C7orf50
C7orf50 | ||||||
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Identifiers | ||||||
Ensembl | ||||||
UniProt | ||||||
RefSeq (mRNA) |
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RefSeq (protein) |
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Location (UCSC) | Chr 7: 1 – 1.14 Mb | Chr 5: 139.35 – 139.45 Mb | ||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
C7orf50 (Chromosome 7, Open Reading Frame 50) is a
Gene
Background
C7orf50, also known as YCR016W, MGC11257, and LOC84310, is a protein coding gene of poor characterization in need of further research. This gene can be accessed on NCBI at the accession number NC_000007.14, on HGNC at the ID number 22421, on ENSEMBL at the ID ENSG00000146540, on GeneCards at GCID:GC07M000996, and on UniProtKB at the ID Q9BRJ6.
Location
C7orf50 is located on the short arm of chromosome 7 (7p22.3), starting at base pair (bp) 977,964 and ending at bp 1,138,325. This gene spans 160,361 bps on the minus (-) strand and contains a total of 13 exons.[5]
Gene Neighborhood
Genes within the neighborhood of C7orf50 are the following: LOC105375120,
mRNA
Alternative Splicing
C7orf50 has a total of 7 experimentally curated
C7orf50 Experimentally Determined
NCBI Reference Sequences (RefSeq) mRNA Transcripts | |||||
Name | NCBI Accession # | Transcript Length | # of Exons | Protein Length | Isoform |
Transcript Variant 1 | NM_032350.5 | 1311bp | 5 | 194aa | a |
Transcript Variant 2 | NM_001134395.1 | 1301bp | 5 | 194aa | a |
Transcript Variant 3 | NM_001134396.1 | 1282bp | 5 | 194aa | a |
Transcript Variant 4 | NM_001318252.2 | 2138bp | 5 | 194aa | a |
Transcript Variant 7 | NM_001350968.1 | 1081bp | 6 | 193aa | b |
Transcript Variant 8 | NM_001350969.1 | 1500bp | 5 | 180aa | c |
Transcript Variant 9 | NM_001350970.1 | 1448bp | 3 | 60aa | d |
Alternatively, when the primary genomic assembly, GRCh38.p13, is used for annotation (NCBI: NC_000007.14), there are 10 computationally predicted mRNA transcripts.[5] The most complete and supported of these transcripts (transcript variant X6) is 1896bp, producing a 225aa-long protein.[14] In total, there are 6 different isoforms predicted for C7orf50. Of these transcripts, 5 of them encode for the same isoform (X3).[15] The remaining transcripts encode isoforms X2, X4, X5, X6, and X7 as represented below.
C7orf50 Computationally Determined
NCBI Reference Sequences (RefSeq) mRNA Transcripts | ||||
Name | NCBI Accession # | Transcript Length | Protein Length | Isoform |
Transcript Variant X2 | XM_017012719.1 | 1447bp | 375aa | X2 |
Transcript Variant X3 | XM_011515582.3 | 1192bp | 225aa | X3 |
Transcript Variant X4 | XM_024446977.1 | 1057bp | 193aa | X4 |
Transcript Variant X5 | XM_011515581.3 | 1240bp | 225aa | X3 |
Transcript Variant X6 | XM_011515584.2 | 1896bp | 225aa | X3 |
Transcript Variant X7 | XM_017012720.2 | 1199bp | 225aa | X3 |
Transcript Variant X8 | XM_011515583.2 | 1215bp | 225aa | X3 |
Transcript Variant X9 | XM_017012721.2 | 2121bp | 211aa | X5 |
Transcript Variant X10 | XM_024446978.1 | 2207bp | 180aa | X6 |
Transcript Variant X11 | XM_024446979.1 | 933bp | 93aa | X7 |
5' and 3' UTR
Based on the experimentally determined C7orf50 mRNA transcript variant 4, the 5' UTR of C7orf50 is 934 nucleotides (nt) long, while the 3' UTR is 619nt. The coding sequence (CDS) of this transcript spans nt 935..1519 for a total length of 584nt and is encoded in reading frame 2.[12] Interestingly, the 5'UTR of C7orf50 contains a uORF in need of further study, ranging from nt 599 to nt 871 also in the second reading frame.[16]
Protein
General Properties
The C7orf50 Isoform a's 194aa protein sequence from NCBI [13] is as follows:
>NP_001127867.1 uncharacterized protein C7orf50 isoform a [Homo sapiens] MAKQKRKVPEVTEKKNKKLKKASAEGPLLGPEAAPSGEGAGSKGEAVLRPGLDAEPELSPEEQRVLERKL 70 KKERKKEERQRLREAGLVAQHPPARRSGAELALDYLCRWAQKHKNWRFQKTRQTWLLLHMYDSDKVPDEH 140 FSTLLAYLEGLQGRARELTVQKAEALMRELDEEGSDPPLPGRAQRIRQVLQLLS 194
The underlined region within the sequence is indicative of a domain known as DUF2373 ("domain of unknown function 2373"), found in isoforms a, b, and c.
