TMCO4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | TMCO4 , transmembrane and coiled-coil domains 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 1924306 HomoloGene: 57112 GeneCards: TMCO4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane and coiled-coil domains 4, TMCO4, is a protein in humans that is encoded by the TMCO4 gene. Currently, its function is not well defined. It is transmembrane protein that is predicted to cross the endoplasmic reticulum membrane three times. TMCO4 interacts with other proteins known to play a role in cancer development, hinting at a possible role in the disease of cancer.
TMCO4 is located on the minus strand of the first chromosome at 1p36.13. [6] The gene consists of 118,172 base pairs stretching from base pair 19,682,213 through 19,800,385. [6] There are no common aliases for TMCO4. Genes CAPZB and LOC105376823 neighbor TMCO4 on chromosome 1. [5] TMCO4 consists of 16 exons. [5]
There are twenty mRNA transcript variants (X1-X20) produced through different combinations of sixteen different exons. [7] The most common variant is X1, which includes all exons and spans the entire 118,172 base pairs. [5]
The most common protein encoded by TMCO4 is 634 amino acids in length with accession number XP_011539488.1. [6]
The molecular weight of TMCO4 is 67.9 kilodaltons. The isoelectric point is 5.48. As a whole protein, TMCO4 does not have abnormal amino acid distributions. It does have three long stretches of no charge that correspond with the location of the three different transmembrane regions. The first cytosolic domain of TMCO4 does have abnormally high amounts of leucine and glutamic acid and abnormally low amounts of asparagine. The larger lumenal domain of TMCO4 also has an abnormally low amount of asparagine and phenylalanine.
Two main areas of interest within the TMCO4 protein are the three transmembrane regions and the large Abhydrolase region. [8] The N-terminus of TMCO4 is predicted to be within the cytosol of the cell, and the C-terminus is predicted to be within the lumen of the endoplasmic retiticulum. TMCO4 is also predicted to have a leucine zipper and a large coiled coil domain. [9]
The secondary structure of TMCO4 is predicted to be dominated by alpha helices based on predictions by iTASSER software. [10]
Many phosphorylation sites were predicted for the two cytosolic regions of TMCO4. [11] O-linked glycosylation sites were predicted to occur in the end of the second lumenal region of TMCO4. [12] These predicted sites can be seen on both the schematic illustration of TMCO4 found above, or in the conceptual translation of TMCO4 found below.
TMCO4 is consistently predicted to be located in the endoplasmic reticulum membrane across many homologs. [9]
Organism | Common Name | Endoplasmic Reticulum | Golgi | Mitochondrial | Nuclear | Plasma Membrane |
Homo sapiens | Human | 44.4% | 22.2% | 22.2% | 11.1% | - |
Mus musculis | Mouse | 39.1% | 4.3% | 17.4% | 8.7% | 21.7% |
Xenopus laevis | Frog | 55.6% | - | 22.2% | 11.1% | - |
Danio rerio | Zebra fish | 33.3% | 11.1% | 11.1% | - | 22.2% |
Callorhinchus milii | Australian Ghostshark | 33.3% | 11.1% | 33.3% | - | 22.2% |
TMCO4 has been found to interact with many proteins. One protein of interest that TMCO4 interacts with is FLT1. [13] FLT1 is a VEGF receptor. [14] VEGF is known to play a significant role in cancer development. Other proteins that TMCO4 has been experimentally shown to interact with are UBB, UBC, KPTN, and BVLF1. [13] UBB and UBC are polyubiquitins that target molecules for degradation, suggesting that TMCO4 is degraded at some point. [15] [16] KPTN is a protein that is essential in neuromorphogenesis. [17] BVLF1 is an Epstein-Barr virus protein. [18]
TMCO4 does not have any paralogs.
Orthologs to TMCO4 can be found in bacteria, protists, plants, fungi, trichoplax, invertebrates, fish, amphibians, reptiles, birds and mammals. [19] Some of these orthologs can be found in the table below. [19] The orthologs are sorted in descending order of date of evolution from humans and then descending order of percent sequence identity. TMCO4 is a fast evolving gene that has been highly conserved throughout evolution. [19] Regions of TMCO4 that are highly conserved across the orthologs include the various transmembrane domains and the abhydrolase region.
