GPATCH11

GPATCH11 is a protein that in humans is encoded by the G-patch domain containing protein 11 gene. The gene has four transcript variants encoding two functional protein isoforms and is expressed in most human tissues. The protein has been found to interact with several other proteins, including two from a splicing pathway. In addition, GPATCH11 has orthologs in all taxa of the eukarya domain.

Gene

G-patch domain containing protein 11 is a protein that in humans is encoded by the gene GPATCH11 and located on chromosome 2, location 2p22.2.[1] It also contains several aliases including CCDC75, and CENPY.[2] The gene is 14,484 bp long and contains 9 exons. Though the function of the protein is not yet known, it is predicted to serve in nucleic acid binding and protein binding.[2][3]

G-patch containing protein 11
Identifiers
SymbolGPATCH11
Alt. symbolsCCDC75, CENPY
NCBI gene253635
HGNC26768
RefSeqNP_777591.3
UniProtQ8N954
Other data
LocusChr. 2 p22.2

mRNA

GPATCH11 has four predicted transcript variants, though only two are known to code for functional protein. Its longest form is unspliced and contains 9 exons whereas the second functional variant has 7 exons with exons 3 and 4 cut out.

This figure depicts the transcript variants of GPATCH11 and was obtained from NCBI Aceview.[4] Transcripts a and b have known functioning proteins.

Protein

GPATCH11 has a molecular weight of about 33.3 kdal and is 285 amino acids long.[2][5] It also comes in a second isoform that is 156 amino acids long. The gene contains a G-patch domain and the DUF 4138 domain. The G-patch domain itself is a novel domain found only in eukarya. BLAST searches of the human gene against bacteria, archaea, and viruses, support this finding.[2]

Primary structure

The following is the primary sequence of the long form of GPATCH11:

Human GPATCH11 protein sequence: The yellow region depicts the G-patch domain, while the blue region depicts the DUF domain.

The protein is rich in glutamic acid and is very highly charged. In addition, it is low in amino acids such as valine, threonine, phenylalanine, and proline. It is a soluble protein and has a nuclear export signal and bipartite nuclear import signal implying that it is localized in the nucleus.

This is the predicted tertiary structure of GPATCH11 obtained from I-tasser.

Secondary structure

The conserved areas of the protein have a secondary structure composed only of alpha-helices and coiled-coil regions.

Tertiary structure

The image to the right is the predicted tertiary structure of GPATCH11 based on results obtained from I-tasser. The confidence score was very low though, so reliability is uncertain. However, it does match up with the secondary structure prediction of the protein being composed primarily of alpha-helices and coiled coils.

Protein expression

Protein expression has been found in the endocrine and nervous system, along with the eye, breast, colon, liver, ovary, and 55 other tissues. Gene expression is found to be about 1.1 times the average. The highest expression is found in the brain and spinal cord, followed by the spleen. There are six areas in the brain where GPATCH11 is expressed above average including the olfactory areas, hippocampus, midbrain, pons, medulla, and cerebellum.[6] In addition, expression levels increase in cancerous tissue compared to normal tissue.

Predicted Post-Translational Modification

Using various tools at ExPASy[7] the following are possible post-translational modifications for GPATCH11.

  • 3 possible CK2 phosphorylation sites
  • 6 possible PKC phosphorylation sites
  • 2 possible N-mirystoylation sites
  • 6 possible glycation sites

Protein Interaction
Protein Abbreviation Location Function
Brain-specific angiogenesis inhibitor 3 BAI3 x Plays a role in the regulation of synaptogenesis and dendritic spine formation
Jun proto-oncogene JUN Nucleus[8] Highly similar to the avian viral sarcoma protein, and which interacts directly with specific target DNA sequences to regulate gene expression
Zinc finger (CCCH type) RNA-binding motif and serine/arginine rich 2 ZRSR2 Nucleus[8] Encodes an essential splicing factor, and may play a role in network interactions during spliceosome assembly.
U2 small nuclear RNA auxiliary factor 1 U2AF1 Nucleus[8] Plays a critical role in both constitutive and enhancer-dependent splicing

The interaction between GPATCH11 and BAI3 was found via PSICQUIC,[9] mentha,[9] and STRING.[8] The confidence score given by mentha is only .454, however, according to STRING the interaction between the two proteins has been experimentally determined by a validated two-hybrid approach. The two proteins are thought to have a direct physical interaction. BAI3 is a transmembrane protein and a p53 target gene. BAI3 may regulate the number of excitatory synapses that are formed on the hippocampus neurons, and may be involved in angiogenesis inhibition and suppression of glioblastoma. As GPATCH11does have higher expression than the average gene in the hippocampus and the spinal cord, this could be a real interaction.

The interaction between GPATCH11 and JUN could be real as JUN is both localized in the nucleus and associated with cancers. GPATCH11 tends to have higher expression in cancerous tissue compared to normal tissue, so interaction with other proteins highly expressed in cancers seems plausible.