C7orf50 has a predicted
Domains and Motifs
DUF2373 is a domain of unknown function found in the C7orf50 protein. This is a highly conserved c-terminal region found from fungi to humans.[22] As for motifs, a bipartite nuclear localization signal (NLS) was predicted from aa6 to aa21, meaning that C7orf50 is likely localized in the nucleus.[23] Interestingly, a nuclear export signal (NES) is also found within the C7orf50 protein at the following amino acids: 150, and 153 - 155, suggesting that C7orf50 has function both inside and outside the nucleus.[24][25]
Structure
Secondary Structure
The majority of C7orf50 (isoform a) secondary structure is made up of alpha helices, with the remainder being small portions of random coils, beta turns, or extended strands.[26][27]
Tertiary Structure
The tertiary structure of C7orf50 consists primarily of alpha helices as determined I-TASSER.[9][28][29]
Quaternary Structure
The interaction network (
Biological Processes | rRNA processing | maturation of 5.8S, LSU, and SSU rRNA |
Molecular Functions | catalytic activity, acting on RNA | ATP-dependent RNA helicase activity |
Cellular Components | nucleolus | preribosomes |
Reactome Pathways | major pathway of rRNA processing in the nucleolus and cytosol | rRNA modification in the nucleus and cytosol |
Protein Domains and Motifs | helicase conserved C-terminal domain | DEAD/DEAH box helicase |
The closest predicted functional partners of C7orf50 are the following proteins: DDX24, DDX52, PES1, EBNA1BP2, RSLD1, NOP14, FTSJ3, KRR1, LYAR, and PWP1. These proteins are predicted to co-express rather than bind directly C7orf50 and each other.
Regulation
Gene Regulation
Promoter
C7orf50 has 6 predicted
Promoter ID | Start Position | End Position | Length | # of Coding Transcripts | Greatest # of CAGE Tags in Transcripts |
GXP_9000582 | 1013063 | 1013163 | 1101bp | 0 | N/A |
GXP_6755691 | 1028239 | 1030070 | 1832bp | 4 | 169233 |
GXP_6053282 | 1055206 | 1056306 | 1101bp | 1 | 449 |
GXP_3207505 | 1127288 | 1128388 | 1101bp | 1 | 545 |
GXP_9000584 | 1130541 | 1131641 | 1101bp | 0 | N/A |
GXP_6755694 | 1137965 | 1139325 | 1361bp | 16 | 100,070 |
The CpG island associated with this promoter has 75 CpGs (22% of island), and is 676bp long. The C count plus G count is 471, the percentage C or G is 70% within this island, and the ratio of observed to expected CpG is 0.91.[32][33]
Transcription Factor Binding Sites
As determined by MatInspector at Genomatix, the following transcription factor (TFs) families are most highly predicted to bind to C7orf50 in the promoter region.[31]
Transcription Factor | Detailed Family Information |
NR2F | Nuclear receptor subfamily 2 factors |
PERO | Peroxisome proliferator-activated receptor |
HOMF | Homeodomain transcription factors |
PRDM | PR (PRDI-BF1-RIZ1 homologous) domain transcription factor |
VTBP | Vertebrate TATA binding protein factor |
HZIP | Homeodomain-leucine zipper transcription factors |
ZTRE | Zinc transcriptional regulatory element |
XBBF | X-box binding factors |
SP1F
|
GC-Box factors SP1/GC |
