C12orf60

Last updated
C12orf60
Identifiers
Aliases C12orf60 , chromosome 12 open reading frame 60
External IDs MGI: 3605234 HomoloGene: 52193 GeneCards: C12orf60
Orthologs
SpeciesHumanMouse
Entrez

144608

320135

Ensembl

ENSG00000182993

ENSMUSG00000047515

UniProt

Q5U649

Q810N5

RefSeq (mRNA)

NM_175874

NM_178776

RefSeq (protein)

NP_787070

NP_848891

Location (UCSC) Chr 12: 14.8 – 14.91 Mb Chr 6: 136.8 – 136.82 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Uncharacterized protein C12orf60 is a protein that in humans ( Homo sapiens ) is encoded by the C12orf60 gene. The gene is also known as LOC144608 or MGC47869. The protein lacks transmembrane domains and helices, but it is rich in alpha-helices. It is predicted to localize in the nucleus. [5]

Contents

The C12orf60 mature mRNA transcript is 1139 nucleotides long [6] and encodes a protein containing 245 amino acids. [7] The protein lacks transmembrane domains and helices, but it is rich in alpha-helices. It is predicted to localize in the nucleus, but its function is not yet well understood by the scientific community. The gene was listed as a potential biomarker for detecting the efficacy of allergen immunotherapy. [8]

The gene is highly expressed in the testes and colon, but it is also expressed in the kidney, breast carcinomas, brain, and various endocrine glands. [9]

Gene

Locus and size

Location of C12orf60 on Chromosome 12 C12orf60 Cytogenic.pdf
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]

Common aliases

C12orf60 is also known as LOC144608 and MGC47869.

mRNA

A total of 22 exons exist within the gene.5 From these exons, there are 13 transcript variants. 12 of these transcript variants are predicted, and only a further 7 of these are predicted to encode a protein. Furthermore, they are predicted to encode the same protein.

Spatial distribution of the C12orf60 splice isoforms between cytogenic bands 12p12.3 and 12p13.1. All isoforms beginning with an "X" are predicted. The purple transcripts are non-coding, and the green transcripts all encode the same protein sequence. Ticks on the lines indicate the locations of exons, while introns lie in-between. C12orf60 Transcript Isoforms.pdf
Spatial distribution of the C12orf60 splice isoforms between cytogenic bands 12p12.3 and 12p13.1. All isoforms beginning with an “X” are predicted. The purple transcripts are non-coding, and the green transcripts all encode the same protein sequence. Ticks on the lines indicate the locations of exons, while introns lie in-between.

The notable features of the mRNA sequence include two polyadenylation signals in the 3' untranslated region (UTR), and it is the target of several RNA-binding proteins (RBP) including RBP-MBNL1 in the 5' UTR. A single intron splice site exists in the primary transcript, as does an upstream in-frame stop codon.

Protein

Predicted tertiary structure for C12orf60 protein by I-TASSER. The amino acid termini are labeled. Regions located within DUF4533 are colored red if it is a coiled-coil and purple/blue if it is an alpha-helix. Otherwise, coiled-coils are colored grey and alpha-helices are colored gray/blue. C12orf60 I-TASSER Predicted 3D Structure.png
Predicted tertiary structure for C12orf60 protein by I-TASSER. The amino acid termini are labeled. Regions located within DUF4533 are colored red if it is a coiled-coil and purple/blue if it is an alpha-helix. Otherwise, coiled-coils are colored grey and alpha-helices are colored gray/blue.

Composition

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. C12orf60 rotation.gif
Rotating predicted protein model for C12orf60 by I-TASSER.

Topology

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]

Conserved domains

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.

Post-translational modification

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

Subcellular localization

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.

Expression

Tissue expression

Microarray-assessed tissue expression profile of C12orf60. GDS3113 Profile on C12orf60.png
Microarray-assessed tissue expression profile of C12orf60.

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. 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 C12orf60 Brain Expression Profile.pdf
Micrarray-assessed brain expression profile of C12orf60. 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

Transcriptional regulation

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]

Protein interactions

C12orf60 protein interaction (left) and co-expression (right). C12orf60 protein interaction and co-expression.png
C12orf60 protein interaction (left) and co-expression (right).

Rolland et al. found that C12orf60 interacts with BMP4 (bone morphogenetic protein 4). [26] BMP4 induces bone and cartilage formation. It also acts in mesoderm induction and fracture repair.

