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Chromosome 12 open reading frame 71

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C12orf71
Identifiers
AliasesC12orf71, chromosome 12 open reading frame 71
External IDsMGI: 1920594; HomoloGene: 53485; GeneCards: C12orf71; OMA:C12orf71 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

728858

73344

Ensembl

ENSG00000214700

ENSMUSG00000040163

UniProt

A8MTZ7

Q80W69

RefSeq (mRNA)

NM_001080406
NM_001384983

NM_001164236
NM_028509

RefSeq (protein)

NP_001073875

NP_001157708
NP_082785

Location (UCSC)Chr 12: 27.08 – 27.08 MbChr 6: 146.85 – 146.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Chromosome 12 open reading frame 71 (c12orf71) is a protein which in humans is encoded by c12orf71 gene. The protein is also known by the alias LOC728858.[5]

Gene

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The gene is located on the minus strand of chromosome 12 (12p11.23).[6][7] The DNA sequence of the c12orf71 gene is 3071 base pairs long and 8 significant structural variations have been identified including deletions, duplications, gain- and loss-of-function mutations.[8] c12orf71 gene was determined to be altered (gain of 21 Mb) in the chromosomal region 12p11.21-p13.3 of a male patient with chromosomal aberrations and in a duplication (gain of 411 kb) at chromosome 12p11.23 along with c12orf70, the coding regions of STK38L and ARNTL2 and a portion of PPFIBP1.[9][10] Manual inspection of alignments, has determined that c12orf71 gene is mammalian specific.[11] Furthermore, genome-wide screening has identified c12orf71 as one of 1000 disrupted genes that are positively selected by cisplatin, a chemotherapy drug.[12]

RNA

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Figure 1. Conceptual translation of human c12orf71 with labeled domains, motifs, post-translational modifications and conserved amino acids.

c12orf71 transcript variant 1 mRNA is 1022 nucleotides long and consists of 2 exons.[6] There is one more, slightly longer transcript variant of c12orf71, with a length of 1087 nucleotides.[13] The mRNA sequence of c12orf71 transcript variant 1 consists of a coding sequence that spans over two exons and 2 poly-A signal sequences. [6]

Expression

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In humans c12orf71 has shown an intermediate expression level in testis and low expression in the bone marrow, skin, spleen, lymph node and liver. Human c12orf71 is expressed after the fetal-development stage.[14] RNA-sequencing analysis has revealed that c12orf71 was expressed at a very low level or not expressed at all in osteoarthritis and non-osteoarthritis hip cartilage. [15] A genome engineering study that studied mice knock-outs has found that c12orf71 has a decreased expression in humans compared to mouse testis, however the absence of the c12orf71 had no effect on mouse fertilization.[16]

Protein

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c12orf71 protein is 269 amino acids long and the unmodified precursor protein has a predicted molecular weight of 30.4 kDa and a theoretical isoelectric point of 5.21.[17] Additionally, the protein is rich in Serine and Aspartic Acid and has a relatively low amount of Valine and Tyrosine. [18]

Cellular localization

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Cellular localization analysis showed that human c12orf71 protein is found in the cytoplasm of the cell. All of the orthologs of the protein were also localized to the cytoplasm.[19] Immunohistochemistry with polyclonal antibody for c12orf71 localized the protein in the cytosol of the cell.[20]

Domains

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The first 21 amino acids of the coding sequence are comprising a disordered region, followed by a domain of unknown function (DUF4640) which spans almost the whole coding sequence.[21] Additionally, the human protein also contains a vacuolar domain, which is mammal specific and may be modulated by phosphorylation.[7]

Post-translation modifications

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Figure 2. c12orf71 Protein diagram with labeled domains and post-translational modifications.

c12orf71 protein has multiple predicted phosphorylation sites,[19] which can have an impact on the protein interactions and sub-cellular localization as well as affect the protein's stability and activity. The protein has one predicted SUMOylation[22] and one ubiquitination predicted site, which can influence many biological functions of the protein, such as cellular response to stress and degradation, respectively. Five different Lysine acetylation[23] sites were predicted, which can neutralize the positive charge on the Lysine, but at the same time the transfer of acetyl group can increase the expression of the protein. 2 N-glycosylation,[19] multiple O-glycosylation[19] and O-linked-N-acetylglucosaminylation[19] sites were predicted, which could potentially affect the protein stability. There is a competition for Lysine-acetylation and ubiquitination at K130, suggesting that a deacetylase enzyme is acting at this site.

