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C1orf167

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Chromosome 1 open reading frame (C1orf167) is a protein which in humans is encoded by the C1orf167 gene.[1] The NCBI accession number is NP_001010881. The protein is 1468 amino acids in length with a molecular weight of 162.42 kDa. The mRNA sequence was found to be 4689 base pairs in length.[2][3]

Gene

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Locus

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It can be located on chromosome 1 at position 1p36.22 on the plus strand and spans from positions 11,824,457 to 1,849,503.[2][4]

Aliases

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C1orf167 has one known alias with the name Chromosome 1 Open Reading Frame 167.[5]

Number of Exons

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There are 26 exons associated with the protein.[1]

mRNA

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Alternative Splicing

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A splice region that is conserved in primate orthologs of the C1orf167 mRNA was located between exon 1 and exon 2.[6]

Known mRNA Isoforms

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The mRNA sequence has 8 known splice isoforms as determined by the conserved domains.[7] The isoforms span the regions 426-863, 981-1418, 954-1391, 999-1329, 999-1400, 999-1436, 999-1404. and 999-1463 of the mRNA sequence.[8]

Protein

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Conceptual Translation of C1orf167 showcasing the conserved Domain of Unknown Function that begins at the break between exon 13 and exon 14.

Known Protein Isoforms

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Alternative splicing produces two known isoforms of the human protein. They are XP_006711141.1 which is 1489aa in length and XP_003307860.2 which is 713aa in length.[9][10]

Composition

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The protein has an isoelectric point (pI) of 11. The predicted molecular weight (mW) is 160kDa for the human protein, but ranges from 140-180kDa for more distant orthologs.[11] Compositional analysis revealed the most abundant amino acid to be Alanine (A) at 12.4% of the total protein. The analysis also revealed C1orf167 protein to be rich in Tryptophan (W) and deficient in Tyrosine (Y) and Isoleucine (I).[12]

Subcellular Localization

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C1orf167 is predicted to be localized to the cell nucleus.[13]

Post-Translational Modifications

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C1orf167 is predicted to undergo phosphorylation, O-Glycosylation, SUMOylation, glycation, and cleavage by staphylococcal peptidase I (Q105, Q321) and Glutamyl endopeptidase (Q1101).[14][15][16][17][18]

Species
H. sapiens T. manatus latirostris U. parryii D. novaehollandiae P. vitticeps C. milli
SUMOylation K22 IVTLE447-451,

K604,

K605,

VRVVP 684-688,

VAVVD502-506 K434 K57,K128,K578,

K993, K1388

ISILH 121-125,

K264,K477,

K497, K522

IVSIC 621-625

LCLVY 703-707

VVVLR 975-979,

VLQLR 1027-1031

K1199

K1208

O-GlcNAcylation Many* Similar Distribution (but more sites) Similar Distribution

(but fewer sites)

Similar Distribution

(but fewer sites)

Similar Distribution Similar Distribution

(but fewer sites)

Glycation of ε amino groups of lysines K -22, 114, 323,399,

433,505,

701, 710,720,

832,975,

1138,1279,

1306,1394, 1418

K-335,516,

534,605,

747,757,

1080,1125,

1189, 1382

K-114, 123,333,

462,651,

660,661, 938, 1111, 1149

K-72,103,128,

133, 183,240,241,

248,290,398,

437,466,483,

494,505,552,

589,718, 767,772,820, 974,1106

K-14,57,60,89,96,

128,133,157,275,

423,488,578,619,

647,890,900,952,

983,993,1208,1279, 1288,

K-4,56,106,131,163,169,

177,235,291, 480,

566,660,666,717,

780,814,827, 853,

857, 936, 954,

964,974, 986,

1015, 1079, 1208

Nuclear Export Signal L84 L808 L84 L589 V869, L874 L186, L188, L1117
Phosphorylation Many* Similar Distribution Similar Distribution Similar Distribution Similar Distribution Similar Distribution
Proteinase Cleavage Sites Q105, Q321, Q1101 Q441, Q1030 Q72 Q60 Q90, Q155, Q498 Q520, Q809, Q908,

Table 1. Post-Translational Modifications determined for C1orf167.

Schematic Illustration of predicted post-translational modifications for C1orf167 made using the Dog 2.0 [19] The DUF at locations 954-1418 is labeled

*GPS, NetPhos results indicated hyper-phosphorylation of C1orf167 in H. sapiens and five of its orthologs.

Domain and Motifs by Homology

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One domain of unknown function, located from 954aa-1418aa, is 465 amino acids in length.

