KIAA2013

Last updated

KIAA2013
Identifiers
Aliases KIAA2013
External IDs MGI: 1924284; HomoloGene: 12668; GeneCards: KIAA2013; OMA:KIAA2013 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

90231

77034

Ensembl

ENSG00000116685

ENSMUSG00000044496

UniProt

Q8IYS2

Q91X21

RefSeq (mRNA)

NM_138346

NM_029841

RefSeq (protein)

NP_612355

NP_084117

Location (UCSC) Chr 1: 11.92 – 11.93 Mb Chr 4: 148.03 – 148.03 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

KIAA2013, also known as Q8IYS2 [5] or MGC33867, [6] is a single-pass transmembrane protein encoded by the KIAA2013 gene in humans. [5] The complete function of KIAA2013 has not yet been fully elucidated.

Contents

Gene

The KIAA2013 gene is located on the short arm of chromosome 1, in location 36.22 (1p36.22). [7] It can be found on the minus strand of the previously mentioned chromosome, running from 11,986,485 to 11,979,643. [8] The gene contains 3 exons, 2 introns, and is 6,838 base pairs long. [7]

mRNA

Splice variants

There are two alternate splice variants. One retains a transcript length of 2539 bp and the other retains a transcript length of 2170. [9]

Structure

The longest mRNA splice variant of the KIAA2013 protein contains 634 amino acid residues. The predicted weight of the protein is 69.2 kDa [10] and its isoelectric point is 8.44. There is also a lysine multiplet of six amino acid residues in a row, beginning in position 28. [11] This sequence, however, is located within the cleavable signal peptide and will most likely not remain a part of the mature protein.

Conserved domains

KIAA2013 contains one conserved protein domain of unknown function by the name of DUF2152, or pfam10222. This protein has remained conserved from mammals to invertebrates. [12] The conserved domain extends from amino acid position 6 to 629.

Secondary structure

Secondary structure as analyzed via GOR4: [13]

StructurePercentage
Alpha helix 38%
Beta sheet 61.2%

Tertiary structure

An AlphaFold prediction has been generated that was further analyzed through the use of iCn3D. [14] The following images highlight the transmembrane regions of the KIAA2013 protein, as well as the three disulfide bridges that can be seen to form.

iCn3D rendering of tertiary structure of KIAA2013 with the three disulfide bridges shown to form. Disulfide Bonds iCn3D.png
iCn3D rendering of tertiary structure of KIAA2013 with the three disulfide bridges shown to form.
iCn3D illustration of the transmembrane region of the KIAA2013 protein. This region is entirely a helical structure. Transmembrane iCn3D.png
iCn3D illustration of the transmembrane region of the KIAA2013 protein. This region is entirely a helical structure.

Gene level regulation

Promoter

The singular human KIAA2013 promoter is a 1194 bp long sequence that precedes the gene. [15]

Transcription factor binding sites

There are hundreds of possible transcription factor binding sites that can be found on the promoter sequence of KIAA2013. Here is a list of some that retain a high matrix similarity:

Tissue expression

NCBI GEO KIAA2013 expression data as it stands regarding normal tissue samples in the human body. KIAA2013 expression across normal tissues in the human body.png
NCBI GEO KIAA2013 expression data as it stands regarding normal tissue samples in the human body.

The KIAA2013 protein has been shown to be expressed ubiquitously across many differing human tissues. However, studies suggest that the small intestine, most specifically the duodenum, as well as the colon and kidneys express higher levels of this protein. [16] RNA-seq data has indicated that this gene is also expressed within the intestine of 20-week-old fetuses. [7] NCBI GEO data of preimplantation embryos indicates that KIAA2013 expression begins to be expressed in high amounts after the 4-cell embryo has developed. [17]

Transcript level regulation

3' UTR

As can be seen in the image, this final portion of the KIAA2013 3' UTR contains the poly-A signal as well as multiple ELAVL1 miRNA binding sites. ELAVL1 is a necessary RNA binding protein during the process of placental branching and general embryonic development. Out of the womb, ELAVL1 promotes angiogenesis, or the formation of new blood vessels. [18]

This image captures the end of the 3' UTR, wherein several ELAVL1 miRNA binding sites and one poly-A site can be seen. Portion of the 3' UTR of KIAA2013.png
This image captures the end of the 3' UTR, wherein several ELAVL1 miRNA binding sites and one poly-A site can be seen.
5' UTR illustrating the miRNA binding sites of EIF4b, FUS, RBM4, as well as a couple of stop-codons. 5' UTR of KIAA2013 protein.png
5' UTR illustrating the miRNA binding sites of EIF4b, FUS, RBM4, as well as a couple of stop-codons.

