Gene
The cytogenic locus is found at 10q11.23. [1] C10orf71 encodes 28294 base pairs (bp) within chromosome 10 at 49299193-49327487 bp. [1] It is located on the plus strand and is flanked by several other genes. [1]
Cardiac-enriched FHL2-interacting protein (CEFIP) is a protein encoded by the gene C10orf71 on chromosome 10 open reading frame 71. [1] [2] It is primarily understood that this gene is moderately expressed in muscle tissue and cardiac tissue. [3] [4]
The cytogenic locus is found at 10q11.23. [1] C10orf71 encodes 28294 base pairs (bp) within chromosome 10 at 49299193-49327487 bp. [1] It is located on the plus strand and is flanked by several other genes. [1]
The mRNA sequence of C10orf71 has 3 exons and 10 stop codons in the favorable splice form. [1] [6] The two alternative splice forms had 47 and 75 stop codons interspersed throughout the sequence so they were not utilized to obtain further sequence information. The main splice form that was analyzed had the ten stop codons interspersed throughout the 5' and 3' UTR, which was why this splice form was utilized to further analyze. The mRNA of the Homo sapiens ortholog of C10orf71was 5286 bp in length. [1] [6]
| Splice 1 | Stop Codons found starting at bp: 4, 150, 247, 310, 4645, 4774, 4783, 4855, 4986, and 5250 Exons found between bp: 431/432, 544/545, and 5285/5286 Kozak site found at bp 332-334 |
| Splice 2 | 47 Stop Codons found interspersed throughout the entire sequence |
| Splice 3 | 75 stop codons found interspersed throughout the entire sequence |
The three alternative splice forms found of C10orf71 mRNA sequence and the locations stop codons, exons and the Kozak site found in Splice 1. Splice 1 was utilized to analyze and obtain information about as all of the stop codons found in this splice form were found in the 5' and 3' UTR regions of the sequence. There were three exons found in Splice 1 with a Kozak consensus sequence in the overall sequence as well. [1] [6]
The mature Homo sapiens homolog of the CEFIP protein encoded by C10orf71 is 1435 amino acids (aa) in length and weighs approximately 156.5 kDa. [6] This homolog has an isoelectric point of 5.94. [6] The range of pH values from Homo sapiens to the latest ortholog analyzed, Rhincodon types, ranged from 5.94-6.93, with it gradually increasing as it went later in the divergence of the ortholog. [6]
| Species | Length (aa) | Molecular Weight (kDa) | Isoelectric point |
| Homo sapiens | 1,435 | 156.5 | 5.94 |
| Gorilla gorilla | 1,435 | 156.2 | 5.91 |
| Mus muculus | 1,412 | 154.5 | 5.81 |
| Gallus gallus | 1,521 | 167.7 | 6.15 |
| Rhincodon typus | 1,253 | 138.8 | 6.93 |
Comparison of some of the orthologs analyzed when compared to Homo sapiens. The orthologs are arranged from species that are most closely related to the Homo sapiens ortholog to least closely related (top to bottom respectively). [6]
CEFIP is predicted to be a non-transmembrane, soluble protein. [7] It is predicted to be a nuclear protein with 91.3% confidence with it being fairly confident to be a nuclear protein throughout the orthologs. There was one positive charge cluster found in CEFIP protein sequence, that is located from amino acids 1165–1193. [6] This cluster was moderately conserved throughout the orthologs analyzed. There was also a mixed charge cluster found in the Homo sapiens' sequence of this protein, located from amino acid 750–778, although this cluster was not highly conserved throughout the analyzed orthologs. [6] There was one repeat sequence found as well, TASKPPA, located at amino acids 163-169 and 116–1172. This protein is Proline and Serine rich as well. [6]
| Species | Nuclear | Cytoplasmic | Cytoskeletal |
| Homo sapiens | 91.3% | 4.3% | 4.3% |
| Gorilla gorilla | 91.3% | 4.3% | 4.3% |
| Mus musculus | 82.6% | 13.0% | — |
| Gallus gallus | 69.6% | 17.4% | 4.3% |
| Rhincodon typus | 69.6% | 21.7% | — |
One confirmed domain of unknown function (DUF) was found within the CEFIP protein sequence, DUF4585. [1] DUF4585 is located on the Homo sapiens protein sequence from amino acid 311–334. DUF4585 was highly conserved throughout the orthologs that were analyzed. There was also a small vacuolar targeting motif (VAC) found within the analyzed protein sequence spanning amino acids 543–546.
