# C1orf52

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 lanclets. 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 | Flordia Lanclet | 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).