5' UTR

The 5' UTR has two main conserved regions, located at the very beginning and very end of the sequence. Not only that, but it has two sequences coding for stop codons, as can be seen in the image. Most miRNA seem to congregate around the two conserved domains. EIF4B is known as eukaryotic translation initiation factor 4B and is needed to bind mRNAs to ribosomes as well as assist with the translation of longer 5' UTRs. [19] It binds to the mRNA in the presence of ATP. FUS actually mediates gene silencing. [20] It has also been clinically linked with ALS diagnosis cases. [20] Finally, RBM4 helps to control translation as well as alternative splicing events. Reduced expression of this miRNA has been linked to Down syndrome. [21]

Protein level regulation

Subcellular localization

KIAA2013 has been found to intracellularly localize to the Golgi apparatus and endoplasmic reticulum. This has been validated through the use of GFP fusion and antibody specific experimentation. [22] DeepLoc analysis has indicated that there is an 81.94% chance that this protein is found in the Golgi apparatus and 16.77% that it is localized to the endoplasmic reticulum. [23] The likelihood that KIAA2013 is a membrane protein sits at 99.98%. [23]

Post-translational modifications

There is a predicted signal peptide spanning across amino acids 1-40. [24] The cleavage site for this signal peptide is located between amino acid positions 40 and 41. There are also a collection of post-translational modifications that can be connected with KIAA2013. They include:

KIAA2013 Post-Translational Modifications
ModificationLocation
Glycosylation T224 [25]
Glycosylation N363 [25]
Phosphorylation S159 [26]
Phosphorylation S381 [26]
Ubiquitylation K629 [27]

Homology

Paralogs

There are currently no known paralogs of KIAA2013.

Pseudogene

KIAA2013 has one pseudogene found within Homo sapiens named LOC728138. The length of this pseudogene is 633 amino acid residues and it shares a 96.8% sequence identity with KIAA2013. [28]

Orthologs

There are orthologs for KIAA2013 ranging from mammals all the way back to invertebrates. As of now, there are 419 organisms that are known to contain orthologs of this gene. [29]

Table of KIAA2013 Orthologs
KIAA2013Genus, speciesCommon NameDivergence Date (MYA)Accession NumberProtein LengthSeq. IdentitySeq. Similarity
Mammalia Homo sapiens Human0 NP_612355.1 634100%100%
Mus caroli Ryuku mouse90 XP_021016690.1 63491.8%95.9%
Mirounga leonina Southern elephant seal94 XP_034875674.1 62994.8%96.8%
Felis catus Cat96 XP_003989629.3 63494.8%97.1%
Aves Falco rusticolus Gyrfalcon312 XP_037236550.1 61261.7%71%
Reptilia Gopherus evgoodei Goode's thornscrub tortoise312 XP_030393408.1 62364.9%74.9%
Amphibian Xenopus laevis African clawed frog352 XP_018083185.1 61455.5%69.1%
Microcaecelia unicolor Tiny Cayenne Caecilian352 XP_030078049.1 62353%68.4%
Fish Acipenser ruthenus Sterlet435 XP_033899255.2 61056.5%69.3%
Lepisosteus oculatus Spotted gar435 XP_006642029.2 62355.1%68.1%
Invertebrates Anopheles merus Mosquito797 XP_041777166.1 62527.5%44.5%
Pollicipes pollicipes Goose Neck Barnacle797 XP_037086897.1 63927.6%44.3%
Drosophila subpulchrella Fly797 XP_037708712.1 63726%43%
Limulus polyphemus Atlantic Horseshoe crab797 XP_013773544.2 51621.8%36.8%

Evolution

The graph to the right illustrates the rate of divergence of the protein KIAA2013, as compared to cytochrome c and fibrinogen alpha. This graph utilized a molecular clock approach wherein the evolution of the protein KIAA2013 was compared to the rate of the two previously mentioned proteins. Cytochrome c has a much slower rate of divergence as compared to fibrinogen alpha, while KIAA2013 lies in between the two. [30]

The evolution of KIAA2013, as compared to fibrinogen alpha and cytochrome c. Protein Divergence.png
The evolution of KIAA2013, as compared to fibrinogen alpha and cytochrome c.

Interacting proteins

KIAA2013 has been found to interact with two proteins: TMEM60 and IBP5 via a validated two-hybrid array. [31]

Clinical significance

KIAA2013 has been found to play a role in the endocannabinoid system. This system is made up of cannabinoid receptors 1 and 2 (CB1 and CB2) as well as the various ligands and enzymes that interact. The protein KIAA2013 has been found to be expressed within CB2 expressing cells. [32] Both cannabinoid receptors are labeled as class A G protein-coupled receptors, and CB2 is highly expressed within the human spleen and leukocytes. CB2, and by extension KIAA2013, are therefore targets of interest for therapeutic studies looking into diseases such as inflammatory bowel disease and rheumatoid arthritis. [33]