The mature CEFIP protein contains nuclear localization signals (NLS), pat4 (RKPK at aa 382, RPRK at aa 640, KRRK at aa 1190) and pat7 (PPWRKPK at aa 379 and PWRKPKT at aa 380) with an NLS score of 0.94. A secondary structure was constructed with a 6.1% confidence level. [7]
There were seven GlcNAc O-glycosylation sites predicted within the protein sequence found at amino acids 116, 120, 139, 165, 468, 470, and 844. [7] There were also several phosphorylation sites found interspersed throughout the sequence. One propeptide cleavage site was predicted at amino acid 38. [7] There were three predicted sumoylation sites found at amino acids 599, 890, and 1176.
The C10orf71 mRNA was found to be highly expressed in cardiac, muscle, and liver tissue (biology). [1]
There were 6 possible promoters found in the sequence. Promoter GXP_6729162 is 1403 bp in length. [9] This promoter had several transcription factors of interest including those involved with myocytes. [9]
There is little scientific information known about the function of CEFIP.
There was a total of 25 proteins generated that were predicted to interact with CEFIP (Homo sapiens ortholog). [10] [11] Most of the interactions predicted were physical interactions with CEFIP. [10] These interactions were discovered through a variety of mechanisms including, but not limited to: affinity chromatography, microarray analysis, and tandem mass spectrometry among others. [10] [11] Refer to table for details about the interacting proteins of CEFIP. [12]
| Interacting Protein | Name of Protein | Known Function | Location Expressed or Associated Diseases |
| C20orf78 | Chromosome 20 Open Reading Frame 78 | Unknown | Unconfirmed |
| BPIFA2 [13] | BPI Fold Containing Family A Member 2 | Plays a role in antibacterial resistance in upper respiratory pathway | Expressed in salivary glands |
| PPIL6 [14] | Peptidyl Prolyl Isomerase Like 6 | Accelerates folding of proteins | Unconfirmed |
| KIF17 [15] | Kinesin Family Member 17 | Transports vesicles containing NMDA receptor 2B | Expressed in microtubules |
| KRT78 [16] | Keratin 78 | Forms cytoplasmic network; encodes proteins with intermediate filament domains | Expressed in intermediate filaments |
| TBX4 [17] | T-box4 Transcription Factor | Encode transcription factors involved in regulation of developmental processes; assists with regulation of mesoderm differentiation; could play a role in limb pattern formation | Associated with Small Patella Syndrome and Heritable Pulmonary Arterial Hypertension |
| DNAH8 [18] | Dynein Axonemal Heavy Chain 8 | heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. | Associated with Colchicine Resistance and Mitochondrial Complex V Deficiency, Nuclear Type 1 |
| TSPAN17 [19] | Tetraspanin 17 | Predicted to regulate ADAM10 maturation | Unconfirmed |
| C14orf80 [20] | Chromosome 14 Open Reading Frame 80 | Unknown | Unconfirmed |
| SLC35F4 [21] | Solute Carrier Family 35 Member F4 | Solute transporter | Unconfirmed |
| LHX4 [22] | LIM Homeobox 4 | Predicted to play a role in maturing lungs, development of respiratory mechanisms, and development of the pituitary gland | Associated with Pituitary Hormone Deficiency, Combined 4 and Lhx4=Related Combined Pituitary Hormone |
| FAM53A [23] | Family With Sequence Similarity 53 Member A | Plays a role in neural development | Possibly expressed in ventricle tissue |