Interacting proteins

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There is a direct interaction between c12orf71 and AP2B1, with a moderate confidence level. Adaptor related protein complex 2 subunit beta (AP2B1) helps establish a link between clathrin and receptors in coated vesicles.[24] c12orf71 protein has been found to be present in a protein-protein interaction (PPI) network of the Carboxypeptidase M (CPM) gene, along with nine more genes.[25]

Human c12orf71 interacting proteins
Protein Function
YEATS4 YEATS domain-containing protein 4; Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A.
CPM Carboxypeptidase M; Specifically removes C-terminal basic residues (Arg or Lys) from peptides and proteins. It is believed to play important roles in the control of peptide hormone and growth factor activity at the cell surface, and in the membrane-localized degradation of extracellular proteins; Belongs to the peptidase M14 family
ZNF215 Zinc finger protein 215; May be involved in transcriptional regulation; SCAN domain containing
SPACA5B Sperm acrosome associated 5B; Enable lysozyme activity
SPACA5 Sperm acrosome-associated protein 5; Belongs to the glycosyl hydrolase 22 family
LYZL4 Lysozyme-like protein 4; May be involved in fertilization (By similarity). Has no detectable bacteriolytic and lysozyme activities in vitro (By similarity); Belongs to the glycosyl hydrolase 22 family
LYZL6 Lysozyme-like protein 6; May be involved sperm-egg plasma membrane adhesion and fusion during fertilization. Exhibits bacteriolytic activity in vitro against Micrococcus luteus and Staphylococcus aureus. Shows weak bacteriolytic activity against Gram-positive bacteria at physiological pH. Bacteriolytic activity is pH- dependent, with a maximum at around pH 5.6; Lysozymes, c-type
NUP107 Nuclear pore complex protein Nup107; Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. Required for the assembly of peripheral proteins into the NPC. May anchor NUP62 to the NPC; Belongs to the nucleoporin Nup84/Nup107 family
SPRYD4 Spry domain-containing protein 4; SPRY domain containing 4
CPSF6 Cleavage and polyadenylation specificity factor subunit 6; Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping; RNA binding motif containing

Structure

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Figure 3. Predicted tertiary structure of human c12orf71.
Figure 3. Predicted tertiary structure of human c12orf71 from AlphaFold

Homology and evolution

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Orthologs of the c12orf71 gene have been found only in mammals, in particular Theria (marsupials and placentals). No orthologs in monotremes, birds or reptiles, amphibians, fish, invertebrates, fungi, plants, bacteria, and viruses[26]

Human c12orf71 gene orthologs
Species Common name Order Date of divergence (MYA) Percent identity (%) Percent similarity (%) Length (amino acids) Accession number
Primate mammals Homo sapiens Human Primates 0 100.0 100.0 269 NP_001073875.1
Pan paniscus Pygmy chimpanzee Primates 6.4 99.3 100.0 269 XP_003828900.1
Gorilla gorilla gorilla Gorilla Primates 8.6 96.3 98.1 269 XP_004052946.1
Pongo abelii Sumatran orangutan Primates 15.2 95.9 97.0 269 XP_002823096.1
Nomascus leucogenys Gibbon Primates 19.6 93.7 95.5 269 XP_003265679.1
Placental mammals Equus quagga Zebra Perissodactyla 87 59.9 72.0 279 XP_046519988.1
Loxodonta africana African savannah elephant Proboscidea 87 61.3 73.5 279 XP_023410800.1
Mus musculus Mouse Rhodentia 94 38.2 51.0 300 NP_001157708.1
Bos taurus Cattle Artiodactyla 94 45.6 56.4 347 XP_010803693.1
Panthera uncia Snow leopard Carnivora 94 49.7 62.9 325 XP_049483174.1
Vulpes vulpes Red fox Carnivora 94 55.0 69.1 281 XP_025851313.1
Leptonychotes weddellii Weddell seal Carnivora 94 55.0 70.9 281 XP_006740901.1
Orycteropus afer afer Aardvark Tubulidentata 94 55.6 69.9 277 XP_007947992.1
Pteropus alecto Black flying fox Chiroptera 94 55.9 72.2 278 XP_024903180.1
Canis lupus familiaris Dog Carnivora 99 49.4 62.2 319 XP_005637089.1
Marsupials Gracilinanus agilis Agile gracile opossum Didelphimorphia 160 26.4 43.0 341 XP_044534595.1
Trichosurus vulpecula Common brushtail possum Diprotodontia 160 30.1 44.2 320 XP_036616685.1
Sarcophilus harrisii Tasmanian devil Dasyuromorphia 160 30.2 45.9 318 XP_003772759.2
Vombatus ursinus Common wombat Diprotodontia 160 31.7 44.6 321 XP_027700114.1
Dromiciops gliroides Colocolo opossum Microbiotheria 160 32.3 45.9 317 XP_043823568.1

Evolutionary history

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It has been estimated that c12orf71 gene first appeared in marsupials approximately 160 million years ago. Among the marsupial species, based on the sequence similarity, the gene has first appeared in species from the Microbotheria taxonomic group, represented by the Dromiciops Gliroides (Colocolo opossum) species. Only one isoform of the c12orf71 protein has been found in this species.

