CXorf66 | |||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | CXorf66 , SGPX, chromosome X open reading frame 66 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 3779666; HomoloGene: 82551; GeneCards: CXorf66; OMA:CXorf66 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
CXorf66 also known as Chromosome X Open Reading Frame 66, is a 361aa protein in humans that is encoded by the CXorf66 gene. The protein encoded is predicted to be a type 1 transmembrane protein; however, its exact function is currently unknown. [5]
There is a patent for CXorf66 under the file US 8586006 by the Institute for Systems Biology and Integrated Diagnostics, Inc. [6]
CXorf66 protein is a potential novel cancer biomarker. [7]
CXorf66 is located on Chromosome X at Xq27.1 and is on the complement strand. [8] The CXorf66 gene is located between ATP11C ATPase, MIR505, and HNRNPA3P3. [8] In addition to this, according to OMIM, CXorf66 is positioned between SOX3, SPANXB1, and CDR1. [9]
CXorf66 only consists of one known splice variant with three exons (1-117, 118-271, and 272-1288bp) and two introns. [10] Locations of junctions occur at 30aa [G] and 81aa [M]. [10]
CXorf66 has only been found to have only one polyadenylation site. [11]
With 57 serines and 42 lysines, the CXorf66 protein is both serine and lysine rich. [12] CXorf66 has a molecular weight of 39.9kdal and an isoelectric point of 9.89. [12]
CXorf66 protein has a predicted signal peptide from 1-19aa, a topological domain from 20-47aa, a transmembrane domain from 48-68aa, and a second topological domain from 69-361aa. [13] A signal peptide cleavage site is predicted to occur between the 17-18aa. [14] Upon analyzing the protein's composition (serine and lysine rich) and post-translational modifications (high levels of phosphorylation), it is predicted that the first topological domain [20-47aa] is extracellular, while the topological domain [69-361aa] is cytoplasmic. A visual can be seen in Figure II. [15]
Three repeat motifs of DKPV [31-34 and 204-207aa], SEAK [97-100 and 287-290aa], and PKRS [161-164 and 245-248aa] have been found in the human CXorf66 protein. These repeats are conserved in other primates like Gorilla gorilla gorilla and Macaca mulatta , but are not present in other mammals. [16]
There is one natural variant of the population (frequency 0.436) at 233aa from proline to leucine in the CXorf66 protein, with proline being the ancestral encoded amino acid. No effects have been observed with this missense mutation. [13] [17]
Based on STRING's predicted protein interaction, CXorf66 has medium level scoring for being tied to the proteins listed in Figure III. [18] It is important to note that all proteins listed are not experimentally determined.
There is only one known promoter predicted by Genomatix for the CXorf66 protein on the negative strand from 139047554-139048298 that is 745bp in length. [19] When BLAT Search Alignment was used for the CXorf66 promoter generated, numerous hits with high identity were retrieved for various genes on different chromosomes. The following are a few generated top scoring search results that share a high percent identity: [20]
Name | Gene ID | Score | Span (bp) out of 745 | Identity | Chromosome | Strand | Start | End |
---|---|---|---|---|---|---|---|---|
ZBTB8A | 653121 | 282 | 656 | 88.2% | 1 | - | 32994892 | 32995547 |
TESK2 | 10420 | 263 | 624 | 90.3% | 1 | - | 45843093 | 45843716 |
TBCK | 93627 | 244 | 639 | 91.5% | 4 | + | 107146630 | 107147268 |
USP48 | 84196 | 241 | 631 | 89.0% | 1 | + | 22014725 | 22015355 |
PTPN22 | 26191 | 227 | 281 | 90.0% | 1 | - | 114365307 | 114365587 |
PSPH | 5723 | 220 | 605 | 90.6% | 7 | - | 56098319 | 56098923 |
Uniquely, TESK2 is a testis-specific protein kinase, which correlates with predicted CXorf66 tissue expression.
