TEDC2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | TEDC2 , C16orf59, chromosome 16 open reading frame 59, tubulin epsilon and delta complex 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | MGI: 1919266 HomoloGene: 45943 GeneCards: TEDC2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Tubulin epsilon and delta complex 2 (TEDC2), also known as Chromosome 16 open reading frame 59 (C16orf59), is a protein that in humans is encoded by the TEDC2 gene. Its NCBI accession number is NP_079384.2. [5]
TEDC2 is found on chromosome 16 at location 16p13.3, or chr16:2,460,080-2,464,963 (spanning 4883 bp) on the plus strand. [6]
TEDC2 appeared between 684-797 million years ago. Its most distant ortholog is found in Branchiostoma floridae, the Florida lancelet, [7] which diverged from other chordates around 684 million years ago. [8] However, the gene arose more recently than 797 million years ago, when protostomes and deuterostomes diverged, [8] as it is not found in any invertebrates. A table showing 20 selected orthologs is below, found with NCBI BLAST. [5]
Genus and species | Common name | Clade | Date of divergence (estimated) [8] | Accession number | Length | Identity | Similarity |
Homo sapiens | Human | Mammalia | 0 MYA | NP_079384.2 | 433 aa | 100% | 100% |
Pan troglodytes | Chimpanzee | Mammalia | 6.65 MYA | XP_001163226.2 | 433 aa | 98% | 98% |
Mus musculus | House mouse | Mammalia | 90 MYA | NP_082332.1 | 436 aa | 62% | 72% |
Orcinus orca | Orca | Mammalia | 96 MYA | XP_012388677.1 | 445 aa | 71% | 78% |
Vulpes vulpes | Red fox | Mammalia | 96 MYA | XP_025840713.1 | 432 aa | 68% | 74% |
Dasypus novemcinctus | Nine-banded armadillo | Mammalia | 105 MYA | XP_012385078.1 | 469 aa | 69% | 77% |
Cyanistes caeruleus | Eurasian blue tit | Aves | 312 MYA | XP_023792200.1 | 366 aa | 44% | 59% |
Pygoscelis adeliae | Adélie penguin | Aves | 312 MYA | XP_009325519.1 | 490 aa | 43% | 58% |
Columba livia | Rock dove | Aves | 312 MYA | XP_021147488.1 | 511 aa | 43% | 56% |
Numida meleagris | Helmeted guineafowl | Aves | 312 MYA | XP_021267460.1 | 574 aa | 40% | 67% |
Dromaius novaehollandiae | Emu | Aves | 312 MYA | XP_025956253.1 | 547 aa | 40% | 68% |
Anolis carolinensis | Green anole | Reptilia | 312 MYA | XP_008122311.2 | 473 aa | 32% | 47% |
Python bivittatus | Burmese python | Reptilia | 312 MYA | XP_007433089.1 | 607 aa | 32% | 50% |
Pogona vitticeps | Bearded dragon | Reptilia | 312 MYA | XP_020663843.1 | 578 aa | 31% | 45% |
Xenopus tropicalis | Western clawed frog | Amphibia | 352 MYA | XP_002932464.1 | 452 aa | 30% | 45% |
Lepisosteus oculatus | Spotted gar | Osteichthyes | 435 MYA | XP_015215377.1 | 193 aa | 37% | 48% |
Scleropages formosus | Asian arowana | Osteichthyes | 435 MYA | XP_018598511.1 | 186 aa | 29% | 47% |
Paramormyrops kingsleyae | Elephantfish | Osteichthyes | 435 MYA | XP_023666461.1 | 473 aa | 29% | 46% |
Callorhinchus milii | Australian ghostshark | Chondrichthyes | 473 MYA | XP_007891790.1 | 540 aa | 32% | 49% |
Branchiostoma floridae | Florida lancelet | Cephalochordata | 684 MYA | XP_002611730.1 | 602 aa | 23% | 42% |
There are no other members of the TEDC2 gene family, as it has no paralogs in any living organisms. [5]
Conserved predicted transcription factor binding sites found in the 5' region upstream of TEDC2 are WT1, ZKSCAN3 (x2), AREB6, MZF1 (x2), ATF6, ER, and P53. [9] This suggests that these transcription factors in particular, and especially ZKSCAN3 and MZF1 on the basis of multiple conserved binding sites, are crucial in the regulation of TEDC2. ZKSCAN3 is a transcriptional repressor of autophagy, [10] and MZF1 is thought to play a role as a tumor suppressor and regulator of cell proliferation. [11] These conserved MZF1 sites, along with the conserved p53 site, suggest that TEDC2 could play a role in cell proliferation and can therefore impact the genesis and development of cancer.
