| DENND2C | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | DENND2C , dJ1156J9.1, DENN domain containing 2C | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 3036254; HomoloGene: 19542; GeneCards: DENND2C; OMA:DENND2C - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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DENN/MADD domain containing 2C (DENND2C) is a protein that in humans is encoded by the DENND2C gene. [5]
DENND2C is located on human chromosome 1 at 1p13.2 on the minus strand. The gene spans about 87,200 nucleotides. [6] and has 21 exons.
The main DENND2C mRNA isoform is 6177 nucleotides long. There are three isoforms. [5] [8]
Protein isoform 1, the longest variant, is 928 amino acids long with a predicted weight of 106.9 kDa. [8] It is alanine-poor relative to other proteins. The theoretical isoelectric point is 8.8. The protein is found in the nucleoplasm.
The three-dimensional structure of DENND2C contains a central beta sheet flanked by alpha-helices. [8] Details about its quaternary structure are currently unavailable.
DENND2C’s importance in cancer is highlighted by its regulation by the tumor suppressor p53. [9] As a guanine nucleotide exchange factor for Rab (G-protein), DENND2C plays a key role in intracellular trafficking and cellular signaling. p53 helps maintain cellular balance and prevent cancer by regulating various pathways. Since DENND2C is part of the p53-regulated network, it is predicted to be involved in cancer suppression.
Disruptions in DENND2C's function or its interaction with p53 can interfere with these pathways and contribute to tumor progression. DENND2C’s role in p53-regulated pathways can be used for developing targeted cancer therapies and identifying new biomarkers for cancer diagnosis and prognosis.
DENND2C has orthologs in most vertebrates: mammals, birds, reptiles, amphibians, and fish. [10] This broad conservation highlights its significant role in vertebrates.
| Genus/Species | Common Name | Taxonomic Group | Med. Date of Divergence (MYA) | Accession Number | Sequence Length (aa) | Sequence Identity (%) | |
| Mammalia | Homo sapiens | Human | Primates | 0 | NP_001243333.1 | 928 | 100 |
| Mus musculus | House mouse | Rodentia | 87 | XP_006501667.1 | 920 | 83.1 | |
| Orcinus orca | Killer whale | Artiodactyla | 94 | XP_049566111.1 | 935 | 89.6 | |
| Phascolarctos cinereus | Koala | Diprotodontia | 160 | XP_020857927.1 | 938 | 81.2 | |
| Reptilia | Chelonia mydas | Green sea turtle | Testudines | 319 | XP_027677849.2 | 938 | 72.5 |
| Podarcis muralis | Common wall lizard | Squamata | 319 | XP_028590394.1 | 927 | 69.9 | |
| Python bivittatus | Burmese python | Squamata | 319 | XP_007429931.1 | 928 | 69.4 | |
| Alligator mississippiensis | American alligator | Crocodilia | 319 | XP_059573447.1 | 946 | 67.9 | |
| Aves | Aptenodytes forsteri | Emperor penguin | Sphenisciformes | 319 | XP_009270985.1 | 932 | 67.5 |
| Gallus gallus | Chicken | Galliformes | 319 | XP_046788775.1 | 988 | 66.7 | |
| Tyto alba | Common barn owl | Strigiformes | 319 | XP_032843159.2 | 1018 | 65.8 | |
| Chroicocephalus ridibundus | Black-headed gull | Charadriiformes | 319 | XP_063212431.1 | 987 | 65.7 | |
| Amphibia | Microcaecilia unicolor | Microcaecilia unicolor | Gymnophiona | 352 | XP_030076672.1 | 941 | 65.4 |
| Hyla sarda | Sardinian tree frog | Anura | 352 | XP_056414351.1 | 944 | 63.1 | |
| Actinistia | Latimeria chalumnae | West Indian Ocean coelacanth | Coelacanthiformes | 415 | XP_064425280.1 | 959 | 58 |
| Actinopterygii | Erpetoichthys calabaricus | Reedfish | Polypteriformes | 429 | XP_028652273.2 | 908 | 50.4 |
| Lepisosteus oculatus | Spotted gar | Lepisosteiformes | 429 | XP_015197870.1 | 904 | 49.9 | |
| Amphiprion ocellaris | Clown anemonefish | Perciformes | 429 | XP_023154128.2 | 936 | 47.3 | |
| Phycodurus eques | Leafy seadragon | Syngnathiformes | 429 | XP_061527912.1 | 912 | 45.9 | |
| Amblyraja radiata | Thorny skate | Rajiformes | 462 | XP_032898655.1 | 1045 | 53 |
DENND2C has no known orthologs in invertebrates, bacteria, archaea, protists, plants, fungi and trichoplax. DENND2C probably evolved in more advanced multicellular organisms and is important for their specific biological functions - instead of simpler life forms like the organisms listed above.