Secondary Structure

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C1orf167 was determined to be rich in alpha helices. No notable regions of beta pleated sheets or coils were predicted.[20] In particular, high confidence was indicated for 42 alpha helices with the longest alpha helix region spanning from residues 450aa to 1182aa. This long alpha helix region includes a significant portion of the conserved DUF which spans 954aa-1418aa.[21][22][23][24][25]

Tertiary Structure

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The best-aligned structural analog, generated by I-TASSER, of C1orf167 had a confidence (c-score) score of -0.68 given a range of [-5,2] with higher values indicating a higher confidence.[25] Per Swiss Model, two monomers are predicted to form an alpha helix.[26] Both of the helices are aligned facing outwards with hydrophobic amino acids such as glutamic acid (E) on the interior and asparagine (R), Serine (and lysine (K) on the exterior. Asparagine residues may serve as an important oligosaccharide binding site.[27]

Expression

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C1orf167 has high expression in the larynx, blood, placenta, testis and prostate, with the highest expression found in the testis.[28] The promoter GXP_5109290 spans 1507 base pairs on chromosome 1.[29] GXP_5109290 was found to be conserved in the bonobo (Pan Paniscus), gorilla (Gorilla Gorilla Gorilla), mouse (Mus musculus), chimp (Pan Troglodytes), and rhesus monkey (Macaca mulata).[30][31]

Protein Interactions

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There were 10 interactions identified by STRING.[32]

Homology

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Paralogs

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No known paralogs or paralogous domains were identified for C1orf167.

Orthologs

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Using NCBI BLAST, orthologs of C1orf167 were determined. No orthologs could be found in single-celled organisms, or fungi whose genomes have been sequenced. In terms of multi-cellular organisms, orthologs were found in mammals, aves, reptiles, and cartilaginous fishes. The table below shows a representative sample of 20 of the orthologs for C1orf167. The table is organized based on the time of divergence from humans in millions of years (MYA) and then by sequence similarity.

Genus and Species Common Name Taxonomic Group Date of Divergence Accession # Sequence Length Sequence Identity Sequence Similarity
Homo sapiens Humans Mammalia 0 NP_001010881.1 1449aa 100% 100%
Pan troglodytes Chimpanzee Mammalia (primate) 6.6 XP_024212133.1 1442 aa 97% 97%
Piliocolobus tephrosceles Ugandan Red Colobus Mammalia (primate) 29 XP_026303745.1 1453aa 87% 90%
Macaca fascicularis Crab-eating Macaque Mammalia (primate) 29.4 XP_015298104.1 1444aa 87% 90%
Trichechus manatus latirostris American Manatee Mammalia (sirenia) 76 XP_023587965.1 1631aa 49% 56%
Marmota flaviventris Yellow-bellied Marmot Mammalia (rodentia) 90 XP_027803235.1 1284aa 49.16% 57%
Galeopterus variegatus Sunda Flying Lemur Mammalia (primate) 90 XP_008588133.1 1439aa 54% 60%
Camelus ferus Bactrian Camel Mammalia (artiodactyla) 90 XP_014421294.1 1442aa 53% 62%
Miniopterus natalensis Natal Clinging Bat Mammalia (chiroptera) 96 XP_016061116.1 1644aa 48.64% 56%
Desmodus rotundus Common Vampire Bat Mammalia (chiroptera) 96 XP_024410696.1 1548aa 47.97% 56%
Ictidomys tridecemlineatus Thirteen-lined Ground Squirrel Mammalia (rodentia) 96 XP_021576066.1 1349aa 47.59% 56%
Urocitellus parryii Arctic Ground Squirrel Mammalia (rodentia) 96 XP_026253666.1 1299aa 46.47% 55%
Myotis brandtii Brandt's Bat Mammalia (chiroptera) 105 XP_014400940.1 1390aa 50.19% 59%
Dromaius novaehollandiae Emu Aves 312 XP_025951247.1 1154aa 31.56% 47%
Pseudopodoces humilis Ground Tit Aves 312 XP_014112713.1 1415aa 30.34% 47%
Columba livia Rock Dove Aves 312 XP_021137589.1 1430aa 30.45% 46%
anser cygnoides domesticus Swan Goose Aves 312 XP_013043263.1 1126aa 27% 40%
Alligator sinensis Chinese Alligator Reptilia 312 XP_025067177.1 1626aa 34% 45%
Pogona vitticeps Central Bearded Dragon Reptilia 312 XP_020637641.1 1388aa 27.76% 38%
Callorhinchus milii Australian Ghostshark Chondrichthyes 473 XP_007896104.1 1210aa 29% 43%

Table 2. This table shows the divergence timeline of the C1orf167 orthologs. It is sorted by date of divergence, color according to taxonomic group or class and then by sequence similarity.