Several other proteins might also interact with C12orf60, [27] and some are predicted to be co-expressed with the protein. [28] Possible protein interactions include L3MBTL4, C3orf67, FAM78A, and PXDC1. Rats that overexpressed L3MBTL4 had higher blood pressure and heart rate. [29]

Proteins that are thought to be co-expressed alongside C12orf60 include ELMOD2, TTC30B, and BCDIN3D. ELMOD2 is thought to be involved in antiviral responses and causing familial idiopathic pulmonary fibrosis. [30] TTC30B is involved in the organelle biogenesis and maintenance pathway as well as intraflagellar transport. BCDIN3D is a methyltransferase and serves as a negative regulator of miRNA processing. [31] As there is no agreement from various sources on any protein-protein interaction, it is difficult to determine if any of these interactions actually occur.

Homology

Paralogs

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.

Orthologs

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

Table of Select C12orf60 Orthologs in Other Species Compared to Human C12orf60
Genus and SpeciesCommon NameEstimated Time Since LCA of Protein (MY)Accession # (mRNA)Accession # (Protein)Corrected Protein Sequence Identity

Deviation (%)

Homo sapiens Humans 0NM_175874.3NP_787070.20
Pongo abelii Sumatran orangutan 15.76XM_002822980.2XP_002823026.12.94
Rhinopithecus bieti Black snub-nosed monkey 29.44XM_017873538.1XP_017729027.19.87
Cebus capucinus imitator White-headed capuchin 43.2XM_017528453.1XP_017383942.19.87
Saimiri boliviensis boliviensis Bolivian squirrel monkey 43.2XM_003934554.2XP_003934603.110.3
Propithecus coquereli Coquerel's sifaka 74XM_012652172.1XP_012507626.128.6
Ceratotherium simum simum Southern white rhinoceros 96XM_004435503.2XP_004435560.133.1
Physeter catodon Sperm whale 96XM_007107758.1XP_007107820.135.4
Equus caballus Horse 96XM_001497318.3XP_001497368.138.3
Miniopterus natalensis Natal long-fingered bat 96XM_016197505.1XP_016052991.140.8
Felis catus Domestic cat 96XM_003988472.3XP_003988521.141.4
Ovis aries Sheep 96XM_004007552.3XP_004007601.143.9
Ursus maritimus Polar bear 96XM_008707031.1XP_008705253.144.0
Choloepus hoffmanni Hoffman's two-toed sloth 105N/AN/A44.5
Canis lupus familiaris Dog 96XM_005637113.2XP_005637170.148.1
Erinaceus europaeus Western European hedgehog 96XM_007533153.1XP_007533215.148.8
Dasypus novemcinctus Nine-banded armadillo 105XM_004460316.1XP_004460373.156.0
Echinops telfairi Small Madagascar hedgehog 105XM_004713800.1XP_004713857.156.0
Ochotona princeps American pika 90XM_004592653.2XP_004592710.156.7
Myotis brandtii Brandt's bat 96XM_005866788.2XP_005866850.159.2
Mus musculus House mouse 90NM_178776.3NP_848891.262.0
Rattus norvegicus Norway rat 90NM_001037797.1NP_001032886.167.3
Sorex araneus European shrew 96XM_004611368.1XP_004611425.175.1
Leptosomus discolor Cuckoo roller 312XM_009947218.1XP_009945520.1129 (100%)
Melopsittacus undulatus Budgerigar 312N/AN/A160 (100%)

Clinical significance

References in literature

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]

Related Research Articles

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<span class="mw-page-title-main">PRR29</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TMCO4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">C17orf53</span>

C17orf53 is a gene in humans that encodes a protein known as C17orf53, uncharacterized protein C17orf53. It has been shown to target the nucleus, with minor localization in the cytoplasm. Based on current findings C17orf53 is predicted to perform functions of transport, however further research into the protein could provide more specific evidence regarding its function.

<span class="mw-page-title-main">C21orf58</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">C7orf26</span> Human protein-encoding gene on chromosome 7

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<span class="mw-page-title-main">FAM98C</span> Gene

Family with sequence 98, member C or FAM98C is a gene that encodes for FAM98C has two aliases FLJ44669 and hypothetical protein LOC147965. FAM98C has two paralogs in humans FAM98A and FAM98B. FAM98C can be characterized for being a Leucine-rich protein. The function of FAM98C is still not defined. FAM98C has orthologs in mammals, reptiles, and amphibians and has a distant orhtologs in Rhinatrema bivittatum and Nanorana parkeri.