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000116685 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000044496 – 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. 1 2 "KIAA2013 – Uncharacterized protein KIAA2013 precursor – Homo sapiens (Human) – KIAA2013 gene & protein". www.uniprot.org. Retrieved 2021-12-17.
  6. ↑ "KIAA2013".
  7. 1 2 3 "KIAA2013 KIAA2013 [Homo sapiens (human)] – Gene – NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-17.
  8. ↑ "AceView: Gene:KIAA2013, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2021-12-17.
  9. ↑ "Gene: KIAA2013 (ENSG00000116685) – Splice variants – Homo_sapiens – Ensembl genome browser 105". useast.ensembl.org. Retrieved 2021-12-18.
  10. ↑ "KIAA2013 Antibody (27886-1-AP)". www.thermofisher.com. Retrieved 2021-12-18.
  11. ↑ "PSORT II Prediction". psort.hgc.jp. Retrieved 2021-12-18.
  12. ↑ "CDD Conserved Protein Domain Family: DUF2152". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  13. ↑ "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2021-12-18.
  14. ↑ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2021-12-18.
  15. ↑ "GXP_42188(KIAA2013/human)".
  16. ↑ "GDS3113 / 706030". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  17. ↑ "GDS3959 / 224706_at". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  18. ↑ Chang SH, Elemento O, Zhang J, Zhuang ZW, Simons M, Hla T (December 2014). "ELAVL1 regulates alternative splicing of eIF4E transporter to promote postnatal angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 111 (51): 18309–18314. Bibcode:2014PNAS..11118309C. doi: 10.1073/pnas.1412172111 . PMC   4280608 . PMID   25422430.
  19. ↑ Sen ND, Zhou F, Harris MS, Ingolia NT, Hinnebusch AG (September 2016). "eIF4B stimulates translation of long mRNAs with structured 5' UTRs and low closed-loop potential but weak dependence on eIF4G". Proceedings of the National Academy of Sciences of the United States of America. 113 (38): 10464–10472. Bibcode:2016PNAS..11310464S. doi: 10.1073/pnas.1612398113 . PMC   5035867 . PMID   27601676.
  20. 1 2 Zhang T, Wu YC, Mullane P, Ji YJ, Liu H, He L, et al. (March 2018). "FUS Regulates Activity of MicroRNA-Mediated Gene Silencing". Molecular Cell. 69 (5): 787–801.e8. doi:10.1016/j.molcel.2018.02.001. PMC   5836505 . PMID   29499134.
  21. ↑ Dhananjaya D, Hung KY, Tarn WY (June 2018). "RBM4 Modulates Radial Migration via Alternative Splicing of Dab1 during Cortex Development". Molecular and Cellular Biology. 38 (12). doi:10.1128/MCB.00007-18. PMC   5974434 . PMID   29581187.
  22. ↑ Kandasamy K, Keerthikumar S, Goel R, Mathivanan S, Patankar N, Shafreen B, et al. (January 2009). "Human Proteinpedia: a unified discovery resource for proteomics research". Nucleic Acids Research. 37 (Database issue): D773–D781. doi:10.1093/nar/gkn701. PMC   2686511 . PMID   18948298.
  23. 1 2 "Summary of 1 predicted sequences".
  24. ↑ "RecName: Full=Uncharacterized protein KIAA2013; Flags: Precursor – Protein – NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  25. 1 2 "KIAA2013 – Uncharacterized protein KIAA2013 precursor – Homo sapiens (Human) – KIAA2013 gene & protein". www.uniprot.org. Retrieved 2021-12-18.
  26. 1 2 "KIAA2013 (human)". www.phosphosite.org. Retrieved 2021-12-18.
  27. ↑ "KIAA2013 (RP5-1077B9.1) Result Summary | BioGRID". thebiogrid.org. Retrieved 2021-12-18.
  28. ↑ "LOC728138 protein [Homo sapiens] – Protein – NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  29. ↑ "ortholog_gene_90231[group] – Gene – NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-12-18.
  30. ↑ Ho SY, Duchêne S (December 2014). "Molecular-clock methods for estimating evolutionary rates and timescales". Molecular Ecology. 23 (24): 5947–5965. Bibcode:2014MolEc..23.5947H. doi:10.1111/mec.12953. PMID   25290107. S2CID   21704137.
  31. ↑ Luck K, Kim DK, Lambourne L, Spirohn K, Begg BE, Bian W, et al. (April 2020). "A reference map of the human binary protein interactome". Nature. 580 (7803): 402–408. Bibcode:2020Natur.580..402L. doi:10.1038/s41586-020-2188-x. PMC   7169983 . PMID   32296183.
  32. ↑ Sharaf A, Mensching L, Keller C, Rading S, Scheffold M, Palkowitsch L, et al. (2019). "Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome". Frontiers in Molecular Neuroscience. 12: 224. doi: 10.3389/fnmol.2019.00224 . PMC   6763791 . PMID   31616248.
  33. ↑ Oyagawa CR, Grimsey NL (2021-01-01). Shukla AK (ed.). Cannabinoid receptor CB1 and CB2 interacting proteins: Techniques, progress and perspectives. Biomolecular Interactions Part A. Vol. 166. Academic Press. pp. 83–132. doi:10.1016/bs.mcb.2021.06.011. ISBN   978-0-12-823351-1. PMID   34752341. S2CID   240248917.{{cite book}}: |journal= ignored (help)
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