CAAT | CCAAT binding factors |
ZF57 | KRAB domain zinc finger protein 57 |
CTCF | CTCF and BORIS gene family, transcriptional regulators with highly conserved zinc finger domains |
MYOD | Myoblast determining factors |
KLFS | Krueppel like transcription factors |
Expression Pattern
C7orf50 shows ubiquitous expression in the kidneys, brain, fat, prostate, spleen and 22 other tissues and low tissue and immune cell specificity .[5][6] This expression is very high, 4 times above the average gene; therefore, there is a higher abundance of C7orf50 mRNA than the average gene within a cell.[34] There does not appear to be a definitive cell type in which this gene is not expressed.[35]
Transcription Regulation
Splice Enhancers
The mRNA of C7orf50 is predicted to have exonic splicing enhancers, in which SR proteins can bind, at bp positions 45 (SRSF1 (IgM-BRCA1)), 246 (SRSF6), 703 (SRSF5), 1301 (SRSF1), and 1308 (SRSF2) [36][37]
Stem Loop Prediction
Both the 5' and 3' UTRs of the mRNA of C7orf50 are predicted to fold into structures such as bulge loops,
miRNA Targeting
There are many poorly conserved miRNA binding sites predicted within the 3’UTR of C7orf50 mRNA. The notable miRNA families that are predicted to bind to C7orf50 mRNA and regulate/repress transcription are the following: miR-138-5p, miR-18-5p, miR-129-3p, miR-124-3p.1, miR-10-5p, and miR-338-3p.[39][40][41]
Protein Regulation
Subcellular Localization
The C7orf50 protein is predicted to localize intercellularly in both the nucleus and cytoplasm, but primarily within the nucleoplasm and nucleoli.[42][43][23][44]
Post-Translational Modification
The C7orf50 protein is predicted to be mucin-type GalNAc o-glycosylated at the following amino acid sites: 12, 23, 36, 42, 59, and 97.[45][46] Additionally, this protein is predicted to be SUMOylated at aa71 with the SUMO protein binding from aa189 through aa193.[47][48][49] C7orf50 is also predicted to be kinase-specific phosphorylated at the following amino acids: 12, 23, 36, 42, 59, 97, 124, 133, 159, and 175.[50][51][52][53][54] Interestingly, many of these sites overlap with the o-glycosylation sites. Of these phosphorylation sites, the majority are serines (53%) with the remainder being either tyrosines or threonines. The most associated kinases with these sites are the following kinase groups: AGC, CAMK, TKL, and STE. Finally, this protein is predicted to have 8 glycations of the ε amino groups of lysines at the following sites: aa3, 5, 14, 15, 17, 21, 76, and 120.[55][56]
Homology
Paralogs
No
Orthologs
Below is a table of a variety of orthologs of the human C7orf50 gene.[58][7] The table includes closely, moderately, and distantly related orthologs. C7orf50 is highly evolutionary conserved from mammals to fungi. When these ortholog sequences are compared, the most conserved portions are those of DUF2373, highlighting this domain's importance in the functioning of C7orf50. C7orf50 has evolved moderately and evenly over time with a divergence rate greater than Hemoglobin but less than Cytochrome C.
