Wikipedia

C11orf49

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]

CSTPP1
Identifiers
AliasesCSTPP1, chromosome 11 open reading frame 49, C11orf49, centriolar satellite-associated tubulin polyglutamylase complex regulator 1
External IDsMGI: 1915079; HomoloGene: 11471; GeneCards: CSTPP1; OMA:CSTPP1 - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 2: 91.11 – 91.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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Aliases

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

Location

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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

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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.

Protein

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Homo sapiens C11orf49 Conceptual Translation
 
Predicted secondary structure from Phyre2
 
Predicted tertiary structure from i-Tasser (Ribbon style)
 
Predicted tertiary structure from i-Tasser (Sphere style)

Isoforms

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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.

Composition

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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

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

Secondary Structure

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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

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

Post-Translational Modifications

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Phosphorylation

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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

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

Subcellular Localization

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

Gene Level Regulation

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Promoters

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Promoter locations on C11orf49 gene found in humans

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

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Transcription factor binding sites for C11orf49 promoter found in humans

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

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Microarray expression patterns for C11orf49
 
C11orf49 RNA-Seq data

Tissue Specific Expression

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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

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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

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C11orf49 5' UTR Stem-Loop Structure
 
C11orf49 Transcript 3' UTR Stem-Loop Structures and miRNA Binding Sites

5' UTR

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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

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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

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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.

Homology and Evolution

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Orthologs and Paralogs

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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.

Evolution

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C11orf49 Evolutionary Rate Graph

History

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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

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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

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Protein Kinase Activity

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

Clinical Significance

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000149179 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040591 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e "C11orf49 chromosome 11 open reading frame 49 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-17.
  6. ^ "GDS596 / 203257_s_at". www.ncbi.nlm.nih.gov. Retrieved 2020-12-17.
  7. ^ a b c "C11orf49 Gene - GeneCards | CK049 Protein | CK049 Antibody". www.genecards.org. Retrieved 2020-12-17.
  8. ^ a b c d "Phyre 2 Results for Undefined". www.sbg.bio.ic.ac.uk. Retrieved 2020-12-17.[permanent dead link‍]
  9. ^ a b c d "PSICQUIC View". www.ebi.ac.uk. Retrieved 2020-12-17.
  10. ^ "Human BLAT Search". genome.ucsc.edu. Retrieved 2020-12-17.
  11. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2020-12-17.
  12. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-12-18.
  13. ^ "Bioinformatics Toolkit". toolkit.tuebingen.mpg.de. Retrieved 2020-12-18.
  14. ^ a b "I-TASSER results". zhanglab.ccmb.med.umich.edu. Retrieved 2020-12-18.[permanent dead link‍]
  15. ^ a b "SIB Swiss Institute of Bioinformatics | Expasy". www.expasy.org. Retrieved 2020-12-18.
  16. ^ "PSORT II Prediction". psort.hgc.jp. Retrieved 2020-12-18.
  17. ^ "Genomatix: Retrieve and analyze promoters: Query Input". www.genomatix.de. Retrieved 2020-12-18.[permanent dead link‍]
  18. ^ "Genomatix: MatInspector Input". www.genomatix.de. Retrieved 2020-12-18.[permanent dead link‍]
  19. ^ "GDS596 / 203257_s_at". www.ncbi.nlm.nih.gov. Retrieved 2020-12-18.
  20. ^ a b "59175105 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  21. ^ a b "14476184 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  22. ^ a b "RNAfold web server". rna.tbi.univie.ac.at. Retrieved 2020-12-19.
  23. ^ "TargetScanHuman 7.2 predicted targeting of Human C11orf49". www.targetscan.org. Retrieved 2020-12-19.
  24. ^ a b c d "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2020-12-19.
  25. ^ a b c "Human BLAT Search". genome.ucsc.edu. Retrieved 2020-12-19.
  26. ^ "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-12-19.
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