# C1orf21

Uncharacterized protein C1orf21, also known as Proliferation-Inducing Protein 13, is a protein that in humans is encoded by the C1orf21 gene. C1orf21 is an intracellular protein that flows between the nucleus and the cytoplasm in the cell. It has been linked with cell growth and reproduction and there has been strong links with various types of cancers. There are no paralogs for this gene, however, many conserved orthologs have been found in all invertebrates. C1orf21 has low to moderate level of expression in most tissues in humans, however, it has the most expression in the skin, lung and prostate.

## Gene
### Locus

C1orf198 is a protein-encoding gene found on the reverse strand of chromosome 1 at the locus 1q25.3.

### Gene neighborhood

C1orf21 is located on the long arm of chromosome 1. It is found at position 5q23.1.
Cytogenic band: 1q25.3

### Size

Chromosome one is one of the longest chromosomes, in which C1orf21 spans from 184,385,826 to 184,390,390 bases, resulting with mRNA transcript that is 10,278 nucleotides long with 4 exons. The protein is 121 amino acids long, containing a domain of unknown function known as DUF4612.

### Expression

NCBI gene and RNA-Seq revealed that C1orf21 is expressed in all tissues at a low to moderate level, however, it is mostly expressed in the skin, brain and prostate.

## Gene level regulation
### Promoter

There was over 7 promoters that were predicted, but the true promoter was 1111 base pairs long known as .

### Transcription factor binding sites

Many transcription factor (TF) binding sites have been predicted through Genomatix. Some important binding cites include MYRE, MARs, and Bright.
MYRE is a myelin regulatory factor. Myelin is produced in the central nervous system and plays a large role in axons. MARs is a special AT-rich sequence-binding protein 1, predominantly expressed in thymocytes, binds to matrix attachment regions. Bright helps with B cell regulator of IgH transcription.

## Protein
### Subcellular location

It was predicted that the location of C1orf21 is in the nucleus with 62.2% certainty. The mitochondria was predicted at 17.4%: mitochondrial, while the cytoskeleton, and vascular system at 4.3%.

### Structure

C1orf21 protein is 121 amino acids long with a molecular weight of 18,7 kDa with an isoelectric point of 5.08. It is believed that the protein interacts with the nuclear membrane and contains an unknown domain known as DUF4612. For the secondary and tertiary structure it is predicted that there are many alpha helices in the structure, with the rest of the protein having a disordered structure.
* I-TASSER software generated a prediction of the tertiary structure of C1orf21.

## Protein level regulation

* O-glycosylation sites: Serine 5, Threonine 11, Serine 66, Serine 68, and Serine 69.
* Palmitioyaltion site: Cysteine 3
* Phosphorylation: Serine 34, Serine 44, Serine 66, Serine 69, Serine 75, Serine 95, Serine 115, Serine 121
* Sumoylation site: Lysine 46 and Lysine 106
* Tyrosine sulfation site: Tyrosine 113

## Interacting proteins

| Protein | Function |
| Calcineurin-binding protein cabin-1 (Cabin1) | Required for replication-independent chromatin assembly |
| Centrosomal protein of 162 kDa (CEP162) | Required to promote assembly of the transition zone in primary cilia. |
| CD97 antigen | Receptor potentially involved in both adhesion and signaling processes early after leukocyte activation. |
| Chromosome 11 open reading frame 57 (C11orf57) | Unknown |
| Chromosome 5 open reading frame 51 (C5orf51) | Unknown |
| Homeobox protein Nkx-2.8; (NKX2-8) | NKL subclass homeoboxes and pseudogenes |
| NACHT, LRR and PYD domains-containing protein 13 (NLPR13) | Involved in inflammation |
| Semaphorin-3C (SEMA3C) | Binds to plexin family members and plays an important role in the regulation of developmental processes |
| Zinc finger protein 19 (ZNF19) | transcriptional regulation |

## Homology
### Paralogs

There are no isoforms or paralogs of C1orf21 that are known.

### Orthologs

C1orf21 is found in most classes of vertebrates and some invertebrates. The most distant ortholog of C1orf21 is Acropora digitifera, which diverged an estimated 824 million years ago. There is no traces of the C1orf21 gene in organisms that are traced beyond invertebrates, such as fungi, plants, protists, or single celled organisms.

### Homologous domains

The domain of unknown function 4612 (DUF4612) was highly conserved in most orthologs.
| Species | Common name | Taxonomic group | DOD (MYA) | Accession number | Sequence length (aa) | Identity | Similarity |
| Homo sapiens | Human | Primates | 0 | NP_110433 | 121 | 100 | 100 |
| Pan troglodytes | Chimpanzee | Primates | 7 | NP_001229539 | 121 | 100 | 100 |
| Gorilla gorilla gorilla | Gorilla | Primates | 9 | XP_018883443 | 121 | 100 | 100 |
| Macaca mulatta | Rhesus macaque | Primates | 30 | NP_001247792 | 121 | 100 | 100 |
| Cercocebus atys | Sooty mangabey | Primates | 30 | XP_011903171 | 121 | 100 | 100 |
| Ursus maritimus | Polar bear | Carnivora | 96 | XP_008695366 | 121 | 97 | 99 |
| Pogona vitticeps | Central bearded dragon | Amphioxiformes | 312 | XP_020650764 | 121 | 94 | 97 |
| Gallus gallus | Red junglefowl | Galliformes | 312 | XP_422292 | 121 | 93 | 98 |
| Haliaeetus leucocephalus | Bald eagle | Accipitriformes | 312 | XP_010578992 | 121 | 93 | 98 |
| Fulmarus glacialis | Northern fulmar | Procellariiformes | 312 | KFV96345 | 90 | 93 | 98 |
| Ophiophagus hannah | King cobra | Squamata | 312 | ETE66728 | 121 | 91 | 96 |
| Xenopus tropicalis | Western clawed frog | Anura | 352 | NP_001072652 | 121 | 77 | 85 |
| Nothobranchius furzeri | Turquoise killifish | Cyprinodontiformes | 435 | XP_015827000 | 116 | 61 | 73 |
| Echeneis naucrates | Live sharksucker | Perciformes | 435 | XP_029355762 | 116 | 61 | 73 |
| Haplochromis burtoni | Burton's mouthbrooder | Cichliformes | 435 | XP_005932528 | 116 | 61 | 73 |
| Anabas testudineus | Blue perch | Anabantiformes | 435 | XP_026201702 | 116 | 47 | 60 |
| Callorhinchus milii | Australian ghostshark | Chimaeriformes | 473 | XP_007893787 | 135 | 69 | 79 |
| Rhincodon typus | Whale Shark | Orectolobiformes | 473 | XP_020373635 | 91 | 68 | 82 |
| Branchiostoma belcheri | Belcher's lancelet | Amphioxiformes | 684 | XP_019640980 | 114 | 33 | 56 |
| Acropora digitifera | Stony coral pulp | Scleractinia | 824 | XP_015747227 | 140 | 55 | 65 |

## Function

C1orf21 is most likely involved in the growth of cells, especially in the nucleus where replication of DNA occurs.

## Clinical significance

Even though there is not a lot known about C1orf21, there have been some links with diseases. In many studies it has been found that there are links with cancer. Since C1orf21 is associated with cell proliferation, in another study by Sooda et al. there was an interest in the transcript map of the HPC1 locus, to help them identify the susceptibility genes involved in prostate cancer and jaw tumor. It was seen that overall there are several studies where C1orf21 has been studied on role it plays in cancer for different body areas among many other genes. It was also found that there is a large correlation with affects on keratinocytes since C1orf21 plays a role in ZNF750 silencing.