Through the use of Genomatix, a table was generated of the top 20 transcription factors and their binding sites in the CXorf66 promoter (see Figure IV). [19]
CXorf66 has two miRNAs, hsa-mir-1290 Archived 2021-03-05 at the Wayback Machine and hsa-miR-4446-5p Archived 2016-03-04 at the Wayback Machine predicted to bind to the 3' UTR region of the mRNA. [21]
An N-glycosylation site has been predicted by Expasy's NetNGlyc at NGSS [24aa] with a secondary site also possible at NGTN [21aa]. [22] Utilizing NetPhos, a total of 48 phosphorylation sites have been predicted (41 Serines, 2 Threonines, and 5 Tyrosines), all of which occur after the predicted transmembrane domain, suggesting cytoplasmic topology. [23] Using YinOYang, many O-GlcNAc sites have been predicted. All that include high potential occur after the 48-68aa transmembrane region. [24] A SUMOplot Analysis conducted of Homo sapiens CXorf66 protein, discovered a high probability of a sumoylation motif at position K241, alongside low probability motifs at K316 and K186. With sumoylation having a role in various cellular processes like nuclear-cytosolic transport and transcriptional regulation, it is expected CXorf66 is modified by a SUMO protein post-translation. [25]
Using PSORT II, there is a nuclear localization signal of PYKKKHL at 268aa. [26] This signal can be seen to be conserved in fellow primate species; however, is not present in other mammals. In addition to this, following SDSC's Biology Workbench's SAPS kNN-Prediction, the CXorf66 protein for humans and the mouse homolog have a 47.8% likelihood to end up in the nuclear region of a cell. For more distant homologs, like Bos taurus, that do not have nuclear localization signals however, CXorf66 has a 34.8% likelihood to end up in the extracellular, including cell wall region, or plasma membrane regions. [12] [26] To view several homologs and their nuclear localization signals, see Figure V.
CXorf66 has no known paralogs in humans; however CXorf66 has conserved homologs throughout the Mammalia kingdom. Highly conserved in primates, a noticeable rapid evolution has been spotted for CXorf66, see Figure VI, explaining the greater number of orthologs in mammals, rather than in invertebrates, birds, and reptiles. [27]
CXorf66 Protein | Species | Date of divergence (MYA) [28] | ncbi accession Number | query cover | E value | Identity |
---|---|---|---|---|---|---|
CXorf66 homolog | Chimpanzee (Pan troglodytes) | 6.3 | XP_001139133.1 | 100% | 0 | 98% |
CXorf66 homolog | Gorilla (Gorilla gorilla gorilla) | 8.8 | XP_004065002.1 | 100% | 0 | 98% |
LOC631784 isoform X1 | Mouse (Mus musculus) | 92.3 | XP_006528296.1 | 98% | 2E-41 | 34% |
CXorf66-like isoform X1 | Rat (Rattus norvegicus) | 92.3 | XP_001068529.2 | 84% | 6E-32 | 32% |
CXorf66 homolog | Cow (Bos taurus) | 94.2 | XP_005200949.1 | 96% | 2.00E-46 | 35% |
CXorf66 homolog | White rhino (Ceratotherium simum simum) | 94.2 | XP_004441715.1 | 100% | 8.00E-86 | 48% |
CXorf66 homolog | Horse (Equus caallus) | 94.2 | XP_005614614.1 | 96% | 8.00E-58 | 44% |
Neurofilament medium polypeptide | Zebra finch (Taeniopygia guttata) | 296 | XP_002197538.1 | 44% | 2.00E-08 | 30% |
Triadin-like, partial | Alligator (Alligator mississippiensis) | 296 | XP_006271227.1 | 53% | 2.00E-12 | 23% |
LOC590028 | Sea urchin (Strongylocentrotus purpuratus) | 742.9 | XP_794743.3 | 45% | 2.00E-05 | 35.40% |
Alpha-L-fucosidase | Streptococcus mitis | 2535.8 | WP_001083113.1 | 47% | 7.00E-38 | 22% |
From Unigene's EST cDNA Tissue Abundance display and Protein Atlas, CXorf66 has a moderately high expression levels in testes, in addition to higher expression levels in fetus tissue in comparison to other developmental stages. [29] [30] CXorf66 protein also has a notable low presence in both the control endometrium total RNA and endometriosis total RNA. [31] CXorf66 has been portrayed to have notable presence in the plasma and platelet. [5] Based upon PaxDb data, CXorf66 has been found ranking in the top 5% for one study of human plasma and in the top 25% for another study conducted with human platelet. [32] In addition to this, there has been a noticeable 60–100% CXorf66 protein presence in both non-failing and dilated cardiomyopathy septum tissue. [33] Furthermore, CXorf66 has a ~75% protein presence in peripheral blood mononuclear cells. [34]
Zinc finger protein 280D, also known as Suppressor Of Hairy Wing Homolog 4, SUWH4, Zinc Finger Protein 634, ZNF634, or KIAA1584, is a protein that in humans is encoded by the ZNF280D gene located on chromosome 15q21.3.
Transmembrane protein 242 (TMEM242) is a protein that in humans is encoded by the TMEM242 gene. The tmem242 gene is located on chromosome 6, on the long arm, in band 2 section 5.3. This protein is also commonly called C6orf35, BM033, and UPF0463 Transmembrane Protein C6orf35. The tmem242 gene is 35,238 base pairs long, and the protein is 141 amino acids in length. The tmem242 gene contains 4 exons. The function of this protein is not well understood by the scientific community. This protein contains a DUF1358 domain.