Finally, the interactions between GPATCH11 and ZRSR2 and GPATCH11 and U2AF1 appear to be real due to the fact that ZRSR2 and U2AF1 are known to interact with each other, and all three proteins are localized in the nucleus.

Evolutionary History

The protein is found in all taxa of the domain eukarya, including unicellular organisms. Aligning the human gene with the various taxids revealed high conservation in the G-patch domain area and the DUF 4187 area.[2] Alignments with closely related taxids such as birds and reptiles revealed conservation over the majority of the sequence. However, alignments with more distantly related taxids such as fungi and plants had less conservation with identities of less than 40%, though the G-patch domain and the DUF domain still had high conservation.[10] Overall, the protein is composed mainly of charged amino acids, both acidic and basic. There were no regions of sustained non-polarity. This implies that this is not a transmembrane protein as that requires a long region of non-polarity.

Obtained via SDSC Biology Workbench. The tree encompasses a representative orthologs within the eukarya domain.

When comparing the rate of evolution of GPATCH11 to known proteins such as fibrinogen and cytochrome c, GPATCH11 is evolving quite rapidly, similar to the rate of the fibrinogen protein. An unrooted evolutionary tree[10] can be seen to the right including representatives of species ranging from invertebrates to mammals. This shows the hypothetical relationship of the GPATCH11 sequence among the different taxa, and is supported by divergence time of the taxa from humans as well as sequence identity/similarity.

Homology

The protein is highly conserved among the domain eukarya. The table below lists a number of species from all different taxids whose GPATCH11 sequence was compared to the human GPATCH11 sequence. Protein sequence lengths, similarities, and identities are represented, including divergence in millions of years.

Genus and Species Common Name Divergence (MYA)[11] Accession number Sequence length (amino acids) Sequence identity (%) Sequence similarity (%)
Homo sapiens Human 0 NP_777591.3 285 100 100
Equus asinus African ass 97.5 XP_014688350.1 285 94 97
Picoides pubescens Downy woodpecker 320.5 XP_009910012.1 256 73 86
Merops nubicus Northern carmine bee-eater 320.5 XP_008934567.1 258 73 87
Chrysemys picta bellii Western painted turtle 320.5 XP_005296317.1 257 76 89
Alligator mississippiensis American Alligator 320.5 XP_006272937.1 260 71 85
Xenopus tropicalis Western clawed frog 355.7 NP_001005035.1 261 63 80
Neolamprologus brichardi Fairy (lyretail) cichlid 429.6 XP_006807714.1 260 60 78
Stegastes partitus Bicolor damselfish 429.6 XP_008301855.1 265 58 78
Branchiostoma floridae Florida lancelet 743 XP_002610131.1 264 45 65
Saccoglossus kowalevskii Acorn worm 747.8 XP_002731571.2 311 48 67
Crassostrea gigas Pacific oyster 847 XP_011417222.1 262 43 61
Bombus terrestris Buff-tailed bumblee 847 XP_012173875.1 246 40 63
Monomorium pharaonis Pharaoh ant 847 XP_012521549.1 248 38 61
Halyomorpha halys Brown marmorated stink bug 847 XP_014272647.1 258 41 61
Trichoplax adhaerens Placozoan 936 XP_002108305.1 256 42 60
Batrachochytrium dendrobatidis Chytrid fungus 1302.5 XP_006681792.1 277 31 55
Saccharomyces cerevisiae Baker's Yeast 1302.5 NP_013373.1 274 42 62
Musa acuminata malaccensis Wild banana 1513.9 XP_009405687.1 248 33 51
Capsella rubella Pink Shepherd's-Purse 1513.9 XP_006290276.1 269 33 54
Elaeis guineensis African oil palm 1513.9 XP_010928444.1 253 34 52

Clinical significance

Clinical significance is not yet known, however, GPATCH11 is present in much higher amounts in cancerous tissue than normal tissue, and has shown possible protein interaction with oncogenes, so might somehow be involved in cancer.

References
  1. "http://genecards.org/". genecards.org. Archived from the original on 2016-02-29. Retrieved 2016-02-29. External link in |title= (help)
  2. "National Center for Biotechnology Information". ncbi.nlm.nih.gov. Retrieved 2016-02-29.
  3. "UniProt". uniprot.org. Retrieved 2016-02-29.
  4. "AceView a comprehensive annotation of human and worm genes with mRNAs or ESTsAceView". ncbi.nlm.nih.gov. Retrieved 2016-05-09.
  5. "Ensembl genome browser 83". ensembl.org. Retrieved 2016-02-29.
  6. "ISH Data :: Allen Brain Atlas: Mouse Brain". mouse.brain-map.org. Retrieved 2016-05-09.
  7. ExPASy Proteomics Server
  8. "STRING: functional protein association networks". string-db.org. Retrieved 2016-05-09.
  9. PSICQUIC. "PSICQUIC View". ebi.ac.uk. Retrieved 2016-05-09.
  10. "SDSC Biology Workbench". workbench.sdsc.edu. Retrieved 2016-02-29.
  11. "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2016-02-29.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.