| GRIK5 [24] | Glutamate Ionotropic Receptor Kainase Type Subunit 5 | Forms functional heteromeric kainite-preferring ionic channels | Associated with Schizophrenia |
| FADS2 [25] | Fatty Acid Denaturase 2 | Regulates unsaturation of fatty acids through introduction of double bonds between define Cysteines of the fatty acid chains | Associated with Best Vitelliform Macular Dystrophy |
| GDF2 [26] | Growth Differentiation Factor 2 | Regulates cartilage and bone development; differentiation of cholinergic receptors in CNS | Unconfirmed |
| C17orf77 [27] | Chromosome 17 Open Reading Frame 77 | Unknown | Unconfirmed |
| CFAP45 (CCDC19) [28] | Cilia And Flagella Associated Protein 45 | Associated with pharynx cancer | Unconfirmed |
| DCST2 [29] | DC-STAMP Domain Containing 2 | Unknown | Unconfirmed |
| CTXN1 [30] | Cortexin 1 | Predicted to play a role in IC or EC signaling of the cortical neurons during the development of the forebrain. | Unconfirmed |
| C19orf68 [31] | Chromosome 19 Open Reading Frame 68 | Unknown | Unconfirmed |
| DCAF7 [32] | DDB1 And CUL4 Associated Factor 7 | It's been shown to function as a scaffold protein in kinase signaling. It's also been known to be involved with craniofacial development | Unconfirmed |
| DYRK1A [33] | Dual Specificity YAK1-Related Kinase | May play a role in brain development and cell proliferation; nuclear localized protein | Associated with Mental Retardation, Autosomal Dominant 7 and Microcephaly |
| DYRK1B [34] | Dual Specificity Tyrosine-(Y)-Phosphorylation Regulated Kinase 1B | Plays a role in the cell cycle; nuclear-localized protein | Associated with Abdominal Obesity-Metabolic Syndrome 3 and Abdominal Obesity-Metabolic Syndrome |
| FNTA [35] | Protein Farnesyltransferase/Geranylgeranyltransferase Type-1 Subunit Alpha | Helps regulate neuromuscular junction development | Unconfirmed |
| FNTB [36] | Protein Farnesyltransferase Subunit Beta | Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine | Unconfirmed |
Interacting proteins, their function if known, and any tissues they have been found or predicted to be expressed in and any diseases they have been associated with. [10] [11] [12]
There are currently no known paralogs to the C10orf71 gene.
C10orf71 is known to have 68 orthologs in various species including primates (11 species), rodents (8 species), Laurasiatheria carnivores (14 species), Placental mammals (38 species), Sauropsida birds and reptiles (7 species), and fish (11 species). [37] The highly conserved sequences are primarily from primates with the identity percentage of these species being >90%, whereas species such as reptiles, birds, and fish had an identity percentage ≤30%. [6] Refer to table for additional information on dates of divergence, sequence length, and sequence identity and similarity for orthologs. C10orf71 is not present in prokaryotes, archaea, or fungi. [37]
| Abbreviation (for Phylogenetic Tree) | Species | Common Name | Protein Accession # | Estimated Date of Divergence (MYA) | Sequence Length (aa) | Sequence Identity to Human mRNA/protein (%) | Sequence Similarity to Human mRNA/protein (%) |
| HomS | Homo sapiens | human | NP_001128668.1 | 1435 | 100 | 100 | |
| GorG | Gorilla gorilla | western gorilla | XP_018889898.1 | 9.06 | 1435 | 98.3 | 98.7 |
| RhiR | Rhinopithecus roxellana | Golden snub-nosed monkey | XP_010381152.1 | 29.44 | 1435 | 93.4 | 95.3 |
| OtoG | Otolemur garnettii | small-eared galago | XP_003801705.1 | 74 | 1419 | 74.9 | 81.5 |