Figure 4. c12orf71 Time-calibrated Unrooted Phylogenetic Tree. The colored circles correspond to the species classification. Common names of the species were used. The phylogenetic tree was created using the One-Click Phylogeny Tool [25].

Clinical association

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There is only one disease associated with c12orf71 gene, common warts.[7] A study of global gene methylation of common warts caused by HPV infection found that c12orf71 gene is differentially methylated in Arab male patients with common warts. In particular, c12orf71 is hypomethylated in skin infected with common warts compared to normal skin.[27] 10 SNPs from the GWAS catalog associate c12orf71 gene with obsolete and androgenic alopecia, healing of bone mineral density and educational attainment.[8]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000214700 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040163 – 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. ^ "C12orf71 Gene - GeneCards | CL071 Protein | CL071 Antibody". www.genecards.org. Retrieved 2022-12-16.
  6. ^ a b c "Homo sapiens chromosome 12 open reading frame 71 (C12orf71), transcript variant 1, mRNA". Nucleotide. 2022-06-09.
  7. ^ a b c "AceView: Gene:C12orf71, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2022-09-30.
  8. ^ a b "C12orf71 Gene - GeneCards | CL071 Protein | CL071 Antibody". www.genecards.org. Retrieved 2022-09-30.
  9. ^ Gomes, Alexandra Galvão (2014-06-26). Caracterização citogenômica de aberrações cromossômicas (text thesis) (in Brazilian Portuguese). Universidade de São Paulo.
  10. ^ Pyatt RE, Astbury C (December 2011). "Interpretation of copy number alterations identified through clinical microarray-comparative genomic hybridization". Clinics in Laboratory Medicine. 31 (4): 565–80, viii. doi:10.1016/j.cll.2011.08.007. PMID 22118737.
  11. ^ Cañas, Villanueva (2015-11-20). Insights into mammalian adaptive evolution through genomics data (Ph.D. Thesis thesis). Universitat Pompeu Fabra. hdl:10803/397756.
  12. ^ Ko, Tengyu (2018). Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene-Induced Apoptosis (Thesis). ProQuest 2665131757.
  13. ^ "Homo sapiens chromosome 12 open reading frame 71 (C12orf71), transcript variant 2, mRNA". Nucleotide. 2022-08-19.
  14. ^ "C12orf71 chromosome 12 open reading frame 71 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-09-30.
  15. ^ Johnson, Katherine (2016). Functional analysis of the osteoarthritis susceptibility loci marked by the polymorphisms rs10492367 and rs9350591 (Thesis thesis). Newcastle University. hdl:10443/3247.
  16. ^ Miyata H, Castaneda JM, Fujihara Y, Yu Z, Archambeault DR, Isotani A, et al. (July 2016). "Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice". Proceedings of the National Academy of Sciences of the United States of America. 113 (28): 7704–7710. Bibcode:2016PNAS..113.7704M. doi:10.1073/pnas.1608458113. PMC 4948324. PMID 27357688.
  17. ^ "Compute pI/MW - SIB Swiss Institute of Bioinformatics | Expasy". www.expasy.org. Retrieved 2022-12-08.
  18. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2022-12-08.
  19. ^ a b c d e "Services". DTU Health Tech. Retrieved 2022-12-08.
  20. ^ "C12orf71 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2022-12-08.
  21. ^ "uncharacterized protein C12orf71 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-09-30.
  22. ^ "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". sumosp.biocuckoo.org. Archived from the original on 2013-05-10. Retrieved 2022-12-08.
  23. ^ "GPS-PAIL 2.0 - Prediction of Acetylation on Internal Lysines". pail.biocuckoo.org. Retrieved 2022-12-08.
  24. ^ "PSICQUIC View". www.ebi.ac.uk. Retrieved 2022-12-08.
  25. ^ a b Asghari Alashti F, Goliaei B, Minuchehr Z (2022-01-15). "Analyzing large scale gene expression data in colorectal cancer reveals important clues; CLCA1 and SELENBP1 downregulated in CRC not in normal and not in adenoma". American Journal of Cancer Research. 12 (1): 371–380. PMC 8822279. PMID 35141024.
  26. ^ "C12orf71 orthologs". NCBI. Retrieved 2022-09-30.
  27. ^ Alghamdi MA, Al-Eitan LN, Tarkhan AH, Al-Qarqaz FA (January 2021). "Global gene methylation profiling of common warts caused by human papillomaviruses infection". Saudi Journal of Biological Sciences. 28 (1): 612–622. doi:10.1016/j.sjbs.2020.10.050. PMC 7783806. PMID 33424347. S2CID 228813393.
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