralogs of C11orf49. Genus and SpeciesCommon nameTaxonomic groupDivergence (MYA)Accession #AA lengthIdentity (%)Similarity (%)Mus musculusMouseRodentia89NP_780332.13319295.5Gallus gallusChickenAves318XP_015142672.133176.783.5Chelonia mydasGreen Sea TurtleReptilia318XP_007054360.236273.479.9Geotrypetes seraphiniGaboon caecilianAmphibia352XP_033784118.132969.981.7Xenopus tropicalisTropical Clawed FrogAmphibia352NM_001079316.133061.977.3Danio rerioZebrafishCyprinoidae433NP_001002479.133154.772.2Sacoglossus kowalevskiiAcorn WormHemichordata627XP_006821066.129943.658.2Nematostella vectensisStarlet Sea AnemoneCnidaria687XP_032240720.130042.457.3Macrostomum lignanoFlatwormPlatyhelminthes692PAA77967.140429.742.3Stegodyphus mimosarumAfrican Velvet SpiderArthropoda736KFM74201.132124.338.5Trichoplax adhaerensTrichoplaxPlacozoa747XP_002108042.126324.739.6Salpingoeca rosettaN/AChoanoflagellate928XP_004994083.123115.525.5Spizellomyces palustrisAustralian fungusSpizellomyces1017TPX67906.129821.432.7Saprolegnia diclinaCotton MouldOomycota1552XP_008621502.131422.935.6 Table 7. List of selected orthologs of C11orf49.
Evolution
History Saprolegnia diclina is the most distantly related ortholog of C11orf49 known, with its divergence from ancestral humans approximately 1,552 MYA.
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.
Clinical Significance C11orf49 has been shown to interact with proteins HTT and APOE2, which are associated with Huntington's disease and Alzheimer's, respectively. 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.
C11orf49 expression is significantly decreased after the treatment of camptothecin on a renal epithelial cell line.
References