| TupC | Tupaia chinensis | Chinese tree shrew | XP_014439281.1 | 82 | 1186 | 61.5 | 67.8 |
| MusM | Mus musculus | house mouse | NP_001182026.1 | 90 | 1412 | 65.4 | 74.3 |
| OctD | Octodon degus | Common degu | XP_004647022.1 | 90 | 1407 | 63.3 | 73.1 |
| HetG | Heterocephalus glaber | Naked mole-rat | XP_004874589.1 | 90 | 1411 | 63.2 | 73.3 |
| CerS | Ceratotherium simum simum | Southern white rhinoceros | XP_004432504.1 | 96 | 1436 | 74 | 81 |
| OrcO | Orcinus orca | killer whale | XP_004286436 | 96 | 1433 | 72.6 | 79.4 |
| LoxA | Loxodonta Africana | African bush elephant | XP_003408977.1 | 105 | 1438 | 65.5 | 74.5 |
| SarH | Sarcophilus harrisii | Tasmanian devil | XP_003755230.2 | 159 | 1470 | 49.0 | 62.5 |
| GavG | Gavialis gangeticus | crocodile | XP_019358113.1 | 312 | 1538 | 32.8 | 46.7 |
| TinG | Tinamus guttatus | White-throated tinamou | XP_010216992.1 | 312 | 1529 | 32.4 | 46.3 |
| PelS | Pelodiscus sinensis | turtle | XP_006118195.1 | 312 | 1505 | 32.0 | 46.2 |
| GalG | Gallus gallus | chicken | XP_421655.3 | 312 | 1521 | 30.5 | 44.7 |
| MelU | Melopsittacus undulates | parrot | XP_005153970 | 312 | 1538 | 30.3 | 45.1 |
| OreN | Oreochromis niloticus | Nile tilapia | XP_019221822 | 435 | 661 | 12.0 | 18.7 |
| SclF | Scleropages formosus | Asian arowana | XP_018580403 | 435 | 3125 | 11.5 | 17.9 |
| DanR | Danio rerio | Zebrafish | XP_005157004.1 | 435 | 3591 | 9.2 | 16.0 |
| CluH | Clupea harengus | Atlantic herring | XP_012687674.1 | 435 | 3633 | 9.1 | 13.8 |
| RhiT | Rhincodon typus | whale shark | XP_020385611.1 | 473 | 1253 | 40.0 | 24.8 |
Ortholog table in descending order to latest ortholog diverged. This table compares the orthologs analyzed, their species names, common names, dates of divergence from Homo sapiens ortholog (MYA), length (aa), and percentage of similarity and identity. [1] [6] [37] [38]
A phylogenetic tree was constructed for the orthologs that were analyzed in comparison to Homo sapiens. With the species of latest divergence being Rhincodon types, or the whale shark. [37] [38]
C10orf71's rate of divergence was faster than that of fibrinogen or Cytochrome C . [37]
There was a microarray experiment that also showed evidence that C10orf71's expression was lowered in skeletal muscle tissues that experienced sepsis. [39] There was clinical significance found in the expression level of C10orf71 in an experiment looking at those with Myotonic dystrophy. [39] One microarray analysis produced results that showed C10orf71's expression level decreased in those with prostate cancer as well. [39]
METTL26, previously designated C16orf13, is a protein-coding gene for Methyltransferase Like 26, also known as JFP2. Though the function of this gene is unknown, various data have revealed that it is expressed at high levels in various cancerous tissues. Underexpression of this gene has also been linked to disease consequences in humans.
WD repeat-containing protein 90 is a protein that, in humans, is encoded by the WDR90 gene (16p13.3). This human protein is 1750 amino acids, and has a molecular weight of 187.7 kDa. It contains multiple WD40 repeat domains and one domain of unknown function. This protein is conserved all the way back to invertebrates. Proteins containing WD transducin repeating domains have been found to play a role in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control, autophagy and apoptosis.