KIAA0090 is a human gene coding for a protein of unknown function. KIAA0090 has two aliases OTTHUMP00000002581 and RP1-43E13.1. The gene codes for multiple transcript variants which can localize to different subcellular compartments. KIAA0090 interacts with multiple effector proteins. KIAA0090 contains a conserved COG1520 WD40 like repeat domain thought to be the method of such interaction.
UPF0172 protein FAM158A, also known as c14orf122 or CGI112, is a protein that in humans is encoded by the FAM158A gene located on chromosome 14q11.2.
Transmembrane protein 131 (TMEM131) is a protein that is encoded by the TMEM131 gene in humans. The TMEM131 protein contains three domains of unknown function 3651 (DUF3651) and two transmembrane domains. This protein has been implicated as having a role in T cell function and development. TMEM131 also resides in a locus (2q11.1) that is associated with Nievergelt's Syndrome when deleted.
Protein FAM46B also known as family with sequence similarity 46 member B is a protein that in humans is encoded by the FAM46B gene. FAM46B contains one protein domain of unknown function, DUF1693. Yeast two-hybrid screening has identified three proteins that physically interact with FAM46B. These are ATX1, PEPP2 and DAZAP2.
Coiled-coil domain containing 130 is a protein that in humans is encoded by the CCDC130 gene. It is part of the U4/U5/U6 tri-snRNP in the U5 portion. This tri-snRNP comes together with other proteins to form complex B of the mature spliceosome. The mature protein is approximately 45 kilodaltons (kDa) and is extremely hydrophilic due to the abnormally high number of charged and polar amino acids. CCDC130 is a highly conserved protein, it has orthologous genes in some yeasts and plants that were found using nucleotide and protein versions of the basic local alignment search tool (BLAST) from the National Center for Biotechnology Information. GEO profiles for CCDC130 have shown that this protein is ubiquitously expressed, but the highest levels of expression are found in T-lymphocytes.
Family with Sequence Similarity 203, Member B (FAM203B) is a protein encoded by the FAM203B gene (8q24.3) in humans. While FAM203B is only found in humans and possibly non-human primates, its paralog, FAM203A, is highly conserved. The FAM203B protein contains two conserved domains of unknown function, DUF383 and DUF384, and no transmembrane domains. This protein has no known function yet, although the homolog of FAM203A in Caenorhabditis elegans (Y54H5A.2) is thought to help regulate the actin cytoskeleton.
Protein FAM214A, also known as protein family with sequence similarity 214, A (FAM214A) is a protein that, in humans, is encoded by the FAM214A gene. FAM214A is a gene with unknown function found at the q21.2-q21.3 locus on Chromosome 15 (human). The protein product of this gene has two conserved domains, one of unknown function (DUF4210) and another one called Chromosome_Seg. Although the function of the FAM214A protein is uncharacterized, both DUF4210 and Chromosome_Seg have been predicted to play a role in chromosome segregation during meiosis.
Coiled-coil domain containing 94 (CCDC94) is a protein that in humans is encoded by the CCDC94 gene. The CCDC94 protein contains a coiled-coil domain, a domain of unknown function (DUF572), an uncharacterized conserved protein (COG5134), and lacks a transmembrane domain.
TM6SF2 is the Transmembrane 6 superfamily 2 human gene which codes for a protein by the same name. This gene is otherwise called KIAA1926. Its exact function is currently unknown.
EVI5L is a protein that in humans is encoded by the EVI5L gene. EVI5L is a member of the Ras superfamily of monomeric guanine nucleotide-binding (G) proteins, and functions as a GTPase-activating protein (GAP) with a broad specificity. Measurement of in vitro Rab-GAP activity has shown that EVI5L has significant Rab2A- and Rab10-GAP activity.
C3orf70 also known as Chromosome 3 Open Reading Frame 70, is a 250aa protein in humans that is encoded by the C3orf70 gene. The protein encoded is predicted to be a nuclear protein; however, its exact function is currently unknown. C3orf70 can be identified with known aliases: Chromosome 3 Open Reading Frame 70, AK091454, UPF0524, and LOC285382.
C12orf40, also known as Chromosome 12 Open Reading Frame 40, HEL-206, and Epididymis Luminal Protein 206 is a protein that in humans is encoded by the C12orf40 gene.
TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.
Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.
Transmembrane protein 221 (TMEM221) is a protein that in humans is encoded by the TMEM221 gene. The function of TMEM221 is currently not well understood.
SH3 Domain Binding Kinase Family Member 3 is an enzyme that in humans is encoded by the SBK3 gene. SBK3 is a member of the serine/threonine protein kinase family. The SBK3 protein is known to exhibit transferase activity, especially phosphotransferase activity, and tyrosine kinase activity. It is well-conserved throughout mammalian organisms and has two paralogs: SBK1 and SBK2.
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.
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.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)