Multiple Sequence Alignment of Strict Orthologs for C1orf167. Beginning of the conserved DUF region at the break between exon 13 and 14 is shown.[33]

Function

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At this time the function of C1orf167 is uncharacterized.

Clinical Significance

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Pathology

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According to the EST profile for breakdown by healthy state, the expression levels of C1orf167 were higher than healthy cells for leukemia, head, neck and lung cancers.[28] Based on the results from NCBI GeoProfiles, C1orf167 was found to have increased expression on dendritic cells for patients experiencing Chlamydia pneumoniae infections. Increased expression of C1orf167 was also indicated for Human Pulmonary Tuberculosis tissues given the presence of caseous tuberculosis granulomas in the lungs when compared to normal lung tissues.[34]

References

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  1. ^ a b NCBI. "C1orf167 chromosome 1 open reading frame 167 [ Homo sapiens (human) ])". NCBI. Retrieved February 9, 2019.
  2. ^ a b "C1orf167 Gene". www.genecards.org. Retrieved 9 February 2019.
  3. ^ "Homo sapiens chromosome 1 open reading frame 167 (C1orf167), mRNA". NCBI. 30 June 2018. Retrieved 8 February 2019.
  4. ^ "RCSB PDB - Gene View - C1orf167 - chromosome 1 open reading frame 167". www.rcsb.org. Archived from the original on 2019-05-05. Retrieved 2019-03-04.
  5. ^ "C1orf167 chromosome 1 open reading frame 167 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-04-22.
  6. ^ "Genome Browser FAQ". genome.ucsc.edu. Retrieved 2019-04-22.
  7. ^ "C1orf167 GeneCards".
  8. ^ "C1orf167 chromosome 1 open reading frame 167 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-04-27.
  9. ^ "C1orf167 (human)". www.phosphosite.org. Retrieved 2019-03-04.
  10. ^ "HomoloGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-03-04.
  11. ^ "ExPASy: SIB Bioinformatics Resource Portal - Categories". www.expasy.org. Retrieved 2019-04-27.
  12. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-04-27.
  13. ^ "PSORT II Tool". PSORT II.[permanent dead link]
  14. ^ "SUMOplot analysis program". SUMOplot. Archived from the original on 2005-01-03. Retrieved 2019-05-05.
  15. ^ "GPS 3.0 - Kinase-specific Phosphorylation Site Prediction". gps.biocuckoo.org. Retrieved 2019-04-22.
  16. ^ "YinOYang O-GLcNAc sties". YinOYang.
  17. ^ "NetOGlyc 4.0 Server". www.cbs.dtu.dk. Retrieved 2019-04-22.
  18. ^ "C1orf167 NetCorona entry".
  19. ^ "DOG 2.0 - Protein Domain Structure Visualization". dog.biocuckoo.org. Retrieved 2019-05-02.
  20. ^ "PHYRE2 Protein Fold Recognition Server". www.sbg.bio.ic.ac.uk. Retrieved 2019-04-22.
  21. ^ "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2019-04-22.
  22. ^ "Phyre2 Database". Phyre2.
  23. ^ "SOPMA secondary prediction".
  24. ^ "GOR protein prediction".
  25. ^ a b "I-TASSER results". zhanglab.ccmb.med.umich.edu. Archived from the original on 2019-05-05. Retrieved 2019-05-05.
  26. ^ "SWISS-MODEL Interactive Workspace". swissmodel.expasy.org. Retrieved 2019-05-05.
  27. ^ Kornfeld, R.; Kornfeld, S. (1985). "Assembly of asparagine-linked oligosaccharides" (PDF). Annual Review of Biochemistry. 54: 631–664. doi:10.1146/annurev.bi.54.070185.003215. PMID 3896128.
  28. ^ a b "EST Profile - Hs.585415". www.ncbi.nlm.nih.gov. Retrieved 2019-04-22.
  29. ^ "ElDorado Introduction". www.genomatix.de. Archived from the original on 2016-06-02. Retrieved 2019-04-22.
  30. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2019-04-22.
  31. ^ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-04-22.
  32. ^ "C1orf167 protein (human) - STRING interaction network". string-db.org. Retrieved 2019-04-19.
  33. ^ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-05-01.
  34. ^ "c1orf167 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-01.
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