DENND2A, DENND2B, and DENND2D are closely related paralogs of DENND2C. [11]
| Protein | Accession Number | Sequence Identity (%) | Sequence Similarity (%) |
| DENND2C | NP_001243333.1 | 100 | 100 |
| DENND2A | NP_056504.3 | 43.4 | 57.7 |
| DENND2B | NP_001363424.1 | 38.1 | 50.6 |
| DENND2D | NP_079177.2 | 22.9 | 32.6 |
The protein DENND2C evolves at half the rate of fibrinogen alpha and slightly faster than cytochrome C, indicating that DENND2C has a moderately slow rate of evolution.
Cytochrome c stays similar over time (highly conserved), but fibrinogen alpha changes a lot (less conserved). The graph supports the idea that genetic changes happen steadily over time (linear), as predicted by the molecular clock hypothesis.
Basic Leucine Zipper and W2 Domain-Containing Protein 2 is a protein that is encoded by the BZW2 gene. It is a eukaryotic translation factor found in species up to bacteria. In animals, it is localized in the cytoplasm and expressed ubiquitously throughout the body. The heart, placenta, skeletal muscle, and hippocampus show higher expression. In various cancers, upregulation tends to lead to higher severity and mortality. It has been found to interact with SARS-CoV-2.
E3 ubiquitin-protein ligase RNF128 is an enzyme that in humans is encoded by the RNF128 gene.
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.
Intermediate filament family orphan 1 is a protein that in humans is encoded by the IFFO1 gene. IFFO1 has uncharacterized function and a weight of 61.98 kDa. IFFO1 proteins play an important role in the cytoskeleton and the nuclear envelope of most eukaryotic cell types.
PROSER2, also known as proline and serine rich 2, is a protein that in humans is encoded by the PROSER2 gene. PROSER2, or c10orf47(Chromosome 10 open reading frame 47), is found in band 14 of the short arm of chromosome 10 (10p14) and contains a highly conserved SARG domain. It is a fast evolving gene with two paralogs, c1orf116 and specifically androgen-regulated gene protein isoform 1. The PROSER2 protein has a currently uncharacterized function however, in humans, it may play a role in cell cycle regulation, reproductive functioning, and is a potential biomarker of cancer.
WD Repeat and Coiled-coiled containing protein (WDCP) is a protein which in humans is encoded by the WDCP gene. The function of the protein is not completely understood, but WDCP has been identified in a fusion protein with anaplastic lymphoma kinase found in colorectal cancer. WDCP has also been identified in the MRN complex, which processes double-stranded breaks in DNA.
Coiled-coil domain containing 121 (CCDC121) is a protein encoded by the CCDC121 gene in humans. CCDC121 is located on the minus strand of chromosome 2 and encodes three protein isoforms. All isoforms of CCDC121 contain a domain of unknown function referred to as DUF4515 or pfam14988.
MIPOL1 , also known as CCDC193 , is a protein that in humans is encoded by the MIPOL1 gene. Mutation of this gene is associated with mirror-image polydactyly in humans, which is a rare genetic condition characterized by mirror-image duplication of digits.
Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.
PANO1 is a protein which in humans is encoded by the PANO1 gene. PANO1 is an apoptosis inducing protein that is able to regulate the function of tumor suppressor. More specifically, P14ARF is a protein in which in humans is modulated by the PANO1 gene. P14ARF is known to function as a tumor suppressor. When PANO1 is highly expressed in the cells, it is able to modulate p14ARF by stabilizing it and protecting it from degradation. With a confidence level of 5 out of 5, PANO1 has been theorized to be expressed in the nucleolus of the cell. PANO1 is an intron-less gene. Intron-less genes only make up about 3% of the human genome. A functional analysis of these types of genes revealed that they often have tissue-specific expression in tissues such as the nervous system and testis. This kind of expression is commonly associated with neuropathies, disease, and cancer. The tissue types that PANO1 has the highest expression in, are the cerebellum regions of the brain as well as pituitary and testis tissues.
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.
TBC1D30 is a gene in the human genome that encodes the protein of the same name. This protein has two domains, one of which is involved in the processing of the Rab protein. Much of the function of this gene is not yet known, but it is expressed mostly in the brain and adrenal cortex.
Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of five 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.
C1orf159 is a protein that in human is encoded by the C1orf159 gene located on chromosome 1. This gene is also found to be an unfavorable prognosis marker for renal and liver cancer, and a favorable prognosis marker for urothelial cancer.
NADP-dependent oxidoreductase domain-containing protein 1 is a protein that in humans is encoded by the NOXRED1 gene. An alias of this gene is Chromosome 14 Open Reading Frame 148 (c14orf148). This gene is located on chromosome 14, at 14q24.3. NOXRED1 is predicted to be involved in pyrroline-5-carboxylate reductase activity as part of the L-proline biosynthetic pathway. It is expressed in a wide variety of tissues at a relatively low level, including the testes, thyroid, skin, small intestine, brain, kidney, colon, and more.
C10orf53 is a protein that in humans is encoded by the C10orf53 gene. The gene is located on the positive strand of the DNA and is 30,611 nucleotides in length. The protein is 157 amino acids and the gene has 3 exons. C10orf53 orthologs are found in mammals, birds, reptiles, amphibians, fish, and invertebrates. It is primarily expressed in the testes and at very low levels in the cerebellum, liver, placenta, and trachea.
Leucine-rich repeat-containing protein 74A (LRRC74A), is a protein encoded by the LRRC74A gene. The protein LRRC74A is localized in the cytoplasm. It has a calculated molecular weight of approximately 55 kDa. The LRRC74A protein is nominally expressed in the testis, salivary gland, and pancreas.
NKAPD1 is a protein, which in humans, is encoded by the gene NKAPD1. This protein is also commonly referred to as C11ORF57.
ZNF839 or zinc finger protein 839 is a protein which in humans is encoded by the ZNF839 gene. It is located on the long arm of chromosome 14. Zinc finger protein 839 is speculated to play a role in humoral immune response to cancer as a renal carcinoma antigen (NY-REN-50). This is because NY-REN-50 was found to be over expressed in cancer patients, especially those with renal carcinoma. Zinc finger protein 839 also plays a role in transcription regulation by metal-ion binding since it binds to DNA via C2H2-type zinc finger repeats.
ZNF730 or zinc finger protein 730 is a protein which in humans is encoded by the ZNF730 gene. It is located on the short arm of chromosome 19. Zinc finger protein 730 is speculated to play a role in transcriptional regulation in acute myeloid leukemia and endometrial cancer. This is because ZNF730 was found to be expressed in higher levels in endometrial cancerous tumor samples and has been reported as a core binding factor in acute myeloid leukemia. Zinc Finger protein 730 is a C2H2-type zinc finger protein containing a β/β/α structure, held in place by a Zinc ion. The C2H2-type protein motifs can regulate transcription by recognizing and binding to DNA sequences.
