C12orf60

Location of C12orf60 on Chromosome 12

C12rf60 is located on Chromosome 12 beginning at 14,803,572 bp and ending at 14,823,858 bp, spanning 20,287 base pairs[10] It is located on the forward/positive strand between the 12p12.3 and 12p13.1 cytogenic bands.[11] Other genes that are within 100 kilobases of this gene include:[12]

• Positive/Forward Strand
  • H2A histone family member J (H2AFJ)
• Negative/Backwards Strand
  • Single-pass membrane protein with coiled-coil domains 3 (SMCO3)
  • WW domain binding protein 11 (WBP11)
  • ADP-ribosyltransferase 4 (ART4)
  • Histone cluster 4, H4 (HIST4H4)
  • LOC105369669
  • Matrix Gla protein (MGP)

C12orf60 is also known as LOC144608 and MGC47869.

C12orf60 has a predicted isoelectric point of 8.19 and a molecular weight of 27.6 kiloDaltons. Glycine and tyrosine residues are relatively less prevalent compared to other proteins in the human proteome, while methionine is more prevalent.

Rotating predicted protein model for C12orf60 by I-TASSER.

The protein product is predicted to have multiple α-helices, coiled coil, and one β-sheet. It is suggested that the protein does not contain transmembrane regions or helices, meaning that the protein is not anchored to the cell membrane nor an intracellular membrane like the Golgi apparatus.[14]

In the predicted protein product, C12orf60 contains a conserved protein domain of 225 amino acids. This domain (DUF4533) is within in the pfam15047 family of proteins. Only one other gene is listed within this family: C12orf69, which is also known as SMOC3 (single-pass membrane protein with coiled-coil domains 3).[15]

Analysis of human C12orf60 and 9 of its orthologs reveals a highly conserved ERL motif starting at the 10th residue of the human protein sequence. It is not known whether this motif occurs in other proteins.

Other conserved residues are Asp25, Ser28, Phe37, Met41, Glu69, Leu85, Lys88, Leu143, Pro147, Ile148, Leu151, Gln164, Lys189, Leu191, Ala207, and Glu212, Leu225, and Lys227. Furthermore, these residues lie within DUF4533, suggesting that these conserved amino acids are important for the function of the domain. Also, the region between the 100 and 150 residues are not conserved. Thus, this region is not likely vital to the protein's function.

Since it is predicted that the protein product is intracellular, extracellular modifications are not predicted to occur on C12orf60. Other modifications such as acetylation, phosphorylation, picornaviral protease cleavage, sumoylation, and O-beta-GlcNAcylation are predicted to occur on C12orf60 as well as several of its orthologous proteins. There are two amino acids that serve as sites of both phosphorylation and O-beta-GlcNAcylation, which may indicate a site of protein activation or inactivation.

Schematic diagram of post-translational modifications that C12orf60 is predicted to undergo.

C12orf60 is predicted to be localized in the nucleus, cytoplasm, or outside the cell.[16][17][18][19][20][21] However, current literature supports its localization in the nucleus.

Microarray-assessed tissue expression profile of C12orf60.[22]

Expression of C12orf60 is regulated. The gene is highly expressed in the testes and colon, but it is also expressed in the kidney, breast carcinomas, various endocrine glands, and some regions of the brain.[23][24][25] It is also expressed in the embryo body and fetus during development.[23]

Micrarray-assessed brain expression profile of C12orf60.[24] Expression locations are as follows (high expression locations bolded): 1) Cerebral cortex, 2) cerebral nuclei, 3) epithalamus, 4) hypothalamus, 5) subthalamus, 6) thalamus, 7) midbrain tectum, 8) midbrain tegmentum, 9) cerebellum, 10) pons, 11) myelencephalon, 12) telencephalic white matter, 13) ventricles

The promoter GXP_71811 regulates the expression of C12orf60. The promoter is 1373 base pairs long and is also located on the positive strand. There are over 400 transcription factors that are possible matches for binding to this promoter, including those of the SOX/SRY-sex/testis determining, human and murine ETS, and homeodomain transcription factors.[10]

There are no known paralogs to this gene within the human genome, and no paralogs of C12orf60 were found within the selected species that have a C12orf60 protein ortholog.

Many orthologs are found in mammals and a couple of bird species.

The gene is within 1 Mb of SNPs that were associated with obesity, height, and weight.[32]

The gene was listed along with two other genes in a patent as a potential biomarker for detecting the efficacy of allergen immunotherapy.[8] Specifically, detection of 3 copies of C12orf60 meant that immunotherapy was ineffective.

In one study, the gene was among several identified genes that were translocated in a single patient with recurrent acute lymphoblastic leukemia.[33] This translocation was associated with apoptosis and tumorigenesis.

Another study found that the gene is upregulated by at least 1.5 fold in cells that expressed Constitutive Myocyte Enhancer Factor 2 (MEF2CA).[34] MEF2CA is expressed naturally in the brain.

One study stated the gene contains a “perfect potential antioxidant protein 1 (ATOX1) DNA interaction site in the promoter region.”[35]