DENN/MADD domain containing 2C (DENND2C) is a protein that in humans is encoded by the DENND2C gene.
Gene DENND2C is located on human chromosome 1 at 1p13.2 on the minus strand. The gene spans about 87,200 nucleotides. and has 21 exons.
It is a member of the DENN (Differentially Expressed in Normal and Neoplastic cells) domain-containing protein family. These proteins regulate the activity of Rab GTPases and act as Rab-specific guanine nucleotide exchange factors (GEFs). DENND2C also plays a crucial role in the self-renewal of human embryonic stem cells.
mRNA The main DENND2C mRNA isoform is 6177 nucleotides long. There are three isoforms.
Protein Protein isoform 1, the longest variant, is 928 amino acids long with a predicted weight of 106.9 kDa. It is alanine-poor relative to other proteins. The theoretical isoelectric point is 8.8. The protein is found in the nucleoplasm.
Structure The three-dimensional structure of DENND2C contains a central beta sheet flanked by alpha-helices. Details about its quaternary structure are currently unavailable.
Clinical significance DENND2C’s importance in cancer is highlighted by its regulation by the tumor suppressor p53. 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.
Evolutional history Orthologs DENND2C has orthologs in most vertebrates: mammals, birds, reptiles, amphibians, and fish. This broad conservation highlights its significant role in vertebrates.
+Genus/SpeciesCommon NameTaxonomic GroupMed. Date of Divergence (MYA)Accession NumberSequence Length (aa)Sequence Identity (%)Homo sapiensHumanPrimates0NP_001243333.1928100Mus musculusHouse mouseRodentia87XP_006501667.192083.1Orcinus orcaKiller whaleArtiodactyla94XP_049566111.193589.6Phascolarctos cinereusKoalaDiprotodontia160XP_020857927.193881.2Chelonia mydasGreen sea turtleTestudines319XP_027677849.293872.5Podarcis muralisCommon wall lizardSquamata319XP_028590394.192769.9Python bivittatusBurmese pythonSquamata319XP_007429931.192869.4Alligator mississippiensisAmerican alligatorCrocodilia319XP_059573447.194667.9Aptenodytes forsteriEmperor penguinSphenisciformes319XP_009270985.193267.5Gallus gallusChickenGalliformes319XP_046788775.198866.7Tyto albaCommon barn owlStrigiformes319XP_032843159.2101865.8Chroicocephalus ridibundusBlack-headed gullCharadriiformes319XP_063212431.198765.7Microcaecilia unicolorMicrocaecilia unicolorGymnophiona352XP_030076672.194165.4Hyla sardaSardinian tree frogAnura352XP_056414351.194463.1Latimeria chalumnaeWest Indian Ocean coelacanthCoelacanthiformes415XP_064425280.195958Erpetoichthys calabaricusReedfishPolypteriformes429XP_028652273.290850.4Lepisosteus oculatusSpotted garLepisosteiformes429XP_015197870.190449.9Amphiprion ocellarisClown anemonefishPerciformes429XP_023154128.293647.3Phycodurus equesLeafy seadragonSyngnathiformes429XP_061527912.191245.9Amblyraja radiataThorny skateRajiformes462XP_032898655.1104553
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.
Parlaogs DENND2A, DENND2B, and DENND2D are closely related paralogs of DENND2C. +ProteinAccession NumberSequence Identity (%)Sequence Similarity (%)DENND2CNP_001243333.1100100DENND2ANP_056504.343.457.7DENND2BNP_001363424.138.150.6DENND2DNP_079177.222.932.6
Rate of Evolution 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.
Conceptual human translation
References