Synaptic plasticity regulator Plasticity Associated Neural Transcript (PANTS) is a protein which in humans is encoded by the C22orf39 gene. C22orf39 is expressed at high levels throughout the body, though expression is highest in skeletal muscle and the heart.
Gene The human C22orf39 gene is located on the minus strand on chromosome 22 (22q11.21), has 3 exons, and spans 6,826 bp. Transcript Human C22orf39 has 2 main transcripts. Variant 1 is 318 nt long and differs from Variant 2 by having a longer but overlapping 3’ exon and encoding a different C-terminus of the C22orf39 protein. Both transcripts are the same total length with the same number of exons.
Protein In humans, C22orf39 comes in two isoforms, 1 (105 aa) and 2 (80 aa). Isoform 1 of C22orf39 has a calculated molecular weight of approximately 12.4 kDa and an isoelectric point (pI) of 7.71 in humans, though pI is not conserved throughout homologs. C22orf39 has a domain of unknown function (DUF3128). The C22orf39 protein is tryptophan and arginine rich and low in threonine.
Regulation
Gene
C22orf39 has variable expression at relatively high levels throughout most tissues in the body. mRNA expression of C22orf39 is highest in skeletal muscle and the heart. The C22orf39 protein is also found abundantly throughout the whole organism. Antibody imaging reveals that C22orf39 is localized to the endoplasmic reticulum.
Transcript C22orf39 has a highly conserved miRNA binding site in the 3' UTR.
Protein (post-translational modifications) C22orf39 is localized to the cytoplasm or mitochondria. C22orf39 has several predicted phosphorylation sites and an acetylation site.
Homology/evolution
C22orf39 has no paralogs.
C22orf39 orthologs are found in almost all multicellular animals, excluding several select taxonomic groups including flatworms and roundworms. The most distant related orthologs are sponges. Orthologs range in sequence identity from 24% to 98%: mammals (60-98%), birds/reptiles (50-59%), amphibians (46-50%), fish (49-50%), and invertebrates (24-39%).
+C22orf39 Orthologs Genus/SpeciesCommon NameTaxonomic GroupDate of Divergence (MYA)Accession #Sequence LengthSequence Identity %Sequence Similarity %MammalsHomo sapiensHumanPrimate0NP_776154.4105100100Piliocolobus tephroscelesRed Colobus MonkeyPrimate28.8XP_023048350.214298100Mus musculusMouseRodentia87NP_001028336.1817282Trichosurus vulpeculaBushtail PossumMarsupial160XP_036613470.11086075Birds/ReptilesGallus gallusChickenAvian319XP_015131179.11055968Pelodiscus sinensisChinese Softshell TurtleTestudines319XP_006135010.31235175Ahaetulla prasinaVine SnakeSquamata319XP_058014370.11065072AmphibiansLeptodactylus fuscusRufous FrogAmphibian352XP_075132091.11064870Xenopus tropicalisWestern Clawed FrogAmphibian352XP_004910632.11064769Bufo bufoCommon ToadAmphibian352XP_040272282.11064671FishAcipenser ruthenusSterlet SturgeonFish429XP_058888772.11085066Plectropomus leopardusLeopard Coral GrouperFish429XP_042344043.11094969Invertebrates: CnidariansOrbicella faveolataStar CoralAnthozoa685XP_020628890.11092453Hydra viridissimaHydraHydrozoa685XP_079916326.11082442Invertebrates: AnthropodsPenaeus japonicusPrawnCrustacean686XP_042862443.11493656Vespula pensylvanicaWestern Yellow JacketInsect686XP_043677143.11453558Uloborus diversusOrb WeaverSpider686XP_054709478.11563151Invertebrates: MollusksGigantopelta aegisSea SnailGastropod686XP_041347459.11503958Invertebrates: SpongesHalichondria paniceaBreadcrumb SpongePorifera758XP_064392711.11153340Corticium candelabrumMarine SpongePorifera758XP_062516804.11192734
Comparing C22orf39 ortholog data to the known evolution rates of cytochrome C and complement factor 1 suggests that the C22orf39 gene evolves relatively quickly.
Clinical significance In a study inducing hepatocarcinogenesis (production of liver cancer) in mice through overexpression of the human MYC gene, the C22orf39 gene was shown to be silenced in PICM-19 cells (a liver cell line from fetal pigs) following MYC-induction (the overexpression of MYC oncogenes), suggesting that the absence of the C22orf39 protein is necessary for carcinogenesis.
C22orf39 is part of the regulatory network of transcription factor breast cancer type 1 susceptibility protein (BRCA1), the up-regulation of which has a high connectivity with differentially expressed genes (DEG’s) that may contribute to increased risk of esophageal squamous cell carcinoma (ESCC).
Individuals with Duchenne muscular dystrophy are shown to have lower C22orf39 expression, though this is likely an effect of the condition rather than a cause.
A study of 22q11.2 deletion syndrome in mice (a condition that increases risk of schizophrenia, among other neurological and physiological issues), identified a C22orf39 ortholog in mice (referred to as mouse Pants). In control mice, Pants was found to have increased expression in the hippocampus of aging mouse brains. This study suggests that the loss of C22orf39 in 22q11.2 deletion syndrome could be a major contributor to the age-related plasticity deficits displayed by mice with this deletion.
References