PDCD10 and GCKIII kinases-associated protein 1 is a protein which in humans is encoded by the PGCKA1 gene (previously C4orf19). It is thought to act as a tumor suppressor through its interaction with the KEAP1/USP17/ELK1/CDK6 axis.
Gene The C4orf19 gene is located at 4p14 on the plus strand of chromosome 4 and spans 170.04 kb and contains 7 exons. The genetic neighborhood of C4orf19 includes LOC101928721, LOC105374402, MIR4801, and NWD2, all located upstream of C4orf19. RELL1 is located downstream of C4orf19.
mRNA
There are four known transcript variants that encode isoforms known as transcript variant 1, transcript variant 2, X1, and X2.
Protein
C4orf19 encodes a protein with 314 amino acids and a molecular weight of 33.7 kDa. The theoretical isoelectric point of C4orf19 is 4.4.
Domains and motifs In humans, the C4orf19 protein contains one domain of unknown function, DUF4699. In eukaryotes the DUF4699 family of proteins are typically between 303 and 319 amino acids in length. DUF4699 spans from amino acid 9 to amino acid 314 in C4orf19. Amongst orthologous proteins, the N-terminus and C-terminus of C4orf19 are most highly conserved.
Secondary structure Alpha helices are predicted near the N-terminus and C-terminus of C4orf19 in areas that are conserved amongst orthologous proteins.
Post-translational modifications C4orf19 is predicted to undergo several post-translation modifications, including phosphorylation, glycosylation, and SUMOylation.
Subcellular localization C4orf19 is predicted to be to be localized in cellular junctions.
Expression C4orf19 is highly expressed in tissues of the salivary gland, duodenum, small intestine, colon, rectum and kidney. The protein also shows medium levels of expression in tissues of the stomach.
Interacting proteins Studies using yeast two-hybrid screening have experimentally determined interactions between C4orf19 and PDCD10.
Homology
Paralogs There are currently no known paralogs or paralogous domains for C4orf19.
Orthologs Orthologs of C4orf19 have been found in mammals, birds, and reptiles. Within class Mammalia, orthologs have been identified in orders Primates, Rodentia, Artiodactyla, Chirpotera, Carnivora, Cingulata, and Diprotodontia. The Burmese python (Python bivittatus) and Eastern fence lizard (Sceloporus undulatus) contain the most distantly related orthologs of C4orf19. Both species diverged from humans an estimated 312 million years ago. C4orf19 orthologs have not yet been identified in bacteria, archaea, protists, plants, fungi, trichoplax, invertebrates, or bony and cartilaginous fish. The following table represents a selection of orthologs found using searches in BLAST. +C4orf19 OrthologsC4orf19Genus, speciesCommon NameTaxonomic GroupEstimated Divergence Date (MYA)Accession NumberSequence Length (aa)Sequence Identity (%)Sequence Similarity (%)MammaliaHomo sapiensHumansPrimates0NP_060772.2314100100Mus musculisHouse mouseRodentia90XP_011239094.131356.265.7Meriones unguiculatusMongolian gerbilRodentia90XP_021503387.131150.660.5Bos taurusCattleArtiodactyla96NP_001098443.132159.267.3Myotis brandtiiBrandt's batChiroptera96XP_005859800.132061.269.6Ailuropoda melanoleucaGiant pandaCarnivora96XP_019662032.231959.968.7Odobenus rosmarus divergensPacific walrusCarnivora96XP_004396233.131959.269Felis catusDomestic catCarnivora96XP_023108981.131957.766.8Puma concolorPumaCarnivora96XP_025778193.131956.165.2Dasypus novemcinctus9 banded armadilloCingulata105XP_012386176.131662.871.9Phascolarctos cinereusKoalaDiprotodontia159XP_020847725.130942.653.8AvesPhasianus colchiusRing-necked pheasantGalliformes312XP_031444602.132930.744.9Anas platyrhynchosMallard duckAnseriforms312XP_027313057.132732.445.9Falco peregrinusPeregrine falconFalconiformes312XP_005243272.132328.446.1Tyto albaBarn owlStriniformes312XP_032855182.232731.544.5Dromaius novaehollandiaeEmuCasuariiformes328XP_025949540.13283347.7ReptiliaChrysemys picta belliiPainted turtleTestudines312XP_023962455.134331.546.6Chelonia mydasGreen sea turtleTestudines312XP_007059772.234433.449.4Alligator mississippiensisAmerican alligatorCrocodilia312XP_019336018.134031.746.7Python bivittatusBurmese pythonSquamata312XP_015743375.131928.242.2Sceloporus undulatusEastern fence lizardSquamata312XP_042324918.131029.842.6
References