C8orf48 is a protein that in humans is encoded by the C8orf48 gene. C8orf48 is a nuclear protein specifically predicted to be located in the nuclear lamina. C8orf48 has been found to interact with proteins that are involved in the regulation of various cellular responses like gene expression, protein secretion, cell proliferation, and inflammatory responses. This protein has been linked to breast cancer and papillary thyroid carcinoma.
TMEM156 is a gene that encodes the transmembrane protein 156 (TMEM156) in Homo sapiens. It has the clone name of FLJ23235.
Chromosome 10 open reading frame 67 (C10orf67), also known as C10orf115, LINC01552, and BA215C7.4, is an un-characterized human protein-coding gene. Several studies indicate a possible link between genetic polymorphisms of this and several other genes to chronic inflammatory barrier diseases such as Crohn's Disease and sarcoidosis.
Glutamate Rich Protein 2 is a protein in humans encoded by the gene ERICH2. This protein is expressed heavily in male tissues specifically in the testes, and proteins are specifically found in the nucleoli fibrillar center and the vesicles of these testicular cells. The protein has multiple protein interactions which indicate that it may play a role in histone modification and proper histone functioning.
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.
C21orf62 is a protein that, in humans, is encoded by the C21orf62 gene. C21orf62 is found on human chromosome 21, and it is thought to be expressed in tissues of the brain and reproductive organs. Additionally, C21orf62 is highly expressed in ovarian surface epithelial cells during normal regulation, but is not expressed in cancerous ovarian surface epithelial cells.
Chromosome 6 open reading frame 62 (C6orf62), also known as X-trans-activated protein 12 (XTP12), is a gene that encodes a protein of the same name. The encoded protein is predicted to have a subcellular location within the cytosol.
C17orf53 is a gene in humans that encodes a protein known as C17orf53, uncharacterized protein C17orf53. It has been shown to target the nucleus, with minor localization in the cytoplasm. Based on current findings C17orf53 is predicted to perform functions of transport, however further research into the protein could provide more specific evidence regarding its function.
Chromosome 21 Open Reading Frame 58 (C21orf58) is a protein that in humans is encoded by the C21orf58 gene.
Chromosome 16 open reading frame 46 is a protein of yet to be determined function in Homo sapiens. It is encoded by the C16orf46 gene with NCBI accession number of NM_001100873. It is a protein-coding gene with an overlapping locus.
C2orf81 is a human gene encoding protein c2orf81, which is predicted to have nuclear localization.
Chromosome 19 open reading frame 44 is a protein that in humans is encoded by the C19orf44 gene. C19orf44 is an uncharacterized protein with an unknown function in humans. C19orf44 is non-limiting implying that the protein exists in other species besides human. The protein contains one domain of unknown function (DUF) that is highly conserved throughout its orthologs. This protein is most highly expressed in the testis and ovary, but also has significant expression in the thyroid and parathyroid. Other names for this protein include: LOC84167.
Chromosome 9 open reading frame 50 is a protein that in humans is encoded by the C9orf50 gene. C9orf50 has one other known alias, FLJ35803. In humans the gene coding sequence is 10,051 base pairs long, transcribing an mRNA of 1,624 bases that encodes a 431 amino acid protein.
Chromosome 1 open reading frame (C1orf167) is a protein which in humans is encoded by the C1orf167 gene. The NCBI accession number is NP_001010881. The protein is 1468 amino acids in length with a molecular weight of 162.42 kDa. The mRNA sequence was found to be 4689 base pairs in length.
C20orf202 is a protein that in humans is encoded by the C20orf202 gene. In humans, this gene encodes for a nuclear protein that is primarily expressed in the lung and placenta.
Chromosome 1 Opening Reading Frame 94 or C1orf94 is a protein in human coded by the C1orf94 gene. The function of this protein is still poorly understood.
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.
Chromosome 4 open reading frame 50 is a protein that in humans is encoded by the C4orf50 gene. The protein localizes in the nucleus. C4orf50 has orthologs in vertebrates but not invertebrates