TEDC2 is predicted to be localized to the nucleus and may also be present in the cytoplasm, mitochondria, peroxisomes, and extracellular space. [12]
It is highly expressed in the testis and EBV-transformed lymphocytes. [13] It is also highly expressed in lymph node, fetal liver, early erythroid cell, and B-lymphoblasts. [14] It is also seen at higher levels in both embryonic stem cells and induced pluripotent stem cells than fibroblasts. [14] Finally, relative to other genes, TEDC2 expression significantly decreases in breast cancer cells upon estrogen starvation. [14]
The gene has 10 exons. [15] The gene has 13 alternatively spliced transcripts, with 6 coding for a protein, 1 undergoing nonsense-mediated decay, and 6 being retained introns. [16]
TEDC2 is encoded by the TEDC2 gene with NCBI accession number NM_025108.3. The protein is 433 amino acids long with a predicted molecular weight of 46.4 kDa. [6] There is an antibody against the protein, but a sample western blot image is not available. [17]
TEDC2 contains a domain of unknown function, DUF4693, which in humans spans from proteins 148-431, approximately the last two-thirds of the protein. [5]
Using online bioinformatics tools, TEDC2 is predicted to have many alpha helices, and it has two well-conserved predicted beta-pleated sheets near the end of the protein. [18] [19]
TEDC2 is predicted to form tertiary structure based on its alpha helices. Many of these predicted alpha helices are highly conserved in orthologs, and one example of predicted tertiary structure generated by I-TASSER is shown to the right. [20]
TEDC2 has a well conserved predicted O-GlcNAc site at S114 in humans. [22] O-GlcNAcylated proteins are found mostly in the nucleus, sometimes also being found in the cytoplasm, and this is a dynamic modification, frequently being removed and reattached. [23]
TEDC2 also has three conserved, predicted C-mannosylation sites. [24] The function of C-mannosylation is still unclear, but it is the attachment of an alpha-mannose to a tryptophan. [25]
TEDC2 also has many possible phosphorylation sites, including seven that are well-conserved. [26] Phosphorylation is an important means of protein regulation, activation, and inactivation, so it is difficult to determine any specific function from the presence of a serine or threonine that could be phosphorylated. [27]
KDM1A, a lysine-specific demethylase, was shown to be physically associated with TEDC2. [28] [29] TEDC2 also interacts with FEZ1, a fasciculation and elongation protein. FEZ1, or fasciculation and elongation protein 1, is necessary for axon growth but is also thought to be involved in transcriptional control. [30]
There is also experimental evidence for TEDC2 interaction with TUBE1 and C14orf80. TUBE1, or Tubulin epsilon 1, is involved with the centrioles during cell division, and the function of C14orf80 is unknown. [31] TEDC2 is also co-expressed with CDC45, or cell division control protein 45, which is required for initiation of chromosomal DNA replication, as well as co-expression with CDT1, a DNA replication licensing factor required for pre-replication assembly. [32]
The function of TEDC2 is not yet known with certainty by the scientific community, but its expression profile, predicted transcription factor binding sites, and other protein-protein interactions enable some predictions. TEDC2 is localized in the nucleus and is often expressed in developing tissues such as stem cells as well as differentiated fetal tissue, so it likely plays a role in DNA replication and/or cell division. [12] [14] This also fits with TEDC2's predicted or known protein-protein interactions, as it may interact with proteins involved in cell division (TUBE1, CDC45, CDT1), as well as remain under transcriptional control of tumor suppressors (WT1, MZF1, P53). [9] Additionally, given the presence of an estrogen-response element binding-site, it is possible that TEDC2 plays a role in tumor development when mutated. [9]
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.
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.