Genus and species | Accession number | Sequence length | Sequence identity | Sequence similarity |
Homo sapiens (Human) | NP_859070.3 | 634 | 100% | 100% |
Papio anubus (Baboon) | XP_017813266.1 | 568 | 96% | 97% |
Mus musculus (Mouse) | AAH13471.1 | 631 | 83% | 88% |
Ursus maritimus (Polar Bear) | XP_008692882.1 | 608 | 87% | 90% |
Gavia stellata (Red-throated loon) | XP_009808720.1 | 610 | 78% | 87% |
Python bivittatus (Burmese python) | XP_007441490.1 | 617 | 70% | 83% |
Xenopus laevis (Frog) | XP_018083828.1 | 635 | 75% | 87% |
Danio rerio (Zebra fish) | XP_003201275.2 | 688 | 59% | 74% |
Parasteatoda tepidariorum (Spider) | XP_015925328.1 | 642 | 56% | 74% |
Caenorhabditis elegans | NP_494812.2 | 617 | 42% | 59% |
Trichoplax adhaerens | XP_002107886.1 | 378 | 52% | 70% |
Aspergillus clavatus | XP_001275560.1 | 686 | 40% | 58% |
Vibrio parahaemolyticus | WP_069539226.1 | 412 | 28% | 48% |
TMCO4 is highly expressed in many tissues. Highest expression occurs within the prostate, trachea, uterus, small intestine, placenta, thyroid, salivary gland, and adrenal gland. Expression of TMCO4 is predicted to be controlled by many transcription factors.
TMCO4 is not currently directly linked to any disease or phenotype. However, interacting with a VEGF receptor may be indicative of a possible role in cancer.
Transmembrane protein 268 is a protein that in humans is encoded by TMEM268 gene. The protein is a transmembrane protein of 342 amino acids long with eight alternative splice variants. The protein has been identified in organisms from the common fruit fly to primates. To date, there has been no protein expression found in organisms simpler than insects.
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.
Ankyrin repeat domain-containing protein 24 is a protein in humans that is coded for by the ANKRD24 gene. The gene is also known as KIAA1981. The protein's function in humans is currently unknown. ANKRD24 is in the protein family that contains ankyrin-repeat domains.
TMEM156 is a gene that encodes the transmembrane protein 156 (TMEM156) in Homo sapiens. It has the clone name of FLJ23235.
PRR29 is a protein encoded by the PRR29 gene located in humans on chromosome 17 at 17q23.
Coiled-coil domain containing protein 180 (CCDC180) is a protein that in humans is encoded by the CCDC180 gene. This protein is known to localize to the nucleus and is thought to be involved in regulation of transcription as are many proteins containing coiled-coil domains. As it is expressed most highly in the testes and is regulated by SRY and SOX transcription factors, it could be involved in sex determination.
Transmembrane Protein 176B, or TMEM176B is a transmembrane protein that in humans is encoded by the TMEM176B gene. It is thought to play a role in the process of maturation of dendritic cells.
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.
Uncharacterized protein C12orf60 is a protein that in humans is encoded by the C12orf60 gene. The gene is also known as LOC144608 or MGC47869. The protein lacks transmembrane domains and helices, but it is rich in alpha-helices. It is predicted to localize in the nucleus.
Retrotransposon Gag Like 6 is a protein encoded by the RTL6 gene in humans. RTL6 is a member of the Mart family of genes, which are related to Sushi-like retrotransposons and were derived from fish and amphibians. The RTL6 protein is localized to the nucleus and has a predicted leucine zipper motif that is known to bind nucleic acids in similar proteins, such as LDOC1.
Chromosome 19 open reading frame 18 (c19orf18) is a protein which in humans is encoded by the c19orf18 gene. The gene is exclusive to mammals and the protein is predicted to have a transmembrane domain and a coiled coil stretch. This protein has a function that is not yet fully understood by the scientific community.
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.
Cilia and flagella associated protein 157 (CFAP157) also known as chromosome 9 open reading frame 117 (c9orf117) is a protein that in humans is encoded by the CFAP157 gene.
C15orf39 is a protein that in humans is encoded by the Chromosome 15 open reading frame 15 (C15orf39) gene.
Transmembrane protein 44 is a protein that in humans is encoded by the TMEM44 gene.
TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.
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.
Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.
C1orf122 is a gene in the human genome that encodes the cytosolic protein ALAESM.. ALAESM is present in all tissue cells and highly up-regulated in the brain, spinal cord, adrenal gland and kidney. This gene can be expressed up to 2.5 times the average gene in its highly expressed tissues. Although the function of C1orf122 is unknown, it is predicted to be used for mitochondria localization.
Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of 5 transmembrane domains and localizes in the plasma membrane and endoplasmic reticulum. TMEM212 has orthologs in vertebrates but not invertebrates. TMEM212 has been associated with sporadic Parkinson's disease, facial processing, and adiposity in African Americans.
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