Genus and Species | Common Name | Taxon Class | Date of Divergence (MYA) | Accession # | Length (AA) | % identity w/ human |
---|---|---|---|---|---|---|
Homo sapiens
|
Human | Mammalia | N/A | NM_001318252.2 | 194aa | 100% |
Tupaia chinensis | Chinese Tree Shrew | Mammalia | 82 | XP_006167949.1 | 194aa | 76% |
Dasypus novemcinctus | Nine-banded Armadillo | Mammalia | 105 | XP_004483895.1 | 198aa | 70% |
Miniopterus natalens | Natal Long-fingered Bat | Mammalia | 96 | XP_016068464.1 | 199aa | 69% |
Protobothrops mucrosquamatus | Brown-spotted Pit Viper | Reptilia | 312 | XP_015673296.1 | 196aa | 64% |
Balearica regulorum gibbericeps | Grey-crowned Crane | Aves | 312 | XP_010302837.1 | 194aa | 61% |
Falco peregrinus | Peregrine Falcon | Aves | 312 | XP_027635198.1 | 193aa | 59% |
Xenopus laevis | African Clawed Frog | Amphibia | 352 | XP_018094637.1 | 198aa | 50% |
Electrophorus electricus | Electric Eel | Actinopterygii | 435 | XP_026880604.1 | 195aa | 53% |
Rhincodon typus | Whale Shark | Chondrichthyes | 465 | XP_020372968.1 | 195aa | 52% |
Ciona intestinalis | Sea Vase | Ascidiacea | 676 | XP_026696561.1 | 282aa | 37% |
Octopus bimaculoides | California Two-spot Octopus | Cephalopoda | 797 | XP_014772175.1 | 221aa | 40% |
Priapulus caudatus | Priapulus | Priapulida | 797 | XP_014663190.1 | 333aa | 39% |
Bombus terrestris | Buff-tailed Bumblebee | Insecta | 797 | XP_012171653.1 | 260aa | 32% |
Actinia tenebrosa | Australian Red Waratah Sea Anemone | Anthozoa | 824 | XP_031575029.1 | 330aa | 43% |
Trichoplax adhaerens | Trichoplax | Trichoplacidae | 948 | XP_002110193.1 | 137aa | 44% |
Spizellomyces punctatus | Branching Chytrid Fungi | Fungi | 1105 | XP_016610491.1 | 412aa | 29% |
Eremothecium cymbalariae | Fungi | Fungi | 1105 | XP_003644395.1 | 266aa | 25% |
Quercus suber | Cork Oak Tree | Plantae | 1496 | XP_023896156.1 | 508aa | 30% |
Plasmopara halstedii | Downy Mildew of Sunflower | Oomycetes | 1768 | XP_024580369.1 | 179aa | 26% |
Function
The consensus prediction of C7orf50 function (GO terms), as determined by I-TASSER,[59][28][29] predicts the molecular function to be protein binding, the biological process to be protein import (specifically into the nucleus), and the associated cellular component to be a pore complex (specifically of the nuclear envelope). It can be predicted that the function of C7orf50 is one in which C7orf50 imports ribosomal proteins into the nucleus in order to be made into ribosomes, but further research is needed to solidify this function.
Interacting Proteins
Name of Protein | Name of Gene | Function | UniProt Accession # |
---|---|---|---|
THAP1 domain-containing protein 1 | THAP1 | DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression.[62] | Q9NVV9 |
Protein Tax-2 | tax | Transcriptional activator that activates both the viral long terminal repeat (LTR) and cellular promoters via activation of CREB, NF-kappa-B, SRF and AP-1 pathways.[63] | P03410 |
Major Prion Protein | PRNP
|
Its primary physiological function is unclear. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May promote myelin homeostasis through acting as an agonist for ADGRG6 receptor. May play a role in iron uptake and iron homeostasis.[64] | P04156 |
Aldehyde dehydrogenase X, mitochondrial | ALDH1B1 | Pay a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation.[65] | P30837 |
Cell growth-regulating nucleolar protein | LYAR | Plays a role in the maintenance of the appropriate processing of 47S/45S pre-rRNA to 32S/30S pre-rRNAs and their subsequent processing to produce 18S and 28S rRNAs.[66][67] | Q9NX58 |
Coiled-coil domain-containing protein 85B | CCDC85B | Functions as a transcriptional repressor.[68][69] | Q15834 |
Nucleolar protein 56 | NOP56
|
Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs.[70] | O00567 |
rRNA 2'-O-methyltransferase fibrillarin | FBL | Has the ability to methylate both RNAs and proteins. Involved in pre-rRNA processing by catalyzing the site-specific 2'-hydroxyl methylation of ribose moieties in pre-ribosomal RNA.[71][72][73] | P22087 |
40S ribosomal protein S6 | RPS6
|
May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA.[74] | P62753 |
Clinical Significance
C7orf50 has been noted in a variety of genome-wide association studies (GWAS) and has been shown to be associated with type 2 diabetes among sub-Saharan Africans,[75] daytime sleepiness in African-Americans,[76] prenatal exposure to particulate matter,[77] heritable DNA methylation marks associated with breast cancer,[78] DNA methylation in relation to plasma carotenoids and lipid profile,[79] and has significant interactions with prion proteins.[80]
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