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Uncharacterized protein C1orf21, or known as Proliferation-Inducing Protein 13, is a protein that in humans is encoded by the C1orf21 gene.[5][6] C1orf21 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. [7]There are no paralogs for this gene, however, many conserved orthologs have been found in all invertebrate.[8] 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.

AliasesC1orf21, PIG13, chromosome 1 open reading frame 21
External IDsMGI: 1916649 HomoloGene: 12776 GeneCards: C1orf21
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for C1orf21
Genomic location for C1orf21
Band1q25.3Start184,387,029 bp[1]
End184,629,019 bp[1]
RNA expression pattern
PBB GE C1orf21 221272 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 184.39 – 184.63 MbChr 1: 151.85 – 152.09 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse




C1orf198 is a protein-encoding gene found on the reverse strand of chromosome 1 at the locus 1q25.3. [9]

Gene NeighborhoodEdit

C1orf21 is located on the long arm of chromosome 1. It is found at position 5q23.1.


Cytogenic band: 1q25.3


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 nucleotide with 4 exons. The protein is 121 amino acids, containing a domain of unknown function known as DUF4612.


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 RegulationEdit


There was over 7 promoters that were predicted, but the true promoter was 1111 base pairs long known as .[10]

Transcription Factor Binding SitesEdit

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 neverous 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.


Subcellular LocationEdit

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 ate 4.3%.[11]


C1orf21 protein is 121 amino acids 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 helix in the structure, with the rest of the protein having a disordered structure.[12]

PHYRE. An α-helix from 18 amino acids of C1orf21.

I-TASSER software generated a prediction of the tertiary structure of C1orf21.

Protien Level RegulationEdit

  • O-glycosylation sites: Serine 5, Threonine 11, Seiner 66, Serine 68, and Serine 69.[13]
  • Palmitioyaltion site: Cysteine 3
  • Phosphorylation: Serine 34, Serine 44, Serine 66, Serine 69, Serine 75, Serine 95, Serine 115, Serine 121 [14]
  • Sumoylation site: Lysine 46 and Lysine 106 [15]
  • Tyrosine Sulfation site: Tyrosine 113

Interacting ProteinsEdit



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



Figure 3.  Unrooted phylogenetic tree of C1orf21 orthologs. Adi [Acropora digitifera, Stony Coral pulp], Ate [Anabas testudineus], Bbe [Branchiostoma belcheri, crown-of-thorns starfish],  Cat [Cercocebus atys], Cmi [Callorhinchus milli], Ena [Echeneis naucrates], Fgl [Fulmarus glacialis], Gga [Gallus gallus, chicken], Ggg [Gorilla gorilla gorilla], Hbu [Haplochromis burtoni], Hle [Haliaeetus leucocephalus], Hsa [Homo sapiens, human], Mul [Macaca mulatta], Nfu [Nothobranchius furzeri], Oha [Ophiophagus Hannah], Ptr [Pan troglodytes], Pvi [Pogona vitticeps, central bearded dragon], Rty [ Rhincodon typus], Xla [Xenopus laevis, African clawed frog] Uma [Ursus maritimus].   Tree made with a Neighbor-Joining method using a ClustalW-formatted set of sequences as input1.1 Clustal W [16]

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


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.[17] There is no traces of the C1orf21 gene in organisms that are traced beyond invertebrates, such as fungi, plants, protists, or single celled organisms. [18]

Homologous domainsEdit

The domain of unknown function 4612 (DUF4612) was highly conserved in most orthologs.

Genus and species Common name Taxonomic group DOD


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


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

Clinical SignificanceEdit

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 is links between cancer. Since C1orf21 is associated with cell prefoliation, 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 is a several studies were 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.


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000116667 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032666 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Sood R, Bonner TI, Makalowska I, Stephan DA, Robbins CM, Connors TD, Morgenbesser SD, Su K, Faruque MU, Pinkett H, Graham C, Baxevanis AD, Klinger KW, Landes GM, Trent JM, Carpten JD (Apr 2001). "Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus". Genomics. 73 (2): 211–22. doi:10.1006/geno.2001.6500. PMID 11318611.
  6. ^ "Entrez Gene: C1orf21 chromosome 1 open reading frame 21".
  7. ^ "Expression of C1orf21 in cancer - Summary - The Human Protein Atlas". Retrieved 2019-08-08.
  8. ^ "Protein BLAST: search protein databases using a protein query". Retrieved 2019-02-28.
  9. ^ Retrieved 2019-08-08. Missing or empty |title= (help)
  10. ^ "Genomatix - NGS Data Analysis & Personalized Medicine". Retrieved 2019-08-08.
  11. ^ "PSORT II Prediction". Retrieved 2019-08-01.
  12. ^ "DisEMBL 1.5 - Predictors of intrinsic protein disorder". Retrieved 2019-08-01.
  13. ^ "NetOGlyc 4.0 Server - prediction results". Retrieved 2019-08-04.
  14. ^ "NetPhos 3.1 Server - prediction results". Retrieved 2019-08-04.
  15. ^ "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". Retrieved 2019-08-04.
  16. ^ "Multiple Sequence Alignment - CLUSTALW". Retrieved 2019-08-08.
  17. ^ "TimeTree :: The Timescale of Life". Retrieved 2019-07-01.
  18. ^ "BLAST: Basic Local Alignment Search Tool". Retrieved 2019-08-01.


External linksEdit

Further readingEdit