<span class="mw-page-title-main">C2orf72</span> Human protein encoding gene

C2orf72 is a gene in humans that encodes a protein currently named after its gene, C2orf72. It is also designated LOC257407 and can be found under GenBank accession code NM_001144994.2. The protein can be found under UniProt accession code A6NCS6.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000182993 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000047515 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Thierry-Mieg, Danielle; Thierry-Mieg, Jean. "AceView: Gene:C12orf60, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2017-02-19.
  6. ↑ "Homo sapiens chromosome 12 open reading frame 60 (C12orf60), mRNA - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-02-19.
  7. ↑ "uncharacterized protein C12orf60 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-02-19.
  8. 1 2 Hiroi, T., & Okubo, K. (2010). U.S. Patent Application No. 13/498,267.
  9. ↑ Marchler-Bauer, A., Bo, Y., Han, L., He, J., Lanczycki, C. J., Lu, S., ... & Gwadz, M. (2016). CDD/SPARCLE: functional classification of proteins via subfamily domain architectures. Nucleic Acids Research, gkw1129.
  10. 1 2 "Genome Annotation and Browser". Genomatix. Archived from the original on 2021-12-02.
  11. ↑ "C12orf60 Gene". www.genecards.org. Retrieved 2017-02-19.
  12. ↑ "C12orf60 chromosome 12 open reading frame 60 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-30.
  13. ↑ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2017-04-24.
  14. ↑ "ExPASy: SIB Bioinformatics Resource Portal - Categories". www.expasy.org. Retrieved 2017-04-24.
  15. ↑ "NCBI CDD Conserved Protein Domain DUF4533". www.ncbi.nlm.nih.gov. Retrieved 2017-02-27.
  16. ↑ "SLP-Local". sunflower.kuicr.kyoto-u.ac.jp. Archived from the original on 2016-01-22. Retrieved 2017-04-30.
  17. ↑ "Hum-mPLoc 2.0 server". www.csbio.sjtu.edu.cn. Retrieved 2017-04-30.
  18. ↑ "BaCelLo". gpcr.biocomp.unibo.it. Retrieved 2017-04-30.
  19. ↑ "CELLO:Subcellular Localization Predictive System". cello.life.nctu.edu.tw. Archived from the original on 2016-03-04. Retrieved 2017-04-30.
  20. ↑ "Hslpred: A svm based method for the subcellular localization of human proteins". www.imtech.res.in. Retrieved 2017-04-30.
  21. ↑ "ESLPred2 : Improved version of ESLPred". www.imtech.res.in. Retrieved 2017-04-30.
  22. ↑ "GDS3113 / 107275". www.ncbi.nlm.nih.gov. Retrieved 2017-04-30.
  23. 1 2 "Home - UniGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-04-24.
  24. 1 2 "Microarray Data :: Allen Brain Atlas: Human Brain". human.brain-map.org. Retrieved 2017-04-30.
  25. ↑ "Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2017-04-24.
  26. ↑ Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, et al. (November 2014). "A proteome-scale map of the human interactome network". Cell. 159 (5): 1212–1226. doi:10.1016/j.cell.2014.10.050. PMC   4266588 . PMID   25416956.
  27. ↑ "STRING: functional protein association networks". string-db.org. Retrieved 2017-04-24.
  28. ↑ "GeneMANIA". genemania.org. Retrieved 2017-04-24.
  29. ↑ "OMIM Entry - * 617135 - L3MBT-LIKE 4; L3MBTL4". www.omim.org. Retrieved 2017-04-24.
  30. ↑ "ELMOD2 Gene". www.genecards.org. Retrieved 2017-04-24.
  31. ↑ "BCDIN3D Gene". www.genecards.org. Retrieved 2017-04-24.
  32. ↑ Zhou L, Ji J, Peng S, Zhang Z, Fang S, Li L, Zhu Y, Huang L, Chen C, Ma J (December 2016). "A GWA study reveals genetic loci for body conformation traits in Chinese Laiwu pigs and its implications for human BMI". Mammalian Genome. 27 (11–12): 610–621. doi:10.1007/s00335-016-9657-4. PMID   27473603. S2CID   24327418.
  33. ↑ Chen C, Bartenhagen C, Gombert M, Okpanyi V, Binder V, Röttgers S, Bradtke J, Teigler-Schlegel A, Harbott J, Ginzel S, Thiele R, Husemann P, Krell PF, Borkhardt A, Dugas M, Hu J, Fischer U (September 2015). "Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients". Leukemia Research. 39 (9): 990–1001. doi:10.1016/j.leukres.2015.06.005. PMID   26189108.
  34. ↑ Chan SF, Huang X, McKercher SR, Zaidi R, Okamoto SI, Nakanishi N, Lipton SA (March 2015). "Transcriptional profiling of MEF2-regulated genes in human neural progenitor cells derived from embryonic stem cells". Genomics Data. 3: 24–27. doi:10.1016/j.gdata.2014.10.022. PMC   4255278 . PMID   25485232.
  35. ↑ Muller PA, Klomp LW (June 2009). "ATOX1: a novel copper-responsive transcription factor in mammals?". The International Journal of Biochemistry & Cell Biology. 41 (6): 1233–6. doi:10.1016/j.biocel.2008.08.001. PMID   18761103.
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