Chromosome 12 Open Reading Frame 42 (C12orf42) is a protein-encoding gene in Homo sapiens.
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 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.
Testis-expressed protein 9 is a protein that in humans is encoded the TEX9 gene. TEX9 that encodes a 391-long amino acid protein containing two coiled-coil regions. The gene is conserved in many species and encodes orthologous proteins in eukarya, archaea, and one species of bacteria. The function of TEX9 is not yet fully understood, but it is suggested to have ATP-binding capabilities.
Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.
Chromosome 4 open reading frame 51 (C4orf51) is a protein which in humans is encoded by the C4orf51 gene.
Uncharacterized protein C16orf86 is a protein in humans that is encoded by the C16orf86 gene. It is mostly made of alpha helices and it is expressed in the testes, but also in other tissues such as the kidney, colon, brain, fat, spleen, and liver. For the function of C16orf86, it is not well understood, however it could be a transcription factor in the nucleus that regulates G0/G1 in the cell cycle for tissues such as the kidney, brain, and skeletal muscles as mentioned in the DNA microarray data below in the gene level regulation section.
Cilia- and flagella-associated protein 299 (CFAP299), is a protein that in humans is encoded by the CFAP299 gene. CFAP299 is predicted to play a role in spermatogenesis and cell apoptosis.
Chromosome X Open Reading Frame 38 (CXorf38) is a protein which, in humans, is encoded by the CXorf38 gene. CXorf38 appears in multiple studies regarding the escape of X chromosome inactivation.
Testis expressed 55 (TEX55) is a human protein that is encoded by the C3orf30 gene located on the forward strand of human chromosome three, open reading frame 30 (3q13.32). TEX55 is also known as Testis-specific conserved, cAMP-dependent type II PK anchoring protein (TSCPA), and uncharacterized protein C3orf30.
Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.
Transmembrane protein 155 is a protein that in humans is encoded by the TMEM155 gene. It is located on human chromosome 4, spanning 6,497 bases. It is also referred to as FLJ30834 and LOC132332. This protein is known to be expressed mainly in the brain, placenta, and lymph nodes and is conserved throughout most placental mammals. The function and structure of this protein is still not well understood, but its level of expression has been studied pertaining to various pathologies.
Chromosome 1 open reading frame 185, also known as C1orf185, is a protein that in humans is encoded by the C1orf185 gene. In humans, C1orf185 is a lowly expressed protein that has been found to be occasionally expressed in the circulatory system.
C16orf90 or chromosome 16 open reading frame 90 produces uncharacterized protein C16orf90 in homo sapiens. C16orf90's protein has four predicted alpha-helix domains and is mildly expressed in the testes and lowly expressed throughout the body. While the function of C16orf90 is not yet well understood by the scientific community, it has suspected involvement in the biological stress response and apoptosis based on expression data from microarrays and post-translational modification data.
ProteinFAM89A is a protein which in humans is encoded by the FAM89A gene. It is also known as chromosome 1 open reading frame 153 (C1orf153). Highest FAM89A gene expression is observed in the placenta and adipose tissue. Though its function is largely unknown, FAM89A is found to be differentially expressed in response to interleukin exposure, and it is implicated in immune responses pathways and various pathologies such as atherosclerosis and glioma cell expression.
Leucine rich single-pass membrane protein 2 is a single-pass membrane protein rich in leucine, that in humans is encoded by the LSMEM2 gene. The LSMEM2 protein is conserved in mammals, birds, and reptiles. In humans, LSMEM2 is found to be highly expressed in the heart, skeletal muscle and tongue.
Family with Sequence Similarity 166, member C (FAM166C), is a protein encoded by the FAM166C gene. The protein FAM166C is localized in the nucleus. It has a calculated molecular weight of 23.29 kDa. It also contains DUF2475, a protein of unknown function from amino acid 19–85. The FAM166C protein is nominally expressed in the testis, stomach, and thyroid.
C11orf98 is a protein-encoding gene on chromosome 11 in humans of unknown function. It is otherwise known as c11orf48. The gene spans the chromosomal locus from 62,662,817-62,665,210. There are 4 exons. It spans across 2,394 base pairs of DNA and produces an mRNA that is 646 base pairs long.
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