Chromosome 1 open reading frame 52 is a protein in humans encoded by the C1orf52 gene. C1orf52 is localized in the nucleus and ubiquitously expressed in human tissues.
Gene C1orf52 is located on the minus strand at 1p22.3. The gene is 9,720 base pairs and has 3 exons.
Gene neighborhood
The gene neighborhood of C1orf52 consists of B-cell lymphoma 10 (BCL10), B-cell lymphoma antisense 1 (BCL-AS1), dimethylarginine dimethylaminohydrolase 1 (DDAH1), and synapse defective Rho GTPase homolog 2 (SYDE2). The BCL10 gene encodes the BCL10 scaffolding protein that controls immune and pro-inflammatory pathways by connecting antigen receptor signaling to NF-kB activation in B cells and T cells. DDAH1 regulates intracellular ROS levels and apoptosis sensitivity via a SOD2-dependent pathway. SYDE2 converts Rho-type GTPases into an inactive guanosine diphosphate-bound state.
Transcript Including untranslated regions, the mRNA is 3254 nucleotides long.
Transcript variants There is a transcript variant that includes an additional exon. This alternate exon in the coding region in variant 2 results in a frameshift and early stop codon. This transcript does not form the C1orf52 protein because the product is significantly truncated and the transcript is a candidate for nonsense-mediated decay. + Exons 1 2 3 4 Protein Length (amino acids) Transcript Variant 1 306 - 199 2750 182 Transcript Variant 2 306 127 199 2750 none
Protein The C1orf52 protein consists of 182 amino acids with a molecular weight of 20 kDa and an isoelectric point of 5 pI. The protein contains a domain of unknown function (DUF4660), also known as pFAM15559, that is 98 amino acids long. The domain of unknown function is flanked by two disordered regions, which make up the majority of the protein. Compared to other proteins, C1orf52 is lysine and histidine deficient as well as glutamine and proline rich.
No protein isoforms of C1orf52 have been reported.
Structure There is a high amount of disorder in the secondary and tertiary protein structure, with very few predicted alpha helixes or beta sheets.
Regulation
Gene C1orf52 is ubiquitously expressed at high levels in human tissues, with higher abundance in bone marrow, brain regions, and immune organs (thymus and thyroid), with lower expression in digestive organs.
Protein The C1orf52 protein has 21 times the average abundance in humans compared to other proteins. There are 3 phosphorylation sites identified through mass spectrometry. Within the cell, C1orf52 is localized to the nucleus and contains a bipartite nuclear localization signal.
Homology
Paralogs No paralogs of C1orf52 have been identified in the human genome.
Orthologs C1orf52 orthologs are in all common classes of vertebrates. Orthologs are also in invertebrates including sponges, marine tunicate, and lancelets. Orthologs were not found in insects, fungi, plants or protists. Genus and Species Common Name Taxonomic Order Date of Divergence from Humans (MYA) Assession Number Sequence Length Sequence Identity to Humans Sequence Similarity to Humans Homo Sapiens Human Primate 0 NP_932343.1 182 100% 100% Mus musculus House Mouse Rodentia 87 NP_079831.1 180 85.2% 89.0% Ornithorhynchus anatinus Platypus Monotreme 180 XP_028917768.1 191 61.7% 71.0% Harpia harpyja Harpy Owl Accipitriformes 319 XP_052658103.1 183 64.6% 75.1% Gallus gallus Chicken Galliformes 319 NP_001264489.2 183 63.0% 71.4% Taeniopygia guttata Zebra finch Passeriformes 319 XP_030134956.3 183 62.1% 73.2% Gopherus evgoodei Goode's thornscrub tortoise Testudines 319 XP_038601107.1 187 64.7% 73.3% Alligator mississippiensis Alligator Crocodilia 319 XP_014450079.3 187 62.6% 70.5% Protobothrops mucrosquamatus Pit viper Squamata 319 XP_015668904.1 187 61.5% 69.7% Microcaecilia unicolor Tiny Cayenne Caecilian Gymnophiona 352 XP_030062820.1 184 62.2% 72.0% Xenopus laevis African clawed frog Anura 352 NP_001089243.1 171 60.9% 70.8% Pleurodeles waltl Iberian ribbed newt Urodela 352 KAJ1114225.1 182 57.1% 67.9% Protopterus annectens West African Lung Fish Ceratodontiformes 408 XP_043941971.1 181 53.5% 70.1% Polypterus senegalus Gray bichir Polypteriformes 429 XP_039591352 188 54.3% 64.5% Danio rerio Zebrafish Cypriniformes 429 NP_956836.1 214 45.9% 58.3% Pristis pectinata Smalltooth Sawfish Rhinopristiformes 462 XP_051869055.1 205 44.9% 58.9% Lampetra fluviatilis European river lamprey Petromyzontiformes 563 CAL5931002.1 242 26.7% 36.0% Branchiostoma floridae Florida Lancelet Amphioxiformes 581 XP_035684389.1 234 24.7% 37.7% Styela clava Sea squirt Stolidobranchia 596 XP_039271545.1 236 25.4% 39.9% Geodia barretti Deep Sea Sponge Tetractinellida 758 CAI8039110.1 221 27.1% 38.1%
Evolution The C1orf52 gene appears most distantly in sea sponges which diverged from humans approximately 758 million years ago. C1orf52 evolves moderately quickly at a rate of 3.8 times faster than slowly evolving Cytochrome C and 0.61 times the rate of fast evolving Fibrinogen Alpha.
Interacting proteins High throughput affinity capture-mass spectrometry supports a physical association between C1orf52 and MAD1L1 (Mitotic Arrest Deficient 1 Like 1), DENN Domain Containing 2D (DENND2D), Differentially expressed in FDCP 6 homolog (DEF6), Insulin gene enhancer protein ISL2 (ISL2), and LIM/homeobox protein 4 (LHX4).
Clinical Significance Single nucleotide polymorphisms within the second intron of human C1orf52 have been linked to metabolic syndrome, high density lipoprotein cholesterol levels, response to levetiracetam in genetic generalized epilepsy, multiple sclerosis, body mass index, and protein quantitative trait (liver).
References